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Management of retinoblastoma
Dr Roopsi Sharma
DNB JR
MAX Hospital Saket
STAGING and CLASSIFICATION
bull ReesendashEllsworth system of classifying retinoblastoma (1964)
bull Predicts the outcome after EBRT
Based on
noof lesion size of lesion
Location of lesion and viterous seeding
ReesendashEllsworth system of classifying retinoblastoma (1964)
Group I Very favorableASolitary tumor less than 4 DD at or behind the
equator B Multiple tumors none larger than 4 DD all at or behind the
equatorGroup II Favorable A Solitary tumor 4ndash10 DD at or behind the equator B Multiple tumors 4ndash10 DD all at or behind the equator
Group III Doubtful A Any lesion anterior to the equator B Solitary tumors larger than 10 DD behind the equator
ReesendashEllsworth system of classifying retinoblastoma (1964)
Group IV Unfavorable
A Multiple tumors some larger than 10 DD
BAny lesion extending anterior to the oraserrata
Group V Very unfavorable
A Massive tumors involving more than half of the retina
BVitreous seeding
RE system DEMERITS
bull Doesnrsquot take into account retinal detachment or subretinal
tumor seeding prognostic factors for vision preservation
bull Small anterior tumors were placed in group 3 or 4 because
they were not usually controlled by ExRT technique in use
at that time but they are quite responsive to modern RT
techniques cryotherapy or RT plaque therapy
bull Vitreous seeding classified as group 5b although local
vitreous seeding can often be treated with RT plaque
International classification of retinoblastoma- 2006
Group A small intraretinal tumors away from the disc and foveola
bull No tumor greater than 3 mm in diameter
bull Located at least (3 mm) from fovea or 15 mm) from Optic disc
Group B all remaining discrete tumors confined to retina
All other tumors confined to retina not in group A
Subretinal fluid (without subretinal seeding) lt3 or 3 mm from base of the tumor
Group C local subretinal fluid or seeding
Local subretinal fluid alone gt3 to 6orlt6 mm from the tumor
Viterous seeding or subretinal seeding lt3 or 3 mm from tumor
Group D diffuse subretinal fluid or seeding bull Subretinal fluid alone gt6 mm from the tumorbull Viterous seeding or subretinal seeding gt3mm from tumor
Group E presence of one or more of these poor prognostic factors More than 23 of the globe filled with tumor Tumor in the anterior segment Tumor in or on the ciliary body Iris neovascularization Neovascular glaucoma Opaque media from hemorrhage Phthisical or prephthisical eye Orbital cellulitis-like presentation
Modified from Shields CL etalinternation classification predicts chemoreduction successopthamology 1132276-22802006
International retinoblastoma staging system proposed - 2006
Stage 0 Patient treated conservatively
stage-1 eye eneucleated completely resectedhistologicaly
stage-2 eye eneucleated micoscopic residual tumor
stage-3 regional extension
3a- overt orbital disease
3b- preauricular or cervical lymphnode extension
bull stage-4 metastatic diseasebull 4a- heamatogenous metastasis without CNS
involvementbull 1- single lesionbull 2- multiple lesionbull 4b-CNS extension with or without any other site
of regional or metastatic diseasebull 1-prechiasmatic lesionbull 2 CNS massbull 3 leptomeningeal and cerebrospinal fluid disease
Goal of treatment
bull Save life (main goal)
bull Preserve useful vision
bull Attention on late functional and craniogeniceffect as sequale to treatment
TREATMENT
MODALITIES
Surgery Enucleation exenteration
Focal therapies
Cryotherapy
Laser hyperthermia
Laser photocoagulation
Radioactive plaque applications
External beam radiotherapy
Chemotherapy
ENUCLEATIONIndications
bull UL or BL Rb when eye is blind
bull Presence of neovascular glaucoma
bull When disease cannot be controlled by chemo or local treatment
bull Tumor invasion into anterior chamber
bull Direct visulization of an active tumor is obstucted by condition like ndash
hemorrhage corneal opacity or cataract
In co BL Rb
Eye with RD Vitreous hemorrhage glaucoma painful blind eye should
be enucleated and other eye should be treated as per the disease
status
Structures removed
bull Gentle removal of intact eye globe without
perforation to avoid seeding of orbit
bull Optic nerve long segment (15mm) for presence of
tumor extension
bull Enucleation is curative in 95 of patient with ul ds
bull Now a days orbital implants are used at mosr centers
EXENTERATION
Indications
bull Extensive local tumor breaching the globe- orbital involvement
bull (exenteration in this situation generally is followed by postoperative
radiotherapy and chemotherapy)
bull Recurrence of tumor in the socket after enucleation
Structures removed
bull The globe
bull Extraocular muscles
bull Lids
bull Optic nerve
bull Orbital fat
FOCAL THERAPIES
Small tumors( 3-6mm)
Used in combination with chemo
Used as a part of consevative therapy to avoid enucleation and EBRT in ul ds
PHOTOCOAGULATION
INDICATIONS
bull Tumors up to 45 mm at the base and up to 25 mm thick not close to the macula or disk with no
evidence of viteros seeds
bull Tumors situated at or posterior to equator of the eye
bull May be used for small tumor recurrences after irradiation
bull Local control of intraocular disease post chemoreduction
TECHNIQUE
Argon laser diode laser or xenon arc photocoagulation are used
bull Based on obliteration of the retinal vessels
bull 2-3 monthly sessions are required
bull LOCAL TUMOR CONTROL 70
Shields JA et alThe expanding role of laser photocoagulation for intraocular tumors The 1993 H Christian
Zweng Memorial Lecture Retina 199414(4)310-22
Complications
Transient serous retinal detachment
bull Retinal traction
bull Retinal hole
bull Visually significant retinal vascular occlusion
CRYOTHERAPY
INDICATIONS
bull Small equatorial and peripheral lesion that lt35 mm at the base and lt2mm in
height
bull Local recurrence
bull Tumor persistence after irradiation
bull In conjunction with chemotherapy
TECHNIQUE
Nitrous oxide probe (-80 C) 1-2 monthly session of triple freeze thaw cycle
SIDE EFFECTS transient serous retinal detachment retinal tear localized preretinal
fibrosis
Transpupillary thermotherapy
PRINCIPLE
bull thermotherapy has synergistic effect with chemotherapy9 ( carboplatin) ndash enhances the platinum
DNA adduct thus ndash antitumor effect
INDICATIONS
bull Small (lt 3mm) tumors posterior to the equator
bull Larger tumors post chemotherapy
TECHNIQUE
bull With diode laser focused heat at sub photocoagulation level- 42C to 60C for 5-20 min to tumor is
applied with relatively sparing of retinal vessels from photocoagulation
bull Local control of 70-80
COMPLICATIONS
bull Retinal traction fibrosis transient serous retinal detachment
RADIOACTIVE PLAQUE APPLICATION
INDICATIONS
1Primary plaque therapy ndash localized RB typically limited to 1-2 foci not involving optic disc or macula
2 In conjunction with chemoreduction therapy- -small or moderate size lesion including those with focal
viterous seeding immediately overlying the tumor
3 Tumors lt1616mm at base and lt8mm in thickness
4 Local failure after other therapy (EBRT chemotherapy laser cryotherapy)
ADVANTAGES (vs EBRT)
bull Better dose localization
bull Lesser risk of cataract
bull Minimal risk of bone hypoplasia
bull Lesser risk of second malignancies
PLAQUE TYPES and features
bull Co60
bull I125 (27 to 35 kev half- life ndash 60 days)- gamma rays
emitter
bull Au198 Ir192Ru106- beta emitter
bull Ir-192- (295-612kevhalflife- 74 days)
bull Ru-106( 35 Mev374 days)
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
STAGING and CLASSIFICATION
bull ReesendashEllsworth system of classifying retinoblastoma (1964)
bull Predicts the outcome after EBRT
Based on
noof lesion size of lesion
Location of lesion and viterous seeding
ReesendashEllsworth system of classifying retinoblastoma (1964)
Group I Very favorableASolitary tumor less than 4 DD at or behind the
equator B Multiple tumors none larger than 4 DD all at or behind the
equatorGroup II Favorable A Solitary tumor 4ndash10 DD at or behind the equator B Multiple tumors 4ndash10 DD all at or behind the equator
Group III Doubtful A Any lesion anterior to the equator B Solitary tumors larger than 10 DD behind the equator
ReesendashEllsworth system of classifying retinoblastoma (1964)
Group IV Unfavorable
A Multiple tumors some larger than 10 DD
BAny lesion extending anterior to the oraserrata
Group V Very unfavorable
A Massive tumors involving more than half of the retina
BVitreous seeding
RE system DEMERITS
bull Doesnrsquot take into account retinal detachment or subretinal
tumor seeding prognostic factors for vision preservation
bull Small anterior tumors were placed in group 3 or 4 because
they were not usually controlled by ExRT technique in use
at that time but they are quite responsive to modern RT
techniques cryotherapy or RT plaque therapy
bull Vitreous seeding classified as group 5b although local
vitreous seeding can often be treated with RT plaque
International classification of retinoblastoma- 2006
Group A small intraretinal tumors away from the disc and foveola
bull No tumor greater than 3 mm in diameter
bull Located at least (3 mm) from fovea or 15 mm) from Optic disc
Group B all remaining discrete tumors confined to retina
All other tumors confined to retina not in group A
Subretinal fluid (without subretinal seeding) lt3 or 3 mm from base of the tumor
Group C local subretinal fluid or seeding
Local subretinal fluid alone gt3 to 6orlt6 mm from the tumor
Viterous seeding or subretinal seeding lt3 or 3 mm from tumor
Group D diffuse subretinal fluid or seeding bull Subretinal fluid alone gt6 mm from the tumorbull Viterous seeding or subretinal seeding gt3mm from tumor
Group E presence of one or more of these poor prognostic factors More than 23 of the globe filled with tumor Tumor in the anterior segment Tumor in or on the ciliary body Iris neovascularization Neovascular glaucoma Opaque media from hemorrhage Phthisical or prephthisical eye Orbital cellulitis-like presentation
Modified from Shields CL etalinternation classification predicts chemoreduction successopthamology 1132276-22802006
International retinoblastoma staging system proposed - 2006
Stage 0 Patient treated conservatively
stage-1 eye eneucleated completely resectedhistologicaly
stage-2 eye eneucleated micoscopic residual tumor
stage-3 regional extension
3a- overt orbital disease
3b- preauricular or cervical lymphnode extension
bull stage-4 metastatic diseasebull 4a- heamatogenous metastasis without CNS
involvementbull 1- single lesionbull 2- multiple lesionbull 4b-CNS extension with or without any other site
of regional or metastatic diseasebull 1-prechiasmatic lesionbull 2 CNS massbull 3 leptomeningeal and cerebrospinal fluid disease
Goal of treatment
bull Save life (main goal)
bull Preserve useful vision
bull Attention on late functional and craniogeniceffect as sequale to treatment
TREATMENT
MODALITIES
Surgery Enucleation exenteration
Focal therapies
Cryotherapy
Laser hyperthermia
Laser photocoagulation
Radioactive plaque applications
External beam radiotherapy
Chemotherapy
ENUCLEATIONIndications
bull UL or BL Rb when eye is blind
bull Presence of neovascular glaucoma
bull When disease cannot be controlled by chemo or local treatment
bull Tumor invasion into anterior chamber
bull Direct visulization of an active tumor is obstucted by condition like ndash
hemorrhage corneal opacity or cataract
In co BL Rb
Eye with RD Vitreous hemorrhage glaucoma painful blind eye should
be enucleated and other eye should be treated as per the disease
status
Structures removed
bull Gentle removal of intact eye globe without
perforation to avoid seeding of orbit
bull Optic nerve long segment (15mm) for presence of
tumor extension
bull Enucleation is curative in 95 of patient with ul ds
bull Now a days orbital implants are used at mosr centers
EXENTERATION
Indications
bull Extensive local tumor breaching the globe- orbital involvement
bull (exenteration in this situation generally is followed by postoperative
radiotherapy and chemotherapy)
bull Recurrence of tumor in the socket after enucleation
Structures removed
bull The globe
bull Extraocular muscles
bull Lids
bull Optic nerve
bull Orbital fat
FOCAL THERAPIES
Small tumors( 3-6mm)
Used in combination with chemo
Used as a part of consevative therapy to avoid enucleation and EBRT in ul ds
PHOTOCOAGULATION
INDICATIONS
bull Tumors up to 45 mm at the base and up to 25 mm thick not close to the macula or disk with no
evidence of viteros seeds
bull Tumors situated at or posterior to equator of the eye
bull May be used for small tumor recurrences after irradiation
bull Local control of intraocular disease post chemoreduction
TECHNIQUE
Argon laser diode laser or xenon arc photocoagulation are used
bull Based on obliteration of the retinal vessels
bull 2-3 monthly sessions are required
bull LOCAL TUMOR CONTROL 70
Shields JA et alThe expanding role of laser photocoagulation for intraocular tumors The 1993 H Christian
Zweng Memorial Lecture Retina 199414(4)310-22
Complications
Transient serous retinal detachment
bull Retinal traction
bull Retinal hole
bull Visually significant retinal vascular occlusion
CRYOTHERAPY
INDICATIONS
bull Small equatorial and peripheral lesion that lt35 mm at the base and lt2mm in
height
bull Local recurrence
bull Tumor persistence after irradiation
bull In conjunction with chemotherapy
TECHNIQUE
Nitrous oxide probe (-80 C) 1-2 monthly session of triple freeze thaw cycle
SIDE EFFECTS transient serous retinal detachment retinal tear localized preretinal
fibrosis
Transpupillary thermotherapy
PRINCIPLE
bull thermotherapy has synergistic effect with chemotherapy9 ( carboplatin) ndash enhances the platinum
DNA adduct thus ndash antitumor effect
INDICATIONS
bull Small (lt 3mm) tumors posterior to the equator
bull Larger tumors post chemotherapy
TECHNIQUE
bull With diode laser focused heat at sub photocoagulation level- 42C to 60C for 5-20 min to tumor is
applied with relatively sparing of retinal vessels from photocoagulation
bull Local control of 70-80
COMPLICATIONS
bull Retinal traction fibrosis transient serous retinal detachment
RADIOACTIVE PLAQUE APPLICATION
INDICATIONS
1Primary plaque therapy ndash localized RB typically limited to 1-2 foci not involving optic disc or macula
2 In conjunction with chemoreduction therapy- -small or moderate size lesion including those with focal
viterous seeding immediately overlying the tumor
3 Tumors lt1616mm at base and lt8mm in thickness
4 Local failure after other therapy (EBRT chemotherapy laser cryotherapy)
ADVANTAGES (vs EBRT)
bull Better dose localization
bull Lesser risk of cataract
bull Minimal risk of bone hypoplasia
bull Lesser risk of second malignancies
PLAQUE TYPES and features
bull Co60
bull I125 (27 to 35 kev half- life ndash 60 days)- gamma rays
emitter
bull Au198 Ir192Ru106- beta emitter
bull Ir-192- (295-612kevhalflife- 74 days)
bull Ru-106( 35 Mev374 days)
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
ReesendashEllsworth system of classifying retinoblastoma (1964)
Group I Very favorableASolitary tumor less than 4 DD at or behind the
equator B Multiple tumors none larger than 4 DD all at or behind the
equatorGroup II Favorable A Solitary tumor 4ndash10 DD at or behind the equator B Multiple tumors 4ndash10 DD all at or behind the equator
Group III Doubtful A Any lesion anterior to the equator B Solitary tumors larger than 10 DD behind the equator
ReesendashEllsworth system of classifying retinoblastoma (1964)
Group IV Unfavorable
A Multiple tumors some larger than 10 DD
BAny lesion extending anterior to the oraserrata
Group V Very unfavorable
A Massive tumors involving more than half of the retina
BVitreous seeding
RE system DEMERITS
bull Doesnrsquot take into account retinal detachment or subretinal
tumor seeding prognostic factors for vision preservation
bull Small anterior tumors were placed in group 3 or 4 because
they were not usually controlled by ExRT technique in use
at that time but they are quite responsive to modern RT
techniques cryotherapy or RT plaque therapy
bull Vitreous seeding classified as group 5b although local
vitreous seeding can often be treated with RT plaque
International classification of retinoblastoma- 2006
Group A small intraretinal tumors away from the disc and foveola
bull No tumor greater than 3 mm in diameter
bull Located at least (3 mm) from fovea or 15 mm) from Optic disc
Group B all remaining discrete tumors confined to retina
All other tumors confined to retina not in group A
Subretinal fluid (without subretinal seeding) lt3 or 3 mm from base of the tumor
Group C local subretinal fluid or seeding
Local subretinal fluid alone gt3 to 6orlt6 mm from the tumor
Viterous seeding or subretinal seeding lt3 or 3 mm from tumor
Group D diffuse subretinal fluid or seeding bull Subretinal fluid alone gt6 mm from the tumorbull Viterous seeding or subretinal seeding gt3mm from tumor
Group E presence of one or more of these poor prognostic factors More than 23 of the globe filled with tumor Tumor in the anterior segment Tumor in or on the ciliary body Iris neovascularization Neovascular glaucoma Opaque media from hemorrhage Phthisical or prephthisical eye Orbital cellulitis-like presentation
Modified from Shields CL etalinternation classification predicts chemoreduction successopthamology 1132276-22802006
International retinoblastoma staging system proposed - 2006
Stage 0 Patient treated conservatively
stage-1 eye eneucleated completely resectedhistologicaly
stage-2 eye eneucleated micoscopic residual tumor
stage-3 regional extension
3a- overt orbital disease
3b- preauricular or cervical lymphnode extension
bull stage-4 metastatic diseasebull 4a- heamatogenous metastasis without CNS
involvementbull 1- single lesionbull 2- multiple lesionbull 4b-CNS extension with or without any other site
of regional or metastatic diseasebull 1-prechiasmatic lesionbull 2 CNS massbull 3 leptomeningeal and cerebrospinal fluid disease
Goal of treatment
bull Save life (main goal)
bull Preserve useful vision
bull Attention on late functional and craniogeniceffect as sequale to treatment
TREATMENT
MODALITIES
Surgery Enucleation exenteration
Focal therapies
Cryotherapy
Laser hyperthermia
Laser photocoagulation
Radioactive plaque applications
External beam radiotherapy
Chemotherapy
ENUCLEATIONIndications
bull UL or BL Rb when eye is blind
bull Presence of neovascular glaucoma
bull When disease cannot be controlled by chemo or local treatment
bull Tumor invasion into anterior chamber
bull Direct visulization of an active tumor is obstucted by condition like ndash
hemorrhage corneal opacity or cataract
In co BL Rb
Eye with RD Vitreous hemorrhage glaucoma painful blind eye should
be enucleated and other eye should be treated as per the disease
status
Structures removed
bull Gentle removal of intact eye globe without
perforation to avoid seeding of orbit
bull Optic nerve long segment (15mm) for presence of
tumor extension
bull Enucleation is curative in 95 of patient with ul ds
bull Now a days orbital implants are used at mosr centers
EXENTERATION
Indications
bull Extensive local tumor breaching the globe- orbital involvement
bull (exenteration in this situation generally is followed by postoperative
radiotherapy and chemotherapy)
bull Recurrence of tumor in the socket after enucleation
Structures removed
bull The globe
bull Extraocular muscles
bull Lids
bull Optic nerve
bull Orbital fat
FOCAL THERAPIES
Small tumors( 3-6mm)
Used in combination with chemo
Used as a part of consevative therapy to avoid enucleation and EBRT in ul ds
PHOTOCOAGULATION
INDICATIONS
bull Tumors up to 45 mm at the base and up to 25 mm thick not close to the macula or disk with no
evidence of viteros seeds
bull Tumors situated at or posterior to equator of the eye
bull May be used for small tumor recurrences after irradiation
bull Local control of intraocular disease post chemoreduction
TECHNIQUE
Argon laser diode laser or xenon arc photocoagulation are used
bull Based on obliteration of the retinal vessels
bull 2-3 monthly sessions are required
bull LOCAL TUMOR CONTROL 70
Shields JA et alThe expanding role of laser photocoagulation for intraocular tumors The 1993 H Christian
Zweng Memorial Lecture Retina 199414(4)310-22
Complications
Transient serous retinal detachment
bull Retinal traction
bull Retinal hole
bull Visually significant retinal vascular occlusion
CRYOTHERAPY
INDICATIONS
bull Small equatorial and peripheral lesion that lt35 mm at the base and lt2mm in
height
bull Local recurrence
bull Tumor persistence after irradiation
bull In conjunction with chemotherapy
TECHNIQUE
Nitrous oxide probe (-80 C) 1-2 monthly session of triple freeze thaw cycle
SIDE EFFECTS transient serous retinal detachment retinal tear localized preretinal
fibrosis
Transpupillary thermotherapy
PRINCIPLE
bull thermotherapy has synergistic effect with chemotherapy9 ( carboplatin) ndash enhances the platinum
DNA adduct thus ndash antitumor effect
INDICATIONS
bull Small (lt 3mm) tumors posterior to the equator
bull Larger tumors post chemotherapy
TECHNIQUE
bull With diode laser focused heat at sub photocoagulation level- 42C to 60C for 5-20 min to tumor is
applied with relatively sparing of retinal vessels from photocoagulation
bull Local control of 70-80
COMPLICATIONS
bull Retinal traction fibrosis transient serous retinal detachment
RADIOACTIVE PLAQUE APPLICATION
INDICATIONS
1Primary plaque therapy ndash localized RB typically limited to 1-2 foci not involving optic disc or macula
2 In conjunction with chemoreduction therapy- -small or moderate size lesion including those with focal
viterous seeding immediately overlying the tumor
3 Tumors lt1616mm at base and lt8mm in thickness
4 Local failure after other therapy (EBRT chemotherapy laser cryotherapy)
ADVANTAGES (vs EBRT)
bull Better dose localization
bull Lesser risk of cataract
bull Minimal risk of bone hypoplasia
bull Lesser risk of second malignancies
PLAQUE TYPES and features
bull Co60
bull I125 (27 to 35 kev half- life ndash 60 days)- gamma rays
emitter
bull Au198 Ir192Ru106- beta emitter
bull Ir-192- (295-612kevhalflife- 74 days)
bull Ru-106( 35 Mev374 days)
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
ReesendashEllsworth system of classifying retinoblastoma (1964)
Group IV Unfavorable
A Multiple tumors some larger than 10 DD
BAny lesion extending anterior to the oraserrata
Group V Very unfavorable
A Massive tumors involving more than half of the retina
BVitreous seeding
RE system DEMERITS
bull Doesnrsquot take into account retinal detachment or subretinal
tumor seeding prognostic factors for vision preservation
bull Small anterior tumors were placed in group 3 or 4 because
they were not usually controlled by ExRT technique in use
at that time but they are quite responsive to modern RT
techniques cryotherapy or RT plaque therapy
bull Vitreous seeding classified as group 5b although local
vitreous seeding can often be treated with RT plaque
International classification of retinoblastoma- 2006
Group A small intraretinal tumors away from the disc and foveola
bull No tumor greater than 3 mm in diameter
bull Located at least (3 mm) from fovea or 15 mm) from Optic disc
Group B all remaining discrete tumors confined to retina
All other tumors confined to retina not in group A
Subretinal fluid (without subretinal seeding) lt3 or 3 mm from base of the tumor
Group C local subretinal fluid or seeding
Local subretinal fluid alone gt3 to 6orlt6 mm from the tumor
Viterous seeding or subretinal seeding lt3 or 3 mm from tumor
Group D diffuse subretinal fluid or seeding bull Subretinal fluid alone gt6 mm from the tumorbull Viterous seeding or subretinal seeding gt3mm from tumor
Group E presence of one or more of these poor prognostic factors More than 23 of the globe filled with tumor Tumor in the anterior segment Tumor in or on the ciliary body Iris neovascularization Neovascular glaucoma Opaque media from hemorrhage Phthisical or prephthisical eye Orbital cellulitis-like presentation
Modified from Shields CL etalinternation classification predicts chemoreduction successopthamology 1132276-22802006
International retinoblastoma staging system proposed - 2006
Stage 0 Patient treated conservatively
stage-1 eye eneucleated completely resectedhistologicaly
stage-2 eye eneucleated micoscopic residual tumor
stage-3 regional extension
3a- overt orbital disease
3b- preauricular or cervical lymphnode extension
bull stage-4 metastatic diseasebull 4a- heamatogenous metastasis without CNS
involvementbull 1- single lesionbull 2- multiple lesionbull 4b-CNS extension with or without any other site
of regional or metastatic diseasebull 1-prechiasmatic lesionbull 2 CNS massbull 3 leptomeningeal and cerebrospinal fluid disease
Goal of treatment
bull Save life (main goal)
bull Preserve useful vision
bull Attention on late functional and craniogeniceffect as sequale to treatment
TREATMENT
MODALITIES
Surgery Enucleation exenteration
Focal therapies
Cryotherapy
Laser hyperthermia
Laser photocoagulation
Radioactive plaque applications
External beam radiotherapy
Chemotherapy
ENUCLEATIONIndications
bull UL or BL Rb when eye is blind
bull Presence of neovascular glaucoma
bull When disease cannot be controlled by chemo or local treatment
bull Tumor invasion into anterior chamber
bull Direct visulization of an active tumor is obstucted by condition like ndash
hemorrhage corneal opacity or cataract
In co BL Rb
Eye with RD Vitreous hemorrhage glaucoma painful blind eye should
be enucleated and other eye should be treated as per the disease
status
Structures removed
bull Gentle removal of intact eye globe without
perforation to avoid seeding of orbit
bull Optic nerve long segment (15mm) for presence of
tumor extension
bull Enucleation is curative in 95 of patient with ul ds
bull Now a days orbital implants are used at mosr centers
EXENTERATION
Indications
bull Extensive local tumor breaching the globe- orbital involvement
bull (exenteration in this situation generally is followed by postoperative
radiotherapy and chemotherapy)
bull Recurrence of tumor in the socket after enucleation
Structures removed
bull The globe
bull Extraocular muscles
bull Lids
bull Optic nerve
bull Orbital fat
FOCAL THERAPIES
Small tumors( 3-6mm)
Used in combination with chemo
Used as a part of consevative therapy to avoid enucleation and EBRT in ul ds
PHOTOCOAGULATION
INDICATIONS
bull Tumors up to 45 mm at the base and up to 25 mm thick not close to the macula or disk with no
evidence of viteros seeds
bull Tumors situated at or posterior to equator of the eye
bull May be used for small tumor recurrences after irradiation
bull Local control of intraocular disease post chemoreduction
TECHNIQUE
Argon laser diode laser or xenon arc photocoagulation are used
bull Based on obliteration of the retinal vessels
bull 2-3 monthly sessions are required
bull LOCAL TUMOR CONTROL 70
Shields JA et alThe expanding role of laser photocoagulation for intraocular tumors The 1993 H Christian
Zweng Memorial Lecture Retina 199414(4)310-22
Complications
Transient serous retinal detachment
bull Retinal traction
bull Retinal hole
bull Visually significant retinal vascular occlusion
CRYOTHERAPY
INDICATIONS
bull Small equatorial and peripheral lesion that lt35 mm at the base and lt2mm in
height
bull Local recurrence
bull Tumor persistence after irradiation
bull In conjunction with chemotherapy
TECHNIQUE
Nitrous oxide probe (-80 C) 1-2 monthly session of triple freeze thaw cycle
SIDE EFFECTS transient serous retinal detachment retinal tear localized preretinal
fibrosis
Transpupillary thermotherapy
PRINCIPLE
bull thermotherapy has synergistic effect with chemotherapy9 ( carboplatin) ndash enhances the platinum
DNA adduct thus ndash antitumor effect
INDICATIONS
bull Small (lt 3mm) tumors posterior to the equator
bull Larger tumors post chemotherapy
TECHNIQUE
bull With diode laser focused heat at sub photocoagulation level- 42C to 60C for 5-20 min to tumor is
applied with relatively sparing of retinal vessels from photocoagulation
bull Local control of 70-80
COMPLICATIONS
bull Retinal traction fibrosis transient serous retinal detachment
RADIOACTIVE PLAQUE APPLICATION
INDICATIONS
1Primary plaque therapy ndash localized RB typically limited to 1-2 foci not involving optic disc or macula
2 In conjunction with chemoreduction therapy- -small or moderate size lesion including those with focal
viterous seeding immediately overlying the tumor
3 Tumors lt1616mm at base and lt8mm in thickness
4 Local failure after other therapy (EBRT chemotherapy laser cryotherapy)
ADVANTAGES (vs EBRT)
bull Better dose localization
bull Lesser risk of cataract
bull Minimal risk of bone hypoplasia
bull Lesser risk of second malignancies
PLAQUE TYPES and features
bull Co60
bull I125 (27 to 35 kev half- life ndash 60 days)- gamma rays
emitter
bull Au198 Ir192Ru106- beta emitter
bull Ir-192- (295-612kevhalflife- 74 days)
bull Ru-106( 35 Mev374 days)
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
RE system DEMERITS
bull Doesnrsquot take into account retinal detachment or subretinal
tumor seeding prognostic factors for vision preservation
bull Small anterior tumors were placed in group 3 or 4 because
they were not usually controlled by ExRT technique in use
at that time but they are quite responsive to modern RT
techniques cryotherapy or RT plaque therapy
bull Vitreous seeding classified as group 5b although local
vitreous seeding can often be treated with RT plaque
International classification of retinoblastoma- 2006
Group A small intraretinal tumors away from the disc and foveola
bull No tumor greater than 3 mm in diameter
bull Located at least (3 mm) from fovea or 15 mm) from Optic disc
Group B all remaining discrete tumors confined to retina
All other tumors confined to retina not in group A
Subretinal fluid (without subretinal seeding) lt3 or 3 mm from base of the tumor
Group C local subretinal fluid or seeding
Local subretinal fluid alone gt3 to 6orlt6 mm from the tumor
Viterous seeding or subretinal seeding lt3 or 3 mm from tumor
Group D diffuse subretinal fluid or seeding bull Subretinal fluid alone gt6 mm from the tumorbull Viterous seeding or subretinal seeding gt3mm from tumor
Group E presence of one or more of these poor prognostic factors More than 23 of the globe filled with tumor Tumor in the anterior segment Tumor in or on the ciliary body Iris neovascularization Neovascular glaucoma Opaque media from hemorrhage Phthisical or prephthisical eye Orbital cellulitis-like presentation
Modified from Shields CL etalinternation classification predicts chemoreduction successopthamology 1132276-22802006
International retinoblastoma staging system proposed - 2006
Stage 0 Patient treated conservatively
stage-1 eye eneucleated completely resectedhistologicaly
stage-2 eye eneucleated micoscopic residual tumor
stage-3 regional extension
3a- overt orbital disease
3b- preauricular or cervical lymphnode extension
bull stage-4 metastatic diseasebull 4a- heamatogenous metastasis without CNS
involvementbull 1- single lesionbull 2- multiple lesionbull 4b-CNS extension with or without any other site
of regional or metastatic diseasebull 1-prechiasmatic lesionbull 2 CNS massbull 3 leptomeningeal and cerebrospinal fluid disease
Goal of treatment
bull Save life (main goal)
bull Preserve useful vision
bull Attention on late functional and craniogeniceffect as sequale to treatment
TREATMENT
MODALITIES
Surgery Enucleation exenteration
Focal therapies
Cryotherapy
Laser hyperthermia
Laser photocoagulation
Radioactive plaque applications
External beam radiotherapy
Chemotherapy
ENUCLEATIONIndications
bull UL or BL Rb when eye is blind
bull Presence of neovascular glaucoma
bull When disease cannot be controlled by chemo or local treatment
bull Tumor invasion into anterior chamber
bull Direct visulization of an active tumor is obstucted by condition like ndash
hemorrhage corneal opacity or cataract
In co BL Rb
Eye with RD Vitreous hemorrhage glaucoma painful blind eye should
be enucleated and other eye should be treated as per the disease
status
Structures removed
bull Gentle removal of intact eye globe without
perforation to avoid seeding of orbit
bull Optic nerve long segment (15mm) for presence of
tumor extension
bull Enucleation is curative in 95 of patient with ul ds
bull Now a days orbital implants are used at mosr centers
EXENTERATION
Indications
bull Extensive local tumor breaching the globe- orbital involvement
bull (exenteration in this situation generally is followed by postoperative
radiotherapy and chemotherapy)
bull Recurrence of tumor in the socket after enucleation
Structures removed
bull The globe
bull Extraocular muscles
bull Lids
bull Optic nerve
bull Orbital fat
FOCAL THERAPIES
Small tumors( 3-6mm)
Used in combination with chemo
Used as a part of consevative therapy to avoid enucleation and EBRT in ul ds
PHOTOCOAGULATION
INDICATIONS
bull Tumors up to 45 mm at the base and up to 25 mm thick not close to the macula or disk with no
evidence of viteros seeds
bull Tumors situated at or posterior to equator of the eye
bull May be used for small tumor recurrences after irradiation
bull Local control of intraocular disease post chemoreduction
TECHNIQUE
Argon laser diode laser or xenon arc photocoagulation are used
bull Based on obliteration of the retinal vessels
bull 2-3 monthly sessions are required
bull LOCAL TUMOR CONTROL 70
Shields JA et alThe expanding role of laser photocoagulation for intraocular tumors The 1993 H Christian
Zweng Memorial Lecture Retina 199414(4)310-22
Complications
Transient serous retinal detachment
bull Retinal traction
bull Retinal hole
bull Visually significant retinal vascular occlusion
CRYOTHERAPY
INDICATIONS
bull Small equatorial and peripheral lesion that lt35 mm at the base and lt2mm in
height
bull Local recurrence
bull Tumor persistence after irradiation
bull In conjunction with chemotherapy
TECHNIQUE
Nitrous oxide probe (-80 C) 1-2 monthly session of triple freeze thaw cycle
SIDE EFFECTS transient serous retinal detachment retinal tear localized preretinal
fibrosis
Transpupillary thermotherapy
PRINCIPLE
bull thermotherapy has synergistic effect with chemotherapy9 ( carboplatin) ndash enhances the platinum
DNA adduct thus ndash antitumor effect
INDICATIONS
bull Small (lt 3mm) tumors posterior to the equator
bull Larger tumors post chemotherapy
TECHNIQUE
bull With diode laser focused heat at sub photocoagulation level- 42C to 60C for 5-20 min to tumor is
applied with relatively sparing of retinal vessels from photocoagulation
bull Local control of 70-80
COMPLICATIONS
bull Retinal traction fibrosis transient serous retinal detachment
RADIOACTIVE PLAQUE APPLICATION
INDICATIONS
1Primary plaque therapy ndash localized RB typically limited to 1-2 foci not involving optic disc or macula
2 In conjunction with chemoreduction therapy- -small or moderate size lesion including those with focal
viterous seeding immediately overlying the tumor
3 Tumors lt1616mm at base and lt8mm in thickness
4 Local failure after other therapy (EBRT chemotherapy laser cryotherapy)
ADVANTAGES (vs EBRT)
bull Better dose localization
bull Lesser risk of cataract
bull Minimal risk of bone hypoplasia
bull Lesser risk of second malignancies
PLAQUE TYPES and features
bull Co60
bull I125 (27 to 35 kev half- life ndash 60 days)- gamma rays
emitter
bull Au198 Ir192Ru106- beta emitter
bull Ir-192- (295-612kevhalflife- 74 days)
bull Ru-106( 35 Mev374 days)
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
International classification of retinoblastoma- 2006
Group A small intraretinal tumors away from the disc and foveola
bull No tumor greater than 3 mm in diameter
bull Located at least (3 mm) from fovea or 15 mm) from Optic disc
Group B all remaining discrete tumors confined to retina
All other tumors confined to retina not in group A
Subretinal fluid (without subretinal seeding) lt3 or 3 mm from base of the tumor
Group C local subretinal fluid or seeding
Local subretinal fluid alone gt3 to 6orlt6 mm from the tumor
Viterous seeding or subretinal seeding lt3 or 3 mm from tumor
Group D diffuse subretinal fluid or seeding bull Subretinal fluid alone gt6 mm from the tumorbull Viterous seeding or subretinal seeding gt3mm from tumor
Group E presence of one or more of these poor prognostic factors More than 23 of the globe filled with tumor Tumor in the anterior segment Tumor in or on the ciliary body Iris neovascularization Neovascular glaucoma Opaque media from hemorrhage Phthisical or prephthisical eye Orbital cellulitis-like presentation
Modified from Shields CL etalinternation classification predicts chemoreduction successopthamology 1132276-22802006
International retinoblastoma staging system proposed - 2006
Stage 0 Patient treated conservatively
stage-1 eye eneucleated completely resectedhistologicaly
stage-2 eye eneucleated micoscopic residual tumor
stage-3 regional extension
3a- overt orbital disease
3b- preauricular or cervical lymphnode extension
bull stage-4 metastatic diseasebull 4a- heamatogenous metastasis without CNS
involvementbull 1- single lesionbull 2- multiple lesionbull 4b-CNS extension with or without any other site
of regional or metastatic diseasebull 1-prechiasmatic lesionbull 2 CNS massbull 3 leptomeningeal and cerebrospinal fluid disease
Goal of treatment
bull Save life (main goal)
bull Preserve useful vision
bull Attention on late functional and craniogeniceffect as sequale to treatment
TREATMENT
MODALITIES
Surgery Enucleation exenteration
Focal therapies
Cryotherapy
Laser hyperthermia
Laser photocoagulation
Radioactive plaque applications
External beam radiotherapy
Chemotherapy
ENUCLEATIONIndications
bull UL or BL Rb when eye is blind
bull Presence of neovascular glaucoma
bull When disease cannot be controlled by chemo or local treatment
bull Tumor invasion into anterior chamber
bull Direct visulization of an active tumor is obstucted by condition like ndash
hemorrhage corneal opacity or cataract
In co BL Rb
Eye with RD Vitreous hemorrhage glaucoma painful blind eye should
be enucleated and other eye should be treated as per the disease
status
Structures removed
bull Gentle removal of intact eye globe without
perforation to avoid seeding of orbit
bull Optic nerve long segment (15mm) for presence of
tumor extension
bull Enucleation is curative in 95 of patient with ul ds
bull Now a days orbital implants are used at mosr centers
EXENTERATION
Indications
bull Extensive local tumor breaching the globe- orbital involvement
bull (exenteration in this situation generally is followed by postoperative
radiotherapy and chemotherapy)
bull Recurrence of tumor in the socket after enucleation
Structures removed
bull The globe
bull Extraocular muscles
bull Lids
bull Optic nerve
bull Orbital fat
FOCAL THERAPIES
Small tumors( 3-6mm)
Used in combination with chemo
Used as a part of consevative therapy to avoid enucleation and EBRT in ul ds
PHOTOCOAGULATION
INDICATIONS
bull Tumors up to 45 mm at the base and up to 25 mm thick not close to the macula or disk with no
evidence of viteros seeds
bull Tumors situated at or posterior to equator of the eye
bull May be used for small tumor recurrences after irradiation
bull Local control of intraocular disease post chemoreduction
TECHNIQUE
Argon laser diode laser or xenon arc photocoagulation are used
bull Based on obliteration of the retinal vessels
bull 2-3 monthly sessions are required
bull LOCAL TUMOR CONTROL 70
Shields JA et alThe expanding role of laser photocoagulation for intraocular tumors The 1993 H Christian
Zweng Memorial Lecture Retina 199414(4)310-22
Complications
Transient serous retinal detachment
bull Retinal traction
bull Retinal hole
bull Visually significant retinal vascular occlusion
CRYOTHERAPY
INDICATIONS
bull Small equatorial and peripheral lesion that lt35 mm at the base and lt2mm in
height
bull Local recurrence
bull Tumor persistence after irradiation
bull In conjunction with chemotherapy
TECHNIQUE
Nitrous oxide probe (-80 C) 1-2 monthly session of triple freeze thaw cycle
SIDE EFFECTS transient serous retinal detachment retinal tear localized preretinal
fibrosis
Transpupillary thermotherapy
PRINCIPLE
bull thermotherapy has synergistic effect with chemotherapy9 ( carboplatin) ndash enhances the platinum
DNA adduct thus ndash antitumor effect
INDICATIONS
bull Small (lt 3mm) tumors posterior to the equator
bull Larger tumors post chemotherapy
TECHNIQUE
bull With diode laser focused heat at sub photocoagulation level- 42C to 60C for 5-20 min to tumor is
applied with relatively sparing of retinal vessels from photocoagulation
bull Local control of 70-80
COMPLICATIONS
bull Retinal traction fibrosis transient serous retinal detachment
RADIOACTIVE PLAQUE APPLICATION
INDICATIONS
1Primary plaque therapy ndash localized RB typically limited to 1-2 foci not involving optic disc or macula
2 In conjunction with chemoreduction therapy- -small or moderate size lesion including those with focal
viterous seeding immediately overlying the tumor
3 Tumors lt1616mm at base and lt8mm in thickness
4 Local failure after other therapy (EBRT chemotherapy laser cryotherapy)
ADVANTAGES (vs EBRT)
bull Better dose localization
bull Lesser risk of cataract
bull Minimal risk of bone hypoplasia
bull Lesser risk of second malignancies
PLAQUE TYPES and features
bull Co60
bull I125 (27 to 35 kev half- life ndash 60 days)- gamma rays
emitter
bull Au198 Ir192Ru106- beta emitter
bull Ir-192- (295-612kevhalflife- 74 days)
bull Ru-106( 35 Mev374 days)
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
Group D diffuse subretinal fluid or seeding bull Subretinal fluid alone gt6 mm from the tumorbull Viterous seeding or subretinal seeding gt3mm from tumor
Group E presence of one or more of these poor prognostic factors More than 23 of the globe filled with tumor Tumor in the anterior segment Tumor in or on the ciliary body Iris neovascularization Neovascular glaucoma Opaque media from hemorrhage Phthisical or prephthisical eye Orbital cellulitis-like presentation
Modified from Shields CL etalinternation classification predicts chemoreduction successopthamology 1132276-22802006
International retinoblastoma staging system proposed - 2006
Stage 0 Patient treated conservatively
stage-1 eye eneucleated completely resectedhistologicaly
stage-2 eye eneucleated micoscopic residual tumor
stage-3 regional extension
3a- overt orbital disease
3b- preauricular or cervical lymphnode extension
bull stage-4 metastatic diseasebull 4a- heamatogenous metastasis without CNS
involvementbull 1- single lesionbull 2- multiple lesionbull 4b-CNS extension with or without any other site
of regional or metastatic diseasebull 1-prechiasmatic lesionbull 2 CNS massbull 3 leptomeningeal and cerebrospinal fluid disease
Goal of treatment
bull Save life (main goal)
bull Preserve useful vision
bull Attention on late functional and craniogeniceffect as sequale to treatment
TREATMENT
MODALITIES
Surgery Enucleation exenteration
Focal therapies
Cryotherapy
Laser hyperthermia
Laser photocoagulation
Radioactive plaque applications
External beam radiotherapy
Chemotherapy
ENUCLEATIONIndications
bull UL or BL Rb when eye is blind
bull Presence of neovascular glaucoma
bull When disease cannot be controlled by chemo or local treatment
bull Tumor invasion into anterior chamber
bull Direct visulization of an active tumor is obstucted by condition like ndash
hemorrhage corneal opacity or cataract
In co BL Rb
Eye with RD Vitreous hemorrhage glaucoma painful blind eye should
be enucleated and other eye should be treated as per the disease
status
Structures removed
bull Gentle removal of intact eye globe without
perforation to avoid seeding of orbit
bull Optic nerve long segment (15mm) for presence of
tumor extension
bull Enucleation is curative in 95 of patient with ul ds
bull Now a days orbital implants are used at mosr centers
EXENTERATION
Indications
bull Extensive local tumor breaching the globe- orbital involvement
bull (exenteration in this situation generally is followed by postoperative
radiotherapy and chemotherapy)
bull Recurrence of tumor in the socket after enucleation
Structures removed
bull The globe
bull Extraocular muscles
bull Lids
bull Optic nerve
bull Orbital fat
FOCAL THERAPIES
Small tumors( 3-6mm)
Used in combination with chemo
Used as a part of consevative therapy to avoid enucleation and EBRT in ul ds
PHOTOCOAGULATION
INDICATIONS
bull Tumors up to 45 mm at the base and up to 25 mm thick not close to the macula or disk with no
evidence of viteros seeds
bull Tumors situated at or posterior to equator of the eye
bull May be used for small tumor recurrences after irradiation
bull Local control of intraocular disease post chemoreduction
TECHNIQUE
Argon laser diode laser or xenon arc photocoagulation are used
bull Based on obliteration of the retinal vessels
bull 2-3 monthly sessions are required
bull LOCAL TUMOR CONTROL 70
Shields JA et alThe expanding role of laser photocoagulation for intraocular tumors The 1993 H Christian
Zweng Memorial Lecture Retina 199414(4)310-22
Complications
Transient serous retinal detachment
bull Retinal traction
bull Retinal hole
bull Visually significant retinal vascular occlusion
CRYOTHERAPY
INDICATIONS
bull Small equatorial and peripheral lesion that lt35 mm at the base and lt2mm in
height
bull Local recurrence
bull Tumor persistence after irradiation
bull In conjunction with chemotherapy
TECHNIQUE
Nitrous oxide probe (-80 C) 1-2 monthly session of triple freeze thaw cycle
SIDE EFFECTS transient serous retinal detachment retinal tear localized preretinal
fibrosis
Transpupillary thermotherapy
PRINCIPLE
bull thermotherapy has synergistic effect with chemotherapy9 ( carboplatin) ndash enhances the platinum
DNA adduct thus ndash antitumor effect
INDICATIONS
bull Small (lt 3mm) tumors posterior to the equator
bull Larger tumors post chemotherapy
TECHNIQUE
bull With diode laser focused heat at sub photocoagulation level- 42C to 60C for 5-20 min to tumor is
applied with relatively sparing of retinal vessels from photocoagulation
bull Local control of 70-80
COMPLICATIONS
bull Retinal traction fibrosis transient serous retinal detachment
RADIOACTIVE PLAQUE APPLICATION
INDICATIONS
1Primary plaque therapy ndash localized RB typically limited to 1-2 foci not involving optic disc or macula
2 In conjunction with chemoreduction therapy- -small or moderate size lesion including those with focal
viterous seeding immediately overlying the tumor
3 Tumors lt1616mm at base and lt8mm in thickness
4 Local failure after other therapy (EBRT chemotherapy laser cryotherapy)
ADVANTAGES (vs EBRT)
bull Better dose localization
bull Lesser risk of cataract
bull Minimal risk of bone hypoplasia
bull Lesser risk of second malignancies
PLAQUE TYPES and features
bull Co60
bull I125 (27 to 35 kev half- life ndash 60 days)- gamma rays
emitter
bull Au198 Ir192Ru106- beta emitter
bull Ir-192- (295-612kevhalflife- 74 days)
bull Ru-106( 35 Mev374 days)
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
International retinoblastoma staging system proposed - 2006
Stage 0 Patient treated conservatively
stage-1 eye eneucleated completely resectedhistologicaly
stage-2 eye eneucleated micoscopic residual tumor
stage-3 regional extension
3a- overt orbital disease
3b- preauricular or cervical lymphnode extension
bull stage-4 metastatic diseasebull 4a- heamatogenous metastasis without CNS
involvementbull 1- single lesionbull 2- multiple lesionbull 4b-CNS extension with or without any other site
of regional or metastatic diseasebull 1-prechiasmatic lesionbull 2 CNS massbull 3 leptomeningeal and cerebrospinal fluid disease
Goal of treatment
bull Save life (main goal)
bull Preserve useful vision
bull Attention on late functional and craniogeniceffect as sequale to treatment
TREATMENT
MODALITIES
Surgery Enucleation exenteration
Focal therapies
Cryotherapy
Laser hyperthermia
Laser photocoagulation
Radioactive plaque applications
External beam radiotherapy
Chemotherapy
ENUCLEATIONIndications
bull UL or BL Rb when eye is blind
bull Presence of neovascular glaucoma
bull When disease cannot be controlled by chemo or local treatment
bull Tumor invasion into anterior chamber
bull Direct visulization of an active tumor is obstucted by condition like ndash
hemorrhage corneal opacity or cataract
In co BL Rb
Eye with RD Vitreous hemorrhage glaucoma painful blind eye should
be enucleated and other eye should be treated as per the disease
status
Structures removed
bull Gentle removal of intact eye globe without
perforation to avoid seeding of orbit
bull Optic nerve long segment (15mm) for presence of
tumor extension
bull Enucleation is curative in 95 of patient with ul ds
bull Now a days orbital implants are used at mosr centers
EXENTERATION
Indications
bull Extensive local tumor breaching the globe- orbital involvement
bull (exenteration in this situation generally is followed by postoperative
radiotherapy and chemotherapy)
bull Recurrence of tumor in the socket after enucleation
Structures removed
bull The globe
bull Extraocular muscles
bull Lids
bull Optic nerve
bull Orbital fat
FOCAL THERAPIES
Small tumors( 3-6mm)
Used in combination with chemo
Used as a part of consevative therapy to avoid enucleation and EBRT in ul ds
PHOTOCOAGULATION
INDICATIONS
bull Tumors up to 45 mm at the base and up to 25 mm thick not close to the macula or disk with no
evidence of viteros seeds
bull Tumors situated at or posterior to equator of the eye
bull May be used for small tumor recurrences after irradiation
bull Local control of intraocular disease post chemoreduction
TECHNIQUE
Argon laser diode laser or xenon arc photocoagulation are used
bull Based on obliteration of the retinal vessels
bull 2-3 monthly sessions are required
bull LOCAL TUMOR CONTROL 70
Shields JA et alThe expanding role of laser photocoagulation for intraocular tumors The 1993 H Christian
Zweng Memorial Lecture Retina 199414(4)310-22
Complications
Transient serous retinal detachment
bull Retinal traction
bull Retinal hole
bull Visually significant retinal vascular occlusion
CRYOTHERAPY
INDICATIONS
bull Small equatorial and peripheral lesion that lt35 mm at the base and lt2mm in
height
bull Local recurrence
bull Tumor persistence after irradiation
bull In conjunction with chemotherapy
TECHNIQUE
Nitrous oxide probe (-80 C) 1-2 monthly session of triple freeze thaw cycle
SIDE EFFECTS transient serous retinal detachment retinal tear localized preretinal
fibrosis
Transpupillary thermotherapy
PRINCIPLE
bull thermotherapy has synergistic effect with chemotherapy9 ( carboplatin) ndash enhances the platinum
DNA adduct thus ndash antitumor effect
INDICATIONS
bull Small (lt 3mm) tumors posterior to the equator
bull Larger tumors post chemotherapy
TECHNIQUE
bull With diode laser focused heat at sub photocoagulation level- 42C to 60C for 5-20 min to tumor is
applied with relatively sparing of retinal vessels from photocoagulation
bull Local control of 70-80
COMPLICATIONS
bull Retinal traction fibrosis transient serous retinal detachment
RADIOACTIVE PLAQUE APPLICATION
INDICATIONS
1Primary plaque therapy ndash localized RB typically limited to 1-2 foci not involving optic disc or macula
2 In conjunction with chemoreduction therapy- -small or moderate size lesion including those with focal
viterous seeding immediately overlying the tumor
3 Tumors lt1616mm at base and lt8mm in thickness
4 Local failure after other therapy (EBRT chemotherapy laser cryotherapy)
ADVANTAGES (vs EBRT)
bull Better dose localization
bull Lesser risk of cataract
bull Minimal risk of bone hypoplasia
bull Lesser risk of second malignancies
PLAQUE TYPES and features
bull Co60
bull I125 (27 to 35 kev half- life ndash 60 days)- gamma rays
emitter
bull Au198 Ir192Ru106- beta emitter
bull Ir-192- (295-612kevhalflife- 74 days)
bull Ru-106( 35 Mev374 days)
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
bull stage-4 metastatic diseasebull 4a- heamatogenous metastasis without CNS
involvementbull 1- single lesionbull 2- multiple lesionbull 4b-CNS extension with or without any other site
of regional or metastatic diseasebull 1-prechiasmatic lesionbull 2 CNS massbull 3 leptomeningeal and cerebrospinal fluid disease
Goal of treatment
bull Save life (main goal)
bull Preserve useful vision
bull Attention on late functional and craniogeniceffect as sequale to treatment
TREATMENT
MODALITIES
Surgery Enucleation exenteration
Focal therapies
Cryotherapy
Laser hyperthermia
Laser photocoagulation
Radioactive plaque applications
External beam radiotherapy
Chemotherapy
ENUCLEATIONIndications
bull UL or BL Rb when eye is blind
bull Presence of neovascular glaucoma
bull When disease cannot be controlled by chemo or local treatment
bull Tumor invasion into anterior chamber
bull Direct visulization of an active tumor is obstucted by condition like ndash
hemorrhage corneal opacity or cataract
In co BL Rb
Eye with RD Vitreous hemorrhage glaucoma painful blind eye should
be enucleated and other eye should be treated as per the disease
status
Structures removed
bull Gentle removal of intact eye globe without
perforation to avoid seeding of orbit
bull Optic nerve long segment (15mm) for presence of
tumor extension
bull Enucleation is curative in 95 of patient with ul ds
bull Now a days orbital implants are used at mosr centers
EXENTERATION
Indications
bull Extensive local tumor breaching the globe- orbital involvement
bull (exenteration in this situation generally is followed by postoperative
radiotherapy and chemotherapy)
bull Recurrence of tumor in the socket after enucleation
Structures removed
bull The globe
bull Extraocular muscles
bull Lids
bull Optic nerve
bull Orbital fat
FOCAL THERAPIES
Small tumors( 3-6mm)
Used in combination with chemo
Used as a part of consevative therapy to avoid enucleation and EBRT in ul ds
PHOTOCOAGULATION
INDICATIONS
bull Tumors up to 45 mm at the base and up to 25 mm thick not close to the macula or disk with no
evidence of viteros seeds
bull Tumors situated at or posterior to equator of the eye
bull May be used for small tumor recurrences after irradiation
bull Local control of intraocular disease post chemoreduction
TECHNIQUE
Argon laser diode laser or xenon arc photocoagulation are used
bull Based on obliteration of the retinal vessels
bull 2-3 monthly sessions are required
bull LOCAL TUMOR CONTROL 70
Shields JA et alThe expanding role of laser photocoagulation for intraocular tumors The 1993 H Christian
Zweng Memorial Lecture Retina 199414(4)310-22
Complications
Transient serous retinal detachment
bull Retinal traction
bull Retinal hole
bull Visually significant retinal vascular occlusion
CRYOTHERAPY
INDICATIONS
bull Small equatorial and peripheral lesion that lt35 mm at the base and lt2mm in
height
bull Local recurrence
bull Tumor persistence after irradiation
bull In conjunction with chemotherapy
TECHNIQUE
Nitrous oxide probe (-80 C) 1-2 monthly session of triple freeze thaw cycle
SIDE EFFECTS transient serous retinal detachment retinal tear localized preretinal
fibrosis
Transpupillary thermotherapy
PRINCIPLE
bull thermotherapy has synergistic effect with chemotherapy9 ( carboplatin) ndash enhances the platinum
DNA adduct thus ndash antitumor effect
INDICATIONS
bull Small (lt 3mm) tumors posterior to the equator
bull Larger tumors post chemotherapy
TECHNIQUE
bull With diode laser focused heat at sub photocoagulation level- 42C to 60C for 5-20 min to tumor is
applied with relatively sparing of retinal vessels from photocoagulation
bull Local control of 70-80
COMPLICATIONS
bull Retinal traction fibrosis transient serous retinal detachment
RADIOACTIVE PLAQUE APPLICATION
INDICATIONS
1Primary plaque therapy ndash localized RB typically limited to 1-2 foci not involving optic disc or macula
2 In conjunction with chemoreduction therapy- -small or moderate size lesion including those with focal
viterous seeding immediately overlying the tumor
3 Tumors lt1616mm at base and lt8mm in thickness
4 Local failure after other therapy (EBRT chemotherapy laser cryotherapy)
ADVANTAGES (vs EBRT)
bull Better dose localization
bull Lesser risk of cataract
bull Minimal risk of bone hypoplasia
bull Lesser risk of second malignancies
PLAQUE TYPES and features
bull Co60
bull I125 (27 to 35 kev half- life ndash 60 days)- gamma rays
emitter
bull Au198 Ir192Ru106- beta emitter
bull Ir-192- (295-612kevhalflife- 74 days)
bull Ru-106( 35 Mev374 days)
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
Goal of treatment
bull Save life (main goal)
bull Preserve useful vision
bull Attention on late functional and craniogeniceffect as sequale to treatment
TREATMENT
MODALITIES
Surgery Enucleation exenteration
Focal therapies
Cryotherapy
Laser hyperthermia
Laser photocoagulation
Radioactive plaque applications
External beam radiotherapy
Chemotherapy
ENUCLEATIONIndications
bull UL or BL Rb when eye is blind
bull Presence of neovascular glaucoma
bull When disease cannot be controlled by chemo or local treatment
bull Tumor invasion into anterior chamber
bull Direct visulization of an active tumor is obstucted by condition like ndash
hemorrhage corneal opacity or cataract
In co BL Rb
Eye with RD Vitreous hemorrhage glaucoma painful blind eye should
be enucleated and other eye should be treated as per the disease
status
Structures removed
bull Gentle removal of intact eye globe without
perforation to avoid seeding of orbit
bull Optic nerve long segment (15mm) for presence of
tumor extension
bull Enucleation is curative in 95 of patient with ul ds
bull Now a days orbital implants are used at mosr centers
EXENTERATION
Indications
bull Extensive local tumor breaching the globe- orbital involvement
bull (exenteration in this situation generally is followed by postoperative
radiotherapy and chemotherapy)
bull Recurrence of tumor in the socket after enucleation
Structures removed
bull The globe
bull Extraocular muscles
bull Lids
bull Optic nerve
bull Orbital fat
FOCAL THERAPIES
Small tumors( 3-6mm)
Used in combination with chemo
Used as a part of consevative therapy to avoid enucleation and EBRT in ul ds
PHOTOCOAGULATION
INDICATIONS
bull Tumors up to 45 mm at the base and up to 25 mm thick not close to the macula or disk with no
evidence of viteros seeds
bull Tumors situated at or posterior to equator of the eye
bull May be used for small tumor recurrences after irradiation
bull Local control of intraocular disease post chemoreduction
TECHNIQUE
Argon laser diode laser or xenon arc photocoagulation are used
bull Based on obliteration of the retinal vessels
bull 2-3 monthly sessions are required
bull LOCAL TUMOR CONTROL 70
Shields JA et alThe expanding role of laser photocoagulation for intraocular tumors The 1993 H Christian
Zweng Memorial Lecture Retina 199414(4)310-22
Complications
Transient serous retinal detachment
bull Retinal traction
bull Retinal hole
bull Visually significant retinal vascular occlusion
CRYOTHERAPY
INDICATIONS
bull Small equatorial and peripheral lesion that lt35 mm at the base and lt2mm in
height
bull Local recurrence
bull Tumor persistence after irradiation
bull In conjunction with chemotherapy
TECHNIQUE
Nitrous oxide probe (-80 C) 1-2 monthly session of triple freeze thaw cycle
SIDE EFFECTS transient serous retinal detachment retinal tear localized preretinal
fibrosis
Transpupillary thermotherapy
PRINCIPLE
bull thermotherapy has synergistic effect with chemotherapy9 ( carboplatin) ndash enhances the platinum
DNA adduct thus ndash antitumor effect
INDICATIONS
bull Small (lt 3mm) tumors posterior to the equator
bull Larger tumors post chemotherapy
TECHNIQUE
bull With diode laser focused heat at sub photocoagulation level- 42C to 60C for 5-20 min to tumor is
applied with relatively sparing of retinal vessels from photocoagulation
bull Local control of 70-80
COMPLICATIONS
bull Retinal traction fibrosis transient serous retinal detachment
RADIOACTIVE PLAQUE APPLICATION
INDICATIONS
1Primary plaque therapy ndash localized RB typically limited to 1-2 foci not involving optic disc or macula
2 In conjunction with chemoreduction therapy- -small or moderate size lesion including those with focal
viterous seeding immediately overlying the tumor
3 Tumors lt1616mm at base and lt8mm in thickness
4 Local failure after other therapy (EBRT chemotherapy laser cryotherapy)
ADVANTAGES (vs EBRT)
bull Better dose localization
bull Lesser risk of cataract
bull Minimal risk of bone hypoplasia
bull Lesser risk of second malignancies
PLAQUE TYPES and features
bull Co60
bull I125 (27 to 35 kev half- life ndash 60 days)- gamma rays
emitter
bull Au198 Ir192Ru106- beta emitter
bull Ir-192- (295-612kevhalflife- 74 days)
bull Ru-106( 35 Mev374 days)
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
TREATMENT
MODALITIES
Surgery Enucleation exenteration
Focal therapies
Cryotherapy
Laser hyperthermia
Laser photocoagulation
Radioactive plaque applications
External beam radiotherapy
Chemotherapy
ENUCLEATIONIndications
bull UL or BL Rb when eye is blind
bull Presence of neovascular glaucoma
bull When disease cannot be controlled by chemo or local treatment
bull Tumor invasion into anterior chamber
bull Direct visulization of an active tumor is obstucted by condition like ndash
hemorrhage corneal opacity or cataract
In co BL Rb
Eye with RD Vitreous hemorrhage glaucoma painful blind eye should
be enucleated and other eye should be treated as per the disease
status
Structures removed
bull Gentle removal of intact eye globe without
perforation to avoid seeding of orbit
bull Optic nerve long segment (15mm) for presence of
tumor extension
bull Enucleation is curative in 95 of patient with ul ds
bull Now a days orbital implants are used at mosr centers
EXENTERATION
Indications
bull Extensive local tumor breaching the globe- orbital involvement
bull (exenteration in this situation generally is followed by postoperative
radiotherapy and chemotherapy)
bull Recurrence of tumor in the socket after enucleation
Structures removed
bull The globe
bull Extraocular muscles
bull Lids
bull Optic nerve
bull Orbital fat
FOCAL THERAPIES
Small tumors( 3-6mm)
Used in combination with chemo
Used as a part of consevative therapy to avoid enucleation and EBRT in ul ds
PHOTOCOAGULATION
INDICATIONS
bull Tumors up to 45 mm at the base and up to 25 mm thick not close to the macula or disk with no
evidence of viteros seeds
bull Tumors situated at or posterior to equator of the eye
bull May be used for small tumor recurrences after irradiation
bull Local control of intraocular disease post chemoreduction
TECHNIQUE
Argon laser diode laser or xenon arc photocoagulation are used
bull Based on obliteration of the retinal vessels
bull 2-3 monthly sessions are required
bull LOCAL TUMOR CONTROL 70
Shields JA et alThe expanding role of laser photocoagulation for intraocular tumors The 1993 H Christian
Zweng Memorial Lecture Retina 199414(4)310-22
Complications
Transient serous retinal detachment
bull Retinal traction
bull Retinal hole
bull Visually significant retinal vascular occlusion
CRYOTHERAPY
INDICATIONS
bull Small equatorial and peripheral lesion that lt35 mm at the base and lt2mm in
height
bull Local recurrence
bull Tumor persistence after irradiation
bull In conjunction with chemotherapy
TECHNIQUE
Nitrous oxide probe (-80 C) 1-2 monthly session of triple freeze thaw cycle
SIDE EFFECTS transient serous retinal detachment retinal tear localized preretinal
fibrosis
Transpupillary thermotherapy
PRINCIPLE
bull thermotherapy has synergistic effect with chemotherapy9 ( carboplatin) ndash enhances the platinum
DNA adduct thus ndash antitumor effect
INDICATIONS
bull Small (lt 3mm) tumors posterior to the equator
bull Larger tumors post chemotherapy
TECHNIQUE
bull With diode laser focused heat at sub photocoagulation level- 42C to 60C for 5-20 min to tumor is
applied with relatively sparing of retinal vessels from photocoagulation
bull Local control of 70-80
COMPLICATIONS
bull Retinal traction fibrosis transient serous retinal detachment
RADIOACTIVE PLAQUE APPLICATION
INDICATIONS
1Primary plaque therapy ndash localized RB typically limited to 1-2 foci not involving optic disc or macula
2 In conjunction with chemoreduction therapy- -small or moderate size lesion including those with focal
viterous seeding immediately overlying the tumor
3 Tumors lt1616mm at base and lt8mm in thickness
4 Local failure after other therapy (EBRT chemotherapy laser cryotherapy)
ADVANTAGES (vs EBRT)
bull Better dose localization
bull Lesser risk of cataract
bull Minimal risk of bone hypoplasia
bull Lesser risk of second malignancies
PLAQUE TYPES and features
bull Co60
bull I125 (27 to 35 kev half- life ndash 60 days)- gamma rays
emitter
bull Au198 Ir192Ru106- beta emitter
bull Ir-192- (295-612kevhalflife- 74 days)
bull Ru-106( 35 Mev374 days)
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
ENUCLEATIONIndications
bull UL or BL Rb when eye is blind
bull Presence of neovascular glaucoma
bull When disease cannot be controlled by chemo or local treatment
bull Tumor invasion into anterior chamber
bull Direct visulization of an active tumor is obstucted by condition like ndash
hemorrhage corneal opacity or cataract
In co BL Rb
Eye with RD Vitreous hemorrhage glaucoma painful blind eye should
be enucleated and other eye should be treated as per the disease
status
Structures removed
bull Gentle removal of intact eye globe without
perforation to avoid seeding of orbit
bull Optic nerve long segment (15mm) for presence of
tumor extension
bull Enucleation is curative in 95 of patient with ul ds
bull Now a days orbital implants are used at mosr centers
EXENTERATION
Indications
bull Extensive local tumor breaching the globe- orbital involvement
bull (exenteration in this situation generally is followed by postoperative
radiotherapy and chemotherapy)
bull Recurrence of tumor in the socket after enucleation
Structures removed
bull The globe
bull Extraocular muscles
bull Lids
bull Optic nerve
bull Orbital fat
FOCAL THERAPIES
Small tumors( 3-6mm)
Used in combination with chemo
Used as a part of consevative therapy to avoid enucleation and EBRT in ul ds
PHOTOCOAGULATION
INDICATIONS
bull Tumors up to 45 mm at the base and up to 25 mm thick not close to the macula or disk with no
evidence of viteros seeds
bull Tumors situated at or posterior to equator of the eye
bull May be used for small tumor recurrences after irradiation
bull Local control of intraocular disease post chemoreduction
TECHNIQUE
Argon laser diode laser or xenon arc photocoagulation are used
bull Based on obliteration of the retinal vessels
bull 2-3 monthly sessions are required
bull LOCAL TUMOR CONTROL 70
Shields JA et alThe expanding role of laser photocoagulation for intraocular tumors The 1993 H Christian
Zweng Memorial Lecture Retina 199414(4)310-22
Complications
Transient serous retinal detachment
bull Retinal traction
bull Retinal hole
bull Visually significant retinal vascular occlusion
CRYOTHERAPY
INDICATIONS
bull Small equatorial and peripheral lesion that lt35 mm at the base and lt2mm in
height
bull Local recurrence
bull Tumor persistence after irradiation
bull In conjunction with chemotherapy
TECHNIQUE
Nitrous oxide probe (-80 C) 1-2 monthly session of triple freeze thaw cycle
SIDE EFFECTS transient serous retinal detachment retinal tear localized preretinal
fibrosis
Transpupillary thermotherapy
PRINCIPLE
bull thermotherapy has synergistic effect with chemotherapy9 ( carboplatin) ndash enhances the platinum
DNA adduct thus ndash antitumor effect
INDICATIONS
bull Small (lt 3mm) tumors posterior to the equator
bull Larger tumors post chemotherapy
TECHNIQUE
bull With diode laser focused heat at sub photocoagulation level- 42C to 60C for 5-20 min to tumor is
applied with relatively sparing of retinal vessels from photocoagulation
bull Local control of 70-80
COMPLICATIONS
bull Retinal traction fibrosis transient serous retinal detachment
RADIOACTIVE PLAQUE APPLICATION
INDICATIONS
1Primary plaque therapy ndash localized RB typically limited to 1-2 foci not involving optic disc or macula
2 In conjunction with chemoreduction therapy- -small or moderate size lesion including those with focal
viterous seeding immediately overlying the tumor
3 Tumors lt1616mm at base and lt8mm in thickness
4 Local failure after other therapy (EBRT chemotherapy laser cryotherapy)
ADVANTAGES (vs EBRT)
bull Better dose localization
bull Lesser risk of cataract
bull Minimal risk of bone hypoplasia
bull Lesser risk of second malignancies
PLAQUE TYPES and features
bull Co60
bull I125 (27 to 35 kev half- life ndash 60 days)- gamma rays
emitter
bull Au198 Ir192Ru106- beta emitter
bull Ir-192- (295-612kevhalflife- 74 days)
bull Ru-106( 35 Mev374 days)
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
Structures removed
bull Gentle removal of intact eye globe without
perforation to avoid seeding of orbit
bull Optic nerve long segment (15mm) for presence of
tumor extension
bull Enucleation is curative in 95 of patient with ul ds
bull Now a days orbital implants are used at mosr centers
EXENTERATION
Indications
bull Extensive local tumor breaching the globe- orbital involvement
bull (exenteration in this situation generally is followed by postoperative
radiotherapy and chemotherapy)
bull Recurrence of tumor in the socket after enucleation
Structures removed
bull The globe
bull Extraocular muscles
bull Lids
bull Optic nerve
bull Orbital fat
FOCAL THERAPIES
Small tumors( 3-6mm)
Used in combination with chemo
Used as a part of consevative therapy to avoid enucleation and EBRT in ul ds
PHOTOCOAGULATION
INDICATIONS
bull Tumors up to 45 mm at the base and up to 25 mm thick not close to the macula or disk with no
evidence of viteros seeds
bull Tumors situated at or posterior to equator of the eye
bull May be used for small tumor recurrences after irradiation
bull Local control of intraocular disease post chemoreduction
TECHNIQUE
Argon laser diode laser or xenon arc photocoagulation are used
bull Based on obliteration of the retinal vessels
bull 2-3 monthly sessions are required
bull LOCAL TUMOR CONTROL 70
Shields JA et alThe expanding role of laser photocoagulation for intraocular tumors The 1993 H Christian
Zweng Memorial Lecture Retina 199414(4)310-22
Complications
Transient serous retinal detachment
bull Retinal traction
bull Retinal hole
bull Visually significant retinal vascular occlusion
CRYOTHERAPY
INDICATIONS
bull Small equatorial and peripheral lesion that lt35 mm at the base and lt2mm in
height
bull Local recurrence
bull Tumor persistence after irradiation
bull In conjunction with chemotherapy
TECHNIQUE
Nitrous oxide probe (-80 C) 1-2 monthly session of triple freeze thaw cycle
SIDE EFFECTS transient serous retinal detachment retinal tear localized preretinal
fibrosis
Transpupillary thermotherapy
PRINCIPLE
bull thermotherapy has synergistic effect with chemotherapy9 ( carboplatin) ndash enhances the platinum
DNA adduct thus ndash antitumor effect
INDICATIONS
bull Small (lt 3mm) tumors posterior to the equator
bull Larger tumors post chemotherapy
TECHNIQUE
bull With diode laser focused heat at sub photocoagulation level- 42C to 60C for 5-20 min to tumor is
applied with relatively sparing of retinal vessels from photocoagulation
bull Local control of 70-80
COMPLICATIONS
bull Retinal traction fibrosis transient serous retinal detachment
RADIOACTIVE PLAQUE APPLICATION
INDICATIONS
1Primary plaque therapy ndash localized RB typically limited to 1-2 foci not involving optic disc or macula
2 In conjunction with chemoreduction therapy- -small or moderate size lesion including those with focal
viterous seeding immediately overlying the tumor
3 Tumors lt1616mm at base and lt8mm in thickness
4 Local failure after other therapy (EBRT chemotherapy laser cryotherapy)
ADVANTAGES (vs EBRT)
bull Better dose localization
bull Lesser risk of cataract
bull Minimal risk of bone hypoplasia
bull Lesser risk of second malignancies
PLAQUE TYPES and features
bull Co60
bull I125 (27 to 35 kev half- life ndash 60 days)- gamma rays
emitter
bull Au198 Ir192Ru106- beta emitter
bull Ir-192- (295-612kevhalflife- 74 days)
bull Ru-106( 35 Mev374 days)
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
EXENTERATION
Indications
bull Extensive local tumor breaching the globe- orbital involvement
bull (exenteration in this situation generally is followed by postoperative
radiotherapy and chemotherapy)
bull Recurrence of tumor in the socket after enucleation
Structures removed
bull The globe
bull Extraocular muscles
bull Lids
bull Optic nerve
bull Orbital fat
FOCAL THERAPIES
Small tumors( 3-6mm)
Used in combination with chemo
Used as a part of consevative therapy to avoid enucleation and EBRT in ul ds
PHOTOCOAGULATION
INDICATIONS
bull Tumors up to 45 mm at the base and up to 25 mm thick not close to the macula or disk with no
evidence of viteros seeds
bull Tumors situated at or posterior to equator of the eye
bull May be used for small tumor recurrences after irradiation
bull Local control of intraocular disease post chemoreduction
TECHNIQUE
Argon laser diode laser or xenon arc photocoagulation are used
bull Based on obliteration of the retinal vessels
bull 2-3 monthly sessions are required
bull LOCAL TUMOR CONTROL 70
Shields JA et alThe expanding role of laser photocoagulation for intraocular tumors The 1993 H Christian
Zweng Memorial Lecture Retina 199414(4)310-22
Complications
Transient serous retinal detachment
bull Retinal traction
bull Retinal hole
bull Visually significant retinal vascular occlusion
CRYOTHERAPY
INDICATIONS
bull Small equatorial and peripheral lesion that lt35 mm at the base and lt2mm in
height
bull Local recurrence
bull Tumor persistence after irradiation
bull In conjunction with chemotherapy
TECHNIQUE
Nitrous oxide probe (-80 C) 1-2 monthly session of triple freeze thaw cycle
SIDE EFFECTS transient serous retinal detachment retinal tear localized preretinal
fibrosis
Transpupillary thermotherapy
PRINCIPLE
bull thermotherapy has synergistic effect with chemotherapy9 ( carboplatin) ndash enhances the platinum
DNA adduct thus ndash antitumor effect
INDICATIONS
bull Small (lt 3mm) tumors posterior to the equator
bull Larger tumors post chemotherapy
TECHNIQUE
bull With diode laser focused heat at sub photocoagulation level- 42C to 60C for 5-20 min to tumor is
applied with relatively sparing of retinal vessels from photocoagulation
bull Local control of 70-80
COMPLICATIONS
bull Retinal traction fibrosis transient serous retinal detachment
RADIOACTIVE PLAQUE APPLICATION
INDICATIONS
1Primary plaque therapy ndash localized RB typically limited to 1-2 foci not involving optic disc or macula
2 In conjunction with chemoreduction therapy- -small or moderate size lesion including those with focal
viterous seeding immediately overlying the tumor
3 Tumors lt1616mm at base and lt8mm in thickness
4 Local failure after other therapy (EBRT chemotherapy laser cryotherapy)
ADVANTAGES (vs EBRT)
bull Better dose localization
bull Lesser risk of cataract
bull Minimal risk of bone hypoplasia
bull Lesser risk of second malignancies
PLAQUE TYPES and features
bull Co60
bull I125 (27 to 35 kev half- life ndash 60 days)- gamma rays
emitter
bull Au198 Ir192Ru106- beta emitter
bull Ir-192- (295-612kevhalflife- 74 days)
bull Ru-106( 35 Mev374 days)
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
FOCAL THERAPIES
Small tumors( 3-6mm)
Used in combination with chemo
Used as a part of consevative therapy to avoid enucleation and EBRT in ul ds
PHOTOCOAGULATION
INDICATIONS
bull Tumors up to 45 mm at the base and up to 25 mm thick not close to the macula or disk with no
evidence of viteros seeds
bull Tumors situated at or posterior to equator of the eye
bull May be used for small tumor recurrences after irradiation
bull Local control of intraocular disease post chemoreduction
TECHNIQUE
Argon laser diode laser or xenon arc photocoagulation are used
bull Based on obliteration of the retinal vessels
bull 2-3 monthly sessions are required
bull LOCAL TUMOR CONTROL 70
Shields JA et alThe expanding role of laser photocoagulation for intraocular tumors The 1993 H Christian
Zweng Memorial Lecture Retina 199414(4)310-22
Complications
Transient serous retinal detachment
bull Retinal traction
bull Retinal hole
bull Visually significant retinal vascular occlusion
CRYOTHERAPY
INDICATIONS
bull Small equatorial and peripheral lesion that lt35 mm at the base and lt2mm in
height
bull Local recurrence
bull Tumor persistence after irradiation
bull In conjunction with chemotherapy
TECHNIQUE
Nitrous oxide probe (-80 C) 1-2 monthly session of triple freeze thaw cycle
SIDE EFFECTS transient serous retinal detachment retinal tear localized preretinal
fibrosis
Transpupillary thermotherapy
PRINCIPLE
bull thermotherapy has synergistic effect with chemotherapy9 ( carboplatin) ndash enhances the platinum
DNA adduct thus ndash antitumor effect
INDICATIONS
bull Small (lt 3mm) tumors posterior to the equator
bull Larger tumors post chemotherapy
TECHNIQUE
bull With diode laser focused heat at sub photocoagulation level- 42C to 60C for 5-20 min to tumor is
applied with relatively sparing of retinal vessels from photocoagulation
bull Local control of 70-80
COMPLICATIONS
bull Retinal traction fibrosis transient serous retinal detachment
RADIOACTIVE PLAQUE APPLICATION
INDICATIONS
1Primary plaque therapy ndash localized RB typically limited to 1-2 foci not involving optic disc or macula
2 In conjunction with chemoreduction therapy- -small or moderate size lesion including those with focal
viterous seeding immediately overlying the tumor
3 Tumors lt1616mm at base and lt8mm in thickness
4 Local failure after other therapy (EBRT chemotherapy laser cryotherapy)
ADVANTAGES (vs EBRT)
bull Better dose localization
bull Lesser risk of cataract
bull Minimal risk of bone hypoplasia
bull Lesser risk of second malignancies
PLAQUE TYPES and features
bull Co60
bull I125 (27 to 35 kev half- life ndash 60 days)- gamma rays
emitter
bull Au198 Ir192Ru106- beta emitter
bull Ir-192- (295-612kevhalflife- 74 days)
bull Ru-106( 35 Mev374 days)
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
PHOTOCOAGULATION
INDICATIONS
bull Tumors up to 45 mm at the base and up to 25 mm thick not close to the macula or disk with no
evidence of viteros seeds
bull Tumors situated at or posterior to equator of the eye
bull May be used for small tumor recurrences after irradiation
bull Local control of intraocular disease post chemoreduction
TECHNIQUE
Argon laser diode laser or xenon arc photocoagulation are used
bull Based on obliteration of the retinal vessels
bull 2-3 monthly sessions are required
bull LOCAL TUMOR CONTROL 70
Shields JA et alThe expanding role of laser photocoagulation for intraocular tumors The 1993 H Christian
Zweng Memorial Lecture Retina 199414(4)310-22
Complications
Transient serous retinal detachment
bull Retinal traction
bull Retinal hole
bull Visually significant retinal vascular occlusion
CRYOTHERAPY
INDICATIONS
bull Small equatorial and peripheral lesion that lt35 mm at the base and lt2mm in
height
bull Local recurrence
bull Tumor persistence after irradiation
bull In conjunction with chemotherapy
TECHNIQUE
Nitrous oxide probe (-80 C) 1-2 monthly session of triple freeze thaw cycle
SIDE EFFECTS transient serous retinal detachment retinal tear localized preretinal
fibrosis
Transpupillary thermotherapy
PRINCIPLE
bull thermotherapy has synergistic effect with chemotherapy9 ( carboplatin) ndash enhances the platinum
DNA adduct thus ndash antitumor effect
INDICATIONS
bull Small (lt 3mm) tumors posterior to the equator
bull Larger tumors post chemotherapy
TECHNIQUE
bull With diode laser focused heat at sub photocoagulation level- 42C to 60C for 5-20 min to tumor is
applied with relatively sparing of retinal vessels from photocoagulation
bull Local control of 70-80
COMPLICATIONS
bull Retinal traction fibrosis transient serous retinal detachment
RADIOACTIVE PLAQUE APPLICATION
INDICATIONS
1Primary plaque therapy ndash localized RB typically limited to 1-2 foci not involving optic disc or macula
2 In conjunction with chemoreduction therapy- -small or moderate size lesion including those with focal
viterous seeding immediately overlying the tumor
3 Tumors lt1616mm at base and lt8mm in thickness
4 Local failure after other therapy (EBRT chemotherapy laser cryotherapy)
ADVANTAGES (vs EBRT)
bull Better dose localization
bull Lesser risk of cataract
bull Minimal risk of bone hypoplasia
bull Lesser risk of second malignancies
PLAQUE TYPES and features
bull Co60
bull I125 (27 to 35 kev half- life ndash 60 days)- gamma rays
emitter
bull Au198 Ir192Ru106- beta emitter
bull Ir-192- (295-612kevhalflife- 74 days)
bull Ru-106( 35 Mev374 days)
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
Complications
Transient serous retinal detachment
bull Retinal traction
bull Retinal hole
bull Visually significant retinal vascular occlusion
CRYOTHERAPY
INDICATIONS
bull Small equatorial and peripheral lesion that lt35 mm at the base and lt2mm in
height
bull Local recurrence
bull Tumor persistence after irradiation
bull In conjunction with chemotherapy
TECHNIQUE
Nitrous oxide probe (-80 C) 1-2 monthly session of triple freeze thaw cycle
SIDE EFFECTS transient serous retinal detachment retinal tear localized preretinal
fibrosis
Transpupillary thermotherapy
PRINCIPLE
bull thermotherapy has synergistic effect with chemotherapy9 ( carboplatin) ndash enhances the platinum
DNA adduct thus ndash antitumor effect
INDICATIONS
bull Small (lt 3mm) tumors posterior to the equator
bull Larger tumors post chemotherapy
TECHNIQUE
bull With diode laser focused heat at sub photocoagulation level- 42C to 60C for 5-20 min to tumor is
applied with relatively sparing of retinal vessels from photocoagulation
bull Local control of 70-80
COMPLICATIONS
bull Retinal traction fibrosis transient serous retinal detachment
RADIOACTIVE PLAQUE APPLICATION
INDICATIONS
1Primary plaque therapy ndash localized RB typically limited to 1-2 foci not involving optic disc or macula
2 In conjunction with chemoreduction therapy- -small or moderate size lesion including those with focal
viterous seeding immediately overlying the tumor
3 Tumors lt1616mm at base and lt8mm in thickness
4 Local failure after other therapy (EBRT chemotherapy laser cryotherapy)
ADVANTAGES (vs EBRT)
bull Better dose localization
bull Lesser risk of cataract
bull Minimal risk of bone hypoplasia
bull Lesser risk of second malignancies
PLAQUE TYPES and features
bull Co60
bull I125 (27 to 35 kev half- life ndash 60 days)- gamma rays
emitter
bull Au198 Ir192Ru106- beta emitter
bull Ir-192- (295-612kevhalflife- 74 days)
bull Ru-106( 35 Mev374 days)
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
CRYOTHERAPY
INDICATIONS
bull Small equatorial and peripheral lesion that lt35 mm at the base and lt2mm in
height
bull Local recurrence
bull Tumor persistence after irradiation
bull In conjunction with chemotherapy
TECHNIQUE
Nitrous oxide probe (-80 C) 1-2 monthly session of triple freeze thaw cycle
SIDE EFFECTS transient serous retinal detachment retinal tear localized preretinal
fibrosis
Transpupillary thermotherapy
PRINCIPLE
bull thermotherapy has synergistic effect with chemotherapy9 ( carboplatin) ndash enhances the platinum
DNA adduct thus ndash antitumor effect
INDICATIONS
bull Small (lt 3mm) tumors posterior to the equator
bull Larger tumors post chemotherapy
TECHNIQUE
bull With diode laser focused heat at sub photocoagulation level- 42C to 60C for 5-20 min to tumor is
applied with relatively sparing of retinal vessels from photocoagulation
bull Local control of 70-80
COMPLICATIONS
bull Retinal traction fibrosis transient serous retinal detachment
RADIOACTIVE PLAQUE APPLICATION
INDICATIONS
1Primary plaque therapy ndash localized RB typically limited to 1-2 foci not involving optic disc or macula
2 In conjunction with chemoreduction therapy- -small or moderate size lesion including those with focal
viterous seeding immediately overlying the tumor
3 Tumors lt1616mm at base and lt8mm in thickness
4 Local failure after other therapy (EBRT chemotherapy laser cryotherapy)
ADVANTAGES (vs EBRT)
bull Better dose localization
bull Lesser risk of cataract
bull Minimal risk of bone hypoplasia
bull Lesser risk of second malignancies
PLAQUE TYPES and features
bull Co60
bull I125 (27 to 35 kev half- life ndash 60 days)- gamma rays
emitter
bull Au198 Ir192Ru106- beta emitter
bull Ir-192- (295-612kevhalflife- 74 days)
bull Ru-106( 35 Mev374 days)
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
Transpupillary thermotherapy
PRINCIPLE
bull thermotherapy has synergistic effect with chemotherapy9 ( carboplatin) ndash enhances the platinum
DNA adduct thus ndash antitumor effect
INDICATIONS
bull Small (lt 3mm) tumors posterior to the equator
bull Larger tumors post chemotherapy
TECHNIQUE
bull With diode laser focused heat at sub photocoagulation level- 42C to 60C for 5-20 min to tumor is
applied with relatively sparing of retinal vessels from photocoagulation
bull Local control of 70-80
COMPLICATIONS
bull Retinal traction fibrosis transient serous retinal detachment
RADIOACTIVE PLAQUE APPLICATION
INDICATIONS
1Primary plaque therapy ndash localized RB typically limited to 1-2 foci not involving optic disc or macula
2 In conjunction with chemoreduction therapy- -small or moderate size lesion including those with focal
viterous seeding immediately overlying the tumor
3 Tumors lt1616mm at base and lt8mm in thickness
4 Local failure after other therapy (EBRT chemotherapy laser cryotherapy)
ADVANTAGES (vs EBRT)
bull Better dose localization
bull Lesser risk of cataract
bull Minimal risk of bone hypoplasia
bull Lesser risk of second malignancies
PLAQUE TYPES and features
bull Co60
bull I125 (27 to 35 kev half- life ndash 60 days)- gamma rays
emitter
bull Au198 Ir192Ru106- beta emitter
bull Ir-192- (295-612kevhalflife- 74 days)
bull Ru-106( 35 Mev374 days)
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
RADIOACTIVE PLAQUE APPLICATION
INDICATIONS
1Primary plaque therapy ndash localized RB typically limited to 1-2 foci not involving optic disc or macula
2 In conjunction with chemoreduction therapy- -small or moderate size lesion including those with focal
viterous seeding immediately overlying the tumor
3 Tumors lt1616mm at base and lt8mm in thickness
4 Local failure after other therapy (EBRT chemotherapy laser cryotherapy)
ADVANTAGES (vs EBRT)
bull Better dose localization
bull Lesser risk of cataract
bull Minimal risk of bone hypoplasia
bull Lesser risk of second malignancies
PLAQUE TYPES and features
bull Co60
bull I125 (27 to 35 kev half- life ndash 60 days)- gamma rays
emitter
bull Au198 Ir192Ru106- beta emitter
bull Ir-192- (295-612kevhalflife- 74 days)
bull Ru-106( 35 Mev374 days)
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
PLAQUE TYPES and features
bull Co60
bull I125 (27 to 35 kev half- life ndash 60 days)- gamma rays
emitter
bull Au198 Ir192Ru106- beta emitter
bull Ir-192- (295-612kevhalflife- 74 days)
bull Ru-106( 35 Mev374 days)
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
TECHNIQUE
1 Tumor anatomy assessed by USG
2 Incision at limbus
3 Dummy plaque with 2mm margin
4 Retention Sutures placed in sclera
5 Dummy replaced with radioactive
plaque
6 Retention sutures secured
7 Conjunctiva closed
8 Plaque removed after treatment
completion
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
DOSAGE
bull Target dose -40 Gy to the tumor apex for I-125 at 40-80 cGyhr and 120 Gy at
tumor base ( scleral dose)(Tumor Control = 83 Philadelphia)
bull As adjuvant after chemo 35Gy and 1 month after chemotherapy to reduce
toxicity
COMPLICATIONS
bull Retinopathy ( 5 yr acturial rate= 27)
bull Cataracts(31) (plaque used post EBRT)
bull Maculopathy (25)
bull Papillopathy (26)
bull Glaucoma (11) ( post EBRT)
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
EXTERNAL BEAM RADIOTHERAPY
INDICATIONS
bull When RB is multifocal or close to the macula or optic nerve with preserved vision
bull Large tumors not amenable to focal therapies
bull Vitreous seeding
bull Secondary therapy to salvage chemoreduction and focal therapy failures
bull Tumors involving cut end of optic nerve
bull To palliate or consolidate the systemic therapy of metastatic disease
GOALS
bull Tumoricidal dose to the entire retinal and vitreous since
All retinal cells have a genetic neoplastic potential
Vitreous seeding may have occurred
Tumor may have spread via sub retinal space
bull Opposite eye irradiation be avoided if uninvolved
bull Sparing of lacrimal glands cornea
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
LATERAL BEAM MEGAVOLTAGE TECHNIQUE
Lateral field
Ant border at lateral edge of bony orbit
Posterior border at apex of orbit
Superior border at superior bony ridge
Inferior border at inferior bony ridge
bull Direct lateral field if opposite eye is enucleated
bull If opposite eye present then beam slightly angled posteriorly to avoid exit
radiation to other eye
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
ADVANTAGES lsquoDrsquo shaped field produced after
sheilding pituitary and alveolar processes saves
tooth buds and pituitary
SHORTCOMINGS underdosage of the retina bw
oraserrata anteriorly and equator of the globe to
save the contralateral eye
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
DIRECT ANTERIOR FIELD ( McCormick et al)
Borders
Superior superior orbital margin
Inferior inferior orbital margin
Lateral lateral bony canthus
Medial midline
bull ADVANTAGES Treats entire eye
Saves opposite eye
Easy to set up reproducible
Homogenous dose to entire retina and vitreous
bull DISADVANTAGES Cataract almost inevitable
Lacrimal gland dosage produces impaired tear production
Exit beam through brain
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
PROTON BEAM
ADVANTAGES
bull Superior dose distribution
bull Sparing of other eye because of stopping characteristics
bull In BL cases tissue lying in between two eyes can be saved
bull Lowering the risk of radiation induced malignancies
DISADVANTAGES
bull High bone dose while producing spread out proton beam
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
CONFORMAL RADIATION THERAPY
ADVANTAGES Possible to spare lens while irradiating whole of retina
-Substantially less dose to surrounding soft tissue and bones
DISADVANTAGES
Higher integral dose increases risk of second malignancies
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
ExRT DOSAGE
dose to treat a retinoblastoma with ExRT is
40-45 Gy- 18 Gy to 2 Gy
Dose modification needed when using RT
after chemotherapy for consolidation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
Chemotherapy-
Used in three basic situations1 To locally control the intraocular disease
Chemotherapy is used in neoadjuvant setting to reduce the size of large tumors to a size suitable for eradication by focal therapies (chemoreduction)
2 To produce regression of metastatic disease3 To prevent recurrence or metastases of locally
advanced Rb (Adj CT)Chemo is seldom used as a sole treatment modality
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
Intraocular ( Subconjunctival) CarboplatinIntrathecal Methotrexate cytarabine ( Brain mets trilateral Rb)
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
LATE EFFECTS OF RADIOTHERAPY
1Secondary Malignant Neoplasms
bull Childeren woth heriditary retinoblastoma are 3 fold increased risk as compared to non hereditary
Cumulative incidence of secondary malignancy after 50 years of diagnosis-
bull 36 in hereditary
bull And 57 in sporadic
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
In hereditary group
bull standard incidence -22 times the expected incidence after RT and 7 times without RT
In sporadic cases ndash incidence of second neoplasm (breast cancer) 28 times the normal population
bull Childeren who recived RT in 1 yr of life have higher risk of developing second cancer withinfield of radiation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
bull Osteogenic sarcoma (mc)-75
bull Soft tissue sarcoma and melanoma(25)
bull Epithelial tumors(in late adulthood) ndash lung breast and colon
bull Lipoma
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
bull 2 Bony orbital abnormalites Post RT and post
enucleation significant risks of orbital mal development
and midfacial growth retardation has been observed
bull EBRT (gt35Gy) to lt 6month old children accentuates the
risk
3CataractClinically significant posterior pole cataract
Anterior field techniques -85 lens sparing techniques-28
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
EXTRAOCULAR RETINOBLASTOMA
bull Locoregional including orbital infilterationtumor extending into optic nerve or to cut end of the nerve and lymphatic spread to preauricular lymphnodes
2cns disssemination
3Trilateral retinoblastoma
4 Metastatic retinoblastoma
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
Orbital and locoregionalretinoblastoma
bull Orbital RB occurs as aresult of progression of the tumor via emissary vessels and sclera
bull Treatment ndash systemic chemotherapy and radiotherapy- 60-85 cure rate
bull Pt with macroscopic disease- initial chemo fb surgery (obivates the need of orbital exenteration)---post op chemo and radiation 40-45 Gy (consolidative therapy)
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
bull Pt with isolated optic nerve involvement ndash
bull Systemic chemo with radiation to entire orbit (36 Gy ) and 9-10 Gy boost to chiasma (total 45Gy)
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
CNS disease-
bull Occurs by direct extension by optic nerve
bull Rx- platinum based chemotherapy+ craniospinal irradiation( 234 Gy ndash 36 Gy to neuraxis and a boost to 45 Gy to sites of overt or nodular ds)
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
Trilateral retinoblastoma
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation
CONCLUSIONS
bull Early detection and treatment can save the vision in retinoblastoma
bull With the advent of neoadjuvant chemoradiation treatment goal has now
shifted from enucleation to visual preservation in most of patients
bull Combined approach of Ophthalmologist Radiation Oncologist Pediatric
Oncologist Medical Physicist Pathologist Radiologist Geneticist with
individualization of treatment often leads to favorable outcome in terms
of overall survival and vision preservation