Pediatr Blood Cancer 2004;43:134–139

Episcleral Plaque Brachytherapy for Retinoblastoma

Thomas E. Merchant, DO, PhD,1* Ciara J. Gould, BS,1 Matthew W. Wilson, MD,3,4

Nathan E. Hilton, MD,1 Carlos Rodriguez-Galindo, MD,2 and Barrett G. Haik, MD3,4

INTRODUCTION

The biologic, clinical, and treatment considerations forretinoblastoma are unique among malignant tumors thatarise in humans. Paired organ (bilateral ocular) presenta-tions are relatively common, reported to be as high as 58%in recent series [1] and multifocal tumors are commoneven for patients with unilateral retinoblastoma [2].Organ-specific and lesion-specific treatment is possibleusing currently available local control measures that in-clude surgery (enucleation), external-beam radiation ther-apy (XRT), photocoagulation, cryotherapy, transpupillarythermotherapy, and episcleral plaque brachytherapy(EPBRT). Each treatmentmethod has specific indications,as well as relative advantages and disadvantages.

EPBRThas been usedwidely to treat adult patientswithchoroidal melanoma [3]. The indications for its use anddata detailing its efficacy in these patients have been welldescribed. EPBRT can be used to treat certain patientswith newly diagnosed or recurrent retinoblastoma [4–8].Stannard et al. [9] were the first to publish on the use ofiodine-125 (125I) plaques for retinoblastoma. There arelimited data from which guidelines might be developed todetermine its optimal use and its potential impact ondisease control, vision preservation, treatment-relatedmorbidity, and overall survival. No prospective studieshave been completed, and most patients who receiveEPBRTare treated adjuvantly or at the time of recurrenceafter other eye preservationmeasures have failed although

EPBRTas a primary treatment has been well documented[4,9].

XRT has been a standard therapy for retinoblastomaand remains an integral component in the managementof this disease, despite concerns about its effects ongrowth and development and its potential to induce malig-nant neoplasms. Because of these concerns, current treat-ment strategies aim to delay or eliminate the need forXRT or enucleation and to preserve visual function.EPBRT should be considered among the methods cur-rently used to meet this goal, because it has unique

Background. The purpose of this study was toreport our experience using episcleral plaquebrachytherapy (EPBRT) to treat retinoblastomaand to demonstrate its applicability in multi-modality treatment. Procedure. We treated26 tumors in 25 eyes from a group of 21 childrenwith unilateral (n¼4) or bilateral (n¼ 17) retino-blastoma. The group comprised 8 girls and 13boys; the median age was 25 months (range: 2–64 months) at the time of EPBRT. Iodine-125 (125I)was used for all applications. The median dosewas 44 Gy (range: 35–47.6 Gy). EPBRT wasadministered primarily at the time of relapse afterprimary chemotherapy or radiation therapy.Results. For eyes treated with EPBRT, the eyepreservation rate was 15/25 with a medianfollow-up of 47 months (range: 2–198 months);the lesion control rate was 25/26 with a median

follow-up of 13 months (range: 1–140 months).The median time to additional whole-eye treat-ment after EPBRT was 12 months (range: 2–105months). Conclusions. Similar to previouslyreported series, EPBRT shows a high rate ofsuccessful tumor control as a primary treatmentfor retinoblastoma, as well as a secondary therapyat the time of relapse. EPBRT also allows for aclinically significant delay in the time to addi-tional measures for the affected eye. Therefore,EPBRT should be considered as a form of localophthalmic therapy that avoids or delays the useof external-beam radiotherapy, especially forpatients primarily treated with chemotherapywho might require consolidation therapy.PediatrBlood Cancer 2004;43:134–139.� 2004 Wiley-Liss, Inc.

Key words: brachytherapy; ophthalmology; pediatrics; radiotherapy; retinoblastoma

——————1Division of Radiation Oncology, St. Jude Children’s Research

Hospital, Memphis, Tennessee

2Department of Hematology-Oncology, St. Jude Children’s Research

Hospital, Memphis, Tennessee

3Department of Surgery, St. Jude Children’s Research Hospital,

Memphis, Tennessee

4Department of Ophthalmology, University of Tennessee, Memphis,

Tennessee

Grant sponsor: Cancer Center Support CORE; Grant number: P30 CA

21765; Grant sponsor: American Lebanese Syrian Associated

Charities (ALSAC).

*Correspondence to: Thomas E. Merchant, Division of Radiation

Oncology, St. Jude Children’s Research Hospital, 332 North

Lauderdale Street, Memphis, TN 38105-2794.

E-mail: thomas.merchant@stjude.org

Received 9 September 2003; Accepted 27 April 2004

� 2004 Wiley-Liss, Inc.DOI 10.1002/pbc.20094

physical characteristics that allow for focused irradiationof solitary tumors.

This report details our use of EPBRTwith 125I to treatpatients with retinoblastoma. The objective is to show theapplicability of this method in the multimodality treat-ment of these patients and identify new treatmentstrategies for which EPBRT might be appropriate.

MATERIALS AND METHODS

Patients

We reviewed the records of 21 patients with retino-blastoma treated with EPBRT at St. Jude Children’sResearch Hospital (St. Jude) between 1983 and 2000.Many of the patients received combined-modality therapythat included multiagent chemotherapy, enucleation, XRT,cryotherapy, and laser photocoagulation. The followingclinical and treatment information regarding the patientswas included in this report: age at diagnosis and time ofEPBRT, sex, laterality and number of affected eyes,grouping (Reese–Ellsworth) [10], sequence and type oftherapeutic interventions for all eyes (e.g., enucleation,cryotherapy, photocoagulation,multiagent chemotherapy,XRT, andEPBRT), dates and time intervals to relapse afterspecific interventions, follow-up, and disease-controlstatus.

The clinical and treatment details are summarized inTable I. Briefly, 8 girls and 13 boys were included in thestudy. Among these 21 children, 38 eyes had retinoblas-toma; three were enucleated at presentation, and 35 wereevaluated for eye preservation. The median age at diag-nosis was 7 months (range: 1 week–32 months). Themedian age at time of EPBRTwas 25 months (range: 2–64 months). Four patients exhibited unilateral retinoblas-toma, and 17 exhibited bilateral retinoblastoma. The stageand grouping of tumors, sequence and type of therapeuticinterventions, history of relapse after specific interven-tions, and disease status are summarized in Table II.Table III summarizes the grouping distributions.

Nonradiotherapeutic Local Control Measures

Fifteen of 21 patients (22/38 eyes) were treated withcryotherapy at some time during their treatment courseand usually more than once. Thirteen of 25 eyes treatedwith EPBRT had previously received cryotherapy. Fiveeyes in four patients received laser photocoagulation; lasertreatment preceded EPBRT in three eyes. Among the 38eyes with retinoblastoma, 15 were eventually enucleated:3 at presentation, 2 that did not respond toXRT, and 10 thatreceived EPBRT. Seven of the eyes that received EPBRTand were subsequently enucleated were also treated withXRT, including six that received XRT before EPBRT andone that received XRT after EPBRT. When localophthalmic therapy, cryotherapy or laser photocoagula-tion, was applied to an eye containing a lesion that waseventually plaqued, it can be assumed that the localophthalmic therapy was applied to the plaqued lesion. Ingeneral, nonradiotherapeutic local control measures wereapplied prior to EPBRT.

Chemotherapy

Chemotherapy was the first treatment for ten patientsincluding nine treated with carboplatin and vincristine.Four additional patients received chemotherapy afterconservative measures, including EPBRT, failed. Onepatient received chemotherapy before and after EPBRT.Measured from the initiation of chemotherapy, theprogression-free interval was 2–29 months (median,11 months).

External-Beam Irradiation

Sixteen patients (24 eyes) received XRT. The medianage of the patients who received XRT was 12 months(range: 7–40 months). One patient presented with un-ilateral disease, and the remaining 15 presented withbilateral disease. Of the 15 patients with bilateral disease,2 received treatment to only one eye due to the previousenucleation of the other eye. There were five instances inwhich patients with bilateral disease and both eyes intactreceived XRT in only one eye. One patient received XRTon two different occasions to the same eye.

Ten patients were treated with electrons (12 MeV)delivered en face. Fractionation for these patients rangedfrom 1.6 to 2 Gy prescribed to the 90% isodose line. Theremaining six patients received XRT with photons (4 or6 MeV). Fractionation for patients treated with photonsranged from 1.5 to 2 Gy; the median total dose was 36 Gy(range: 36–45 Gy).

Episcleral Plaque Brachytherapy

EPBRT was used to control the growth of lesionsnot amenable to cryotherapy, laser photocoagulation, orother nonradiotherapeutic local control measures. Only

TABLE I. Summary of Treatment for 21 Children WithRetinoblastoma

Treatment

No. of patients

(n¼ 21)

No. of eyes treated with

EPBRT (n¼ 25)

EPBRT 21 25a

Enucleation 9 10

XRT 16 20

Chemotherapy 15 NA

Cryotherapy 15 16

Laser photocoagulation 4 5

Abbreviations: EPBRT, episcleral brachytherapy; XRT, external-beam

radiation therapy; NA, not applicable.aA total of 26 lesions in 25 eyes were treated with EPBRT.

Brachytherapy for Retinoblastoma 135

TABLEII.Dem

ographics,CourseofTreatm

ent,andOutcomeMeasuresin

21ChildrenWithRetinoblastomaTreatedWithBrachytherapy

Patientdem

ographics

Retinoblastomastaging

Courseoftreatm

enta

Outcome

Patient

no.

Age

(months)

Sex

Affected

eye

RE

SJO

SJM

AJC

C

Overall

survival

Eye

preservation

01

7M

OD

IIA

IBIC

T1N0M0

DX-CT-EUA

(11)-CRYO-EUA

(4)-SD

39

39

OS

IVA

IIA

IET1N0M0

DX-CT-EUA

(9)-PD-EPBRT(35Gy)-EUA

(7)-SD

39

39

02

1F

OD

VB

IIA

IAT3N0M0

DX-X

RT(36.9

Gy)-EUA

(9)-PD-ENUC

48

19

OS

IAIA

IAT1N0M0

DX-X

RT(36.8

Gy)-EUA

(9)-CRYO-EUA

(2)-PD-CT-CRYO-EPBRT

(40Gy)-DM-CT-EUA

(5)-DOD

48

48

03

2F

OD

IAIA

IAT1N0M0

DX-CRYO

(3)-EUA

(5)-PD-X

RT(45Gy)-EUA

(6)-PD-EPBRT

(40Gy)-EUA

(29)

136

136

OS

IBIC

ICT1N0M0

DX-ENUC

136

0

04

2F

OD

IIIA

IBIC

T1N0M0

DX-EPBRT(40Gy)-CRYO-EUA

(10)-ENUC

112

14

OS

IIIB

IAIC

T1N0M0

DX-CRYO-X

RT(36Gy)-CRYO-EUA(7)-PD-X

RT(39.6Gy)-DM-CT-EUA

(26)

112

112

05

7M

OD

IIIA

IAIB

T1N0M0

DX-X

RT

(36Gy)-EUA

(4)-CRYO-EUA-CRYO

(2)-EUA

(5)-PD-EPBRT

(40Gy)-EUA

(6)-CT-EUA

117

117

OS

IIIA

ICIE

T4bN0M0

DX-X

RT(36GY)-EUA

(5)-CRYO

(3)-EPBRT(40.32Gy)-EUA

(3)-CRYO-EUA

(7)-PD-ENUC

117

28

06

17

MOD

IAIA

IBT1N0M0

DX-CT-EUA

(5)-CRYO(2)-EUA(3)-SD

25

25

OS

IIIA

IBIE

T1N0M0

DX-CT-EUA

(5)-PD-CRYO-EPBRT(47.6

Gy)-CRYO-EUA

(3)-XRT

(46Gy)-EUA

(6)

25

25

07

0.5

MOD

IIIA

ICIB

T1N0M0

DX-CT-EUA

(2)-XRT(36Gy)-EUA

(7)-CRYO

(2)-EUA

(4)-CRYO-EUA-

PD-EPBRT(39.15Gy)-EUA

(5)-SD

60

60

OS

IIIA

ICIB

T1N0M0

DX-CT-EUA

(2)-XRT(36Gy)-EUA

(19)-SD

60

60

08

10

FOD

IIIB

IBIB

TC

DX-CT-EUA

(5)-PD-CRYO

(4)-EPBRT(44.2

Gy)-EUA

(3)-LZ(1)-XRT

(44Gy)-PD-ENUC

29

20

OS

IIB

IBIC

TC

DX-CT-EUA

(7)-PD-EPBRT(46.41Gy)-CRYO-EUA

(3)-PD-LZ

(3)-PD-EPBRT(44.29Gy)-EUA

(2)-PD-LZ(2)-CT-LZ(8)

29

29

09

11

MOD

VB

IIA

IET2N0M0

DX-X

RT(43Gy)-CRYO(4)-EPBRT(45Gy)-EUA

(12)-ENUC

105

25

OS

VB

IIA

IIE

T2N0M0

DX-X

RT(43Gy)-CRYO

(4)-EUA

(2)-EPBRT(45.2

Gy)-EUA

(3)-PD-EPBRT(40Gy)-EUA

(2)-PD-ENUC

105

17

OS

VB

IIA

IIE

T2N0M0

DX-X

RT(43Gy)-CRYO

(4)-EUA

(2)-EPBRT(45.2

Gy)-EUA

(3)-PD-EPBRT(40Gy)-EUA

(2)-PD-ENUC

105

17

10

27

MOD

IVA

IIA

IET1N0M0

DX-CT-EUA

(4)-PD-CRYO

(1)-EPBRT(44.64Gy)-CRYO

(2)-PD-ENUC

26

10

11

7M

OS

IAIA

ICT1N0M0

DX-X

RT(36Gy)-EUA

(14)-PD-EPBRT(40Gy)-SD

198

198

12

19

MOD

IAIA

IAT1N0M0

DX-EPBRT(43.38Gy)-EUA(7)

13

13

13

0.25

MOD

VB

ICIE

cT3aN

0Mx

DX-CT-EUA

(8)-PD-X

RT(36Gy)-EUA

(11)-SD

58

58

OS

VA

ICIE

cT3aN

0Mx

DX-CT-EUA

(8)-PD-X

RT(36Gy)-EUA

(9)-PD

(3/99)-LZ-EPBRT

(45.65Gy)-EUA

(8)-ENUC

58

58

14

3M

OD

IBIB

IBT1N0M0

DX-CT-EUA

(6)-EPBRT(40.95Gy)-EUA

18

18

OS

IVB

ICIC

T2N0M0

DX-CT-EUA

(6)-CRYO

(5)-EUA

(5)-LZ-X

RT(44Gy)

18

18

15

13

FOD

IIIA

IBIB

cT1mN0M0

DX-EUA

(2)-CRYO

(2)-EUA

(6)-EPBRT(45Gy)-EUA

(6)

47

47

OS

IVB

IIB

IID

pT3NxM0

DX-ENUC

47

0

16

18

MOS

IIA

IAIA

T1N0M0

DX-CT-EUA-EPBRT(43Gy)-EUA

22

17

84

FOD

Eyeenucleatedat

other

institution

DX-ENUC

68

0

136 Merchant et al.

well-defined, solitary tumor complexes that were less than7mm in height and less or equal to 18mm in diameterwereconsidered. Most were considerably smaller. Twenty-sixlesions in 25 eyes were treated with EPBRT. In addition,one lesion received a second course of EPBRT; the secondapplication is recognized as an ‘‘additional treatmentmeasure.’’ EPBRT was the initial treatment for fivepatients; eight had previously received chemotherapyalone. Thirteen eyes received EPBRT after their diseasefailed to respond to XRT, including four eyes that hadpreviously received both XRT and chemotherapy beforeEPBRT. In all cases, the radioisotope 125I was used. Themedian radiation dose given was 44 Gy (range: 35–47.6Gy). Themedian dose ratewas 42 cGy/hr (range: 30–53 cGy/hr). The prescription point was the apex of thetumor or 5 mm, whichever depth was greater. The medianduration of therapy was 100 hr (range: 71.5–133 hr).Thenumber of sources used per plaque ranged from 1 to 21(median, 7). Custom-made gold plaques were used.

Definitions of Treatment Endpoints

Overall survival was measured from the date of diag-nosis and calculated as a generalmeasure of the efficacy ofthe overall treatment provided to this patient group. Theeye preservation rate was determined to show the actualnumber of eyes preserved compared to the number of eyesconsidered for preservation; the three eyes enucleated atthe time of diagnosis were not included in the finalanalysis. The lesion control rate was determined as ameasure of effectiveness of the plaque to control thetreated lesion. The effectiveness of EPBRTas a treatmentoption was determined by measuring the time intervalbetween plaque placement and the time to additionaltreatment measures that affected the eye treated withEPBRT. This measure applies only to the eyes treated withEPBRT and includes administration of any systemicchemotherapy, XRT, or other treatment that would affectthe EPBRT-treated lesion or entire eye.

OS

IVB

T1N0M0

DX-X

RT(36Gy)-EUA(20)-EPBRT(45Gy)-EUA

(11)-PD-CT-EUA

(10)-ENUC

68

68

18

120

MOD

IIIA

T1N0M0

DX-X

RT(36Gy)-EUA-PD-ENUC

123

18

OS

IAT1N0M0

DX-X

RT(36Gy)-PD-CT-EUA

(2)-CRYO

(2)-EUA-PD-EPBRT

(40Gy)-EUA

(5)-SD

123

123

19

20

FOD

IIIA

T2N0M0

DX-X

RT(38Gy)-EUA(10)-EPBRT(46Gy)-EUA(4)-PD-CT-EUA-ENUC

60

52

OS

IIIA

T2N0M0

DX-X

RT(38Gy)-EUA

(14)-CT-EUA

(4)-SD

60

60

20

24

MOD

IIIA

T1N0M0

DX-CT-EUA

(2)-EPBRT(44Gy)-EUA-PD-ENUC

17

11

OS

IIIB

T1N0M0

DX-CT-EUA

(2)-PD-X

RT(44Gy)-EUA

(5)-CRYO-LZ

(2)-EUA-CRYO-LZ-CRYO-LZ

17

17

21

6M

OD

IIIA

T1N0M0

DX-EPBRT(45Gy)-EUA-PD-CRYO-X

RT(37Gy)-EUA

(7)

107

107

OS

IIIA

T1N0M0

DX-EPBRT(45Gy)-EUA-PD-CRYO-X

RT(35Gy)-EUA

(7)

107

107

Abbreviations:RE,Reese–Ellsw

orth;AJC

C,American

JointCommitteeonCancer;DX,diagnosis;CT,chem

otherapy;EUA,exam

inationunder

anesthesia;SD,stabledisease;PD,progressive

disease;CRYO,cryotherapy;DM,distantmetastasis;DOD,deadofdisease;XRT,external-beam

radiationtherapy;ENUC,enucleation;LZ,laser

therapy;NA,notapplicablesince

theeyedidnot

receiveEPBRT.

aNumbersin

bracketsindicateeither

thedose

ofradiationorthenumber

ofevents,ifknown.

TABLE III. Retinoblastoma Grouping in 21 Pediatric Patients

Reese–Ellsworth [10]

Stage No. Pts

IA 6

IB 2

IIA 2

IIB 1

IIIA 13

IIIB 3

IVA 2

IVB 2

VA 1

VB 5

Brachytherapy for Retinoblastoma 137

RESULTS

Clinical and treatment details are included in the‘‘Ma-terials and Methods’’ and Tables I–III.

Survival

Among the 21 patients included in this report, 20 arealive with a median follow-up of 58 months, (range: 1–198 months). One patient died of metastatic disease48 months after diagnosis. This patient was initially treat-ed with low-dose XRT (36 Gy) to both eyes; however,disease progressed in both eyes, and the patient waseventually treated with enucleation of one eye andchemotherapy and EPBRT to the other eye. Subsequentto these additional treatment measures, distant metastasesdeveloped, and the patient eventually died.

Eye Preservation

Among the 21 patients included in this report, therewere a total of 38 eyes with retinoblastoma: of the 35 eyesevaluated for eye preservation measures, 12 were even-tually enucleated. The preservation rate was, therefore,66%(23/35)with amedian follow-up of 58months (range:2–198 months) for the intact eyes. For the eyes treatedwith EPBRT, the preservation ratewas 60% (15/25) with amedian follow-up after EPBRT of 47 months (range: 2–198 months) for the intact eyes. Among the 10 eyesenucleated after EPBRT, nonewere enucleated because offailure of the lesion to respond toEPBRT.Themedian timeto enucleation for these patients was 20 months afterdiagnosis (range: 10–68 months).

Lesion Control

The lesion control ratewas 25/26with amedian follow-up of 13 months (range: 1–140 months). Progressivedisease at the site of EPBRTwas noted in only one patientand treated with a second plaque. Treatment failure wasprobably due to plaque placement or design; only four 125Isources were used. The lesion was treated successfullywith placement of a second plaque. The eyes that receivedEPBRTand were subsequently enucleated for progressivedisease at other sites within the same eyewere consideredcontrolled at the time of enucleation. Enucleation wasperformed after EPBRT because of parental preference(n¼ 2) or prior history of XRT (n¼ 8).

Time to Additional Whole-Eye Treatment Measures

The durability of lesion control can be measured onlyas long as the lesion that received EPBRT is not subjectedto additional whole-eye treatment measures. The mediantime to additional whole-eye treatment measures was

12 months (range: 2–105 months). Sixteen eyes con-taining 17 EPBRT-treated lesions required additionalwhole-eye treatment measures including XRT (n¼ 4),chemotherapy (n¼ 4), repeat EPBRT (n¼ 1), and enu-cleation (n¼ 7). Nine eyes did not require furthertreatment, seven eyes were enucleated, and nine requiredfurther treatment.

DISCUSSION

The importance of EPBRT in the treatment ofretinoblastoma is well recognized [11]. This recognitionincludes plaque therapy as one of the local forms ofophthalmic therapy that can eliminate or delay the need forXRT or be used as a consolidation treatment for patientstreated with chemotherapy. Plaque therapy continues toserve as an important treatment for patients whose tumorsfail to respond to XRT [5,12]. The logistical and technicalaspects of plaque therapy require considerable coopera-tion among the specialties involved in ophthalmic on-cology. Accurate measurement of the tumor dimensionsand design, placement, and verification of the plaque eachcontribute to the success or failure of this treatment.Minimizing the delay between evaluation and treatment isalso important to ensure that the dimensions of the lesionmatch the design of the plaque.

The use of the episcleral plaque does not compromiseoverall survival or eye preservation. The eye preservationrate in our series of heterogeneously treated patients was60% (15/25) with a median follow-up of 47 months.Although it is too early to determine thevisual outcome forthese patients, if the preservation rate is similar to thefunctional outcome, then these results will hopefullycompare favorably with earlier reports. In 1989, Shieldset al. [7] reported their preliminary results using Cobalt-60, Ruthenium-106, and 125I plaques in 50 patients withretinoblastoma. Ninety-seven plaques were placed in 51affected eyes as the primary or secondary treatment.Among the 15 patients treated primarily, 13 (87%) had agood functional outcome; among the 36 who receivedEPBRT secondarily, 22 (61%) experienced a goodoutcome. This differencewas attributed to more advanceddisease and a lowering of the functional reserve with ex-cess treatment in the latter group. This series was updatedin a 1993 report detailing the use of EPBRT in 103 cases[5]. Tumor control was achieved in 86% of the cases,whereas recurrence after initial response was noted in13%. Functional outcome was acceptable in 62% of thecases, and poor outcomewas noted in 29%.Only 9%of thetreated eyes required enucleation after plaque therapy.More recent follow-up with noted complications has beenpresented by Shields et al. [13].

Because retinoblastoma often involves more than oneeye, multiple tumors, and seeding of the vitreous, thereare many ways to present and analyze the efficacy of

138 Merchant et al.

the EPBRT. We chose to monitor the lesion control rateof the eye treated with a plaque as a measure of diseasecontrol, and we realized that additional treatmentmeasures to the whole eye should be considered as animportant time interval in the analysis. Tumor control wasachieved in 96% (25/26) of the EPBRT-treated lesions.Sixteen of 25 eyes required additional whole-eye treat-ment measures with a median time of 12 months.Unfortunately, the most common whole-eye treatmentmeasure was enucleation. Enucleation was used when thepatient had previously received XRT or when the parentand physician concurred that it was the appropriate choiceof treatment.

Enucleation and irradiation have not been the appro-aches of choice used in the treatment of retinoblastoma.Today, primary treatment options tend toward chemother-apy with nonradiotherapeutic local control measures. Thecurability of retinoblastoma with chemotherapy aloneremains to be proven. A combination of moderate- or low-intensity chemotherapy and local control measures iscurrently being evaluated in a number of settings. Thisapproach should be considered for advanced intraoculardisease or bilateral tumors, as long as the selected chemo-therapy has minimal toxicity, does not induce secondprimary tumors or myelodysplasia, and does not compro-mise efforts to preserve function.

Only one of the patients treated with an episcleralplaque experienced a serious side effect that may or maynot have been related to EPBRT. This patient sufferedvitreous hemorrhagewhen XRTwas given for progressivedisease. The patient’s disease had previously failed torespond to chemotherapy, cryotherapy, and laser photo-coagulation. Toxicity noted in other series (e.g., neovas-cular glaucoma)was not observed in our patients, includingthosewho receivedchemotherapy [11,14] althoughEPBRTwas given after chemotherapy in most cases.

Our current institutional preference is to use che-motherapy (carboplatin and vincristine) at presentation forchildren with early stage intraocular retinoblastoma [15].XRTor EPBRTare used at the time of disease progression,depending on the extent of active disease and the potentialfor acceptable visual outcome. In the future, we plan to useEPBRT early in the course of chemotherapy for non-responding tumors. Our intention is to prolong theprogression-free survival after chemotherapy in a mannersimilar to that described by Friedman et al. [16]. In theirstudy, 75 eyes were followed in 47 children with retino-blastoma treated with six cycles of carboplatin, vin-cristine, and etoposide chemotherapy. Local forms ofophthalmic therapy, including cryotherapy, laser photo-coagulation, thermotherapy, plaque therapy, or a combi-nation of these approaches, were required in 83% ofthe cases. With a median follow-up of 13 months afterthe completion of chemotherapy, 66% of the patientshad avoided enucleation, the preservation rate was 100%

(39/39) in Reese–Ellsworth Groups I–III: 67% (4/6) inGroup IV, and 47% (14/30) in Group V.

CONCLUSIONS

EPBRT should be considered in the primary or adjuvanttreatment of children with retinoblastoma. Its uniquephysical characteristics allow for treatment of a limitedamount of normal tissue in amanner that is consistent withcurrent efforts to minimize radiation side effects. At ourinstitution, EPBRT is considered for patients with isolatedtumors at presentation or at the time of recurrence afterXRT and is used for patients with individual lesions thatfail to respond to cryotherapy, photocoagulation, or cyto-reductive chemotherapy.

REFERENCES

1. Abramson DH, Beaverson K, Sangani P, et al. Screening for

retinoblastoma: Presenting signs as prognosticators of patient and

ocular survival. Pediatrics 2003;112:1248–1255.

2. Brinkert AW,Moll AC, JagerMJ, et al. Distribution of tumors in the

retina in hereditary retinoblastoma patients. Ophthalmic Genet

1998;19:63–67.

3. Freire JE, De Potter P, Brady LW, et al. Brachytherapy in primary

ocular tumors. Semin Surg Oncol 1997;13:167–176.

4. Kiratli H, Bilgic S, Atahan IL. Plaque radiotherapy in the

management of retinoblastoma. Turk J Pediatr 1998;40:393–397.

5. ShieldsCL, Shields JA,DePotter P, et al. Plaque radiotherapy in the

management of retinoblastoma. Use as a primary and secondary

treatment. Ophthalmology 1993;100:216–224.

6. Shields CL, Shields JA, Minelli S, et al. Regression of retino-

blastoma after plaque radiotherapy. Am J of Ophthalmol 1993;

115:181–187.

7. Shields JA, Giblin ME, Shields CL, et al. Episcleral plaque

radiotherapy for retinoblastoma. Ophthalmology 1989;96:530–

537.

8. Spraul CW, Lim JI, Lambert SR, et al. Retinoblastoma recurrence

after iodine 125 plaque application. Retina 1996;16:135–138.

9. Stannard C, Sealy R, Shackleton D, et al. The use of iodine-125

plaques in the treatment of retinoblastoma. Ophthalmic Paediatr

Genet 1987;8:89–93.

10. Reese AB, Ellsworth RM. The evaluation and current concept of

retinoblastoma therapy. Trans Am Acad Ophthalmol Otolaryngol

1963;67:164–172.

11. Stannard C, Sealy R, Hering E, et al. Localized whole eye radio-

therapy for retinoblastoma using a 125I applicator, ‘‘claws’’. Int J

Radiat Oncol Biol Phys 2001;51:399–409.

12. Shields JA, Shields CL, De Potter P, et al. Plaque radiotherapy for

residual or recurrent retinoblastoma in 91 cases. J Pediatr

Opthalmol Strabismus 1994;31:242–245.

13. Shields CL, Shields JA, Cater J, et al. Plaque radiotherapy for

retinoblastoma: Long-term tumor control and treatment complica-

tions in 208 tumors. Ophthalmology 2001;108:2116–2121.

14. MurphreeAL,Villablanca JG,DeeganWF III, et al. Chemotherapy

plus local treatment in the management of intraocular retinoblas-

toma. Arch Ophthalmol 1996;114:1348–1356.

15. Rodriguez-Galindo C, Wilson MW, Haik BG, et al. Treatment of

intraocular retinoblastoma with vincristine and Carboplatin. J Clin

Oncol 2003;21:2019–2025.

16. Friedman D, Himelstein B, Shields C, et al. Chemoreduction and

local ophthalmic therapy for intraocular retinoblastoma. J Clin

Oncol 2000;18:12–17.

Brachytherapy for Retinoblastoma 139