BCT - AIIMS Experience

TMH - 26th October 2007 Breast Conservation Therapy IRCH-AIIMS Experience

Breast Conservation Therapy

IRCH-AIIMS Experience

Dr. Manish Varma, Dr. SVS Deo, Dr.NK Shukla, Dr. Vinod Raina*, Dr.GK Rath**

Dept. of Surgical , Medical* and Radiation oncology**, IRCH, AIIMS, New Delhi


Evolution of Surgery for BC

Ultra RadicalEarly 19 th Century

Conservation, Reconstruction

20 th century

RadicalLate 19 th Century


Morbidity of Mastectomy

Breast - Symbol of Femininity,

Attractiveness and motherhood

Loss of feminine attractiveness Altered body image perceptionPsycho sexual problemsPainful reminder of cancerDepression


Evolution of Modern BCT

• Innovative Pilot studies - 1960-70

BCT promising intervention for EBC

• Retrospective comparative studies - 70s

BCT Safer & effective option

• Prospective Randomized trials – 1980s

MRM Vs BCT- comparable out come

• 20 yrs RCT Results - 2000

20 yrs FU, BCT vs MRM – No survival difference

Scientifically studied & validated therapeutic intervention in Breast Cancer


Rationale of BCT

• Natural history– Breast cancer is a systemic disease with hematogenous

spread early in the disease process• 20% of node negative patients develop distant metastases

• Limits of surgical efficacy– Equivalent results of Radical and Modified radical

mastectomy : More extensive surgery might not result in better cure rates


Rationale of BCT

• Surgery and Radiation as a combined modality– Surgery alone- More failure at margins– Radiotherapy alone- More failure at the epicenter

• Using surgery to remove grossly visible tumor with a small margin and moderate-dose radiotherapy to treat the larger volume of tissue that may harbor residual disease


Surgery and Radiation as combined modality

• First used as an adjuvant after mastectomy to eradicate sub clinical disease in internal mammary,supraclavicular and axillary nodes and chest wall

• BCT uses Radiation for control of sub clinical disease in the residual breast tissue in addition to the above mentioned sites


Randomized Trials - BCT vs MRM Group No 10 Yr Survival (%) Loc. Rec(% )

BCT - MRM BCT - MRM

NSABP 2105 62 - 62 10 - 8

French 179 78 - 79 7 - 9

Milan 701 71 - 69 4 - 2

EORTC 903 75 - 75 13 - 9

Danish 905 79 - 82 3 - 4

NCI 237 77 - 75 17 - 9


Randomized Trials - BCT vs MRM

20 Year Follow up

• Milan Trial – NEJM 2002

Local Relapse – 8 % vs 2.3 % (BCT vs MRM)

OS – 59 % vs 59% (BCT vs MRM)

• NCI Trial - Cancer 2003

DFS – 64 % vs 67 % (BCT vs MRM)

OS – 54 % vs 58% (BCT vs MRM)


NCI Consensus Conference - EBC

In early breast cancer breast conservation treatment is not only equivalent to

mastectomy but also preferable as it preserves the breast with all the attendant

psychological and breast image advantages there by enhancing quality of life.


BCT - Multidisciplinary approach

Surgical OncologistRadiation OncologistMedical OncologistRadiologistPathologist


Goals of Breast Conservation

Acceptable cosmetic outcome Minimal local recurrence Uncompromised - DFS and OS Good quality of life


Breast Conservation TherapyPatient Selection

Indications for BCT

• Patient motivation• Stage I & II B.C (Tumor < 5 cm)• Availability of adequate infrastructure

– Mammography– Radiotherapy– good pathology services

• Reliability regarding Rx compliance & Follow up


Contraindications to BCT

Absolute– High probability of recurrence

– Multicentric disease– Positive surgical margins (EIC)

– High probability of complications from irradiation

– CVD– Prior irradiation to chest wall– Early pregnancy


Contraindications to BCT

Relative

– High probability of subsequent breast cancers

• BRCA1 and BRCA2 mutations

– Poor cosmetic results• Unfavorable tumor-breast ratio• Oncologically necessary removal of nipple-areola

complex• Large medial lesions

– Personal preference of the patient


BCT Surgical Margins

• Ideal margin – No consensus• 3D excision with minimum of 1 cm gross margin(0.5 to 2 cm)

• Local Relapse - Quadrantectomy vs Tumerectomy• Milan study - 5 % vs 13%

• Fine balance between cosmesis and margins• India - Main fear is local relapse - Wide margins


Breast Conservation Surgery Indications for Re-excision

EIC & Margin + ve

> focal microscopic margin +ve

Uncertain resection margins

Residual microcalcification


Breast Conservation Therapy Radiotherapy

• Integral part of BCT• With in 4 to 6 weeks of BCS• To control Microscopic residual disease

• WBRT – 50Gy / 25 Fr / 5 weeks

Linac / Cobalt• Tumor Bed Boost - 15 Gy

– Electron beam– Brachytherapy


Breast Conservation TherapyTumor Bed Boost


Breast Conservation TherapyTumor Bed Boost


Breast Conservation Therapy:Radiotherapy

Meta analysis “ Vinh Hung et al”, JNCI, 2004 Pooled data from all trials on BCT with and with out RT8.6 % survival benefit apartDecreased local relapse

Definite role in eradicating microscopic tumor foci.

Group No. Local Failure (%) - RT + RTNSABP '92 1141 39 12Ontario '92 837 26 6Milan '93 567 9 0.3Sweden '94 381 20 3


BCT- Recent Advances

Accelerated Partial Breast Irradiation (APBI)

• 80- 90 % recurrences after BCT occur around tumor bed

• APBI - R.T . Limited area of Breast over short duration

• Accelerated Partial Breast Irradiation equivalent to WBRT

• Advantages – Short duration of treatment

Limited Breast Irradiation

• Several phase I & II Studies – Promising results

• Technique – Mammosite / IORT / Brachytherapy / IMRT


BCT- Recent Advances

Surgery - Oncoplastic Techniques – BCS

• Recent data – 1 cm tumor free margin is more important than absolute tumor size

• BCT > 5 cm tumor is not an absolute CI for BCT

• Volume loss > 30% • Central quadrant tumors • Cavity – RT – Fibrosis Deformities• Skin loss – Breast Asymmetry

To Improve Cosmesis - Oncoplastic Techniques – BCS


BCT- Recent AdvancesSurgery - Oncoplastic Techniques – BCS

Aims

• Improving Cosmetic outcome, limiting deformity, and reduce scarring

Types of Oncoplasty – BCT

• Volume Displacement Procedures• Volume Replacement Method - Mini LD Flap

Reconstruction (MLDF)

Anderson B et al , Lancet Oncology 2005


Oncoplastic Techniques for BCS : Volume Displacement


Oncoplastic Techniques for BCS : Volume Replacement -Mini Latissimus Dorsi flap

(MLDF)

• Latissmus Dorsi Flap – Skin / Muscle / Fat• Popular flap BR – Tansini - 1906

– Proximity to defect/Long pedicle– Minimal functional impairment & donor site morbidity

• Volume Replacement - Mini LD Flap - BCT

Noguchi et al 1996 & Raja et al 1997

• Improved Cosmetic Results following BCT + MLDF Gendy et al 2003 ,

BJS


Mini Latissimus Dorsi flap (MLDF)


Mini Latissimus Dorsi flap (MLDF)


BCT- Recent Advances MRI in BCT

• Dense Breast on Mammogram

• Post Surg & RT – Breast

• Unknown primary with Axillary node

• Indeterminate Mammogram






BCT – Pushing Frontiers

• Family H/O Breast cancer • Not a contraindication of BCT. Chabner et al 2004

• Lobular carcinoma • Not a contraindication for BCT. Carolin et al , Breast J, 2004

• EIC• Not a contraindication as long as margin status is taken care

of. Smith et al , Cancer 1999

• Young age (< 40 yrs)• Not a contraindication for BCT



Expanded indications of BCT

• BCT for Central tumors & Pagets Disease• Central segmentectomy with Nipple Areola Complex

removal with negative margins is feasible. Pierce et al, Cancer 1999 in subset of patients

• Multifocal BC and BCT• 6 studies > 200 patients acceptable LR• Tumors encompassed in a single margin –ve resection• Cosmetically acceptable lumpectomy



• BCT for Non Palpable lesions

• Mammo guided wire localization and lumpectomy feasible

• Recently “Radio Guided Occult Lesion localization” ROLL is increasingly being used


Mammo guided wire localization and lumpectomy



BCT in LABC Neo Adjuvant Chemotherapy BCT NSABP -18 Trial

1500 pts Increased BCT in T3 group Higher Local recurrences but no effect on overall

survival

Unresolved issues Method of response assessment Tumor Localization in responders Pre chemo titanium clip placement ? Extent of resection


BCT in LABC post NACT

• Better Chemotherapeutic drugs– Response rates in over 2/3rd patients– CR Rates –upto 1/3rd – Progression on chemotherapy – 2-3%

• Attempted in Non-inflammatory LABC


• Increased likelihood of loco-regional recurrence

• Large tumor size• Advanced nodal disease• Multifocal pattern of residual disease after

NACT• LVI

Chen et al. Journal of clinical oncology, 2004



• Contraindications to BCT after NACT

• Residual tumor size >5 cm• Residual skin edema or direct skin involvement• Chest wall fixation• Diffuse microcalcification on post NACT

mammography• Multicentric disease

Chen et al. Journal of clinical oncology, 2004



• Nearly half of these patients can undergo successful breast

conservation with acceptable long term disease free and

overall survivals

– William G et al. Annals of Surgery 2002. (Univ of North Carolina,

USA)

– Allen M. Chen et al.J of Clinical Oncology 2004 (M.D.Anderson,

Texas, USA)

– Viswambharan JK et al. Indian J Cancer. 2005 (JIPMER, India)

– Asoglu O. Acta Chir Belg. 2005 ( Istanbul, Turkey)

– Merajver SD. J Clin Oncol. 1997 (Univ of Michigan, USA)

– Beriwal S, et al. Breast J. 2006 Drexel University College of

Medicine, Philadelphia, USA

– Shen J, et al. Ann Surg Oncol. 2004 (University of Texas M. D.

Anderson Cancer Center, Houston, USA )



BCT Rates

• Recent survey 2002 USA - NCDB• BCT- Grossly underutilized option• BCT rates – 10 to 45 % in USA in EBC• Factors for low BCT

– Age - young age > BCT– Place of treatment- Urban vs Rural, North & east

USA – Socioeconomic factors– ? Low reimbursement for BCT


Breast conservation therapy

• IRCH –AIIMS

– Current BCT rate – 30 % of EBC– Reasons for refusing BCT

• Fear of recurrence in residual breast• Family members not keen for BCT• Second opinion- Physician bias


Breast Conservation Therapy: IRCH Treatment Protocol

SURGERY

• Initial phase - Quadrantectomy• Subsequently - Wide excision - 1.5 cm, 3 dimensional

tumor free margins • Previous lumpectomy patients - Re-excision of scar

and lumpectomy cavity • Re-excision of tumor bed after lumpectomy - specimens

sent separately as medial, lateral, superior, inferior and deep margins

• Titanium clips placed in tumor bed



SURGERY

• All patients - complete axillary lymph node dissection(level I-III)

• Incision - single or double - Single incision for selected UOQ tumors - two incisions in remaining tumors - one for lumpectomy and other for axillary dissection

• A single drain in axilla and no drains in the tumor bed


RADIOTHERAPY

• Whole breast radiotherapy (WBRT)– 45 Gy EBRT - 25 #, 5weeks– 3-4 weeks after surgery

• Tumor bed boost – Using Electrons or low dose rate peri-operative brachytherapy

• Peri-operative brachytherapy– Single or two plane nylon catheters implant in tumor bed after

lumpectomy– Inter-catheter distance 1 cm



RADIOTHERAPY

• Boost delivered through nylon catheters using iridium-192 wires or seeds by remote controlled after loading technique

• 2-3 days after surgery • Electron boost

– After completion of WBRT– Using a linear accelerator – The boost dose - 15 to 20 Gy

• RT to axilla – EBRT ifInvolvement of >3 nodesExtra nodal spread



SYSTEMIC THERAPY • Adjuvant Chemotherapy - All high-risk patients

Pre-menopausal statusTumor size >1 cm,Node positiveER/PR negative High grade tumors Lymphovascular invasion

• Six cycles of DEC/CEF/CMF - depending upon the risk factors and economic status



SYSTEMIC THERAPY • No adjuvant chemotherapy –

Post menopausal women with < 1 cm ER/ PR positive tumor

• Neo-adjuvant chemotherapy - 3 cycles anthracycline based for patients with > 4 cm tumor keen for BCT

• Hormonal therapy - ER/PR positive Tamoxifen/ AIs for 5 years



FOLLOW UP• After completion of treatment in breast cancer clinic

• First 2 years - every 3 monthly and thereafter 6 monthly

• Clinical examination and SAP at each follow up

• Chest X-ray – 6 monthly

• Annual bilateral mammogram

• Cosmesis

Assessed at the end of one year

Graded - good, average and poor - JCRT criteria



IRCH –AIIMS Experience

• Study period - 1998 -2007

• No. of BCT - 272

• Mean Age – 44.2 yrs (23-66 yrs)

• Premenopausal- 37.4%

• Receptor

• +ve – 33%

• -ve – 45%

• Unknown – 22%

• Positive family history– 8.9%



50%

14.7%

20.5%

6.3%

6.8%

Site



• Post op Radiotherapy • EBRT - 92.6%• Brachytherapy – 44.2%

• Stage distribution• EBC – 93.7%• LABC – 6.3%



• Histo-pathology• Margin +ve – 2.1%• Pathological Node +ve - 29%• Extranodal spread – 7.9%

• Recurrence (Total 33 patients, 12%)– Local - 2.6%– Systemic – 8.4%– Local+Systemic – 1.1%


IRCH –AIIMS ExperienceSurvival Function

DFS

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Survival Function

Censored

5 yr DFS – 76%


IRCH –AIIMS ExperienceSurvival Function

OS

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Survival Function

Censored

5 yr OS – 92%


Conclusions

• BCT most scientifically evaluated surgical treatment modality for EBC

• Cosmetic and psychological advantages

• Grossly under-utilized treatment option

• Need to educate patients and physicians

• Recent advances – Expand indications for BCT

• NACT increases the BCT rates in LABC, but may have a higher risk of local recurrence


Thank YouDr. Manish Varma

MS, DNB, MNAMS

Department of Surgical OncologyBRA-IRCH,

All India Institute of Medical SciencesNew Delhi

Economy & Finance

BCT - AIIMS Experience