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Radiotherapy in Early stage invasive breast carcinoma
- 1. Radiotherapy in earlystage invasive breast carcinoma Dr Astha Srivastava Senior Resident,SRMSIMS
- 3. Clinical presentation • painlessor slightly tender breast mass • Abnormal screening mammogram • breast tenderness, bloody nipple discharge, or occasionally change in the shape and size of the breast
- 4. Diagnostic Work-up • General Historywith emphasis on presenting symptoms, menstrual status, parity, family history of cancer, other risk factors Physical examination with emphasis on breast, axilla, supraclavicular area, abdomen Special tests Biopsy (core biopsy directed by physical examination, ultrasound, or mammography as indicated, or needle localization) Radiologic studies Before biopsy Mammography/ultrasonography Chest radiographs Magnetic resonance imaging of breast (selected cases) After positive biopsy Bone scan (when clinically indicated, for stage II or III disease or elevated serum alkaline phosphatase levels) Computed tomography of chest, abdomen and pelvis for stage II or III disease and/or abnormal liver function tests Laboratory studies Complete blood cell count, blood chemistry Urinalysis Other studies Hormone receptor status (ER, PR) HER2/neu status Consider genetic counseling/BRCA testing in selected cases
- 11. • Two majortreatment options • – Mastectomy • – Breast conserving therapy Margin-negative lumpectomy+ ALND Adjuvant radiation therapy • Adjuvant therapy • – Dependent on pathologic variable Chemotherapy Hormonal therapy
- 12. Types of MastectomiesUsed as Treatments for Breast Cancer
- 13. • Segmental mastectomy,lumpectomy, tylectomy: Removal of the primary tumor with a surrounding margin of breast tissue
- 14. • Total orsimple mastectomy :Removal of the breast but not the axillary contents Indications: – Stage I and stage IIa carcinoma – Multifocal or multicentric CIS.
- 15. • Modified radicalmastectomy: Removal of the breast plus an axillary level I/II dissection • Indications: – LABC – Multifocal or multicentric disease
- 16. Modified radical Mastectomy-procedure 1.Patey’s procedure: – The P.minor is removed for better visualization and easy dissection of level III lymph nodes. 2. Scanlon’s procedure: – P.minor is retracted to expose level III nodes and dissected out. 3. Auchincloss procedure: – Level I and II lymph nodes are cleared, level III nodes are left behind.
- 17. • Radical mastectomy:Removal of the parenchyma breast tissue and pectoralis major muscle plus an axillary level I/II dissection
- 18. • Extended radicalmastectomy :Removal of the breast and pectoralis major muscle plus an axillary level I/II and internal mammary lymph node dissection, may also include a level III axillary lymph node dissection • Skin-sparing mastectomy :Total or modified radical mastectomy with preservation of a significant component of the native skin of the breast to optimize the aesthetic result of an immediate reconstruction
- 19. Breast conserving therapy –Wide local excision/Lumpectomy or Quadrantectomy + axillary lymph node clearance + Radiotherapy.
- 20. Contraindications to BCT •Absolute: • Radiation therapy during pregnancy • Diffuse suspicious or malignant-appearing microcalcifications • Widespread disease that cannot be incorporated by local excision through a single incision that achieves negative margins with a satisfactory cosmetic result • Positive pathologic margin
- 21. • Relative: • Priorradiation therapy to the chest wall or breast; knowledge of doses and volumes prescribed is essential. • Active connective tissue disease involving the skin (especially scleroderma and lupus) • Tumors >5 cm • Diffusely positive pathologic margins • Women with a known or suspected genetic predisposition to breast cancer: -May have an increased risk of ipsilateral breast recurrence or contralateral breast cancer with breast-conserving therapy -Prophylactic bilateral mastectomy for risk reduction may be considered
- 22. Treatment Policy forConservative Management of Early Stage Invasive Breast Cancer • Treatment Volume:Whole breast • Indication: routinely following BCS • Fraction Size/Technique: 200 or 180cGy/ tangents with wedges or dynamic wedges to optimize homogeneity • Total Dose: 46 to 50 Gy/23-25 fractions
- 23. • Treatment Volume:Boost •Indication: routinely following whole breast • Fraction Size/Technique: 200 or 180cGy/electrons • Total Dose: 10-16 Gy/4-8 fractions
- 24. • Treatment Volume:Accelerated partial breast • Indication: On protocol or ASTRO guidelines • Fraction Size/Technique: 3.4-3.8 Gy/ext beam conformal, interstitial, or MammoSite • Total Dose: 34-38 Gy /10 fractions.
- 25. Treatment Policy forRegional Nodes • Treatment Volume:Supraclav • Indication: # Clinical N2 or N3 disease # >4 +LN after axillary dissection # 1-3 +LN with high risk features # T>5 cm # Node + sentinel lymph node with no dissection unless risk of additional axillary disease is very small # High risk no dissection Fraction Size/Technique: 180-200 /AP or AP-PA • Total Dose: 45-50.4Gy
- 26. • Treatment Volume:Axilla •Indication: # N+ with extensive ECE # SN+ with no dissection # Inadequate axillary dissection # High risk with no dissection • Fraction Size/Technique: 180-200/AP,consider posterior axillary boost if suboptimal coverage with AP only • Total Dose: 4,500-5,040 cGy
- 27. • Treatment Volume:Internalmammary • Indication: Individualized but consider for- # Positive axillary nodes with central and medial lesions # Stage III breast cancer # +SLN in the IM chain # +SLN in axilla with drainage to IM on lymphosintigraphy • Fraction Size/Technique: 180-200cGy/Partially wide tangents or separate IM electron/photon • Total Dose: 46- 50Gy/23-25#
- 28. Barriers to Breast Conservation •Stage at diagnosis • Lack of screening • Physician and patient attitudes • Access to radiotherapy
- 29. Radiotherapy • Treatment position:Mostpatients are treated in the supine position, with the arm abducted (90 degrees or greater) • Radiation Beams:X-ray energies of 4 to 6 MV are preferred .
- 30. • Use ofbolus results in impaired cosmetic results • Wedges or compensating filters must be used for a portion of the treatment to achieve a uniform dose distribution in the breast
- 32. For tangential fields •Upper border – 2nd ICS (angle of Louis) when supra clavicular field used. When SCF not irradiated – head of clavicle • Medial border – at or 1cm away from midline • Lateral border – 2-3cm beyond all palpable breast tissue – mid axillary line • Lower border – 2cm below inframammary fold
- 33. SCF • Single anteriorfield is used. Field borders – • Upper border : thyrocricoid groove • Medial border : at or 1cm across midline extending upward following medial border of SCM ms to thyrocricoid groove • Lateral border: insertion of deltoid muscle • Lower border : matched with upper order of tangential fields
- 34. Matching SCF andchest wall fields Angulation By inferior angulation of the tangential fields. Half beam block technique Blocking the supraclav field’s inferior half, eliminating its divergence inferiorly . Hanging block technique Superior edge of tangential beam made vertical by vertical hanging block.
- 35. Single isocentre technique •Isocentre placed at the junction of tangential and supraclavicular field • Inferior portion of field blocked for supraclavicular treatment and superior portion blocked for tangential field
- 36. Internalmammary 1. Extension oftangential fields– by extending medial border – 3cm across midline or by using imaging techniques 2. Separate field – • Medial border – midline , matching with tangential field border • Lateral border – 5-6cm from midline • Superior border – abuts inferior border of supraclav field or at 1st ICS (superior border of head of clavicle) if only IMNs are to be treated • Inferior border – at xiphoid or higher if 1st three ICS covered
- 37. MRM vs. BCT(with RT) 6 RCT have shown no OS advantage after mastectomy or BCT
- 38. Whole Breast RadiotherapyReduces Local failure
- 39. The benefit oftumor bed boost • Most authors report that 65-80% of breast recurrence occurs around primary tumour site. • Various studies suggest that patients treated with higher doses have a greater probability of tumor control.
- 40. Boost with electronbeam • Preferred over brachytherapy due to: -Relative ease in set up -Opd setting -Lower cost -Excellent results
- 41. Boost with interstitialimplant • large breast and deep tumors(>4 cm) • HDR is as effective as LDR
- 42. EORTC 22881-10882: RNDBoost Trial • Purpose: – Most large randomized trials providing long term IBTR did not use tumor bed boost Example NSABP trials • Single institution trials suggested a benefit of a tumor bed boost • Endpoint: • •OS and IBTR
- 44. EORTC Boost vs.No Boost Trial
- 45. EORTC Boost trial:subgroup analysis Goal: Determine prognostic factors Central path review SM, LVI, grade, extend of DCIS, Mitotic Index + SM (14%), close (0-2mm) (27%, neg (> 2 mm) Median f/u 10 yrs Results: MVA for LR: –Boost dose, high grade tumor, age < 50 y/o –10 yr Cumulative Incidence of IBTR: •7.3% (low) •8.4% (int) •13.7% (high) Conclusions: -Patients at high risk for recurrence are those < 50 y/o and high grade tumor. Boost helps decrease the absolute risk most in these groups.
- 46. ASTRO Consensus Guidelines2014 Margins for BCS With WBRT in Stages I and II Invasive Breast Cancer • Positive margins • A positive margin, defined as ink on invasive cancer or DCIS -> 2-fold increase in IBTR. – This increased risk in IBTR is not nullified by: Delivery of a boost dose of radiation – Delivery of systemic therapy (endocrine therapy, chemotherapy, or biologic therapy), or – Favorable biology
- 47. • Margin Width •Negative margins (no ink on tumor) minimize the risk of IBTR. • Wider margin widths do not significantly lower this risk. • Systemic chemotherapy does NOT lower risk • The routine practice to obtain negative margin widths wider than no ink on tumor is not indicated
- 48. Hypofractionation • Short treatmentcourse improves experience for patients • Improves access to breast conservation • Biology :Increased dose per fraction without compromising BED • Decreased cost to deliver care • Concerns: Toxicity
- 50. • START-A: (1998-2002) •N=2236 • EBC (pT1-T3a, pN0-N1, M0) • BCS=1900 (85%) & MRM=336 (15%) 3 arms: • 50 Gy/25#/5 weeks • 41.6 Gy/13#/5 weeks • 39 Gy/13#/5 weeks • Median FU=5.1 years • Locoregional relapse rates were 3.6%, 3.5% and 5.2%, respectively • Late effects, based on photographs and patient assessments, were significantly lower with 39 Gy as compared to 50 Gy • This trial estimated α/β of breast cancer as 4.6Gy for tumor control and 3.4Gy for late change in photographic appearance. Lancet Online. March 19,2008
- 51. • START-B: (1999-2001) •N=2215 • EBC (pT1-T3a, pN0-N1, M0) • BCS=2038 (92%) & MRM=177 (8%) 2 arms: • 50 Gy/25#/5 weeks • 40 Gy/15#/3 weeks • Median FU=6 years • Locoregional relapse rates were 3.3% and 2.2%, respectively • Absolute differences in locoregional relapse was -0.7% (95%CI -1.7% to 0.9%), meaning that with 40Gy the relapse rate would be at most 1% worse and at best 1.7% BETTER! Lancet Online. March 19,2008
- 52. UK START B(2001)
- 53. The “Canadian” Trial:Ontario • 1234 Pts ~55yo • T1-2,N0 • 50Gy/25fx WBRT 42.6/16fx No boost
- 56. Accelerated Partial BreastIrradiation • Rationale –Biology: Most recurrences occur within 2cm of lumpectomy from prospective and RND trials. • Decreased Treatment time and QOL • Potential reduction in treatment toxicity • Multiple techniques with short follow up
- 57. APBI - ASTROConsensus Statement
- 58. • Established methods –External beam (3.85gy BID x 5 days) Most common – Interstitial Brachytherapy: LDR, HDR Multi-catheter – Intraoperative Electrons: ELIOT – Intraoperative Orthovoltage Photons: TARGIT-A – Mammosite
- 59. APBI: Current state •Retrospective and registry studies demonstrate excellent local control • Excellent cosmesis is reported • Meta-Analysis (2010) and Seer data (2014) show decreased control
- 60. Comparison of APBItechniques
- 61. Mammosite • Single lumencatheter – Typical dose (and on NSABP B31) RT: 34 Gy in 3.4 Gy fractions, prescribed 1 cm from balloon – About 20% of RND trial – Needed balloon-to-skin dist >5 mm, cavity size < 6 cm – Results at 3 years from registry: IBTR = 2.15% (4 yr=2.65%) – 3 yr axillary recurrence = 0.36% (4 yr=0.6%) – DM=1.1% – OS=95.6% – Toxicity: infection: 9.5%, – Seroma: 27% (13% symptomatic) – 2% fat necrosis • Cosmesis: Good or excellent at 4 yrs: 91% • Conclusions: Data consistent with other APBI techniques
- 62. Mammosite: results Institution Dose Ipsilateral breast recurrencerate Cosmesis & Complications American Society of Breast Surgeons Mammosite Breast Brachytherapy Registry trial (97 institutions) 34 Gy/10# 1.79% 3-yr actuarial LRR Good-excellent cosmesis in >93%. Rush University Medical Centre, Chicago, USA 34 Gy/10# 5.7% (crude) Good-excellent cosmesis in 93%.
- 63. Interstitial APBI • Startedas boost technique initially following WBRT • Multiple catheters are placed at 1-1.5 cm interval.
- 64. HDR interstitial brachytherapy: results InstitutionDose Dose Rate Ipsilateral breast recurrence rate Cosmesis & Complications William Beaumont Hospital, USA 32-34 Gy/8- 10# 50 Gy HDR LDR 2.1% (5-yr) 0.9% (5-yr) >90% achieved good to excellent cosmesis Ochsner Clinic, USA 32-34 Gy/8- 10# 50 Gy HDR LDR 8% 75% achieved good to excellent cosmesis London Regional Cancer Centre, Ontario, Canada 37.2 Gy/10# HDR 16.2% at 5 yrs* Median overall cosmetic score 89%.
- 65. HDR interstitial brachytherapy: results InstitutionDose Dose Rate Ipsilateral breast recurrence rate Cosmesis & Complications National Institute of Oncology, Hungary 30.3-36.4 Gy/7# HDR 6.7% Excellent to good cosmesis in 84.4%. Tufts New England, USA 34 Gy/10# HDR 6.1% (5-yr actuarial) 89% had excellent cosmesis at 5 years. Guy’s Hospital, London 55 Gy LDR 37%* Cosmesis good to excellent in 85%. *= inappropriate selection of patients for APBI
- 69. IORT: results Institution Dose ModalityIpsilateral breast recurrence rate Cosmesis & Complications European Institute of Oncology, Milan 21 Gy Electrons 1% Mild/severe fibrosis in 3%. State University of Buffalo, USA 15-20 Gy 120 kV X rays 29% Acceptable University College, London (TARGIT) 20 Gy 50 kV X rays 0% Acceptable
- 70. Intra-op Conclusions • Randomizeddata demonstrate safety and efficacy • Allows post-surgery RT for high risk groups without toxicity • Statistically Significant increase LRR vs WBRT • Long term data still lacking
- 72.
- 73. IMRT • Dosimetric advantagesinclude: (1) better dose homogeneity for whole breast RT (2) better coverage of tumor cavity (3) feasibility of SIB