1. Radiation Therapy in Breast Cancer MOTP Seminar January 2009 Jacqueline Spayne MD PhD FRCPC Department of Radiation Oncology Odette Cancer Centre

2. Radiation Treatment in Breast Cancer Adjuvant Radiotherapy Toxicities Controversies Salvage Radiation RT for recurrence & metastases

3. Radiation Treatment in Breast Cancer Adjuvant Radiotherapy Breast conserving therapy Post-mastectomy Radiation target volumes Toxicities Controversies Salvage Radiation RT for recurrence & metastases

4. Adjuvant radiation following breast conserving surgery (BCS) in early breast cancer (EBC) 6 (important) RCTs of mastectomy vs lumpectomy + XRT – Equivalent OS and acceptable LC

5. From CCO Guidelines, see: http://www.cancercare.on.ca/pdf/full1_2.pdf

6. Adjuvant radiation following BCS in EBC 4 RCTs of Lumpectomy +/- XRT

7. From CCO Guidelines, see: http://www.cancercare.on.ca/pdf/full1_2.pdf Adjuvant radiation following BCS in EBC

8. Adjuvant radiation following BCS in EBC Meta-analyses EBCTCG Lancet 2000/Cochrane2002 - 40 trials – 1950s-1980s (inc some mastectomy) - 10yr LRR reduced from 27% to 9% - 5% absolute breast cancer mortality benefit - No OS benefit with increased non-BC deaths Vinh-Hung JNCI 2004 - 15 trials (BCS only) - IBT recurrence RR 3.00 with no RT - 8.6% mortality benefit with RT

9. Post-mastectomy Radiation RCTs of mastectomy +/- XRT Danish premenopausal (Overgaard NEJM 97) 10y LRR10y OS CMF32%45% CMF+RT9%54% Danish post-menopausal (Overgaard Lancet 99) 10y LRR10y OS Tam35%36% Tam+RT8%45%

10. Post-mastectomy Radiation BC Trial – 20yr update (Ragaz JNCI 2005) 318 Premenopausal N+, CMF chemo LRR-free Survival

11. Postmastectomy Radiation BC Trial – 20yr update (Ragaz JNCI 2005) 318 Premenopausal N+, CMF chemo Overall Survival

12. Post-mastectomy Radiation Meta-analysis EBCTCG Lancet 2005

13. Post-mastectomy Radiation Meta-analysis Gebski et al JNCI 2006

15. Post-mastectomy Radiation Indications Node positive T3, T4 Other risk factors – Grade 3 – +LVI – Positive margins

16. Radiation Treatment in Breast Cancer Adjuvant Radiotherapy Breast conserving therapy Post-mastectomy Radiation target volumes Toxicities Controversies Salvage Radiation RT for recurrence & metastases

17. Adjuvant radiation in Breast Cancer – Target Volumes RT-geekspeak – GTV, CTV, PTV Post BCS –Breast, underlying chest wall Post-mastectomy –Chest wall N2 disease –Supra-clavicular fossa –?Axilla, IMN

18. Radiation Treatment in Breast Cancer Adjuvant Radiotherapy Breast conserving therapy Post-mastectomy Radiation target volumes Toxicities Controversies Salvage Radiation RT for recurrence & metastases

19. Radiation in Breast Cancer - Toxicity Breast tangents alone – RT well tolerated Acute - common – Skin – Fatigue Sub-acute – very rare – Pneumonitis Late – very rare – Lung – Cardiac – 2 nd malignancies Except - Pigmentation, fibrosis, telangiectasia – up to 30% depends on technique

20. Radiation in Breast Cancer - Toxicity Additional late toxicity of nodal irradiation Lymphedema BC trial – 9% vs 3%; Danish trials – 14% vs 3% Pneumonitis BC trial – 1 patient (0.6%) Impaired shoulder ROM Danish trials – 16% vs 2%

21. Radiation in Breast Cancer - Toxicity Additional late toxicity of nodal irradiation cont’d Asymptomatic lung fibrosis Danish trial – 60% vs ?0% Chronic pulmonary symptoms – ?? Neurological Danish trial -paresthesia/hyperesthesia 21% vs 7% slight decreased strength – 14% vs 2%

22. Adjuvant RT in Breast Cancer - Controversies Omission of radiation in selected patients RT protocols - Fractionation & boost Partial breast radiation Nodal radiation for 1-3 LN+ Radiation of IMC nodes 3 vs 4 field for supraclavicular fossa Patient selection after neo-adjuvant chemo

23. Can adjuvant RT be omitted in some patients? Canadian trial (Fyles NEJM 2004) 769 pts, >50y, T1/2N0, clear margins, on Tam 5y LR5yDFS5y OS All pts – no RT7.7%84%93% All pts - + RT0.6%*91%*93% (NS) T1 ER+ - no RT5.9% T1 ER+ - + RT0.4%* >60y, T</=1cm, ER+ - no RT1.2% (Unplanned analysis) >60y, T</=1cm, ER+ - +RT0% NS

24. Can adjuvant RT be omitted in some patients? CALGB C9343 (Hughes NEJM 2004) 636 pts, >70y, T1N0, clear margins, ER+, on Tamoxifen 5y LRR5y OS No RT4%86% +RT1%*87%

25. Adjuvant RT in Breast Cancer - Controversies Omission of radiation in selected patients RT protocols - Fractionation & boost Partial breast radiation Nodal radiation for 1-3 LN+ Radiation of IMC nodes 3 vs 4 field for supraclavicular fossa Patient selection after neo-adjuvant chemo

26. Radiation Protocols Standard adjuvant treatment – 50Gy in 25 fractions Canadian hypofractionation trial (Whelan JNCI 2002) 4250/16 equivalent to 5000/25 to breast only in selected pts EORTC boost trial (Bartelink NEJM 2001) 50/2550/25+16/8boost LR all pts7.3%4.3%* </=40y19.5%10.2%* 41-509.5%5.8%* >504.1%3%NS

27. Adjuvant RT in Breast Cancer - Controversies Omission of radiation in selected patients RT protocols - Fractionation & boost Partial breast radiation Nodal radiation for 1-3 LN+ Radiation of IMC nodes 3 vs 4 field for supraclavicular fossa Patient selection after neo-adjuvant chemo

28. Partial Breast Radiation Techniques –Intra-operative (Mammosite) –Catheter HDR –Seeds –External beam Short-term follow-up only Remains experimental

29. Adjuvant RT in Breast Cancer - Controversies Omission of radiation in selected patients RT protocols - Fractionation & boost Partial breast radiation Nodal radiation for 1-3 LN+ Nodal radiation fields Patient selection after neo-adjuvant chemo

30. Nodal irradiation with 1-3 +ve nodes Post-lumpectomy – no – Consider if: – <4-6 (?) nodes dissected – Other bad prognostic features (eg large T, LVI, young, ECE) – MA20 trial - closed Post-mastectomy – Guidelines equivocal – Meta-analysis supports chest-wall radiation for N1

31. Adjuvant RT in Breast Cancer - Controversies Omission of radiation in selected patients RT protocols - Fractionation & boost Partial breast radiation Nodal radiation for 1-3 LN+ Nodal radiation fields Patient selection after neo-adjuvant chemo

32. Nodal radiation fields Radiation of IMC chains – Most trials included IMC – Practice variable – Usually only include with IQ tumours and/or N+++ – Techniques variable – risk of increased toxicity Addition of posterior SC (deep axillary) field – Inadequate axillary clearance – ??ECE – Toxicity risk

33. Adjuvant RT in Breast Cancer - Controversies Omission of radiation in selected patients RT protocols - Fractionation & boost Partial breast radiation Nodal radiation – Indications: N1 vs N2; post BCS vs post-mastectomy – Target nodes: axilla, SCF, IMC Patient selection after neo-adjuvant chemo

34. Adjuvant Radiation after Neoadjuvant Chemo No randomized data MDACC 6 neoadjuvant chemo trials 542 patients chemo, mast’y, + RT vs 134 patients chemo, mast’y, no RT Huang et al JCO 2004

35. Adjuvant Radiation after Neoadjuvant Chemo Huang et al JCO 2004

36. Adjuvant Radiation after Neoadjuvant Chemo Cause-Specific Survival – Stage 3B Huang et al JCO 2004

37. Adjuvant Radiation after Neoadjuvant Chemo …….even after pCR McGuire et al in press

38. Adjuvant Radiation after Neoadjuvant Chemo …….even after pCR McGuire et al in press

39. Adjuvant Radiation after Neoadjuvant Chemo Policy –All LABC patients offered adjuvant radiation –Chest wall + regional lymph nodes

40. Radiation Treatment in Breast Cancer Adjuvant Radiotherapy Breast conserving therapy Post-mastectomy Radiation target volumes Toxicities Controversies Salvage Radiation RT for recurrence & metastases

41. Salvage Radiation for Breast Cancer Can have dramatic responses Huang et al IJROBP 2002 38 inoperable patients after anthracycline regimen

42. Salvage Radiation for Breast Cancer 38 patients inoperable after chemo  Loco-regional radiation  32 had mastectomy  6 year follow-up 5 LRR alone 21 distant mets 3 both 9 disease free Huang et al IJROBP 2002

43. Neoadjuvant Radiation for Breast Cancer TRIAL –Neoadjuvant concurrent chemoradiation in LABC

44. Radiation Treatment in Breast Cancer Adjuvant Radiotherapy Breast conserving therapy Post-mastectomy Radiation target volumes Toxicities Controversies Salvage Radiation RT for recurrence & metastases

45. Radiation for Recurrence & Metastases Recurrence – In-breast → mastectomy – Chestwall → consider radiation depends on previous treatment, time interval, prognosis, other treatment options etc Metastases – Whole other topic!!!!

46. QUESTIONS……..