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Radiation Therapy in Breast Cancer

Radiation Therapy in Breast Cancer. MOTP Seminar January 2009 Jacqueline Spayne MD PhD FRCPC Department of Radiation Oncology Odette Cancer Centre. Radiation Treatment in Breast Cancer. Adjuvant Radiotherapy Toxicities Controversies Salvage Radiation RT for recurrence & metastases.

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Radiation Therapy in Breast Cancer

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

  8. Adjuvant radiation following BCS in EBCMeta-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 LRR 10y OS CMF 32% 45% CMF+RT 9% 54% Danish post-menopausal (Overgaard Lancet 99) 10y LRR 10y OS Tam 35% 36% Tam+RT 8% 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

  14. 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 • 2nd 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 LR 5yDFS 5y OS All pts – no RT 7.7% 84% 93% All pts - + RT 0.6%* 91%* 93% (NS) T1 ER+ - no RT 5.9% T1 ER+ - + RT 0.4%* >60y, T</=1cm, ER+ - no RT 1.2% (Unplanned analysis) >60y, T</=1cm, ER+ - +RT 0% 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 LRR 5y OS No RT 4% 86% +RT 1%* 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) 50/25 50/25+16/8boost LR all pts 7.3% 4.3%* </=40y 19.5% 10.2%* 41-50 9.5% 5.8%* >50 4.1% 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 ChemoCause-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……..

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