1. Radiotherapy in Carcinoma of the Breast Patrick S Swift, MD Director, Radiation Oncology Alta Bates Comprehensive Cancer Center Berkeley, CA

2. Breast Conserving Therapy BCT 70-80% of patients with stage I or II disease are candidates for BCT 6 major randomized trials comparing mastectomy to BCT No difference in DFS No difference in OS

3. Distant Failure Trial # Time pt.Mast.BCT WHO1972-7917922 yrs24%23% Milan I1973-807012051%54% NSABP061976-8414062033%40% US NCI1979-892792034%39% EORTC 10801 1980-869031034%30% Denmark 82TM 1983-89859632%34%

4. Overall Survival Trial # Time pt.Mast.BCT WHO1972-7917922 yrs41%42% Milan I1973-807012047%46% NSABP061976-8414062058%53% US NCI1979-892792066%65% EORTC 10801 1980-869031079%82% Denmark 82TM 1983-89859667%

5. Absolute Contraindications to BCT Repeatedly positive margins Multicentric disease ( >2 quadrants) Diffuse malignant calcifications on mammogram Prior RT to breast Pregnancy

6. Relative Contraindications to BCT History of scleroderma Large tumor in small breast Cosmetically undesirable

7. NOT contraindications to BCT Age Skin or nipple retraction Histology other than IDC Extensive intraductal component As long as margins are clear Positive nodes Location of primary in breast Positive family history

8. Positive Margins after Lumpectomy Single most important predictor of local failure in BCT Consider re-excision to get negative margins Focal positivity - may be okay Especially if chemo or HT given Extensive positivity - re-excise!

9. Extensive Intraductal Component (EIC) Intraductal component a prominent part of the main tumor Intraductal carcinoma extends BEYOND the infiltrating margin of the mass Of uncertain significance if margins are clearly negative

10. Treatment by Stage

11. DCIS Ductal Carcinoma in Situ MRM is acceptable no node dissection BCT is an acceptable approach if: Lesion is small (< 3 cm) Margins must be negative preferably > 10 mm in all dimensions Nuclear grade is low to intermediate Adjuvant radiotherapy can be delivered S alone can be considered if margins >10 mm controversial

12. NSABP-17 814 pts. with DCIS, negative margins Randomized to RT v no RT 50 Gy to entire breast, no boost At 12 years, local failure rates 31.7% for no RT 15.7% for RT Only comedo necrosis was a significant factor predicting for local failure

13. EORTC 10853 500 pts with DCIS, clear margins Randomized to 50 Gy whole breast or no RT At 4.25 years, local failure 16% no RT 9% with RT (p=0.005)

14. UKCCCR DCIS Working Group 1030 pts with DCIS, clear margins S alone S + Tam S + RT S + RT + Tam At 4.4.years, local failure 14% in no RT 6% in RT arm S + Tam intermediate

15. Radiation Technique DCIS Opposed tangential fields Breast only No boost 1.8-2.0 Gy daily to 50 Gy 2.65 Gy daily to 40 Gy

18. Van Nuys Prognostic Index Scores of 3-4 - 98% local control without RT Scores of 5-7 - 32% failed without RT, 16% with RT Scores of 8-9 - 100% failure without RT, 60% with RT

19. Radiation Technique T1-2 N0 Opposed tangential fields Breast only Boost optional 50 Gy in 25-28 fractions 42.5 Gy in 16 fractions (Canadian)

20. ASTRO 2008 Plenary 42.5 Gy in 16 fractions v. 50 Gy in 25 fractions

21. ASTRO 2008 Plenary Canadian Trial 1993-1996 N= 1234 women Median followup - 12 years Local recurrence at 10 years - 6% Excellent cosmesis at 10 yrs - 70% No difference between 16 and 25 fractions

23. If getting chemotherapy… Radiation is usually withheld until after the systemic therapy is complete Delay of up to 4-6 months from surgery generally not considered a problem Possible problem with inflammatory cancer or other locally aggressive cancers Hypofractionated schemes may allow for early RT while waiting for Oncotype

24. Surgery alone without RT? Meta-analysis results Lancet. 2005 Dec 17, vol. 366(9503):2087-106 “Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials.” An average of 75% reduction in local failure rates with the addition of RT, in even the lowest risk groups. A survival benefit was seen in the meta-analysis

25. Surgery alone without RT? One possible subset may benefit Patients > 70 years of age with small ER+ tumors who will get tamoxifen No survival benefit with RT

26. Radiation Technique T3-4 (after neoadjuvant chemo) Opposed tangential fields Boost 10 Gy for neg margins 18 Gy for positive or close margins 50 Gy in 25-28 fractions

27. Nodal Irradiation N0 - no role for axillary RT N+ 1-3 nodes, “adequate sampling” - no RT > 4 nodes, RT to SCLV and axilla IM Nodal RT > 4 axillary nodes positive Medial T3 tumors with any nodes positive axilla Awaiting results of two large trials (France and EORTC)

28. Full SCLV Field

29. IM Nodal Radiation Technique

31. Post-mastectomy RT Indications T3 lesions with any positive nodes Smaller lesions with > 3 nodes T4 lesions Pectoralis fascia involvement Technique Tangential beams for the chest wall Axillary/SCLV coverage IM node coverage for medial lesions or > 3 nodes positive

32. Post-MRM RT Trials (all with chemo and modern RT) Local failure Overall Survival Danish 82b1708RT9%54% No RT32%45% Vancouver318RT13%54% No RT33%46% Danish 82c1375RT8%45% No RT35%36%

33. RT Complications Lymphedema After full axillary dissection + RT - 37% Level I/II dissection + RT - 7% Rib fracture - 1.8% Pneumonitis - 1-5% Cardiac toxicity - avoidable Radiation-induced sarcoma 0.78% at 30 yrs.

34. Reducing Risk Respiratory Gating IM nodal techniques IMRT

39. Partial Breast Irradiation RTOG / NSABP Trial comparing Standard whole breast RT 3D conformal technique Mammosite Interstitial Implant technique 5 days, twice daily radiation Outcome results pending