San Antonio Breast Cancer Symposium 2007 Highlights – Radiotherapy

Kathleen C. Horst, M.D.

Assistant Professor Department of Radiation Oncology Stanford University

Post-lumpectomy XRT

Technique Fractionation Partial Breast Irradiation

Post-mastectomy XRT Nodal XRT

The Cambridge Breast Intensity Modulated Radiotherapy (IMRT) Trial: Dosimetry Results Abstract # 4086 Coles, et al.

1089 patients with breast cancer treated with BCT Standard treatment plan < 2 cm 3 of breast tissue > 107% > 2 cm 3 of breast tissue > 107% Non-randomized Randomized Standard RT IMRT

The Cambridge Breast Intensity Modulated Radiotherapy (IMRT) Trial: Dosimetry Results Abstract # 4086 Coles, et al.

317/1089 (29%) had acceptable homogeneity with standard 2D radiotherapy. IMRT significantly reduced both “hot spots” and “cold spots”.

Prospective trial of individual optimal positioning (prone vs supine) for whole breast radiotherapy: results of 224 patients Abstract # 4082 Formenti, et al.

Prospective trial of individual optimal positioning (prone vs supine) for whole breast radiotherapy: results of 224 patients Abstract # 4082 Formenti, et al. CONCLUSIONS: Prone enables best sparing of heart and lung in most patients (204/224) Most patients best treated supine (17/20) had left-sided lesions When prone, heart is displaced anteriorly 5-19 mm (Duke) May limit utility of prone technique

Radiotherapy Fractionation Schedules

Abstract #21 Whelan, et al.

Long-term results of a randomized trial of accelerated hypofractionated whole breast irradiation following breast conserving surgery in women with node negative breast cancer

Node-Negative Post BCS 1234 patients R Standard Whole Breast Irradiation (SWBI)

50 Gy/25 fractions

612 patients Stratification: Age Size Systemic tx Center Accelerated Hypofractionated Whole Breast Irradiation (AHWBI)

42.5 Gy/16 fractions

622 patients Recruitment April ’93- Sept ’96

BASELINE CHARACTERISTICS

SWBI n=612 n (%) Age < 50 yrs Tumor size ≥ 2 cm ER negative Tumor grade high Tamoxifen Chemotherapy 148 (24) 203 (33) 157 (26) 116 (21) 266 (41) 72 (11) AHWBI n=622 n (%) 157 (25) 190 (31) 165 (26) 117 (20) 265 (41) 75 (11)

Radiotherapy Fractionation Schedules

Abstract #21 Whelan, et al.

5 years 10 years

LOCAL RECURRENCE

SWBI

AHWBI

3.2% 6.7%

2.8% 6.2%

No difference in Overall Survival Whelan T, et al. J Natl Cancer Inst. 94(15):1143-50, 2002. Whelan T, et al. Abstract #21. SABCS 2007.

Local Recurrence Rates at 10 years

Age (y) Tumor Size (cm) Systemic Therapy

SWBI

< 50 10.7

≥ 50 5.4

< 2 cm ≥ 2 cm 6.1 7.8 yes no 5.9

7.4

AHWBI

7.5

5.8

5.4

8.0

6.5

5.8

Cosmetic Outcome by Time and Treatment

Baseline SWBI 83% (604) AHWBI 84% (616) 3 yr 5 yr 10 yr 77% (496) 79% (423) 71% (216) 77% (518) 78% (448) 70% (235) % excellent or good (# evaluable)

RTOG/EORTC Late Radiation Morbidity by Time and Treatment

3 yr 5 yr 10 yr

Skin

SWBI AHWBI

Subcutaneous tissue

SWBI AHWBI % Grades 2-3 2% 2% 5% 4% 3% 3% 6% 5% 8% 9% 11% 12%

Cause of Death

Cancer related Non-cancer related Total SWBI (n=612) 13.2% (81) 7.4% (45) 20.6% (126) AHWBI (n=622) 13.7% (85) 5.9% (37) 19.6% (122)

CONCLUSIONS

Accelerated Hypofractionated Whole Breast Irradiation: • Demonstrated excellent local control • Was not associated with long-term morbidity • Skin and soft tissue toxicity • Breast Cosmesis • Non-cancer deaths

Radiotherapy Fractionation Schedules

ASCO 2007 Dewar, et al.

Hypofractionation for early breast cancer: First results of the UK standardisation of breast radiotherapy (START) trials

T1-3, N0-1 Post BCS Recruitment 1999-2002 START A 2236 patients 50 Gy/25 fractions/5 weeks 41.6 Gy/13 fractions/5 weeks 39 Gy/13 fractions/5 weeks 50 Gy/25 fractions/5 weeks START B 2215 patients 40 Gy/15 fractions/3 weeks JCO. 25:18S (June 20 Supplement), 2007: LBA518

Radiotherapy Fractionation Schedules

RATIONALE Tumor response (i.e., local control) thought to be as sensitive to fraction size as late adverse effects Radiation fraction sizes > 2.0 Gy may have advantages in breast cancer treatment 1 Goals: test the benefit of fraction sizes > 2.0 Gy in terms of locoregional control late normal tissue responses 1 Owen R et al. Lancet Oncol 7:467-71, 2006.

Radiotherapy Fractionation Schedules

ASCO 2007 Dewar, et al.

Hypofractionation for early breast cancer: First results of the UK standardisation of breast radiotherapy (START) trials

Median follow up = 5.1 yrs Median follow up = 6.0 yrs

Radiotherapy Fractionation Schedules

ASCO 2007 Dewar, et al.

Hypofractionation for early breast cancer: First results of the UK standardisation of breast radiotherapy (START) trials

Are patients with T1-2 breast cancer with 1-3 +LN suitable candidates for partial breast radiotherapy trial enrollment?

Abstract # 4089 Truong, et al.

Are patients with T1-2 breast cancer with 1-3 +LN suitable candidates for partial breast radiotherapy trial enrollment?

Abstract # 4089 Truong, et al. 5688 women pT1-2, 0-3 N+ breast ca Treated with BCT (1989-1999) N0 (n=4433) vs 1-3 N+ (n=1255) Median follow up = 8.6 yrs

Are patients with T1-2 breast cancer with 1-3 +LN suitable candidates for partial breast radiotherapy trial enrollment?

Abstract # 4089 Truong, et al.

Are patients with T1-2 breast cancer with 1-3 +LN suitable candidates for partial breast radiotherapy trial enrollment?

Abstract # 4089 Truong, et al. CONCLUSIONS: Patients with 1-3 N+ have high risks of regional nodal relapse ~10-15% despite standard whole breast XRT and systemic therapy, particularly young age grade III histology ER- disease >20% positive nodes Such patients should receive standard whole breast XRT and are not ideal candidates for PBI trial enrollment

Update of the Phase II MammoSite Brachytherapy Trial for DCIS Abstract # 4079 Streeter, et al.

Ongoing Trials in Partial Breast Irradiation

NSABP B39/RTOG 0413 Interstitial/intracavitary brachytherapy, 3DCRT European Institute of Oncology Intraoperative electrons TARGIT Intrabeam – photoelectron 50 kV photons RAPID Canadian External Beam Other Intraoperative techniques Stanford University of North Carolina MSKCC (Intraoperative HAM applicator) Protons MGH Permanent radioactive seed University of Toronto, Canada Other Intracavitary applicators Cianna Medical SenoRx North American Scientific Xoft

Identification of Patients for Post-Mastectomy Radiotherapy using the Cambridge Index Abstract # 4093 Wilson, et al. Index designed to help identify intermediate and low risk patients who might be at higher risk of local recurrence after mastectomy.

Applied since 1999. Retrospective review of patients from 2000-2003

Identification of Patients for Post-Mastectomy Radiotherapy using the Cambridge Index Abstract # 4093 Wilson, et al. High risk (n=125) Intermediate risk Score > 3 (n=63) Low risk Score > 3 (n=17) Intermediate risk Score < 3 (n=21) Low risk Score < 3 (n=131) Chest Wall XRT n=198 (55%) No XRT n=159 (45%) Low level of LR in both the Low and Intermediate risk groups confirms that appropriate patients in the Intermediate risk group are receiving PMRT

Increased use of regional radiotherapy is associated with improved outcome in a population based cohort of women with breast cancer and 1-3 positive nodes Abstract # 4076 Wai, et al.

Ongoing Trials in Regional Nodal RT in Breast Conservation Therapy

EORTC 10925

LN+ or any medial/central lesion Breast Only vs Breast + Upper IM/Medial SCV

NCIC MA.20

LN+ and high risk LN Breast Only vs Breast + Upper IM, high axilla, SCV

Post-operative radiotherapy does not adversely affect the outcome of autologous free abdominal flap breast reconstruction Abstract # 4084 Chatterjee, et al. • No significant difference by objective mammometry in the volume of reconstructed breast compared with contralateral breast • No significant difference in fibrosis and thickening in the reconstructed breast • Postoperative XRT does not adversely affect the outcome of immediate DIEP reconstruction following mastectomy