White, JR

Abstract Background: Conventional WBI after lumpectomy for early-stage breast cancer decreases ipsilateral breast tumor recurrence (IBTR), yielding comparable results to mastectomy. Accelerated PBI appears effective in reducing IBTR by treating only the tumor bed area. As the majority of IBTR occur at or in the vicinity of the tumor bed, we hypothesized that PBI would be as effective as WBI in controlling IBTR. The primary aim of NSABP B-39/RTOG 0413 was to determine if PBI provides equivalent local tumor control post lumpectomy compared to WBI in pts with early-stage breast cancer. The equivalency test was based on a 50% margin of increase in the hazard ratio (HR=1.5). Secondary endpoints included: overall survival (OS), recurrence-free interval (RFI), distant disease-free interval (DDFI), and toxicity. Methods: Eligible pts had lumpectomy with histologically-free margins and 0-3 positive axillary nodes. Pts were stratified by stage, menopausal status, hormone receptor status, and intent to receive chemotherapy and then randomized to PBI or WBI. PBI was 10 fractions of 3.4-3.85 Gy, given twice daily with either brachytherapy or 3D external beam radiation. WBI was 50 Gy in 2 Gy fractions given daily with a sequential boost to the surgical cavity. Follow-up was every 6 mos for 5 yrs and then annually. All analyses were by intent-to-treat. Results: From 3-21-05 to 4-16-13, 4216 pts were randomized: 2107 PBI; 2109 WBI. 61% were postmenopausal; 81% were hormone receptor-positive; 29% intended to receive chemotherapy. Stage distribution was: DCIS, 24%; invasive pN0, 65%; invasive pN1, 10%. As of 7-31-18, median follow-up was 10.2 yrs. There were 161 IBTRs as first events: 90 PBI v 71 WBI (HR 1.22; 90%CI 0.94-1.58). Per protocol-defined margin, to declare PBI and WBI equivalent regarding IBTR risk, the 90% CI for the observed HR had to lie entirely between 0.667 and 1.5. The percent of pts IBTR-free at 10 yrs was 95.2% PBI v 95.9% WBI. A statistically significant difference in the 10-yr RFI rate favored WBI (91.9% PBI v 93.4% WBI; HR 1.32; 95%CI 1.04-1.68; p=0.02). No statistically significant differences existed between PBI and WBI in DDFI (HR 1.31; 95%CI 0.91-1.91; p=0.15), OS (HR 1.10; 95%CI 0.90-1.35; p=0.35), or DFS (HR 1.12; 95%CI 0.98-1.29; p=0.11). Grade 3 toxicity was 9.6% PBI v 7.1% WBI, and grade 4-5 toxicity was 0.5% v 0.3%, respectively. Discussion: PBI did not meet the criteria for equivalence to WBI in controlling IBTR based on the upper limit of the hazard ratio confidence interval. However, the absolute difference in 10-yr rate of IBTR was <1% (4.8% PBI v 4.1% WBI). The risk of an RFI event was statistically significantly higher for PBI compared to WBI, but the absolute difference in 10-yr RFI rate was also small (8.1% PBI v 6.6% WBI). DDFI, OS, and DFS were not statistically different for PBI v WBI. Grade 3-5 toxicities, although low, were more common for PBI than WBI. The trial population was heterogeneous, ranging from Stage 0-2 breast cancer, and outcome by risk categories are being analyzed. Support: U10CA180868, -180822, UG1CA189867. Citation Format: Vicini FA, Cecchini RS, White JR, Julian TB, Arthur DW, Rabinovitch RA, Kuske RR, Parda DS, Ganz PA, Scheier MF, Winter KA, Paik S, Kuerer HM, Vallow LA, Pierce LJ, Mamounas EP, Costantino JP, Bear HD, Germaine I, Gustafson G, Grossheim L, Petersen IA, Hudes RS, Curran, Jr. WJ, Wolmark N. Primary results of NSABP B-39/RTOG 0413 (NRG Oncology): A randomized phase III study of conventional whole breast irradiation (WBI) versus partial breast irradiation (PBI) for women with stage 0, I, or II breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS4-04.

Abstract Background: Ongoing phase III trials are comparing accelerated PBI around the lumpectomy site to standard whole breast irradiation in early stage breast cancer. Recent studies have questioned the late toxicity from PBI delivered with 3DCRT. We evaluated late toxicity on patients (pts) treated on RTOG 0319. Methods:52 pts with stage I-II breast cancer, ≥3 cm, negative margins, and < 3 nodes positive were treated with 3DCRT PBI and received 38.5 Gy in 10 BID fractions over 5 days. Median follow-up was 5.3 years (min-max: 1.7-6.4 years). Five pts were deceased at 5 years. NCI CTCAE v3.0 was used to grade adverse events (AEs). At 3 years, 50 pts were available for AE reporting or late toxicity assessment. Results: The treatment-related AEs were primarily grade 1 36.5%, 50% grade 2, and only 3 (5.8%) pts had grade 3 AEs. The grade 3 AEs in these pts were radiation dermatitis, skin fibrosis, telangectasia, and myositis. No baseline self-assessment of breast appearance is available. Patient self-assessment of breast appearance and satisfaction was available in 45 (87%) pts at 1 year and 36 (72%) at 3 years. At 1 year, 82% self reported excellent/good breast appearance and at 3 years, 64%. Pts who reported < excellent/good breast appearance had significantly more grade ≥2 skin AEs (telangectasia, skin atrophy, hyperpigmentation, erythema, skin fibrosis, radiation dermatitis, and breast or nipple/areolar deformity). At 3 years, 31 of 36 pts were satisfied with their treatment, but all 36 would choose 3DCRT PBI again over standard breast RT. Treatment factors were evaluated to establish correlation with patient reported breast appearance. Preliminary observations suggest surgical bed volume, PTV volume, number of beams used, and possible use of bolus are associated with patient reported outcomes (PRO). Surgical factors impacting PRO were not collected. Conclusions: The majority of pts were satisfied with their treatment results at 3 years and would all choose to have 3DCRT PBI again. With a median of 5.3 years, the rate of grade 3 AEs is low. Technical factors from this phase II trial were modified for the phase III NSABP B-39/RTOG 0413 trial, in which bolus is not allowed and both target volumes and required coverage were modified, increasing expectation of improved PRO. Supported by RTOG U10 CA21661, CCOP U10 CA37422 and ATC U24 CA 81647 NCI grants. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-15-07.