Evaluating the Role of Postmastectomy Radiation Therapy Based on Pathological Nodal Response in Clinical Nodal Positive Stage II-III Breast Cancer after Neoadjuvant Chemotherapy: A Multicenter Study of 1963 Cases from China

Abstract

The TARGIT E trial is an international single-arm trial (NCT01299987; Neumaier et al. BMC Cancer 2012) on risk-adapted therapy of elderly patients with low-risk breast cancer, consisting of a single dose of intraoperative radiotherapy (IORT), followed by whole breast radiotherapy (WBRT) in case risk factors are present. We here present the first per-protocol analysis of local recurrence rates and overall survival. Materials/Methods: Eligible patients (70 years, cT1/2 (< 3.5 cm), cN0, cM0, invasive carcinoma of no special type) were enrolled between February 2011 and September 2014. During breast-conserving surgery, a single dose of 20 Gy was applied using low-energy x-rays. In case risk factors (larger size, other histology, free margin < 1 cm, lymphatic vessel invasion, positive nodes, multifocal/-central lesions, extensive intraductal component) were present in the final pathology, patients received whole breast irradiation (46-50 Gy, 1.8-2.0 Gy per fraction). Systemic therapy was applied according to international standards and guidelines. The primary outcome was the local recurrence rate measured at 2.5,5 and 7.5 years using the Kaplan-Meier method. The secondary outcome was overall survival. Termination due to futility was deemed necessary in case local relapse rates exceeded 3/4/6% at 2.5/5/7.5 years. Results: A total of 541 patients were screened, 526 enrolled in the trial and 474 were included in this analysis (38 drop-outs, 13 withdrawals, 1 protocol violation). Of those, 347 (73%) received IORT only, 99 (21%) IORT plus WBRT, 22 (5 %) WBRT only and 7 (1%) surgery only with no subsequent adjuvant therapies. After a median follow-up of 3 years (range: 2-79 months), 4 ipsilateral in-breast recurrences after 11, 33, 42 and 43 months were observed, resulting in estimated local recurrence rates of 0.2 and 1.5% at 2.5 and 5 years. Overall, 20 patients died (3 breast-cancerrelated deaths, 17 non-breast-cancer-related deaths). Estimated overall survival rates at 2.5 and 5 years were 98.9% and 91.4%, respectively. Conclusion: The first per protocol analysis of the prospective TARGIT E trial shows that local relapse rates at 2.5 and 5 years are far below the predefined stopping rules. The current results therefore support the risk-adapted approach of accelerated partial breast radiotherapy (APBI) in selected patients.