Delay in Initiating Postmastectomy Radiotherapy is Associated With Inferior Clinical Oncologic Outcomes for High-Risk Breast Cancer.

Abstract

PURPOSE/OBJECTIVE(S)\nTo investigate the appropriate timing of radiotherapy (RT) after mastectomy and adjuvant chemotherapy for women with high-risk breast cancer.\n\n\nMATERIALS/METHODS\nA total of 584 patients with stage II-III breast cancer were analyzed from a randomized, open-label, phase 3 trial, which evaluated the non-inferiority of hypofractionated to conventional fractionated RT after mastectomy. All patients received mastectomy followed by adjuvant chemotherapy and RT without neoadjuvant treatments. Optimal cut-off value of the interval from the date of surgery to the starting date of RT (SRI) and the interval from the date of last-dose chemotherapy to the starting date of RT (CRI) for oncologic outcomes was calculated by Maxstat. Kaplan-Meier method was used to estimate the rates of locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS), and the differences were compared with log-rank test. Cox proportional hazards regression was performed for multivariate analysis.\n\n\nRESULTS\nMedian follow-up was 83.5 months (IQR 63-109). The median SRI was 168 days (range 93-357). The median CRI was 27 days (range 5-126). Compared to an SRI ≤165 days (5.5 months), an SRI > 165 days was associated with a significantly lower DFS rate (8-year 72.3% vs. 79.0%; P\u202f=\u202f0.019), a higher DM rate (8-year 26.2% vs. 20.6%; P\u202f=\u202f0.031), and a non-significantly higher LRR rate (8-year 9.0% vs. 6.0%, P\u202f=\u202f0.065). Patients with an SRI > 180 days had a significantly lower OS rate compared with those with an SRI ≤180 days (8-year 72.2% vs. 84.1%; P\u202f=\u202f0.012). Furthermore, CRI > 40 days was related to a significant decrease in DFS rate (8-year 67.0% vs. 76.9%; P\u202f=\u202f0.002) and OS rate (8-year 69.0% vs. 83.0%; P\u202f=\u202f0.002); and a significant increase in DM rate (8-year 33.4% vs. 21.8%; P\u202f=\u202f0.001). No significant association between CRI > 40 days and LRR was found (8-year 10.4% vs. 7.2%; P\u202f=\u202f0.238). After accounting for other known prognostic variables, SRI > 165 days, T stage and N stage remained significantly associated with inferior DM and DFS, while SRI > 180 days, T stage and N stage remained significantly associated with inferior OS. Meanwhile, CRI > 40 days, T stage and N stage were independently associated with inferior DM, DFS and OS.\n\n\nCONCLUSION\nDelay in initiating RT in patients with high-risk breast cancer is associated with inferior oncologic outcomes. We recommend RT should start within 165 days after mastectomy, and within 40 days after chemotherapy. NCT00793962.