Regional Control And Dose-Response For Chemoradiotherapy In Locally-Advanced Endometrial Cancer

Endometrial cancers are primarily managed with surgery which includes lymph node staging or debulking of any involved lymph nodes. Currently, there is limited data for nodal control of involved nodes with (chemo) radiotherapy (CRT). The goal of the current study is to assess nodal control with CRT for locally-advanced endometrial cancers managed with preoperative CRT followed by hysterectomy. From July 1999-November 2018, 105 patients with ≥ clinical stage II endometrial cancer treated with pre-operative CRT followed by extrafascial hysterectomy were retrospectively reviewed. Patients not completing therapy (n=6) or receiving CRT at outside institutions were excluded (n=4). Limited nodal dissection after CRT was performed if nodal disease persisted on imaging or was seen intraoperatively. PET/CT was performed for initial nodal staging in 80 (84%). The CTV included pelvic nodes up to the common iliac for node-negative and para-aortic lymph nodes up to the renal vessel for node-positive patients. Involved nodes most commonly received a simultaneous integrated boost of 55Gy in 25 fractions ± 4-6Gy sequential boost for nodes >2cm. Of the included 95 patients, 55 (58%) had clinically positive lymph nodes: 17 (31%) pelvic only, 5 (9%) para-aortic only, and 33 (60%) pelvic + para-aortic. The median number of positive nodes was 4 [interquartile range (IQR): 2-7] with a total number of 300 positive nodes. Nineteen (20%) patients had limited nodal dissection with a median of 3 (IQR:2-5) nodes dissected. At a median follow-up of 25 months (IQR: 9-46), the 3-year regional control was 91% (95%CI: 85-98%). In clinically node-negative patients, 2 (5%) developed isolated recurrence out-of-field in the para-aortic region. In clinically node-positive patients, failure in involved nodes occurred in 4 (7%) and in prophylactic treated nodal regions in 4 (7%), 3 of which had synchronous nodal failure at both sites. Regional recurrence was higher in patients with lymph nodes ≥2cm (3-year regional control 100% <2cm vs. 72% ≥2cm, p=0.005) and nodal maximum SUV (100% <10.6 vs 76% ≥10.6, p=0.045). For the 300 clinically-involved lymph nodes, the median size was 1.2cm (IQR: 0.8-1.7). The 3-year involved nodal control rate was 96% (95%CI: 93-99%). Involved nodal failure was higher in type-II histology (3-year control 100% type-I vs 90% type-II, p=0.002), lymph nodes ≥2cm (98% <2cm vs 84% ≥2cm, p=0.007), and by radiation dose (75% for <55Gy, 98% 55Gy in 25 fractions, and 89% >55Gy, p=0.03). This is largest study looking at regional control rates of involved lymph nodes with CRT. Despite a high burden of clinical involvement and low rates of dissection, nodal failure is low following neoadjuvant CRT, suggesting efficacy of CRT. A dose of at least 55Gy in 25 fractions is suggested for clinically involved nodes, with consideration of higher dose or alternative strategies in non-endometrioid histologies and bulky nodes ≥2cm.