Evaluation of Post-esophagectomy Adverse Events in Patients Who Underwent Neoadjuvant Concurrent Chemoradiation

Abstract

Neoadjuvant chemoradiation is standard of care for patients with Stage II-III esophageal and GE junction cancers. However, this trimodality therapy carries significant risk of morbidity and mortality, particularly in the post-operative setting with complication rates of around 60%. In practice, different radiation modalities, doses, and chemotherapy regimens are employed, however, the impact of these factors on the incidence and severity of post-esophagectomy adverse events is not well established. Recently, the CROSS study group reported the use of the Comprehensive Complication Index (CCI) to assess adverse events for those enrolled in the CROSS trial, finding 85% of patients experienced post-operative complications. We retrospectively evaluated post-operative complications and the correlation with treatment factors using the CCI. Eighty-three patients with mid to distal esophageal cancer were treated with nCRT followed by resection between 2004 and 2016. 94% had adenocarcinoma. Almost all patients had a KPS ≥ 80 at onset of treatment (99%). Total doses ranged from 39.6 to 52.5 Gy. Treatment was planned using IMRT (41%), 3D-CRT (47%) and tomo-IMRT (12%). There were 29 patients who had VMAT. Concurrent chemotherapy regimens were carboplatin/taxol (59%), cisplatin/5-FU (17%), or other (24%). Resection was performed at a median of 9 weeks, generally by Ivor-Lewis (67%), esophagogastrectomy (14%), or trans-hiatal (11%). Complications were evaluated at 30, 60, and 90 day after surgery. Pulmonary, cardiac, gastrointestinal, infectious, and nervous system complications were retrospectively reviewed and graded using the Clavien-Dindo scale. CCI scores were calculated with a web-based calculator at AssessSurgery.com and means were evaluated using ANOVA. Among the 83 patients, 47 experienced post-operative complications (57%). There were a total of 5 post-operative deaths (6%). There were 3 deaths in the cohort receiving up to 45 Gy of total radiation (12%), 2 deaths between >45 and <50 Gy (10%), and zero deaths in the group who received 50.4 Gy or more. The mean CCI scores for all complications within 60 days were 25.1 (< or = to 45 Gy), 28.2 (>45 and <50.4 Gy), and 19.4 (> or = to 50.4), with the majority initiating within 30 days. The mean CCI for IMRT and 3D-CRT was 27.4 and 21.8, respectively. Patients who received concurrent carboplatin/taxol had a mean CCI of 26.2, and those who received concurrent cisplatin/5-FU had a mean CCI of 28.3. No statistical significance was found when mean CCI scores were compared for total radiation doses or when comparing chemotherapy regimens. There did not appear to be a difference in the severity of post-operative complications as measured by the CCI when comparing total radiation dose or concurrent chemotherapy agents. Additional studies are needed to further elucidate the optimal radiation dose combined with systemic agents with the goal of improving disease outcomes and minimizing toxicity.