Risk of Esophagitis in Patients with Limited Stage SCLC Treated with QD or BID Chemoradiotherapy Regimens with Contralateral Esophagus Sparing

Abstract

Recent randomized phase III trials in limited stage (LS) small cell lung carcinoma (SCLC) demonstrate persistent high rates of grade (G) ≥ 3 esophagitis of 16-19% for 45 Gy BID and 66-70 Gy QD radiotherapy (RT). G3 esophagitis dramatically impairs quality of life and is a barrier to treatment intensification. We previously developed a contralateral esophagus sparing technique (CEST) that reduced esophagitis mainly in patients with locally advanced NSCLC treated with chemoRT to 70 Gy/7 weeks. It is not established whether CEST is effective in LS-SCLC patients, especially those receiving BID RT which may limit mucosal esophageal regeneration during treatment. Here, we report our single-institution experience with this approach. We retrospectively analyzed the records of patients with LS-SCLC who received chemoRT between June 2014 and October 2022. Patients were treated with QD or BID schedules at physician discretion though QD has historically been favored at our institution. The esophageal wall contralateral to the tumor was contoured as an avoidance structure. IMRT or VMAT was used to drive steep dose fall-off across the esophagus while maintaining full tumor coverage. Daily cone-beam CT guidance was employed. Toxicity was assessed using CTCAE v5 criteria. Descriptive statistics were used to analyze outcomes. The study was approved by the IRB. We identified 38 consecutive patients with LS-SCLC treated with definitive chemoRT. Median age was 67 years, and 60.5% were female. Twenty-seven were treated with QD RT to a median dose of 63 Gy (range 55.8-70) in 33 fractions (range 31-35). All remaining patients received BID RT 45 Gy in 30 fractions. Median CTV for the QD and BID cohorts was 205 cc and 214 cc, respectively. Almost all patients (n = 37) had tumor located within 1 cm of the esophagus. There were no ≥G3 esophagitis events (95% CI, 0-9.3%). The rate of G2 esophagitis was 21.1% (11.1-36.3%), with no significant difference between QD (26%) and BID (9%) cohorts (p = 0.3). Only two patients required narcotics. For BID patients, CE planning constraints were scaled to reflect the shortened RT course. The median CE maximum dose, V20, and V30 were 44.8 Gy, 7.9 cc, and 6.4 cc, respectively. For the QD cohort, the median CE maximum dose, V45, and V55 were 59.5 Gy, 3.0 cc, and 0.6 cc, respectively. Treatment breaks occurred in nine QD patients due to neutropenia. Median follow-up was 31.0 months. 3-year overall survival was 70.0% (95% CI, 49.8-83.3%). While we are limited by small patient numbers and possible selection bias, our data suggest that CE sparing can be effective in LS-SCLC, with low severe esophagitis risk even for BID RT regimens. CEST is readily adaptable into clinical practice which should facilitate further refinement of empirically derived CE planning constraints.