Citation: International Journal of Radiation Oncology, Biology, Physics. 2020, 106(4), 733-742
Author: J D Fenwick, D B Landau, A Baker, A T Bates, C Eswar, A Garcia-Alonso, S V Harden, M C Illsley, V Laurence, Z Malik, W P M Mayles, E Miles, N Mohammed, J Spicer, P Wells, S Vivekanandan, A M Mullin, L Hughes, L Farrelly, Y Ngai, N Counsell
Abstract: Purpose: The XTRIAL phase 1/2 multicenter trial of isotoxically dose-escalated concurrent chemoradiotherapy for stage II/III non-small cell lung cancer (NSCLC) investigated two 30-fraction schedules of 5 and 6 weeks duration. We report toxicity, tumor response, progression-free survival (PFS) and overall survival (OS) for both schedules, with long-term follow-up for the 6-week schedule.
Patients and methods: Patients received isotoxically-individualized tumor radiation doses of 63-71 Gy in 5 weeks or 63-73 Gy in 6 weeks, delivered concurrently with two cycles of cisplatin and vinorelbine. Eligibility criteria were the same for both schedules.
Results: 120 patients (6% stage IIB, 68% IIIA, 26% IIIB, 1% IV) were recruited from 9 UK centers, 118 starting treatment. Median prescribed doses were 64.5 and 67.6 Gy for the 36 and 82 patients treated using the 5- and 6-week schedules. Grade ≥3 pneumonitis and early esophagitis rates were 3.4% and 5.9% overall, and similar for each schedule individually. Late grade 2 esophageal toxicity occurred in 11.1% and 17.1% of 5- and 6-week patients. Grade ≥4 adverse events occurred in 17 (20.7%) 6-week patients but no 5-week patients. Four adverse events were grade 5, with two considered RT-related. After 51.8 and 26.4 months median follow-up for the 6- and 5-week schedules, median OS was 41.2 and 22.1 months respectively, and median PFS was 21.1 and 8.0 months. In exploratory analyses, OS was significantly associated with schedule (HR=0.56, 95%CI: 0.32-0.98, p=0.04) and fractional clinical/internal target volume receiving ≥95% of the prescribed dose (HR=0.88, 95%CI: 0.77-1.00, p=0.05). PFS was also significantly associated with schedule (HR=0.53, 95%CI: 0.33-0.86, p=0.01).
Conclusions: Toxicity in XTRIAL was acceptable. Survival was promising for 6-week patients, and significantly longer than for 5-week patients. Survival might be further lengthened by following the 6-week schedule with an immune agent, motivating further study of such combined optimized treatments.
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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