A phase I/II radiation dose escalation trial using simultaneous integrated boost technique with elective nodal irradiation and concurrent chemotherapy for unresectable esophageal Cancer

Background To investigate the safety and tolerability of simultaneous integrated boost (SIB) technique concurrent with elective nodal irradiation (ENI) and dual-drug chemotherapy for patients with unresectable esophageal cancer. Methods In phase I, the prophylactic PTV received a stable dose of 50.40Gy/1.80Gy/28f while the boost area was planned with 3 consecutive dose levels: the first dose level was 60.76Gy/2.17Gy/28f, and then escalated approximately every 2 Gy. ENI was incorporated in Clinical Target Volume (CTV), and paclitaxel and nedaplatin were given concurrently for at least 5 weeks. In phase II, enrolled patients were treated with Maximum Tolerated Dose (MTD) obtained in phase I and the compliance rate, survival results and toxicities were evaluated. Results From December 2014 to April 2017, 53 patients were enrolled. In phase I, 2 out of 6 patients developed Dose-Limiting Toxicity (DLT) at dose level 1. Due to excessive treatment-related toxicities, the escalation process was suspended and de-escalated to 59.92Gy /2.14Gy /28 f. Three patients were treated at this dose level, all of whom completed at least 5 weeks of chemotherapy and none of whom reached a DLT, determining the newly added dose level to be the MTD. In phase II, 44 patients were treated with MTD, 31 of them (70.0%) completed at least 5 weeks of chemotherapy. The most common Grade 3 or 4 toxicities in phase II included leukopenia (21%) and esophagitis (15%). With a median follow-up time of 16.9 months, 1-y OS, DFS and local failure-free survival were 76.9, 63.6 and 78.8% respectively. Conclusion The SIB technique was feasible and safe at the MTD (95% PGTV/PTV 59.92/50.40Gy/28f) concurrent with ENI and dual-drug chemotherapy for patients with unresectable esophageal cancer. Trial registration clinicaltrials.gov NCT02429622 . Retrospectively registered on April 24, 2015.