IDEAL-CRT: A phase I/II trial of isotoxic dose-escalated radiotherapy and concurrent chemotherapy in patients with stage II/III non-small cell lung cancer

Background and Purpose: Toxicity and early efficacy data are presented for IDEAL-CRT, a trial of an escalated, concurrent chemoradiotherapy schedule for advanced stage non-small cell lung cancer (NSCLC). Tumor dose-per-fraction-escalation was used in IDEAL-CRT to achieve therapy intensification without prolongation, and tumor doses were prescribed isotoxically to maximum levels consistent with normal tissue dose constraints. Patients and Methods Patients received tumor doses of 63-73Gy in 30 once-daily fractions over 6 weeks with two concurrent cycles of cisplatin and vinorelbine. They were assigned to one of two groups according to esophageal dose. In Group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose which was escalated following a 6+6 design from 65Gy through 68Gy to 71Gy, allowing an esophageal maximum tolerated dose (MTD) to be determined from early and late toxicities. Tumor doses for Group 2 patients were determined by other tissue constraints, often lung. Overall survival (OS), progression-free survival (PFS), tumor response and toxicity were evaluated for both groups combined. Results Eight centres recruited 84 patients: 13, 12 and 10 in the 65Gy, 68Gy and 71Gy cohorts of Group 1, and 49 in Group 2. The mean prescribed tumor dose was 67.6Gy. Five grade 3 esophagitis and three grade 3 pneumonitis events were observed across both groups. Following one fatal esophageal perforation in the 71Gy cohort, 68Gy was declared the esophageal MTD. With a median follow-up of 35 months, median OS was 36.9 months, and OS and PFS were 87.8% and 72.0% at 1 year and 68.0% and 48.5% at 2 years. Conclusions IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal MTD to be identified from relatively few patients.