IDEAL-CRT: A Phase 1/2 Trial of Isotoxic Dose-Escalated Radiation Therapy and Concurrent Chemotherapy in Patients With Stage II/III Non-Small Cell Lung Cancer

• DOI: 10.1016/j.ijrobp.2016.03.031
• Publication Date: 2016-03-28T12:34:41Z
• Authors: David B. Landau; Laura Hughes; Angela Baker; Andrew T. Bates; Michael C. Bayne; Nicholas Counsell; Angel Garcia-Alonso; Susan V. Harden; Jonathan D. Hicks; Simon R. Hughes; Marianne C. Illsley; Iftekhar Khan; Virginia Laurence; Zafar Malik; Helen Mayles; William Philip M....; Elizabeth Miles; Nazia Mohammed; Yenting Ngai; Emma Parsons; James Spicer; Paula Wells; Dean Wilkinson; John D. Fenwick
• Keywords: Male; Cancer Research; Lung Neoplasms; ACCELERATED RADIOTHERAPY; Drug-Related Side Effects and Adverse Reactions; CONFORMAL RADIOTHERAPY; Comorbidity; NSCLC; II TRIAL; CHEMORADIATION; 03 medical and health sciences; 0302 clinical medicine; Carcinoma, Non-Small-Cell Lung; Prevalence; Humans; Clinical Investigation; Radiation Injuries; Aged; Neoplasm Staging; Aged, 80 and over; Science & Technology; Radiation; CONSTRAINTS; Dose-Response Relationship, Radiation; Chemoradiotherapy; Middle Aged; 3. Good health; Survival Rate; Nuclear Medicine & Medical Imaging; Treatment Outcome; Oncology; TISSUE; Radiology Nuclear Medicine and imaging; Female; Dose Fractionation, Radiation; Radiology; Life Sciences & Biomedicine

To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer.Patients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 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 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumor doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined.Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years.IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients.