HI-CHART: A Phase I/II Study on the Feasibility of High-Dose Continuous Hyperfractionated Accelerated Radiotherapy in Patients With Inoperable Non-Small-Cell Lung Cancer

Purpose: To determine the feasibility of high-dose continuous hyperfractionated accelerated radiotherapy in patients with inoperable non-small-cell lung cancer (NSCLC). Patients and Methods: In a prospective, Phase I/II study, according to the risk for radiation pneumonitis, three risk groups were defined: V20 <25%, V20 25-37%, and V20 >37%. The dose was administered in three steps from 61.2 Gy/34 fractions/23 days to 64.8 Gy/36 fractions/24 days to 68.40 Gy/38 fractions/25 days (1.8 Gy b.i.d. with 8-h interval), using a three-dimensional conformal technique. Only the mediastinal lymph node areas that were positive on the pretreatment 18F-deoxy-D-glucose positron emission tomography scan were included in the target volume. The primary endpoint was toxicity. Results: A total of 48 Stage I-IIIB patients were included. In all risk groups, 68.40 Gy/38 fractions/25 days could be administered. Maximal toxicity according to the risk groups was as follows: V20 <25% (n = 35): 1 Grade 4 (G4) lung and 1 G3 reversible esophageal toxicity; V20 35-37% (n = 12): 1 G5 lung and 1 G3 reversible esophageal toxicity. For the whole group, local tumor recurrence occurred in 25% (95% confidence interval 14%-40%) of the patients, with 1 of 48 (2.1%; upper one-sided 95% confidence limit 9.5%) having an isolated nodal recurrence. The median actuarial overall survival was 20 months, with a 2-year survival rate of 36%. Conclusions: High-dose continuous hyperfractionated accelerated radiotherapy up to a dose of 68.40 Gy/38 fractions/25 days (a biologic equivalent of approximately 80 Gy when delivered in conventional fractionation) in patients with inoperable NSCLC and a V20 up to 37% is feasible