Isotoxic Intensity Modulated Radiotherapy in stage III NSCLC - A feasibility study.

Abstract Purpose Not all patients with stage III NSCLC are suitable for concurrent chemoradiotherapy (cCRT). Local failure rate is high for sequential CRT and as such, there is a rationale for treatment intensification. Methods and Materials Isotoxic intensity modulated radiotherapy (IMRT) is a multicentre feasibility study that combines different intensification strategies including hyperfractionation, acceleration and dose escalation facilitated by IMRT. Patients with unresectable stage III NSCLC, ECOG PS 0-2 and unsuitable for cCRT were recruited. A minimum of 2 cycles of platinum-based chemotherapy was compulsory before starting radiotherapy (RT). Radiation dose was increased until a maximum dose of 79.2Gy was reached or ≥ 1 of the organs at risk met pre-defined constraints. RT was delivered in 1.8Gy fractions twice-daily and an RT quality assurance programme was implemented. The primary objective was the delivery of isotoxic IMRT to a dose of > 60Gy equivalent dose in 2Gy fractions (EQD2 assuming an α/β ratio of 10 Gy for acute reacting tissues). Results 37 patients were recruited from 7 UK centres. Median age = 69.9 years (range 46-86). Male:Female ratio = 17:18. ECOG PS=0, 5 (14.2%), PS=1, 27 (77.1%), PS=2, 3 (8.6%). Stage IIIA:IIIB ratio 22 (62.9%):13 (37.1%). Of 37 patients, 2 (5.4%) failed to achieve EQD2 >60Gy. Median prescribed tumor dose was 77.4Gy (61.2 – 79.2Gy). Maximum dose of 79.2Gy was achieved in 14 (37.8%) patients. Grade 3 esophagitis was reported in 2 patients and no patients developed grade 3-4 pneumonitis. There were 3 grade 5 events: acute radiation pneumonitis, bronchopulmonary haemorrhage and acute lung infection. Median follow-up at time of analysis was 25.4 (8.0 – 44.2) months for 11 out of 35 survivors. The median survival was 18.1 months with 95% CI (13.9, 30.6), 2-year overall survival was 33.6%; 95% CI (17.9, 50.1) and progression-free survival was 23.9%; 95% CI (11.3, 39.1). Conclusions Isotoxic IMRT is a well-tolerated and feasible approach to treatment intensification.