RT Journal Article SR Electronic T1 Phase II Study of a Radiotherapy Total Dose Increase in Hypoxic Lesions Identified by 18F-Misonidazole PET/CT in Patients with Non–Small Cell Lung Carcinoma (RTEP5 Study) JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1045 OP 1053 DO 10.2967/jnumed.116.188367 VO 58 IS 7 A1 Pierre Vera A1 Sébastien Thureau A1 Philippe Chaumet-Riffaud A1 Romain Modzelewski A1 Pierre Bohn A1 Maximilien Vermandel A1 Sébastien Hapdey A1 Amandine Pallardy A1 Marc-André Mahé A1 Marie Lacombe A1 Pierre Boisselier A1 Sophie Guillemard A1 Pierre Olivier A1 Veronique Beckendorf A1 Naji Salem A1 Nathalie Charrier A1 Enrique Chajon A1 Anne Devillers A1 Nicolas Aide A1 Serge Danhier A1 Fabrice Denis A1 Jean-Pierre Muratet A1 Etienne Martin A1 Alina Berriolo Riedinger A1 Helène Kolesnikov-Gauthier A1 Eric Dansin A1 Carole Massabeau A1 Fredéric Courbon A1 Marie-Pierre Farcy Jacquet A1 Pierre-Olivier Kotzki A1 Claire Houzard A1 Francoise Mornex A1 Laurent Vervueren A1 Amaury Paumier A1 Philippe Fernandez A1 Mathieu Salaun A1 Bernard Dubray YR 2017 UL http://jnm.snmjournals.org/content/58/7/1045.abstract AB See an invited perspective on this article on page 1043.This multicenter phase II study investigated a selective radiotherapy dose increase to tumor areas with significant 18F-misonidazole (18F-FMISO) uptake in patients with non–small cell lung carcinoma (NSCLC). Methods: Eligible patients had locally advanced NSCLC and no contraindication to concomitant chemoradiotherapy. The 18F-FMISO uptake on PET/CT was assessed by trained experts. If there was no uptake, 66 Gy were delivered. In 18F-FMISO–positive patients, the contours of the hypoxic area were transferred to the radiation oncologist. It was necessary for the radiotherapy dose to be as high as possible while fulfilling dose-limiting constraints for the spinal cord and lungs. The primary endpoint was tumor response (complete response plus partial response) at 3 mo. The secondary endpoints were toxicity, disease-free survival (DFS), and overall survival at 1 y. The target sample size was set to demonstrate a response rate of 40% or more (bilateral α = 0.05, power 1-β = 0.95). Results: Seventy-nine patients were preincluded, 54 were included, and 34 were 18F-FMISO–positive, 24 of whom received escalated doses of up to 86 Gy. The response rate at 3 mo was 31 of 54 (57%; 95% confidence interval [CI], 43%–71%) using RECIST 1.1 (17/34 responders in the 18F-FMISO–positive group). DFS and overall survival at 1 y were 0.86 (95% CI, 0.77–0.96) and 0.63 (95% CI, 0.49–0.74), respectively. DFS was longer in the 18F-FMISO–negative patients (P = 0.004). The radiotherapy dose was not associated with DFS when adjusting for the 18F-FMISO status. One toxic death (66 Gy) and 1 case of grade 4 pneumonitis (>66 Gy) were reported. Conclusion: Our approach results in a response rate of 40% or more, with acceptable toxicity. 18F-FMISO uptake in NSCLC patients is strongly associated with poor prognosis features that could not be reversed by radiotherapy doses up to 86 Gy.