PT  - JOURNAL ARTICLE
AU  - Vera, Pierre
AU  - Thureau, Sébastien
AU  - Chaumet-Riffaud, Philippe
AU  - Modzelewski, Romain
AU  - Bohn, Pierre
AU  - Vermandel, Maximilien
AU  - Hapdey, Sébastien
AU  - Pallardy, Amandine
AU  - Mahé, Marc-André
AU  - Lacombe, Marie
AU  - Boisselier, Pierre
AU  - Guillemard, Sophie
AU  - Olivier, Pierre
AU  - Beckendorf, Veronique
AU  - Salem, Naji
AU  - Charrier, Nathalie
AU  - Chajon, Enrique
AU  - Devillers, Anne
AU  - Aide, Nicolas
AU  - Danhier, Serge
AU  - Denis, Fabrice
AU  - Muratet, Jean-Pierre
AU  - Martin, Etienne
AU  - Riedinger, Alina Berriolo
AU  - Kolesnikov-Gauthier, Helène
AU  - Dansin, Eric
AU  - Massabeau, Carole
AU  - Courbon, Fredéric
AU  - Farcy Jacquet, Marie-Pierre
AU  - Kotzki, Pierre-Olivier
AU  - Houzard, Claire
AU  - Mornex, Francoise
AU  - Vervueren, Laurent
AU  - Paumier, Amaury
AU  - Fernandez, Philippe
AU  - Salaun, Mathieu
AU  - Dubray, Bernard
TI  - Phase II Study of a Radiotherapy Total Dose Increase in Hypoxic Lesions Identified by <sup>18</sup>F-Misonidazole PET/CT in Patients with Non–Small Cell Lung Carcinoma (RTEP5 Study)
AID  - 10.2967/jnumed.116.188367
DP  - 2017 Jul 01
TA  - Journal of Nuclear Medicine
PG  - 1045--1053
VI  - 58
IP  - 7
4099  - http://jnm.snmjournals.org/content/58/7/1045.short
4100  - http://jnm.snmjournals.org/content/58/7/1045.full
SO  - J Nucl Med2017 Jul 01; 58
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.