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)
Pierre Vera, Sébastien Thureau, Philippe Chaumet-Riffaud, Romain Modzelewski, Pierre Bohn, Maximilien Vermandel, Sébastien Hapdey, Amandine Pallardy, Marc-André Mahé, Marie Lacombe, Pierre Boisselier, Sophie Guillemard, Pierre Olivier, Veronique Beckendorf, Naji Salem, Nathalie Charrier, Enrique Chajon, Anne Devillers, Nicolas Aide, Serge Danhier, Fabrice Denis, Jean-Pierre Muratet, Etienne Martin, Alina Berriolo Riedinger, Helène Kolesnikov-Gauthier, Eric Dansin, Carole Massabeau, Fredéric Courbon, Marie-Pierre Farcy Jacquet, Pierre-Olivier Kotzki, Claire Houzard, Francoise Mornex, Laurent Vervueren, Amaury Paumier, Philippe Fernandez, Mathieu Salaun, Bernard Dubray, Pierre Vera, Sébastien Thureau, Philippe Chaumet-Riffaud, Romain Modzelewski, Pierre Bohn, Maximilien Vermandel, Sébastien Hapdey, Amandine Pallardy, Marc-André Mahé, Marie Lacombe, Pierre Boisselier, Sophie Guillemard, Pierre Olivier, Veronique Beckendorf, Naji Salem, Nathalie Charrier, Enrique Chajon, Anne Devillers, Nicolas Aide, Serge Danhier, Fabrice Denis, Jean-Pierre Muratet, Etienne Martin, Alina Berriolo Riedinger, Helène Kolesnikov-Gauthier, Eric Dansin, Carole Massabeau, Fredéric Courbon, Marie-Pierre Farcy Jacquet, Pierre-Olivier Kotzki, Claire Houzard, Francoise Mornex, Laurent Vervueren, Amaury Paumier, Philippe Fernandez, Mathieu Salaun, Bernard Dubray
Abstract
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.
Trial registration: ClinicalTrials.gov NCT01576796.
Keywords: f-misonidasole; fluoro-deoxy-D-glucose; hypoxia; lung cancer; positron emission tomography; radiotherapy dose.
© 2017 by the Society of Nuclear Medicine and Molecular Imaging.
Source: PubMed