Pierre Vera1, Sébastien Thureau2, Philippe Chaumet-Riffaud3, Romain Modzelewski4, Pierre Bohn4, Maximilien Vermandel5, Sébastien Hapdey4, Amandine Pallardy6, Marc-André Mahé7, Marie Lacombe8, Pierre Boisselier9, Sophie Guillemard10, Pierre Olivier11, Veronique Beckendorf12, Naji Salem13, Nathalie Charrier14, Enrique Chajon15, Anne Devillers16, Nicolas Aide17, Serge Danhier18, Fabrice Denis19, Jean-Pierre Muratet20, Etienne Martin21, Alina Berriolo Riedinger22, Helène Kolesnikov-Gauthier23, Eric Dansin24, Carole Massabeau25, Fredéric Courbon26, Marie-Pierre Farcy Jacquet27, Pierre-Olivier Kotzki10,28, Claire Houzard29, Francoise Mornex30, Laurent Vervueren31, Amaury Paumier32, Philippe Fernandez33, Mathieu Salaun34, Bernard Dubray2. 1. Department of Nuclear Medicine, Henri Becquerel Cancer Center and Rouen University Hospital & QuantIF-LITIS, University of Rouen, Rouen, France pierre.vera@chb.unicancer.fr. 2. Department of Radiation Oncology and Medical Physics, Henri Becquerel Cancer Center and Rouen University Hospital & QuantIF-LITIS, Rouen, France. 3. Department of Nuclear Medicine, Hôpitaux universitaires Paris Sud Bicêtre AP-HP and University Paris Sud, Paris, France. 4. Department of Nuclear Medicine, Henri Becquerel Cancer Center and Rouen University Hospital & QuantIF-LITIS, University of Rouen, Rouen, France. 5. University Lille, Inserm, CHU Lille, U1189-ONCO-THAI-Image Assisted Laser Therapy for Oncology, Lille, France. 6. Department of Nuclear Medicine, Nantes University Hospital, Nantes, France. 7. Department of Radiation Oncology, Institut de Cancérologie de l'Ouest (ICO)-René Gauducheau, Nantes, France. 8. Department of Nuclear Medicine, Institut de Cancérologie de l'Ouest (ICO), Nantes, France. 9. Department of Radiation Oncology, Institut régional du Cancer Montpellier (ICM), Montpellier, France. 10. Department of Nuclear Medicine, Institut régional du Cancer Montpellier (ICM), Montpellier, France. 11. Department of Nuclear Medicine, Brabois University Hospital, Nancy, France. 12. Department of Radiation Oncology, Institut de Cancérologie de Lorraine, Nancy, France. 13. Department of Radiation Oncology, Institut Paoli Calmette, Marseille, France. 14. Department of Nuclear Medicine, Institut Paoli Calmette, Marseille, France. 15. Department of Radiation Oncology, Centre regional de lutte contre le cancer de Bretagne Eugène Marquis, Rennes, France. 16. Department of Nuclear Medicine, Centre regional de lutte contre le cancer de Bretagne Eugène Marquis, Rennes, France. 17. Nicolas Aide, Nuclear Medicine and TEP Centre, Caen University Hospital and Inserm U1086 ANTICIPE, Caen, France. 18. Department of Radiation Oncology, François Baclesse Cancer Center, Caen, France. 19. Department of Radiation Oncology, Institut Inter-Régional de Cancérologie (ILC), Centre Jean Bernard/Clinique Victor Hugo, Le Mans, France. 20. Department of Nuclear Medicine, Institut Inter-Régional de Cancérologie (ILC), Centre Jean Bernard/Clinique Victor Hugo, Le Mans, France. 21. Radiation Oncology, Centre Georges-Francois Leclerc, Dijon, France. 22. Department of Nuclear Medicine, Centre Georges Francois Leclerc, Dijon, France. 23. Department of Nuclear Medicine, Oscar Lambret Center, Lille cedex, France. 24. Department of Radiation Oncology, Oscar Lambret Center, Lille cedex, France. 25. Département de Radiothérapie. Institut Universitaire du Cancer, Toulouse cedex 9, France. 26. Department of Nuclear Medicine, Institut Claudius Regaud, IUCT, Toulouse cedex 9, France. 27. Department of Radiation Oncology, CHU de Nîmes, Institut de cancérologie du Gard, Rue Henri Pujol, Nîmes, France. 28. Department of Nuclear Medicine, CHU de Nîmes, Institut de cancérologie du Gard, Nîmes, France. 29. Department of Nuclear Medicine, Hospices Civils de Lyon, Lyon, France. 30. Department of Radiation Oncology, Hospices Civils de Lyon, Lyon, France. 31. Department of Nuclear Medicine, CHU Angers, France. 32. Department of Radiation Oncology, Institut de Cancérologie de l'Ouest, site Paul Papin, France. 33. Department of Nuclear Medicine, Hôpital Pellegrin, CHU de Bordeaux, France; and. 34. Normandy University, UNIROUEN, QuantIF-LITIS EA 4108, Rouen University Hospital, Department of Pulmonology-Thoracic Oncology-Respiratory Intensive Care, Rouen, France.
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.
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 NSCLCpatients is strongly associated with poor prognosis features that could not be reversed by radiotherapy doses up to 86 Gy.
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