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Radiotherapy boost in patients with hypoxic lesions identified by 18F-FMISO PET/CT in non-small-cell lung carcinoma: can we expect a better survival outcome without toxicity? [RTEP5 long-term follow-up]

  • Pierre VeraEmail author
  • Sorina-Dana Mihailescu
  • Justine Lequesne
  • Romain Modzelewski
  • Pierre Bohn
  • Sébastien Hapdey
  • Louis-Ferdinand Pépin
  • Bernard Dubray
  • Philippe Chaumet-Riffaud
  • Pierre Decazes
  • Sébastien Thureau
  • all investigators of RTEP5 study (list in annexe)
Original Article
  • 82 Downloads

Abstract

Purpose

Chemoradiotherapy is the reference curative-intent treatment for nonresectable locally advanced non-small-cell lung carcinoma (NSCLC), with unsatisfactory survival, partially due to radiation resistance in hypoxic tissues. The objective was to update survival and toxicity at 3 years following radiotherapy boost to hypoxic tumours in NSCLC patients treated with curative-intent chemoradiotherapy.

Methods

This was an open-label, nonrandomized, multicentre, phase II clinical trial. 18F-Fluoromisonidazole (18F-FMISO) PET/CT was used to determine the hypoxic profile of the patients. 18F-FMISO-positive patients and those without organ-at-risk constraints received a radiotherapy boost (70–84 Gy); the others received standard radiotherapy (66 Gy). Overall survival (OS), progression-free survival (PFS) and safety were assessed.

Results

A total of 54 patients were evaluated. OS and PFS rates at 3 years were 48.5% and 28.8%, respectively. The median OS in the 18F-FMISO-positive patients was 25.8 months and was not reached in the 18F-FMISO-negative patients (p = 0.01). A difference between the groups was also observed for PFS (12 months vs. 26.2 months, p = 0.048). In 18F-FMISO-positive patients, no difference was observed in OS in relation to dose, probably because of the small sample size (p = 0.30). However, the median OS seemed to be in favour of patients who received the radiotherapy boost (26.5 vs. 15.3 months, p = 0.71). In patients who received the radiotherapy boost, no significant late toxicities were observed.

Conclusion

18F-FMISO uptake in NSCLC patients is strongly associated with features indicating a poor prognosis. In 18F-FMISO-positive patients, the radiotherapy boost seemed to improve the OS by 11.2 months. A further clinical trial is needed to investigate the efficacy of a radiotherapy boost in patients with hypoxic tumours.

Keywords

Positron emission tomography Fluorodeoxy-d-glucose 18F-Fluoromisonidazole Hypoxia Lung cancer Radiotherapy dose 

Notes

Acknowledgments

This study was supported by a grant from the French National Cancer Institute (PHRC 2011). No other potential conflicts of interest relevant to this article were reported. We thank the patients who agreed to participate in this study and their respective referring pneumologists, nuclear medicine physicians and radiation oncologists from the participating centres. The authors thank the technologists of the Department of Nuclear Medicine (Centre Henri Becquerel) for their help in managing the patients. We are particularly grateful to O. Rastelli, L. Burel, P. Gouel, C. Breton and D. Richard for their excellent collaboration.

Funding

This study was supported by a grant from the French National Cancer Institute (PHRC 2011).

Compliance with ethical standards

Conflicts of interest

None.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The protocol and the consent form were approved by the Ethics Committee Nord-Ouest 1. The study was registered in the Clinical Trials Protocol Registration System (NCT01576796; RTEP5 study). The clinical, biological, imaging and toxicity data were monitored by a certified clinical research unit.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Investigators of RTEP5 study

Amandine Pallardy, MD1; Marc-André Mahé, MD, PhD2; Marie Lacombe, MD3; Pierre Boisselier, MD4; Sophie Guillemard, MD5; Pierre Olivier, MD, PhD6; Veronique Beckendorf, MD7; Naji Salem, MD8; Nathalie Charrier, MD9; Enrique Chajon, MD10; Anne Devillers, MD11; Nicolas Aide, MD, PhD12; Serge Danhier, MD13; Fabrice Denis, MD, PhD14; Jean-Pierre Muratet, MD15; Etienne Martin, MD16; Alina Berriolo Riedinger, MD17; Helène Kolesnikov-Gauthier, MD18; Eric Dansin, MD19; Carole Massabeau, MD20; Fredéric Courbon, MD, PhD21; Marie-Pierre Farcy Jacquet, MD22; Pierre-Olivier Kotzki, MD, PhD23; Claire Houzard, MD24; Francoise Mornex, MD, PhD25; Laurent Vervueren, MD26; Amaury Paumier, MD27; Philippe Fernandez MD, PhD28; Mathieu Salaun, MD, PhD29

1. Department of Nuclear Medicine, Nantes University Hospital, Nantes, France; E-mail: amandine.pallardy@gmail.com; Phone Number: +33.2.40.67.99.31

2. Department of Radiation Oncology, Institut de Cancérologie de l’Ouest (ICO), Nantes; France; E-mail: marc-andre.mahe@ico.unicancer.fr; Phone Number: +33.2.40.67.99.31

3. Department of Nuclear Medicine, Institut de Cancérologie de l’Ouest (ICO), Nantes; France; E-mail: marie.lacombe@ico.unicancer.fr; Phone Number: +33.2.40.67.99.31

4. Department of Radiation Oncology, Institut Regional du Cancer (ICM), Montpellier, France; E-mail: pierre.boisselier@icm.unicancer.fr; Phone Number: +33.4.67.61.37.16

5. Department of Nuclear Medicine, Institut Regional du Cancer (ICM), Montpellier, France; E-mail: sophie.guillemard@icm.unicancer.fr; Phone Number: +33.4.67.61.31.90

6. Department of Nuclear Medicine, Brabois University Hospital, Nancy; France; E-mail: p.olivier@chu-nancy.fr; Phone Number: +33.3.83.15.39.65

7. Department of Radiation Oncology, Institut de Cancérologie de Lorraine, Nancy, France; E-mail: v.beckendorf@nancy.unicancer.fr; Phone Number: +33.3.87.39.67.27

8. Department of Radiation Oncology, Institut Paoli Calmette; Marseille, France; E-mail: salemn@ipc.unicancer.fr; Phone Number: +33.4.78.86.42.53

9. Department of Nuclear Medicine, Institut Paoli Calmette; Marseille, France; E-mail: charriern@ipc.unicancer.fr; Phone Number: +33.4.78.86.21.75

10. Department of Radiation Oncology, Centre regional de lutte contre le cancer de Bretagne Eugène Marquis; Rennes, France; E-mail: e.chajon@rennes.unicancer.fr; Phone Number: +33.2.99.25.30.00

11. Department of Nuclear Medicine, Centre regional de lutte contre le cancer de Bretagne Eugène Marquis; Rennes, France; E-mail: a.devillers@rennes.unicancer.fr; Phone Number: +33.2.99.25.30.00

12. Nuclear Medicine and TEP centre, Caen University Hospital and INSERM 1199, Avenue de Nacre, 14000 Caen; aiden@chu-caen.fr; Phone Number: +33.2.31.06.32.44

13. Department of Radiation Oncology, François Baclesse Cancer Center, Caen; France; E-mail: s.danhier@baclesse.fr; Phone Number: +33.2.31.45.50.20

14. Department of Radiation Oncology, Institut Inter-Régional de Cancérologie (ILC). Centre Jean Bernard/Clinique Victor Hugo, 72000, Le Mans, France; f.denis@cjb72.org; Phone Number: +33.2.43.39.13.00; Fax Number: +33.2.43.28.85.34

15. Department of Nuclear Medicine, Institut Inter-Régional de Cancérologie (ILC). Centre Jean Bernard/Clinique Victor Hugo, 72000, Le Mans, France; E-mail : jpmuratet@icloud.com; Phone Number: +33.2.43.39.13.00; Fax Number: +33.2.43.28.85.34

16. Radiation Oncology, Centre Francois Leclerc, Dijon; France; E-mail: eMartin@cgfl.fr; Phone Number: +33.3.80.73.75.00

17. Department of Nuclear Medicine,: Centre Francois Leclerc, Dijon; France; E-mail: ABerrioloRiedinger@cgfl.fr; Phone Number: Phone Number: +33.3.80.73.75.00

18. Helène Kolesnokov-Gauthier. Department of Nuclear Medicine, Oscar Lambret Center, 59020 Lille cedex, France ; E-mail: hgauthier@o-lambret.fr; Phone Number: +33.3.20.29.59.13

19. Eric Dansin. Department of Radiation Oncology. Oscar Lambret Center, 59020 Lille cedex, France; E-mail: e-dansin@o-lambret.fr; Phone Number: +33.3.20.29.59.13

20. Département de Radiothérapie. Institut Universitaire du Cancer, 1 avenue Irène Joliot-Curie, 31059 Toulouse cedex 9, France; E-mail: massabeau.carole@iuct-oncopole.fr; Phone Number: +33.5.31.15.50.50

21. Department of Nuclear Medicine, Institut Universitaire du Cancer, 1 avenue Irène Joliot-Curie, 31059 Toulouse cedex 9, France; Email: courbon.frederic@iuct-oncopole.fr; Phone Number: +33.5.31.15.50.50

22. Department of Radiation Oncology, CHU de Nîmes, Institut de cancérologie du Gard, Rue Henri Pujol, 30000 Nîmes, France; E-mail: marie.pierre.farcy.jacquet@chu-nimes.fr; France; Phone Number: +33.4.66.68.68.68

23. Department of Nuclear Medicine, CHU de Nîmes, Institut de cancérologie du Gard, Rue Henri Pujol, 30000 Nîmes, France; E-mail: pierre-olivier.kotzki@icm.unicancer.fr; Phone Number: +33.4.66.68.68.68

24. Department of Nuclear Medicine, Hospices Civils de Lyon, Lyon; France; E-mail: claire.houzard@chu-lyon.fr; Phone Number: +33.4.78.86.21.75

25. Department of Radiation Oncology, Hospices Civils de Lyon, Lyon; France; E-mail: francoise.mornex@chu-lyon.fr; Phone Number: +33.4.78.86.42.53

26. Department of Radiation Oncology, Institut de Cancérologie de l'Ouest, site Paul Papin, France; E-mail: amaury.Paumier@ico.unicancer.fr; Phone Number: +33.2.41.35.27.00

27. Department of Nuclear Medicine, Institut de Cancérologie de l'Ouest, site Paul Papin, France; E-mail: lavervueren@chu-angers.fr; Phone Number: +33.2.41.35.27.00

28. Department of Nuclear Medicine, Hôpital Pellegrin, CHU de Bordeaux; France, E-mail: philippe.fernandez@chu-bordeaux.fr; Phone Number: +33.5.56.79.55.40

29. Department of Pneumology and QuantIF – LITIS [EA (Equipe d’Accueil) 4108 – FR CNRS 3638], Faculty of Medicine, University of Rouen; France, CHU de Rouen; 1 rue de Germont, 76000 Rouen; luc.thiberville@univ-rouen.fr; Phone Number: +33.2.35.88.89.90

Supplementary material

259_2019_4285_MOESM1_ESM.docx (62 kb)
ESM 1 (DOCX 61 kb)
259_2019_4285_MOESM2_ESM.docx (22 kb)
ESM 2 (DOCX 21.5 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Pierre Vera
    • 1
    Email author
  • Sorina-Dana Mihailescu
    • 2
  • Justine Lequesne
    • 2
  • Romain Modzelewski
    • 1
  • Pierre Bohn
    • 1
  • Sébastien Hapdey
    • 1
  • Louis-Ferdinand Pépin
    • 2
  • Bernard Dubray
    • 3
  • Philippe Chaumet-Riffaud
    • 4
  • Pierre Decazes
    • 1
  • Sébastien Thureau
    • 1
    • 3
  • all investigators of RTEP5 study (list in annexe)
  1. 1.Department of Nuclear Medicine, Henri Becquerel Cancer Center and Rouen University Hospital, & QuantIF – LITIS [EA (Equipe d’Accueil) 4108 – FR CNRS 3638], Faculty of MedicineUniversity of RouenRouenFrance
  2. 2.Department of Statistics and Clinical Research UnitHenri Becquerel Cancer CenterRouenFrance
  3. 3.Department of Radiation OncologyHenri Becquerel Cancer Center and Rouen University Hospital, & QuantIF – LITIS [EA (Equipe d’Accueil) 4108]RouenFrance
  4. 4.Department of Nuclear MedicineBicetre Hospital AP-HP and University Paris SudOrsayFrance

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