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PET-based prognostic survival model after radiotherapy for head and neck cancer

  • Joël CastelliEmail author
  • A. Depeursinge
  • A. Devillers
  • B. Campillo-Gimenez
  • Y. Dicente
  • J. O. Prior
  • E. Chajon
  • F. Jegoux
  • C. Sire
  • O. Acosta
  • E. Gherga
  • X. Sun
  • B. De Bari
  • J. Bourhis
  • R. de Crevoisier
Original Article
  • 178 Downloads

Abstract

Purpose

The aims of this multicentre retrospective study of locally advanced head and neck cancer (LAHNC) treated with definitive radiotherapy were to (1) identify positron emission tomography (PET)-18F-fluorodeoxyglucose (18F-FDG) parameters correlated with overall survival (OS) in a training cohort, (2) compute a prognostic model, and (3) externally validate this model in an independent cohort.

Materials and methods

A total of 237 consecutive LAHNC patients divided into training (n = 127) and validation cohorts (n = 110) were retrospectively analysed. The following PET parameters were analysed: SUVMax, metabolic tumour volume (MTV), total lesion glycolysis (TLG), and SUVMean for the primary tumour and lymph nodes using a relative SUVMax threshold or an absolute SUV threshold. Cox analyses were performed on OS in the training cohort. The c-index was used to identify the highly prognostic parameters. A prognostic model was subsequently identified, and a nomogram was generated. The model was externally tested in the validation cohort.

Results

In univariate analysis, the significant PET parameters for the primary tumour included MTV (relative thresholds from 6 to 83% and absolute thresholds from 1.5 to 6.5) and TLG (relative thresholds from 1 to 82% and absolute thresholds from 0.5 to 4.5). For the lymph nodes, the significant parameters included MTV and TLG regardless of the threshold value. In multivariate analysis, tumour site, p16 status, MTV35% of the primary tumour, and MTV44% of the lymph nodes were independent predictors of OS. Based on these four parameters, a prognostic model was identified with a c-index of 0.72. The corresponding nomogram was generated. This prognostic model was externally validated, achieving a c-index of 0.66.

Conclusions

A prognostic model of OS based on primary tumour and lymph node MTV, tumour site, and p16 status was proposed and validated. The corresponding nomogram may be used to tailor individualized treatment.

Keywords

Head and neck cancer Nomogram Prognostic score PET Radiotherapy 

Notes

Funding

This work was partly supported by the Swiss National Science Foundation with grant agreement PZ00P2_154891 and 205320_179069 (A. Depeursinge).

Compliance with ethical standards

Conflict of interest

All authors declare no conflicts of interest.

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 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

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

Supplementary material

259_2018_4134_MOESM1_ESM.docx (217 kb)
ESM 1 (DOCX 217 kb)

References

  1. 1.
    Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17:1471–4.  https://doi.org/10.1245/s10434-010-0985-4.CrossRefGoogle Scholar
  2. 2.
    Pignon JP, Bourhis J, Domenge C, Designe L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-analysis of chemotherapy on head and neck cancer. Lancet. 2000;355:949–55.CrossRefGoogle Scholar
  3. 3.
    Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefebvre JL, Greiner RH, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004;350:1945–52.  https://doi.org/10.1056/NEJMoa032641.CrossRefGoogle Scholar
  4. 4.
    Bourhis J, Sire C, Graff P, Gregoire V, Maingon P, Calais G, et al. Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial. Lancet Oncol. 2012;13:145–53.  https://doi.org/10.1016/s1470-2045(11)70346-1.CrossRefGoogle Scholar
  5. 5.
    Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010;11:21–8.  https://doi.org/10.1016/s1470-2045(09)70311-0.CrossRefGoogle Scholar
  6. 6.
    Chajon E, Lafond C, Louvel G, Castelli J, Williaume D, Henry O, et al. Salivary gland-sparing other than parotid-sparing in definitive head-and-neck intensity-modulated radiotherapy does not seem to jeopardize local control. Radiat Oncol. 2013;8:132.  https://doi.org/10.1186/1748-717x-8-132.CrossRefGoogle Scholar
  7. 7.
    Schwartz DL, Harris J, Yao M, Rosenthal DI, Opanowski A, Levering A, et al. Metabolic tumor volume as a prognostic imaging-based biomarker for head-and-neck cancer: pilot results from radiation therapy oncology group protocol 0522. Int J Radiat Oncol Biol Phys. 2015;91:721–9.  https://doi.org/10.1016/j.ijrobp.2014.12.023.CrossRefGoogle Scholar
  8. 8.
    Moon SH, Choi JY, Lee HJ, Son YI, Baek CH, Ahn YC, et al. Prognostic value of volume-based positron emission tomography/computed tomography in patients with nasopharyngeal carcinoma treated with concurrent chemoradiotherapy. Clin Exp Otorhinolaryngol. 2015;8:142–8.  https://doi.org/10.3342/ceo.2015.8.2.142.CrossRefGoogle Scholar
  9. 9.
    Cacicedo J, Navarro A, Del Hoyo O, Gomez-Iturriaga A, Alongi F, Medina JA, et al. Role of [18F] fluorodeoxyglucose PET/CT in head and neck oncology: the point of view of the radiation oncologist. Br J Radiol. 2016;89:20160217.  https://doi.org/10.1259/bjr.20160217.CrossRefGoogle Scholar
  10. 10.
    Castelli J, Depeursinge A, de Bari B, Devillers A, de Crevoisier R, Bourhis J, et al. Metabolic tumor volume and total lesion glycolysis in oropharyngeal cancer treated with definitive radiotherapy: which threshold is the best predictor of local control? Clin Nucl Med. 2017;42:e281–e5.  https://doi.org/10.1097/rlu.0000000000001614.CrossRefGoogle Scholar
  11. 11.
    Schinagl DA, Span PN, Oyen WJ, Kaanders JH. Can FDG PET predict radiation treatment outcome in head and neck cancer? Results of a prospective study. Eur J Nucl Med Mol Imaging. 2011;38:1449–58.  https://doi.org/10.1007/s00259-011-1789-x.CrossRefGoogle Scholar
  12. 12.
    Kao CH, Lin SC, Hsieh TC, Yen KY, Yang SN, Wang YC, et al. Use of pretreatment metabolic tumour volumes to predict the outcome of pharyngeal cancer treated by definitive radiotherapy. Eur J Nucl Med Mol Imaging. 2012;39:1297–305.  https://doi.org/10.1007/s00259-012-2127-7.CrossRefGoogle Scholar
  13. 13.
    Cheng NM, Fang YH, Lee LY, Chang JT, Tsan DL, Ng SH, et al. Zone-size nonuniformity of 18F-FDG PET regional textural features predicts survival in patients with oropharyngeal cancer. Eur J Nucl Med Mol Imaging. 2015;42:419–28.  https://doi.org/10.1007/s00259-014-2933-1.CrossRefGoogle Scholar
  14. 14.
    Lin YC, Chen SW, Hsieh TC, Yen KY, Yang SN, Wang YC, et al. Risk stratification of metastatic neck nodes by CT and PET in patients with head and neck cancer receiving definitive radiotherapy. J Nucl Med. 2015;56:183–9.  https://doi.org/10.2967/jnumed.114.148023.CrossRefGoogle Scholar
  15. 15.
    Yabuki K, Shiono O, Komatsu M, Sano D, Nishimura G, Takahashi M, et al. Predictive and prognostic value of metabolic tumor volume (MTV) in patients with laryngeal carcinoma treated by radiotherapy (RT) /concurrent chemoradiotherapy (CCRT). PLoS One. 2015;10:e0117924.  https://doi.org/10.1371/journal.pone.0117924.CrossRefGoogle Scholar
  16. 16.
    Abgral R, Keromnes N, Robin P, Le Roux PY, Bourhis D, Palard X, et al. Prognostic value of volumetric parameters measured by 18F-FDG PET/CT in patients with head and neck squamous cell carcinoma. Eur J Nucl Med Mol Imaging. 2014;41:659–67.  https://doi.org/10.1007/s00259-013-2618-1.CrossRefGoogle Scholar
  17. 17.
    Abgral R, Valette G, Robin P, Rousset J, Keromnes N, Le Roux PY, et al. Prognostic evaluation of percentage variation of metabolic tumor burden calculated by dual-phase (18) FDG PET-CT imaging in patients with head and neck cancer. Head Neck. 2016; 38(Suppl 1:E600-6.  https://doi.org/10.1002/hed.24048.CrossRefGoogle Scholar
  18. 18.
    Park GC, Kim JS, Roh JL, Choi SH, Nam SY, Kim SY. Prognostic value of metabolic tumor volume measured by 18F-FDG PET/CT in advanced-stage squamous cell carcinoma of the larynx and hypopharynx. Ann Oncol. 2013;24:208–14.  https://doi.org/10.1093/annonc/mds247.CrossRefGoogle Scholar
  19. 19.
    Mohan R, Wu Q, Manning M, Schmidt-Ullrich R. Radiobiological considerations in the design of fractionation strategies for intensity-modulated radiation therapy of head and neck cancers. Int J Radiat Oncol Biol Phys. 2000;46:619–30.CrossRefGoogle Scholar
  20. 20.
    Lee N, Chuang C, Quivey JM, Phillips TL, Akazawa P, Verhey LJ, et al. Skin toxicity due to intensity-modulated radiotherapy for head-and-neck carcinoma. Int J Radiat Oncol Biol Phys. 2002;53:630–7.CrossRefGoogle Scholar
  21. 21.
    Dicente Cid Y, Castelli J, Schaer R, Scher N, Pomoni A, Prior JO, et al. Chapter 12 — Quantimage: an online tool for high-throughput 3D radiomics feature extraction in PET-CT. In: Depeursinge A, Al-Kadi OS, Mitchell JR (Eds) Biomedical texture analysis: London, Academic; 2017. pp 349-77.Google Scholar
  22. 22.
    Schemper M, Smith TL. A note on quantifying follow-up in studies of failure time. Control Clin Trials. 1996;17:343–6.CrossRefGoogle Scholar
  23. 23.
    Collins GS, Reitsma JB, Altman DG, Moons KG. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement. Br J Cancer. 2015;112:251–9.  https://doi.org/10.1038/bjc.2014.639.CrossRefGoogle Scholar
  24. 24.
    Harrell FE, Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med. 1996;15:361–87.  https://doi.org/10.1002/(SICI)1097-0258(19960229)15:4<361::AID-SIM168>3.0.CO;2-4.CrossRefGoogle Scholar
  25. 25.
    Efron B, Gong G. A leisurely look at the bootstrap, the jackknife, and cross-validation. Am Stat. 1983;37:36–48.  https://doi.org/10.2307/2685844.Google Scholar
  26. 26.
    Castelli J, De Bari B, Depeursinge A, Simon A, Devillers A, Roman Jimenez G, et al. Overview of the predictive value of quantitative 18 FDG PET in head and neck cancer treated with chemoradiotherapy. Crit Rev Oncol Hematol. 2016;108:40–51.  https://doi.org/10.1016/j.critrevonc.2016.10.009.CrossRefGoogle Scholar
  27. 27.
    Bonomo P, Merlotti A, Olmetto E, Bianchi A, Desideri I, Bacigalupo A, et al. What is the prognostic impact of FDG PET in locally advanced head and neck squamous cell carcinoma treated with concomitant chemo-radiotherapy? A systematic review and meta-analysis. Eur J Nucl Med Mol Imaging. 2018.  https://doi.org/10.1007/s00259-018-4065-5.
  28. 28.
    Apostolova I, Steffen IG, Wedel F, Lougovski A, Marnitz S, Derlin T, et al. Asphericity of pretherapeutic tumour FDG uptake provides independent prognostic value in head-and-neck cancer. Eur Radiol. 2014;24:2077–87.  https://doi.org/10.1007/s00330-014-3269-8.CrossRefGoogle Scholar
  29. 29.
    Castelli J, Depeursinge A, Ndoh V, Prior JO, Ozsahin M, Devillers A, et al. A PET-based nomogram for oropharyngeal cancers. Eur J Cancer. 2017;75:222–30.  https://doi.org/10.1016/j.ejca.2017.01.018.CrossRefGoogle Scholar
  30. 30.
    Tang C, Murphy JD, Khong B, La TH, Kong C, Fischbein NJ, et al. Validation that metabolic tumor volume predicts outcome in head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2012;83:1514–20.  https://doi.org/10.1016/j.ijrobp.2011.10.023.CrossRefGoogle Scholar
  31. 31.
    Hofheinz F, Lougovski A, Zophel K, Hentschel M, Steffen IG, Apostolova I, et al. Increased evidence for the prognostic value of primary tumor asphericity in pretherapeutic FDG PET for risk stratification in patients with head and neck cancer. Eur J Nucl Med Mol Imaging. 2015;42:429–37.  https://doi.org/10.1007/s00259-014-2953-x.CrossRefGoogle Scholar
  32. 32.
    Royston P, Altman DG. External validation of a Cox prognostic model: principles and methods. BMC Med Res Methodol. 2013;13:33.  https://doi.org/10.1186/1471-2288-13-33.CrossRefGoogle Scholar
  33. 33.
    Murphy JD, La TH, Chu K, Quon A, Fischbein NJ, Maxim PG, et al. Postradiation metabolic tumor volume predicts outcome in head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2011;80:514–21.  https://doi.org/10.1016/j.ijrobp.2010.01.057.CrossRefGoogle Scholar
  34. 34.
    Moon SH, Choi JY, Lee HJ, Son YI, Baek CH, Ahn YC, et al. Prognostic value of 18F-FDG PET/CT in patients with squamous cell carcinoma of the tonsil: comparisons of volume-based metabolic parameters. Head Neck. 2013;35:15–22.  https://doi.org/10.1002/hed.22904.CrossRefGoogle Scholar
  35. 35.
    Castelli J, Depeursinge A, de Bari B, Devillers A, de Crevoisier R, Bourhis J, et al. Metabolic tumor volume and total lesion glycolysis in oropharyngeal cancer treated with definitive radiotherapy: which threshold is the best predictor of local control? Clin Nucl Med. 2017;42(6):e281–e285.  https://doi.org/10.1097/RLU.0000000000001614.CrossRefGoogle Scholar
  36. 36.
    Akagunduz OO, Savas R, Yalman D, Kocacelebi K, Esassolak M. Can adaptive threshold-based metabolic tumor volume (MTV) and lean body mass corrected standard uptake value (SUL) predict prognosis in head and neck cancer patients treated with definitive radiotherapy/chemoradiotherapy? Nucl Med Biol. 2015;42:899–904.  https://doi.org/10.1016/j.nucmedbio.2015.06.007.CrossRefGoogle Scholar
  37. 37.
    Cheng NM, Fang YH, Chang JT, Huang CG, Tsan DL, Ng SH, et al. Textural features of pretreatment 18F-FDG PET/CT images: prognostic significance in patients with advanced T-stage oropharyngeal squamous cell carcinoma. J Nucl Med. 2013;54:1703–9.  https://doi.org/10.2967/jnumed.112.119289.CrossRefGoogle Scholar
  38. 38.
    Hanamoto A, Tatsumi M, Takenaka Y, Hamasaki T, Yasui T, Nakahara S, et al. Volumetric PET/CT parameters predict local response of head and neck squamous cell carcinoma to chemoradiotherapy. Cancer Med. 2014;3:1368–76.  https://doi.org/10.1002/cam4.295.CrossRefGoogle Scholar
  39. 39.
    Hentschel M, Appold S, Schreiber A, Abolmaali N, Abramyuk A, Dorr W, et al. Early FDG PET at 10 or 20 Gy under chemoradiotherapy is prognostic for locoregional control and overall survival in patients with head and neck cancer. Eur J Nucl Med Mol Imaging. 2011;38:1203–11.  https://doi.org/10.1007/s00259-011-1759-3.CrossRefGoogle Scholar
  40. 40.
    Alluri KC, Tahari AK, Wahl RL, Koch W, Chung CH, Subramaniam RM. Prognostic value of FDG PET metabolic tumor volume in human papillomavirus-positive stage III and IV oropharyngeal squamous cell carcinoma. AJR Am J Roentgenol. 2014;203:897–903.  https://doi.org/10.2214/AJR.14.12497.CrossRefGoogle Scholar
  41. 41.
    Lin P, Min M, Lee M, Holloway L, Forstner D, Bray V, et al. Nodal parameters of FDG PET/CT performed during radiotherapy for locally advanced mucosal primary head and neck squamous cell carcinoma can predict treatment outcomes: SUVmean and response rate are useful imaging biomarkers. Eur J Nucl Med Mol Imaging. 2017;44(5):801-811  https://doi.org/10.1007/s00259-016-3584-1.CrossRefGoogle Scholar
  42. 42.
    Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.  https://doi.org/10.1016/j.ejca.2008.10.026.CrossRefGoogle Scholar
  43. 43.
    Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomark Prev. 2005;14:467–75.  https://doi.org/10.1158/1055-9965.EPI-04-0551.CrossRefGoogle Scholar
  44. 44.
    Mehanna H, Beech T, Nicholson T, El-Hariry I, McConkey C, Paleri V, et al. Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer--systematic review and meta-analysis of trends by time and region. Head Neck. 2013;35:747–55.  https://doi.org/10.1002/hed.22015.CrossRefGoogle Scholar
  45. 45.
    Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363:24–35.  https://doi.org/10.1056/NEJMoa0912217.CrossRefGoogle Scholar
  46. 46.
    Kendi AT, Magliocca K, Corey A, Nickleach DC, Galt J, Higgins K, et al. Do 18F-FDG PET/CT parameters in oropharyngeal and oral cavity squamous cell carcinomas indicate HPV status? Clin Nucl Med. 2015;40:e196–200.  https://doi.org/10.1097/rlu.0000000000000691.CrossRefGoogle Scholar
  47. 47.
    Brizel DM, Sibley GS, Prosnitz LR, Scher RL, Dewhirst MW. Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 1997;38:285–9.CrossRefGoogle Scholar
  48. 48.
    Graves EE, Hicks RJ, Binns D, Bressel M, Le Q-T, Peters L, et al. Quantitative and qualitative analysis of [(18)F] FDG and [(18)F] FAZA positron emission tomography of head and neck cancers and associations with HPV status and treatment outcome. Eur J Nucl Med Mol Imaging. 2016;43:617–25.  https://doi.org/10.1007/s00259-015-3247-7.CrossRefGoogle Scholar
  49. 49.
    Beck R, Roper B, Carlsen JM, Huisman MC, Lebschi JA, Andratschke N, et al. Pretreatment 18F-FAZA PET predicts success of hypoxia-directed radiochemotherapy using tirapazamine. J Nucl Med. 2007;48:973–80.  https://doi.org/10.2967/jnumed.106.038570.CrossRefGoogle Scholar
  50. 50.
    Thorwarth D, Eschmann SM, Holzner F, Paulsen F, Alber M. Combined uptake of [18F] FDG and [18F] FMISO correlates with radiation therapy outcome in head-and-neck cancer patients. Radiother Oncol. 2006;80:151–6.  https://doi.org/10.1016/j.radonc.2006.07.033.CrossRefGoogle Scholar
  51. 51.
    Kikuchi M, Koyasu S, Shinohara S, Usami Y, Imai Y, Hino M, et al. Prognostic value of pretreatment 18F-fluorodeoxyglucose positron emission tomography/CT volume-based parameters in patients with oropharyngeal squamous cell carcinoma with known p16 and p53 status. Head Neck. 2015;37:1524–31.  https://doi.org/10.1002/hed.23784.CrossRefGoogle Scholar
  52. 52.
    Romesser PB, Qureshi MM, Shah BA, Chatburn LT, Jalisi S, Devaiah AK, et al. Superior prognostic utility of gross and metabolic tumor volume compared to standardized uptake value using PET/CT in head and neck squamous cell carcinoma patients treated with intensity-modulated radiotherapy. Ann Nucl Med. 2012;26:527–34.  https://doi.org/10.1007/s12149-012-0604-5.CrossRefGoogle Scholar
  53. 53.
    Arens AI, Troost EG, Hoeben BA, Grootjans W, Lee JA, Gregoire V, et al. Semiautomatic methods for segmentation of the proliferative tumour volume on sequential FLT PET/CT images in head and neck carcinomas and their relation to clinical outcome. Eur J Nucl Med Mol Imaging. 2014;41:915–24.  https://doi.org/10.1007/s00259-013-2651-0.CrossRefGoogle Scholar
  54. 54.
    Kaalep A, Sera T, Oyen W, Krause BJ, Chiti A, Liu Y, et al. EANM/EARL FDG-PET/CT accreditation — summary results from the first 200 accredited imaging systems. Eur J Nucl Med Mol Imaging. 2018;45:412–22.  https://doi.org/10.1007/s00259-017-3853-7.CrossRefGoogle Scholar
  55. 55.
    Brun E, Kjellen E, Tennvall J, Ohlsson T, Sandell A, Perfekt R, et al. FDG PET studies during treatment: prediction of therapy outcome in head and neck squamous cell carcinoma. Head Neck. 2002;24:127–35.CrossRefGoogle Scholar
  56. 56.
    Chen SW, Hsieh TC, Yen KY, Yang SN, Wang YC, Chien CR, et al. Interim FDG PET/CT for predicting the outcome in patients with head and neck cancer. Laryngoscope. 2014;124:2732–8.  https://doi.org/10.1002/lary.24826.CrossRefGoogle Scholar
  57. 57.
    Min M, Lin P, Lee MT, Shon IH, Lin M, Forstner D, et al. Prognostic role of metabolic parameters of (18)F-FDG PET-CT scan performed during radiation therapy in locally advanced head and neck squamous cell carcinoma. Eur J Nucl Med Mol Imaging. 2015;42:1984–94.  https://doi.org/10.1007/s00259-015-3104-8.CrossRefGoogle Scholar
  58. 58.
    Leijenaar RT, Carvalho S, Hoebers FJ, Aerts HJ, van Elmpt WJ, Huang SH, et al. External validation of a prognostic CT-based radiomic signature in oropharyngeal squamous cell carcinoma. Acta Oncol. 2015;54:1423–9.  https://doi.org/10.3109/0284186x.2015.1061214.CrossRefGoogle Scholar
  59. 59.
    Min M, Lin P, Liney G, Lee M, Forstner D, Fowler A, et al. A review of the predictive role of functional imaging in patients with mucosal primary head and neck cancer treated with radiation therapy. J Med Imaging Radiat Oncol. 2017;61:99–123.  https://doi.org/10.1111/1754-9485.12496.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Joël Castelli
    • 1
    • 2
    • 3
    Email author
  • A. Depeursinge
    • 4
    • 5
  • A. Devillers
    • 6
  • B. Campillo-Gimenez
    • 2
    • 3
    • 7
  • Y. Dicente
    • 4
    • 8
  • J. O. Prior
    • 9
  • E. Chajon
    • 1
  • F. Jegoux
    • 10
  • C. Sire
    • 11
  • O. Acosta
    • 2
    • 3
  • E. Gherga
    • 12
  • X. Sun
    • 12
    • 13
  • B. De Bari
    • 13
  • J. Bourhis
    • 14
  • R. de Crevoisier
    • 1
    • 2
    • 3
  1. 1.Radiotherapy DepartmentCancer Institute Eugène MarquisRennesFrance
  2. 2.INSERM, U1099RennesFrance
  3. 3.University of Rennes 1, LTSIRennesFrance
  4. 4.Ecole Polytechnique Fédérale de LausanneLausanneSwitzerland
  5. 5.University of Applied Sciences Western SwitzerlandSierreSwitzerland
  6. 6.Nuclear Medicine DepartmentCancer Institute Eugène MarquisRennesFrance
  7. 7.Clinical Research DirectionCancer Institute Eugène MarquisRennesFrance
  8. 8.University of GenevaGenevaSwitzerland
  9. 9.Nuclear Medicine and Molecular Imaging DepartmentLausanne University HospitalLausanneSwitzerland
  10. 10.Head and Neck DepartmentCHU RennesRennesFrance
  11. 11.Radiotherapy DepartmentLorient HospitalLorientFrance
  12. 12.Radiotherapy DepartmentCHU BesançonBesançonFrance
  13. 13.Radiotherapy DepartmentHôpital Nord Franche Comté MontbéliardMontbéliardFrance
  14. 14.Radiotherapy DepartmentLausanne University HospitalLausanneSwitzerland

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