PET-based prognostic survival model after radiotherapy for head and neck cancer
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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.
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.
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.
KeywordsHead and neck cancer Nomogram Prognostic score PET Radiotherapy
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.
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 was obtained from all individual participants included in the study.
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedPubMedCentralGoogle Scholar
- 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.CrossRefPubMedPubMedCentralGoogle Scholar
- 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.CrossRefPubMedPubMedCentralGoogle Scholar
- 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.CrossRefPubMedPubMedCentralGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedPubMedCentralGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedPubMedCentralGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedPubMedCentralGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedPubMedCentralGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar