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HEAD AND NECK

Multiparametric functional MRI and 18F-FDG-PET for survival prediction in patients with head and neck squamous cell carcinoma treated with (chemo)radiation Roland M. Martens 1 & Thomas Koopman 1 & Cristina Lavini 2 & Meedie Ali 1 & Carel F. W. Peeters 3 & Daniel P. Noij 1 & Gerben Zwezerijnen 1 & J. Tim Marcus 1 & Marije R. Vergeer 4 & C. René Leemans 5 & Remco de Bree 6 & Pim de Graaf 1 & Ronald Boellaard 1 & Jonas A. Castelijns 1 Received: 21 May 2020 / Revised: 17 June 2020 / Accepted: 6 August 2020 # The Author(s) 2020

Abstract Objectives To assess (I) correlations between diffusion-weighted (DWI), intravoxel incoherent motion (IVIM), dynamic contrast-enhanced (DCE) MRI, and 18F-FDG-PET/CT imaging parameters capturing tumor characteristics and (II) their predictive value of locoregional recurrence-free survival (LRFS) and overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy. Methods Between 2014 and 2018, patients with histopathologically proven HNSCC, planned for curative (chemo) radiotherapy, were prospectively included. Pretreatment clinical, anatomical, and functional imaging parameters (obtained by DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT) were extracted for primary tumors (PT) and lymph node metastases. Correlations and differences between parameters were assessed. The predictive value of LRFS and OS was assessed, performing univariable, multivariable Cox and CoxBoost regression analyses. Results In total, 70 patients were included. Significant correlations between 18F-FDG-PET parameters and DWI-/DCE volume parameters were found (r > 0.442, p < 0.002). The combination of HPV (HR = 0.903), intoxications (HR = 1.065), PT ADCGTV (HR = 1.252), Ktrans (HR = 1.223), and Ve (HR = 1.215) was predictive for LRFS (C-index = 0.546; p = 0.023). N-stage (HR = 1.058), HPV positivity (HR = 0.886), hypopharyngeal tumor location (HR = 1.111), ADCGTV (HR = 1.102), ADCmean (HR = 1.137), D* (HR = 0.862), Ktrans (HR = 1.106), Ve (HR = 1.195), SUVmax (HR = 1.094), and TLG (HR = 1.433) were predictive for OS (C-index = 0.664; p = 0.046). Conclusions Functional imaging parameters, performing DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT, yielded complementary value in capturing tumor characteristics. More specific, intoxications, HPV-negative status, large tumor volume-related parameters, high permeability (Ktrans), and high extravascular extracellular space (Ve) parameters were predictive for adverse

Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00330-020-07163-3) contains supplementary material, which is available to authorized users. * Roland M. Martens [email protected] 1

Department of Radiology and Nuclear Medicine, Amsterdam UMC, De Boelelaan 1117, Amsterdam, The Netherlands

2

Department of Radiology and Nuclear Medicine, Amsterdam UMC, Meibergdreef 9, Amsterdam, The Netherlands

3

Department of Epidemiology and Biostatistics, Amsterdam UMC, De Boelelaan 1117, Amsterdam, The Netherlands

4

D