Multiparametric functional MRI and 18F-FDG-PET for survival prediction in patients with head and neck squamous cell carcinoma treated with (chemo)radiation

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 ADC_GTV (HR = 1.252), K^trans (HR = 1.223), and V_e (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), ADC_GTV (HR = 1.102), ADC_mean (HR = 1.137), D* (HR = 0.862), K^trans (HR = 1.106), V_e (HR = 1.195), SUV_max (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 (K^trans), and high extravascular extracellular space (V_e) parameters were predictive for adverse locoregional recurrence-free survival and adverse overall survival. Low cellularity (high ADC) and high metabolism (high SUV) were additionally predictive for decreased overall survival. These different predictive factors added to estimated locoregional and overall survival.

Key points: • Parameters of DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT were able to capture complementary tumor characteristics. • Multivariable analysis revealed that intoxications, HPV negativity, large tumor volume and high vascular permeability (K^trans), and extravascular extracellular space (Ve) were complementary predictive for locoregional recurrence. • In addition to predictive parameters for locoregional recurrence, also high cellularity (low ADC) and high metabolism (high SUV) were complementary predictive for overall survival.

Keywords: Diffusion magnetic resonance imaging; Magnetic resonance imaging; Positron emission tomography computed tomography; Squamous cell carcinoma of head and neck; Survival analysis.

Fig. 1

The workflow in our prospective study including the inclusion of eligible patients, delineation of the primary tumor and lymph node metastases of the final included patients, the extraction of quantitative imaging parameters, and metastases predictive assessment of locoregional recurrence-free survival and overall survival using the extracted parameters of the primary tumor and lymph node

Fig. 2

Kaplan-Meier survival curves, which show the recurrence-free survival stratified for (a) T-stage and (b) for the recurrence risk score. In a, the recurrence-free survival is shown, which is not significantly predictive. In b, patients were given a risk score by the amount of risk factor points. These risk factors (each with a score of 1 point) were summed up when the predictive quantitative parameters that are higher than the median value of the quantitative parameter or positive clinical parameter (HPV, intoxications, hypopharyngeal PT location or N-stage > 1). The median value of quantitative parameters was calculated based on all included patients. This risk score stratification system is found significantly predictive. In c, the overall survival is shown, which is stratified for T-stage, which is not significant predictive. In d, the overall survival is shown, stratified for the risk score groups, which is found significantly predictive