Imaging Biomarkers Multiparametric 3 Tesla MRI and FMISO Hypoxia PET during Chemoradiotherapy in HNSCC and Their Relation to Outcome

Abstract

To prospectively assess in HNSCC patients the effect of chemoradiotherapy (CRT) on tumor hypoxia and tissue properties with [18F]FMISO PET/CT (FMISO PET) and multiparametric (mp) MRI at baseline and at an early (week 2) and late (week 5) time point during treatment and to analyze whether mpMRI and PET parameters are related with outcome. Patients with stage III to IVb HNSCC undergoing definitive CRT (total dose 70 Gy, 3 cycles of cisplatin over 7 weeks) were included. Patients were prospectively imaged with [18F]FDG PET/CT at baseline and with serial FMISO PET and serial 3 Tesla mpMRI for T1w-, T2w- as well as contrast-enhanced perfusion and diffusion-weighted measurements (ktrans, ve and apparent diffusion coefficient (ADC) maps) in weeks 0, 2 and 5. Patients were identified as responders or non-responders during follow-up regarding loco-regional control (LRC) and overall survival (OS). Tumor volumes were contoured and SUVmax FMISO PET and mean values for mpMRI parameters were compared between responders and non-responders with the t-test and Log Rank test at a significance level of p≤0.05. A complete set of serial FMISO PET data and 3 T MRI was available in 21 patients. Of those, 12 patients were diagnosed with local recurrence. Baseline tumor volume and FMISO-PET-derived tumor hypoxia (SUVmax FMISO) were higher among patients with local recurrence as compared to locally controlled patients (p=n.s.). On Kaplan-Meier analysis stratified at median change in SUVmax FMISO between weeks 0 to 5 (ΔFMISOwk0-5), LRC was higher for ΔFMISOwk0-5 > median (p=n.s.). For ADC, an increase was found from week 0 to 5 (responders > non-responders). LRC was significantly higher for patients with ΔADCwk0-5 and %ΔADCwk0-5 > median (Log Rank, p=0.04 and p=0.005). In perfusion MRI, ktrans increased from week 0 to 5 for both non-responders and responders (p=n.s.). For non-responders, ktrans reached a maximum at week 2, while for responders, ktrans showed a steady increase until week 5. Interstitial space volume fraction ve did not differ significantly between responders and non-responders and increased between week 0 and 5 (p=n.s.). Baseline ADC below median was significantly (p=0.013) correlated with improved OS. ADCweek2 below median was associated with improved OS (p=n.s.). Baseline ve below median was significantly correlated with improved OS (p=0.043) and associated with increased LRC (p=n.s.). Multiparametric MRI parameters ADC and interstitial space volume fraction ve obtained at baseline were significantly correlated with improved OS and an increase of ADC between week 0 to 5 was significantly correlated with improved LRC. FMISO-PET-derived tumor hypoxia and mean values of MRI parameters ktrans and ve differed between relapsing and non-relapsing patients, however without reaching statistical significance in this cohort. The correlations found for ve and ADC may suggest predictive power for OS and LRC depending on baseline imaging and the dynamics of ADC.