(18)F-FMISO-PET Hypoxia Monitoring for Head-and-Neck Cancer Patients: Radiomics Analyses Predict the Outcome of Chemo-Radiotherapy

SIMPLE SUMMARY: In this study, we monitored FMISO-hypoxia during chemo-radiotherapy (CRT) in head-and-neck cancer patients and we aimed to develop a radiomics model for prediction of treatment outcome. The protocol for the prospective patient cohort (N = 35) involved FMISO-PET/CT imaging at three time-points during treatment (weeks 0, 2 and 5). FMISO-hypoxia monitoring was quantified in terms of variations in the size, in the location and in the radiomics features (delta radiomics) of the hypoxia subvolume within the tumor. Local recurrence, distant metastasis, overall survival and progression free survival were employed for the characterization of CRT outcome. ABSTRACT: Tumor hypoxia is associated with radiation resistance and can be longitudinally monitored by (18)F-fluoromisonidazole ((18)F-FMISO)-PET/CT. Our study aimed at evaluating radiomics dynamics of (18)F-FMISO-hypoxia imaging during chemo-radiotherapy (CRT) as predictors for treatment outcome in head-and-neck squamous cell carcinoma (HNSCC) patients. We prospectively recruited 35 HNSCC patients undergoing definitive CRT and longitudinal (18)F-FMISO-PET/CT scans at weeks 0, 2 and 5 (W0/W2/W5). Patients were classified based on peritherapeutic variations of the hypoxic sub-volume (HSV) size (increasing/stable/decreasing) and location (geographically-static/geographically-dynamic) by a new objective classification parameter (CP) accounting for spatial overlap. Additionally, 130 radiomic features (RF) were extracted from HSV at W0, and their variations during CRT were quantified by relative deviations (∆(RF)). Prediction of treatment outcome was considered statistically relevant after being corrected for multiple testing and confirmed for the two (18)F-FMISO-PET/CT time-points and for a validation cohort. HSV decreased in 64% of patients at W2 and in 80% at W5. CP distinguished earlier disease progression (geographically-dynamic) from later disease progression (geographically-static) in both time-points and cohorts. The texture feature low grey-level zone emphasis predicted local recurrence with AUC(W2) = 0.82 and AUC(W5) = 0.81 in initial cohort (N = 25) and AUC(W2) = 0.79 and AUC(W5) = 0.80 in validation cohort. Radiomics analysis of (18)F-FMISO-derived hypoxia dynamics was able to predict outcome of HNSCC patients after CRT.