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

Montserrat Carles; Tobias Fechter; Anca L Grosu; Arnd Sörensen; Benedikt Thomann; Raluca G Stoian; Nicole Wiedenmann; Alexander Rühle; Constantinos Zamboglou; Juri Ruf; Luis Martí-Bonmatí; Dimos Baltas; Michael Mix; Nils H Nicolay

doi:10.3390/cancers13143449

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

Cancers (Basel). 2021 Jul 9;13(14):3449. doi: 10.3390/cancers13143449.

Authors

Montserrat Carles^{1

2

3}, Tobias Fechter^{1

2}, Anca L Grosu^{2

4}, Arnd Sörensen^{2

4}, Benedikt Thomann^{1

2}, Raluca G Stoian^{2

4}, Nicole Wiedenmann^{2

4}, Alexander Rühle^{2

4}, Constantinos Zamboglou^{2

4}, Juri Ruf^{2

4}, Luis Martí-Bonmatí³, Dimos Baltas^{1

2}, Michael Mix^{2

5}, Nils H Nicolay^{2

4}

Affiliations

¹ Department of Radiation Oncology, Division of Medical Physics, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.
² German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Partner Site Freiburg of the German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
³ La Fe Health Research Institute, Biomedical Imaging Research Group (GIBI230-PREBI) and Imaging La Fe node at Distributed Network for Biomedical Imaging (ReDIB) Unique Scientific and Technical Infrastructures (ICTS), 46026 Valencia, Spain.
⁴ Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.
⁵ Department of Nuclear Medicine, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.

Abstract

Tumor hypoxia is associated with radiation resistance and can be longitudinally monitored by ¹⁸F-fluoromisonidazole (¹⁸F-FMISO)-PET/CT. Our study aimed at evaluating radiomics dynamics of ¹⁸F-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 ¹⁸F-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 ¹⁸F-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 ¹⁸F-FMISO-derived hypoxia dynamics was able to predict outcome of HNSCC patients after CRT.

Keywords: 18F-FMISO-PET; head-and-neck squamous cell carcinoma and radiomics; hypoxia; radiotherapy response monitoring.

Abstract

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