Sarah Deschuymer1, Brita Singers Sørensen2, Rüveyda Dok3, Annouschka Laenen4, Esther Hauben5, Jens Overgaard2, Sandra Nuyts6,7. 1. Department of Radiation Oncology, University Hospitals Leuven, KU Leuven - University of Leuven, Herestraat 49, 3000, Leuven, Belgium. 2. Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark. 3. Laboratory of Experimental Radiotherapy, Department of Oncology, KU Leuven - University of Leuven, Leuven, Belgium. 4. Leuven Biostatistics and Statistical Bioinformatics Center, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium. 5. Department of Imaging and Pathology, University Hospitals Leuven, KU Leuven - University of Leuven, Leuven, Belgium. 6. Department of Radiation Oncology, University Hospitals Leuven, KU Leuven - University of Leuven, Herestraat 49, 3000, Leuven, Belgium. Sandra.nuyts@uzleuven.be. 7. Laboratory of Experimental Radiotherapy, Department of Oncology, KU Leuven - University of Leuven, Leuven, Belgium. Sandra.nuyts@uzleuven.be.
Abstract
PURPOSE: A 15-gene hypoxia classifier has been developed and validated as a predictive factor for patients with head and neck squamous cell carcinoma treated with radiotherapy and nimorazole. This paper aimed to investigate the role of this hypoxia classifier as a prognostic factor for patients with oropharyngeal cancer (OPC) treated with accelerated chemoradiotherapy. METHODS: P16 and 15-gene hypoxia classifier status, categorising tumours as more or less hypoxic, were determined for 136 OPC patients. Locoregional recurrence rate (LRR) and overall survival (OS) were estimated with cumulative incidence function and Kaplan-Meier method, respectively, stratified according to p16 and hypoxia status. RESULTS: P16-positive patients (34.6%) had significantly better LRR and OS than p16-negative patients. The 5‑year LRR of patients with more hypoxic OPC was similar to those with less hypoxic OPC in the overall patient population (27.3% versus 25.1%; p = 0.98; HR = 1.01 [CI95% 0.47;2.17]) and in the p16-negative OPC (36.4% versus 30.1%; p = 0.70; HR = 1.17 [CI95% 0.53;2.56]). No significant OS differences could be observed in neither p16-negative nor p16-positive subgroup with a 5-year OS for p16-negative more hypoxic OPC of 44.2% versus 49.0% in the less hypoxic OPC (p = 0.92; HR 0.97 [CI95% 0.51;1.84]). CONCLUSION: No significant outcome differences were observed between more or less hypoxic tumours, as determined by the 15-gene hypoxia classifier. These results suggest that the 15-gene hypoxia classifier may not have prognostic value in an OPC patient cohort treated with accelerated chemoradiotherapy.
PURPOSE: A 15-gene hypoxia classifier has been developed and validated as a predictive factor for patients with head and neck squamous cell carcinoma treated with radiotherapy and nimorazole. This paper aimed to investigate the role of this hypoxia classifier as a prognostic factor for patients with oropharyngeal cancer (OPC) treated with accelerated chemoradiotherapy. METHODS:P16 and 15-gene hypoxia classifier status, categorising tumours as more or less hypoxic, were determined for 136 OPC patients. Locoregional recurrence rate (LRR) and overall survival (OS) were estimated with cumulative incidence function and Kaplan-Meier method, respectively, stratified according to p16 and hypoxia status. RESULTS:P16-positive patients (34.6%) had significantly better LRR and OS than p16-negative patients. The 5‑year LRR of patients with more hypoxic OPC was similar to those with less hypoxic OPC in the overall patient population (27.3% versus 25.1%; p = 0.98; HR = 1.01 [CI95% 0.47;2.17]) and in the p16-negative OPC (36.4% versus 30.1%; p = 0.70; HR = 1.17 [CI95% 0.53;2.56]). No significant OS differences could be observed in neither p16-negative nor p16-positive subgroup with a 5-year OS for p16-negative more hypoxic OPC of 44.2% versus 49.0% in the less hypoxic OPC (p = 0.92; HR 0.97 [CI95% 0.51;1.84]). CONCLUSION: No significant outcome differences were observed between more or less hypoxic tumours, as determined by the 15-gene hypoxia classifier. These results suggest that the 15-gene hypoxia classifier may not have prognostic value in an OPC patient cohort treated with accelerated chemoradiotherapy.
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Keywords:
Accelerated radiotherapy; Biomarker; Chemoradiotherapy; Hypoxia gene classifier; Oropharyngeal cancer