ESTRO 2024 - Abstract Book

S1375

Clinical - Head & neck

ESTRO 2024

Germany, and German Cancer Consortium (DKTK), partner site Dresden, Dresden, Germany. 4 Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. 5 Department of Otorhinolaryngology, Faculty of Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. 6 Institute of Pathology, Faculty of Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. 7 German Cancer Research Center (DKFZ), Division of Radiooncology / Radiobiology, Heidelberg, Germany

Purpose/Objective:

Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) receiving adjuvant radiotherapy show a heterogenous therapy response, which may be explained by the different biological characteristics of the tumor. Previous studies have shown that the expression of cancer stem cell (CSC) markers, hypoxia-induced gene expression and the HPV status may serve as potential biomarkers for stratification of patients with locally advanced HNSCC that are at high risk to develop recurrences. This study aimed to explore whether these biomarkers may also serve as prognostic markers for the subgroup of patients with HNSCC with an intermediate risk profile who are receiving adjuvant radiotherapy.

Material/Methods:

In this retrospective study, patients with intermediate risk HNSCC who were treated with adjuvant radiotherapy between 2005 and 2020 were included. Patients were diagnosed with squamous cell carcinoma localized in the oral cavity (n=120), oropharynx (n=81) as well as hypopharynx (n=6) and larynx (n=19). The median follow-up was 5 years. Overexpression of the HPV surrogate marker p16 and the CSC marker CD44 were assessed by immunohistochemical staining. Further potential biomarkers (hypoxia related gene expression signatures and SLC3A2 gene expression) were studied by nanoString technology. Loco-regional control (LRC) was the primary and overall survival was the secondary endpoint. The impact of potential predictors on these endpoints was assessed by log-rank tests for categorical predictors and by univariable Cox regression for continuous predictors. Relevant predictors were combined in multivariable Cox regression.

Results:

Analyzing the clinical parameters, patients with larger tumors showed a significant lower LRC (p=0.030) and a statistical trend for lower OS (p=0.074) compared to patients with smaller tumors. Less favorable outcome was observed for patients with oral cavity tumors (LRC: p=0.086, OS: p=0.015) compared to other localizations. Patients, who are non-smokers showed longer OS (p<0.001) in univariable analyses compared to smokers. Patients with tumors overexpressing CSC markers (CD44 and/or SLC3A2) were found to have lower LRC (p=0.032, p=0.018) and shorter overall survival (p<0.001, p<0.001) after adjuvant radiotherapy. Tumor hypoxia was not significantly associated with LRC (p=0.088) but with shorter OS (p=0.007). p16 overexpression showed a statistical trend for improved LRC (p=0.054) and significantly improved OS (p<0.001). Multivariable analyses including tumor localization (oral cavity vs others), initial tumor size, p16 overexpression and expression of one of the cancer stem cell markers (SLC3A2 or CD44) revealed no significant independent effect for CSC expression with respect to LRC. However, we showed that these CSC markers (SLC3A2, p=0.015; CD44, p=0.005) are independent prognostic factors for overall survival.