Predicting head and neck cancer immunometabolic status using multiparametric PET/MRI in head and neck squamous cell carcinomas (REISSUE HNSCC)

• Applicants: Dr. Cornelius Kürten; Professor Dr. Benedikt M. Schaarschmidt
• Subject Area: Otolaryngology, Phoniatrics and Audiology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 534353826

Head and neck squamous cell carcinomas (HNSCC) are the 7th most prevalent tumor type globally, with causes including viral (human papillomavirus; HPV) and carcinogenic factors (smoking, alcohol). While standard therapy involves surgery radiation and/or chemotherapy, recent breakthroughs in immunotherapy have led to their integration into palliative care. However, overall response rates between 15-20% to immunotherapy demand the early identification of patients who will benefit most from immunotherapy remains a challenge. Here, two tumor immunophenotypes, "hot" and "cold," have been described. "Hot" tumors have robust immune cell infiltration and exhibit an immunologically active state, and "cold" tumors have limited immune cell infiltration and an immunosuppressive tumor microenvironment. While “hot” tumors tend to exhibit enhanced sensitivity to immunotherapies, “cold” tumors are adept at evading immune surveillance and are therefore generally less responsive to these kind of therapies. Although immunohistological analysis identifies these tumor type, this method is hampered by various limitations, most notably due to sampling errors. Here, novel imaging techniques capable of visualizing all tumor manifestations like 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) might useful. Especially the combined analysis of multiparametric information derived from PET as well as functional MRI datasets might aid patient selection for immunotherapy. However, knowledge gaps exist regarding the relationship between imaging biomarkers and the tumor immune status. Although recent studies have shown a negative correlation between 18F-FDG uptake and tumor immune status and indicate a correlation between low apparent diffusion coefficients (ADC) derived from functional MRI and a high T-cell influx, the clinical relevance of most studies in this field is limited by small patient cohorts. Therefore, the aim of this research endeavor is to investigate these initial leads in a high-quality, prospectively collected cohort of the InterSCCede PET/MRI study with histopathologically confirmed HNSCC. By investigating correlations between immunopathological parameters and imaging biomarkers derived from multiparametric PET/MRI, we aim to identify potential prognostic parameters for future, non-invasive treatment guidance.

• DFG Programme: Research Grants
• Co-Investigators: Professorin Dr. Jadwiga Jablonska-Koch; Professor Dr. Stephan Lang