Larynx preservation is a crucial goal in managing laryngeal/hypopharyngeal squamous cell carcinoma (LHSCC) due to its impact on the patient’s functionality. Currently, patient selection for larynx preservation versus total laryngectomy (TL) is based primarily on limited clinical and radiological criteria. While response to induction chemotherapy (IC) is the most significant prognostic factor for larynx preservation and survival, no predictive biomarker reliably differentiates patients who benefit from IC. Identifying biomarkers for IO response is essential for understanding immune resistance mechanisms and refining treatment strategies. Integrating clinical and biomolecular characteristics enhances patient selection for organ preservation.

Within a previous Era PerMed JTC 2020-funded PRESERVE project, we have developed a robust multi-omic (clinical and genomic) signature predicting IC response and identifying patients free from laryngo-esophageal dysfunction (LED). These insights drive a vision of personalised treatment, optimising IC or chemo-immunotherapy for efficacy and cost-efficiency.

The current project aims to define a tailored approach to locally advanced LHSCC, applying multiomic (clinical, genomic, pathomic) signatures to refine neoadjuvant strategies for surgical laryngeal preservation and curative radiotherapy. To assess functional outcomes, we will use LED-free survival as the primary endpoint—defined as survival with a functional larynx in place. We seek to validate prior findings, integrate pathomic data, and evaluate the impact of adding IO for patients with enriched immune profiles. Additionally, we will position preoperative IO within larynx preservation strategies and refine the “immune cold” subgroup to discover new therapeutic targets.