Effect of co-occurring TP53 and intracellular proliferation pathway mutations on disease recurrence and survival benefits in head and neck cancers.

Abstract

e18046 Background: Head and neck cancer (HNC) is often driven by genetic alterations, particularly co-occurring mutations in TP53 gene and key proliferation pathways. Offering continuous low-dose treatment (Oral metronomic chemotherapy) has shown potential in improving survival outcomes by minimizing toxicity while also targeting cellular molecular drivers. However, treatment of HNC remains challenging due to factors such as tumor heterogeneity, late-stage diagnosis, and treatment resistance. Recurrence in HNC is often due to the presence of residual or drug-resistant tumor cells that poses significant challenges to long-term survival. This study focuses on the genomic profiles of patients with disease recurrence and their association with survival benefits of adjuvant therapy. Methods: We investigated the molecular profiles of 22 HNC patients in adjunct with clinical follow-up data. A total of twenty-one patients had previously undergone surgery and 14 patients had disease recurrence. 6 patients had oral metronomic chemotherapy (OMCT) of which 4 had a combination of nivolumab. 3 patients were also undergoing maintenance immunotherapy. Next Generation Sequencing (NGS) test was performed using OncoIndx Assay (Aarthi et al., 2024). Results: Molecular analysis of 63.6% (n=14) of patients who were reported with clinical recurrence were continued with further treatment. 21.4% (n=3/14) of patients with recurrence were detected with compound TP53 mutations while 64.3% (n=9/14) showed co-occurrence of TP53 mutations with cell progression and intracellular proliferation pathway alterations. 92.9% (n=13/14) of patients with recurrence also showed positive PD-L1 expression. Interestingly, genomic profiling of patients under OMCT showed co-occurrence of TP53 with cell progression (CDKN2A) and intracellular proliferation pathway alterations (MYC, NRAS, KRAS) in 83.3% (n=5/6) patients indicating survival benefits. Conclusions: Although cell proliferative mutations were found predominant in patients with recurrence, it only included downstream intracellular proliferative genes and not cell surface receptors like EGFR. Thus, co-occurrence of TP53 mutations with key proliferative pathways were not only indicative of recurrence but also suggestive of treatment benefits from OMCT in the study cohort since all patients showed overall survival between 8 months to more than 4 years.