Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Program Number: B036
Session Name: Poster Session
Tumor Genomics in Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma and Associated Survival Outcomes
Hannah Thomas, MD1; Danielle Arons, MD2; Andrey Loginov, PhD1; Erin Allor, BS1; Rebecca Krc, DO3; William Silva Mendes, MD3; Matthew J Ferris, MD3; Jason K Molitoris, MD, PhD3; Phuoc Tran, MD3; Ranee Mehra, MD4; Daria A Gaykalova, PhD1; 1University of Maryland School of Medicine; 2The Icahn School of Medicine at Mount Sinai; 3University of Maryland Department of Radiation Oncology; 4University of Maryland Division of Hematology/Oncology.jpg)
Introduction: Head and neck squamous cell carcinoma (HNSCC) prognosis has been correlated with several clinical factors, including gender, alcohol, smoking, and HPV status. Genomic studies done on HNSCC at the time of diagnosis have shown a correlation between treatment response and clinical outcome. However, there is limited data on the genetic profile of recurrent and metastatic (R/M) HNSCC. This study aimed to characterize further the genomic profiles of R/M HNSCC and its correlation to treatment response and survival.
Methods: We conducted a retrospective review of 86 patients with a diagnosis of R/M HNSCC who were treated with curative intent at our institution between 2007 and 2024. Targeted DNA sequencing was performed by Tempus. Clinical data was collected from the electronic health record. Five hundred twenty-six patients with primary HNSCC from The Cancer Genome Atlas (TCGA) were also included in our analysis.
Results: This study included 612 HNSCC patients. Clinical factors that were found to be associated with significantly lower overall survival were PD-L1 combined positive score (CPS) <1, primary nasopharyngeal site, female gender, and having a partial response or progression after the first line of therapy. The top 5 mutated genes in R/M HNSCC tumor samples were TP53, CDKN2A, TERT, FAT1, and KMT2D.
Univariate analysis of the local cohort showed mutations in CASP8, LRP1B, MTAP, and TP53 to be associated with significantly worse overall survival (OS). Mutations associated with significantly improved OS were PIK3CA and ARID1A. Multivariate Cox analysis was conducted controlling for age, sex, treatment response, primary site, and PD-L1 CPS <1. This revealed significantly lower OS associated with mutated LRP1B, CASP8, and MTAP. Despite having statistically significant hazard ratios, Kaplan-Meier curves showed no significant association between OS and any of these gene mutations.
Regarding progression-free survival (PFS), univariate Cox analysis showed significantly worse PFS with mutations of MTAP and TERT and improved PFS with CDKN2A, ARID2, and MYL1 mutations. In multivariate analysis, FGF4 mutations were associated with significantly worse PFS, while PFS improved with mutations in CDKN2A, ARID2, and PIK3CA. Kaplan-Meier analysis found mutations in ARID2 (p-value = 0.01145) and MYL1 (p-value = 0.00474) to be significantly associated with an improved PFS.
A similar analysis was performed in the TCGA cohort. Multivariate Cox analysis showed decreased OS with advanced age, stage, and TP53 mutations. Kaplan-Meier curves showed mutations in TP53 and CASP8 to be significantly associated with decreased OS.
Conclusion: Our data found multiple genetic mutations that were significantly associated with PFS and OS. Alterations in ARID2 and MYL1 correlated with improved PFS. These genes represent potential biomarkers for assessing R/M HNSCC outcomes. Further studies will be conducted to determine whether mutations are associated with response to therapy.