Clinical, molecular, and immunologic profiling of brain metastases (BM) in head and neck squamous cell carcinoma (HNSCC).

• DOI: 10.1200/jco.2024.42.16_suppl.6036
• Publication Date: 2024-06-10T16:19:53Z
• Authors: Michael J. Dennis; Dean Pavlick; Alec Kacew; Michael Wotman; Laura E MacConaill; Stephanie M Jones; Kathleen L. Pfaff; Scott J. Rodig; Emily Reister; Maika Malig; Stephen Eacker; David Eric Piccioni; Santosh Kesari; Kartik Sehgal; Robert I. Haddad; Ezra Cohen; Marshall R. Posner; Ida Deichaite; Glenn J. Hanna
• Keywords: Profiling (computer programming)

6036 Background: BM is a rare complication of HNSCC that carries high rate morbidity and poor prognosis. Clinical risk factors, molecular characteristics, the immunogenicity are not well defined, leaving critical knowledge gap in this field. We performed one largest multi-institutional analyses summarizing clinical, molecular, immunologic profile 61 cases BM-HNSCC. Methods: conducted pooled analysis clinical characteristics pertaining to BM-HNSCC from 3 academic institutions (n=24). Next-generation sequencing (NGS) immune profiling (IP) primary specimens was on subset (n=19 n=16, respectively); there were paired samples for NGS 0 IP. Four (2 2 non-BM) submitted Phase Genomics, Inc evaluation structural variants genomes by proximity ligation (PLS). These results complimented comparative genomic alterations an additional cohort (n=37) local (n=4082) at Foundation Medicine, (FMI). Statistical comparisons done using Fisher’s exact testing 2x2 contingency tables with p-values controlled FDR Benjamini-Hochberg procedure. Results: features as follows: median age diagnosis 59 years, 75% male, 55% current/former smokers, oropharyngeal primary, 84% HPV+ or p16+. The most frequently altered genes (62% HPV/p16+) ATM (54%), KMT2A PTEN (46%), RB1 TP53 (46%). non-BM demonstrated significant levels rearrangement ranging 9 90 PLS. IP identified lower densities CD8+, PD1+, PDL1+, FOXP3+ cells BMs compared tumors. PDL1 combined positive scores <1% 12/13 unpaired (92%; 10 primary). FMI (51% HPV+) CDKN2A (40.5%), (37.8%), PIK3CA (27.0%) genes. Enrichment showed MAP2K2 significantly enriched (11.8% vs 6.4%, P=0.005) TSC1 site (67.3% 37.8%, P=0.008). also (51.25% 26.11%, P=0.001). Overall survival 6m (range 0-27m). Conclusions: patients have higher-than-expected proportions HPV/p16-positivity. frequent commonly found HNSCC, including targetable alterations. samples, which warrants further investigation. tended markers immunogenicity. This latter finding could important implications when considering immunotherapy immune-modulating drugs.