Abstract 2419: Personalized longitudinal ctDNA monitoring is useful for biomarker in head and neck squamous cell carcinoma

Abstract Introduction: There is no established and useful tumor biomarker to evaluate treatment response and predict early locoregional and distant metastatic relapse in head and neck squamous cell carcinoma (HNSCC). Circulating tumor DNA (ctDNA) has a potential for detecting minimal residual diseases (MRDs). However, the absence of specific hotspot mutations in most HNSCCs makes ctDNA-based studies difficult in HNSCC. As a novel biomarker, we investigated whether individualized ctDNA analysis could help monitor and predict treatment response and relapse in HNSCC. Methods: Thirty-two HNSCC patients were enrolled in this study. Twenty-two patients received radical resection and 10 patients were received radical irradiation as initial curative treatment. We collected tumor tissues and paired PBMCs (peripheral blood mononuclear cells) before treatment. Furthermore, we collected serial plasma samples for ctDNA analysis. To identify tumor specific individualized mutation, we isolated DNA from tumor tissue and PBMC and performed mutation analysis using custom SCC panel with frequent altered 31 genes (all exon coverage). We defined tumor-specific mutated genes per patient with variant allele frequency (VAF) 10 % and total coverage 100 as ctDNA candidate genes and performed ctDNA analysis using dPCR. We generated mutation specific primer-probe for droplet digital PCR (ddPCR), quantified the amount of ctDNA in plasma and compared ctDNA level with clinical data. Results: For mutation analysis, most frequent mutated gene was TP53 (21/32, 65. 6%). Longitudinal ctDNA was monitored in a total of 24 cases. In 13 cases, ctDNA tested positive again or did not test negative, and all 13 cases had a residual tumor or relapsed after initial treatment. In 11 cases, after initial treatment, ctDNA remained negative and patients were alive without recurrence. Our cohort included 6 patients in whom it was possible to monitor ctDNA during chemotherapy in recurrent metastatic HNSCC cases. ctDNA alterations correlated well with clinical treatment response in four cases, but not in two cases. Patients who remained negative for ctDNA during follow-up after initial treatment (n=11) had a significantly better prognosis than those who reverted to ctDNA positivity (n=13, P 0. 0001). Conclusion: Custom SCC panel is useful to detect more tumor specific mutation in HNSCC patients. Detection of ctDNA using next generation sequencing and digital PCR is promising strategy capable of monitoring in HNSCC patients. However, this method is not useful in all HNSCC, and there is room for improvement in the selection of ctDNA candidate genes. Citation Format: Ryunosuke Kogo, Tomomi Manako, Takashi Nakagawa. Personalized longitudinal ctDNA monitoring is useful for biomarker in head and neck squamous cell carcinoma abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 2419.