Circulating tumour DNA kinetics in recurrent/metastatic head and neck squamous cell cancer patients

Purpose: Immune checkpoint blockade (ICB) has become a standard of care in the treatment of recurrent/metastatic head and neck squamous cell cancer (R/M HNSCC). However, only a subset of patients benefit from treatment. Quantification of plasma circu-lating tumour DNA (ctDNA) levels and on-treatment kinetics may permit real-time assess-ment of disease burden under selective pressures of treatment.Patients and methods: R/M HNSCC patients treated with systemic therapy, platinum-based chemotherapy (CT) or ICB, underwent serial liquid biopsy sampling. Biomarkers tested in-cluded ctDNA measured by CAncer Personalized Profiling by deep Sequencing (CAPP-Seq) and markers of host inflammation measured by neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR).Results: Among 53 eligible patients, 16 (30%) received CT, 30 (57%) ICB [anti-PD1/L1] monotherapy and 7 (13%) combination immunotherapy (IO). Median progression-free sur-vival (PFS) and overall survival (OS) were 2.8 months (95% CI, 1.3-4.3) and 8.2 months (95% CI, 5.6-10.8), respectively. Seven (13%) patients experienced a partial response and 21 (40%) derived clinical benefit. At baseline, median ctDNA variant allele frequency (VAF) was 4.3%. Baseline ctDNA abundance was not associated with OS (p = 0.56) nor PFS (p = 0.54). However, a change in ctDNA VAF after one cycle of treatment (Delta VAF (T1-2)) was predictive of both PFS (p < 0.01) and OS (p < 0.01). Additionally, decrease in Delta VAF identified patients with longer OS despite early radiological progression, 8.2 vs 4.6 months, hazard ratio 0.44 (95% CI, 0.19-0.87) p = 0.03. After incorporating NLR and PLR into multivariable Cox models, ctDNA increment VAF retained an association with OS.Conclusions: Early dynamic changes in ctDNA abundance, after one cycle of treatment, compared to baseline predicted both OS and PFS in R/M HNSCC patients on systemic therapy.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).