Abstract
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 circulating tumour DNA (ctDNA) levels and on-treatment kinetics may permit real-time assessment 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 included 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 survival (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 (ΔVAF (T1–2)) was predictive of both PFS (p< 0.01) and OS (p< 0.01). Additionally, decrease in ΔVAF 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 ∆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.
Original language | English |
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Pages (from-to) | 29-38 |
Number of pages | 10 |
Journal | European Journal of Cancer |
Volume | 188 |
Early online date | 12 May 2023 |
DOIs | |
Publication status | Published - Jul 2023 |
Bibliographical note
Funding Information:This study is performed and funded under the auspice of the Liquid Biopsy Evaluation and Repository Development at Princess Margaret (LIBERATE) ( NCT03702309 ) study, which is an institutional liquid biopsy programme at the University Health Network supported by the BMO Financial Group Chair in Precision Cancer Genomics (Chair held by Dr. Lillian Siu) and the Princess Margaret Cancer Foundation . This study was also partially funded with support provided by the Government of Ontario , Ministry of Research, Innovation and Science and the Princess Margaret Cancer Foundation.
Publisher Copyright:
© 2023 The Authors
Keywords
- ctDNA kinetics
- HNSCC
- Immune checkpoint blockade
ASJC Scopus subject areas
- Oncology
- Cancer Research