Abstract 958P
Background
HPV detected in oropharyngeal carcinomas is currently the only established biomarker available in head and neck squamous cell carcinoma (HNSCC). Next generation sequencing (NGS) with sophisticated bioinformatics allows the distinct identification of tumour-specific DNA mutations in circulating tumor DNA (ctDNA). The aim of our study was to explore the potential of ctDNA as a biomarker for head and neck squamous cell carcinomas (HNSCC).
Methods
Plasma ctDNA was assessed in samples obtained at baseline and after 2 cycles (C2) of treatment (6 weeks). Target-capture deep sequencing with a panel covering 1021 genes was performed to detected somatic mutations in ctDNA. Molecular tumor burden index (mTBI) was calculated with the mean variant allele frequency of mutations in trunk clonal population.
Results
Between Oct 2018 and May 2020, a total of 21 cases were prospectively included and treated with cisplatin-based treatment with or without anti-EGFR monoclonal antibody. One case wrongly diagnosed was excluded. At the time of analysis, 11 of the 21 enrolled cases had results of mutation status in tumor tissue determined by NGS, giving a sensitivity of 100% (11/11). Mutations were detectable in the baseline ctDNA in 12 of the 14 cases (85.7%). Ten cases were evaluable for the analysis of correlation between tumor molecular burden in tissue (tTMB) and in blood (bTMB) and the association between disease control and variations of ctDNA during treatment. The tTMB and bTMB were positively related (Spearman correlations, r = 0.6433, P = 0.0495). In a bivariate correlations analysis, fold reduction in mTBI was positively related to disease control (Spearman correlations, r = 0.7184, P = 0.0222). The optimal fold reduction in mTBI for predicting disease control, as determined by the ROC curves (ROC area = 1, P = 0.0367), was > 0.3818. Moreover, two cases appeared new lesions emerged new mutations in VEGF-angiogenesis pathway in ctDNA during treatment, but neither of the other cases did.
Conclusions
The bTMB from ctDNA appeared to be a surrogate of tTMB and thus may serve as a biomarker. Variations of mTBI and detection of new mutations in VEGF-angiogenesis pathway in ctDNA during treatment could potentially assist the monitoring of the disease course and inform clinical decision-making.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Department of Medical Oncology, Peking Union Medical College Hospital.
Funding
National Natural Science Foundation of China (81472785, 61435001), CAMS Innovation Fund for Medical Sciences (No. 2016-I2M-1-001).
Disclosure
S. Zhang: Full/Part-time employment: Geneplus Beijing. All other authors have declared no conflicts of interest.