Combined (SoliQ) molecular profiling using whole exome sequencing in advanced HNSCC at baseline: Lessons learned for prognostication and treatment planning.

Abstract

e18025 Background: HNSCC imparts rising incidence and mortality rate worldwide, due to lack of information regarding spatial and temporal heterogeneity of the tumors. Nearly 50 to 60% of advanced node positive HNSCC are known to develop platinum resistance during the course of treatment. Beyond this, Metronomic Chemotherapy (MC; erlotinib 150mg daily, celecoxib 200mg BD daily, methotrexate 9mg/m2 every week) has shown promising effect by impacting the PFS and OS in the palliative setting. Nevertheless, only nearly 50% of these patients get the benefit of MC, which could be attributed to the underlying biology. At this stage, stratifying patients using the tumors’ mutational landscape would be more beneficial. This pilot study was aimed to understand the prognostic implications of adding liquid biopsy to solid tumor profiling in HNSCC. Methods: We adopted Whole Exome Sequencing of Tumor (Solid) and LiQuid biopsy (SoliQ) at the time of diagnosis in 10 HNSCC patients, with advanced stage recurrent/metastatic head and neck cancers, platinum resistant. The NGS libraries were generated as per standard procedures for illumina sequencing. The tumors were sequenced to a coverage depth of 250X, while the plasma cfDNA was sequenced to a coverage depth of 500X. Results: Broad genomic landscape of more than 230 pathogenic genes were unveiled, among which the frequently mutated genes were EGFR, CCND1, PIK3CA, NOTCH1, TP53, CDKN2A, KMT2A, FBXW7 and EP300 . Major findings included: a) 40% concordance in mutations identified between tumor tissue and liquid biopsy at the baseline b) those patients who had positive cfDNA/ctDNA fraction at baseline as measured from mutant allelic fraction, had a poor PFS (cfDNA positive PFS- 2.28 months (95% CI 1.733 -NA) and in cfDNA negative- 4.63 months (95% CI 0.967 -5.27). P= 0.06) and OS (cfDNA positive OS- 7.77 months (95% CI 3.63 -8.1) and in cfDNA negative- 4.92 months (95%CI 1.73 -NA). P= 0.0082) as compared those patients who had negative ctDNA fraction/no clinically relevant or somatic alterations identified in plasma cfDNA. Conclusions: This pilot study is the first of its kind to demonstrate the clinical utility of combining liquid biopsy profiling with tissue biopsy at baseline in HNSCC, using whole exome sequencing approach. Prospective studies on larger number of patients may help in establishing its role as part of the initial diagnostic work-up to be included in future guidelines/standard-of-care practice.