Front-line liquid biopsy for early molecular assessment and treatment of hospitalized lung cancer patients
The primary aim of this study is to evaluate the performance of up-front next-generation sequencing (NGS) through liquid biopsy of hospitalized patients with newly detected lung neoplasm in parallel with conventional diagnosis. Secondary aims include response assessment and longitudinal monitoring through liquid biopsy of patients with oncogenic alterations at baseline.We enrolled 47 consecutive patients, irrespective of smoking history, immediately after hospitalization and subsequent detection of symptomatic, locally advanced or metastatic lung neoplasm. Liquid biopsy from peripheral blood was performed at baseline, in parallel with conventional biopsy, when feasible.Additionally, liquid biopsies were repeated during treatment in 10 patients with actionable gene alterations at baseline.Oncomine Lung cfTNA Research Assay panel was employed for processing plasma samples in NGS. ILiquid biopsy NGS of circulating RNA/DNA from plasma of 47 NSCLC patients at the baseline identified 30 gene alterations (10 EGFR activating mutations, 1 ALK rearrangement, 14 KRAS mutations (including 4 Gly12Cys), 1 ERBB2 duplication, 2 TP53, 1 BRAF and 1 PIK3CA mutations).Liquid biopsy and conventional tumor tissue assessment were consistent in all cases except for two patients who displayed EGFR mutations only in tissue biopsy (exon 19 deletion and exon 21 Leu858Arg). Among patients with actionable oncogenic drivers at liquid biopsy who started target therapy, three cases (one with ALK rearrangement and two with EGFR mutations) did not undergo conventional biopsies due to clinical contraindications.Overall median time to molecular results after liquid biopsy was significantly lower compared to time to molecular report after conventional biopsy (11 versus 19 days), assuming time from plasma sample collection in the first situation, and from histological outcome to complete molecular characterization in case of tissue biopsy.Front-line liquid biopsy might improve the management of symptomatic, hospitalized patients with lung cancer, potentially leading to early start of targeted therapy.