Circulating Tumor DNA as a Biomarker of Radiographic Tumor Burden in SCLC

ntroduction: Blood-based next-generation sequencing as-says of circulating tumor DNA (ctDNA) have the ability to detect tumor-associated mutations in patients with SCLC. We sought to characterize the relationship between ctDNA mean variant allele frequency (VAF) and radiographic total -body tumor volume (TV) in patients with SCLC. Methods: We identified matched blood draws and computed tomography (CT) or positron emission tomography (PET) scans within a prospective SCLC blood banking cohort. We sequenced plasma using our previously developed 14-gene SCLC-specific ctDNA assay. Three-dimensional TV was determined from PET and CT scans using MIM software and reviewed by radiation oncologists. Univariate association and multivariate regression analyses were performed to evaluate the association between mean VAF and total-body TV. Results: We analyzed 75 matched blood draws and CT or PET scans from 25 unique patients with SCLC. Univariate analysis revealed a positive association between mean VAF and total-body TV (Spearman's r = 0.292, p < 0.01), and when considering only treatment-naive and pretreatment patients (n = 11), there was an increase in the magnitude of association (r = 0.618, p = 0.048). The relationship remained significant when adjusting for treatment status and bone metastases (p = 0.046). In the subgroup ofpatients with TP53 variants, univariate analysis revealed a significant association (r = 0.762, p = 0.037) only when considering treatment-naive and pretreatment patients (n = 8). Conclusions: We observed a positive association between mean VAF and total-body TV in patients with SCLC, sug-gesting mean VAF may represent a dynamic biomarker of tumor burden that could be followed to monitor disease status. (c) 2020 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Can-cer. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).