Search

Introduction: Blood-based next-generation sequencing assays 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 ρ = 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 (ρ = 0.618, p  = 0.048). The relationship remained significant when adjusting for treatment status and bone metastases ( p  = 0.046). In the subgroup of patients with TP53 variants, univariate analysis revealed a significant association (ρ = 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, suggesting mean VAF may represent a dynamic biomarker of tumor burden that could be followed to monitor disease status., (© 2020 The Authors.)

Introduction: Most patients (70%) with limited-stage SCLC (LS-SCLC) who are treated with curative-intent therapy suffer disease relapse and cancer-related death. We evaluated circulating tumor DNA (ctDNA) as a predictor of disease relapse and death after definitive therapy in patients with LS-SCLC., Methods: In our previous work, we developed a plasma-based ctDNA assay to sequence 14 genes ( TP53 , RB1 , BRAF , KIT , NOTCH1-4 , PIK3CA , PTEN , FGFR1 , MYC , MYCL1 , and MYCN ) that are frequently mutated in SCLC. In this work, we evaluated 177 plasma samples from 23 patients with LS-SCLC who completed definitive chemoradiation (n = 21) or surgical resection (n = 2) and had an end-of-treatment blood collection (median 4 d, range 0-40 d from treatment completion) plus monthly surveillance blood sampling. Median overall survival (OS) and progression-free survival (PFS) were compared using a Wilcoxon test., Results: The median OS among patients in whom we ever detected ctDNA after definitive treatment (n = 15) was 18.2 months compared with a median OS of greater than 48 months among patients in whom we never detected ctDNA after definitive treatment (n = 8; p  = 0.081). The median PFS among patients in whom we ever detected ctDNA after definitive treatment was 9.1 months compared with a median PFS of greater than 48 months among patients in whom we never detected ctDNA after definitive treatment ( p < 0.001)., Conclusions: Detection of ctDNA in patients with LS-SCLC after curative-intent therapy predicts disease relapse and death. Prospective trials using ctDNA as an integral biomarker for therapeutic selection should be considered in SCLC., (© 2020 The Authors.)