Blood-based surveillance monitoring of circulating tumor DNA from patients with small cell lung cancer detects disease relapse and predicts death in patients with limited stage disease

Abstract Introduction Most patients (70%) with limited-stage small cell lung cancer (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. We examined 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 days, range 0-40 days 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 was 18.2 months compared to a median OS of greater than 48 months among patients in whom we never detected ctDNA after definitive treatment (p=0.081). The median PFS among patients in whom we ever detected ctDNA after definitive treatment was 9.1 months compared to a median PFS of greater than 48 months among patients in whom we never detected ctDNA after definitive treatment (p Conclusions Detection of ctDNA in patients with LS-SCLC after curative intent therapy predicts disease relapse and death. Prospective trials utilizing ctDNA as an integral biomarker for therapeutic selection should be considered in SCLC.