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

摘要

Introduction<br/>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.<br/>Methods<br/>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.<br/>Results<br/>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<0.001).<br/>Conclusions<br/>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.

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