Introduction
Patients with small cell lung cancer (SCLC) have a poor prognosis and limited treatment options. Since access to longitudinal tumor samples is very limited in patients with this disease, we chose to focus our studies on the characterization of plasma cell-free DNA (cfDNA) for rapid, noninvasive monitoring of disease burden.
Methods
We developed a liquid biopsy assay that quantifies somatic variants in cfDNA. The assay detects single nucleotide variants, copy number alterations, and insertions or deletions in 14 genes that are frequently mutated in SCLC, including TP53, RB1, BRAF, KIT, NOTCH1–4, PIK3CA, PTEN, FGFR1, MYC, MYCL1, and MYCN.
Results
Over 26 months of peripheral blood collection, we examined 140 plasma samples from 27 patients. We detected disease-associated mutations in 85% of patient samples with mutant allele frequencies (AFs) ranging from ≤0.1% to 84%. In our cohort, 59% of the patients had extensive stage disease, and the most common mutations occurred in TP53 (70%) and RB1 (52%). In addition to mutations in TP53 and RB1, we detected alterations in 10 additional genes in our patient population (PTEN, NOTCH1–4, MYC, MYCL1, PIK3CA, KIT, and BRAF). Observed AFs and CNAs tracked closely with treatment responses. Notably, in several cases analysis of cfDNA provided evidence of disease relapse before conventional imaging.
Conclusions
These results suggest that liquid biopsies are readily applicable in patients with SCLC and can potentially provide improved monitoring of disease burden, depth of responses to treatment, and timely warning of disease relapse in patients with this disease.