e20017 Background: Genomic studies in small cell lung cancer (SCLC) are hampered by the small amounts of biopsy tissue typically available. The emergence of ‘liquid biopsy’ to identify tumor DNA mutations in plasma (circulating tumor DNA or ctDNA) has the potential to overcome this restriction and also facilitates multiple sampling during disease treatment. Here we use ctDNA to compare mutation profiles in SCLC and non-small cell lung cancer (NSCLC)patients and to identify changes that occur post-relapse in SCLC. Methods: Targeted exome sequencing of 73 genes in plasma from 13 SCLC and 17 NSCLC patients was obtained along with matched patient targeted exome sequencingof 315 genes for 6 SCLC and 8 NSCLC tumor biopsies. Only the 70 genes analyzed by both assays were studied. Results: 3 SCLC and 8 NSCLC ctDNA specimens were collected pre-treatment, with the remainder post-relapse. In SCLC, 46 total gene mutations were detected in ctDNA with a mean allelic fraction (mAF) of 16.0%. TP53 (mAF 30.8%, N= 15) and ARID1A (mAF 16.0%, N= 6) were the most frequently mutated SCLC genes. In NSCLC, 53 gene mutations were detected with a mAF of 2.5%. TP53 (mAF 5.9%, N= 13), EGFR (mAF 2.3%, N= 10) and KRAS (mAF 4.4%, N= 5) were frequently mutated NSCLC genes. 44 and 10 gene amplifications were detected in SCLC and NSCLC ctDNA, respectively. 5 SCLC patients with tumor DNA profiles obtained pre-treatment had matching ctDNA profiles obtained post-relapse. TP53 mutation status agreed in 4 of the matched specimens. 6 new gene mutations occurred post-relapse in ctDNA, notably a TSC1 mutation (AF 8.4%) in one patient. 7 tumor gene mutations were lost post-relapse, notably ARID1A and NTRK1 mutations were lost in two patients each. Remarkably, 23 new gene amplifications were detected post-relapse in ctDNA, including PIK3CA ( N= 5) and CCNE1 ( N= 5), whereas only 1 was detected in pre-treatment tumors. Conclusions: SCLC exhibits much greater ctDNA mAF values than NSCLC, although their overall mutation profiles agree with published tumor DNA mutation profiles. Interestingly, the predominant change observed in SCLC ctDNA profiles in relapsed specimens is increased gene amplification.
Effect of Cerebral Infarction on the Risk of Synchronous Brain Metastasis: Analysis of 307 Consecutive Patients of Newly Diagnosed Non-Small Cell Lung Cancer
