Association of PIK3CA, PTCH1, FGF6, and NRAS mutations with venous thromboembolism in advanced lung and gastrointestinal cancer.

e15087 Background: Venous thromboembolism (VTE) in patients with gastrointestinal (GI) and non‐small cell lung cancer (NSCLC) is common and increases morbidity and mortality. In advanced GI and NSCLC, molecular subtyping has increased use of next-generation sequencing (NGS). The association between tumor mutation profile and VTE risk remains undetermined. Methods: We conducted a retrospective cohort study of consecutive GI/NSCLC patients from 2014-2019 with NGS and follow‐up at Brown Cancer Center. The NGS platform detected substitutions, indels, copy number alterations and select rearrangements in 324 genes. Patients with thrombophilia, anticoagulation use or >1 malignancy were excluded. VTE was defined as deep vein thrombosis, pulmonary embolism or visceral vein thrombosis within 6 months prior to diagnosis or any time after. For statistical analysis SAS 9.5 was used with significance at alpha=0.05. Multinomial logistic regression was performed, in which the log odds of VTE was modeled as a linear combination of the genes. Odds ratios and 95% confidence intervals for VTE were generated. Results: A total of 364 patients were reviewed; after exclusions 326 patients were included comprising Stage III/IV NSCLC (58%), metastatic colorectal (33%) and other metastatic GI cancers - gastric, duodenal, esophageal, pancreatic and cholangiocarcinoma (9%). Approximately half (53%) were males with mean age of 59.1 yrs and 76.4% current/former smokers. There was a low level of microsatellite instability (0.9%). VTE occurred in 75 patients (23%) during a mean follow‐up of 24.5 months. Only 1 patient had surgery within 90 days prior to VTE. Of 248 genes mutated in the VTE group, 9 were more prevalent compared to those without VTE (Table). Statistical analysis showed PIK3CA, PTCH1, FGF6, and NRAS mutations significantly increased odds of VTE, with PIK3CA the most prevalent of these (Table). Conclusions: Patients with PIK3CA, PTCH1, FGF6 and NRAS mutations had significantly higher VTE risk. These tumor mutations and associated pathways may provide novel insight into risk stratification, prevention and targeted treatment of VTE in cancer. [Table: see text]