Abstract Number: PB1098
Meeting: ISTH 2021 Congress
Theme: Venous Thromboembolism » Cancer Associated Thrombosis
Background: Patients with cancer are at increased relative risk of arterial thromboembolic events (ATE) and these increase morbidity and mortality. In advanced GI and NSCLC, molecular subtyping has increased use of next-generation sequencing (NGS).
Aims: To investigate the association between tumor mutation profile and ATE risk.
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, prior anticoagulant use or > 1 malignancy were excluded. ATE was defined as any arterial thromboembolic event including arterial stroke, myocardial infarction, peripheral arterial thrombosis and visceral arterial thromboses; 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 ATE was modeled as a linear combination of the genes. Odds ratios and 95% confidence intervals for ATE were generated.
Table 1: Demographics and characteristics of the study population
Demographics and characteristics of the study population
Table 2: Correlation between tumor mutations and ATE in patients with advanced NSCLC and GI malignancy
| Gene | Odds Ratio for ATE | 95% Confidence Limits |
| BRAF | 1.846 | (0.548,6.218) |
| FGF6 | 10.061 | (0.673,150.344) |
| FGF23 | 1.142 | (0.093,13.968) |
| KRAS | 2.456 | (1.077,5.602) |
| MPL | 2.519 | (0.362,17.519) |
| PIK3CA | 2.172 | (0.709,6.656) |
| PTCH1 | 0.313 | (0.016,6.146) |
| SMAD4 | 0.585 | (0.121,2.831) |
Correlation between tumor mutations and ATE in patients with advanced NSCLC and GI malignancy
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 (Table 1). There was a low level of microsatellite instability (0.9%). ATE occurred in 28 patients (8.6%). Statistical analysis showed KRAS mutation significantly increased odds of ATE (Table 2).
Conclusions: Patients with KRAS mutations had significantly higher ATE risk. This tumor mutation and the associated pathways deserve further investigation in patients with cancer.
To cite this abstract in AMA style:
Maharaj S, Bhandari S, Wu X, Rai S, Sharma V. Association of KRAS Mutation with Arterial Thromboembolism in Advanced Lung and Gastrointestinal Cancer [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/association-of-kras-mutation-with-arterial-thromboembolism-in-advanced-lung-and-gastrointestinal-cancer/. Accessed September 29, 2023.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/association-of-kras-mutation-with-arterial-thromboembolism-in-advanced-lung-and-gastrointestinal-cancer/