Venous Thromboembolism (VTE) is a common cause of death and complications in patients with cancer. Choice of anticoagulant is challenging because of high risk of bleeding and recurrent VTE. Some tumor oncogenes, such as KRAS, a GTPase signaling protein that regulates proliferation, differentiation and cell survival can modulate the expression of genes at the core of hemostasis control. Clinically, KRAS mutation status is a validated predictive biomarker that is currently used to determine those mCRC (metastatic colorectal cancer) patients likely not to benefit from anti-EGFR therapy. A retrospective cohort study with 172 patients with mCRC has suggested that KRAS mutation (codons 12/13) could increase the risk of VTE.

To analyze the risk VTE of patients with mCRC based on KRAS status.

Records of 111 patients with metastatic or unresectable locally advanced colorectal cancer, attended at Clinica AMO (Salvador, Brazil) between January 2015 and January 2020, tested for mutational status of KRAS were reviewed. Seven mutations within codons 12 e 13 of KRAS detected by PCR (Idylla technique) or were considered for this study. Non-metastatic cases, those with insufficient clinical data, VTE provoked by catheter use and superficial vein thrombosis were excluded. This study was approved by an institutional Ethics Committee. Odds Ratios and 95% Confidence Intervals were obtained from the regression coefficients. A value of p < 0.05 was statistically significant.

One-hundred eleven patients were selected; the median age was 64 (22‒79) and 44.1% were male. Sixty-three patients (56.7%) had a KRAS activating mutation and 48 (43.2%) were found to be KRAS wild-type (Fig. 1), the incidence being comparable to the literature (approximately 30%–50%) (6). Twenty-three (20,7%) patients suffered at least 1 episode of VTE, 5 (4,5%) Pulmonary Embolism (PE), 15 (13.5%) low-extremity Deep-Vein Thrombosis (DVT) and 3 (2.7%) presented both PE and DVT. All six patients with thrombosis in catheter had PE or DVT and there was no need to be excluded. KRAS mutated status was not associated with an elevated risk of thrombosis (15.8% vs. 27%, OR = 0.50, 95% CI 0.20‒1.28) as well for the outcome of PE, DVT and both PE and DVT (Table 1). Although Ades, et al. (2015) found mutated KRAS as risk factor for VTE and remained significant despite adjustment for Khorana score and bevacizumab treatment, data are insufficient and conflicting. A Cohort with 194 patients, 41 patients (21.1%) who experienced VTE, ECOG ≥2 was the only independent predictor. Moreover, an abstract of 184 patients with mCRC shown limited evidence that mCRC patients harboring KRAS mutations may be at greater risk for VTE. In Table 2, we described VTE patient's characteristics according to oncogenic status. More than a half were metastatic and all patients had performance status ECOG 0‒1 at diagnosis. Personal characteristics and treatment may interfere in VTE outcome and may be considered in further investigations to analyze if KRAS has impact on patient care and associated morbidity.

In our study, biomarker KRAS have not been associated with an increased risk of VTE in advanced stage CRC patients and there is no evidence to select patients to whom VTE thromboprophylaxis should be offered.