Kras mutation as a risk factor for venous thromboembolism in patients with metastatic pancreatic cancer.
Authors: Serrano Elena , Inga Saavedra Elizabeth , Padilla Vico Maria , Perdomo Eduardo , Cano Osuna Maria Teresa , Toledano Marta , Aranda Enrique 
Published: June 2021

e16267

Background: Venous thromboembolism (VTE) is a common complication in oncology patients. It has been reported that VTE increases morbidity and mortality in these patients. It’s prevalence in metastatic pancreatic cancer (mPC) ranges around 4-7.5% Preclinic studies suggest that the mutation of the KRAS oncogene (KRASm) is associated with a higher risk of VTE among patients with colorectal cancer. KRASm appears to increase the expression of tissue factor, a physiological trigger of coagulation that is found on the surface of tumor cells. This association has not been studied in mPC, where this mutation can be found in 90% of the cases. Our aim is to determine the prevalence and risk factors associated with VTE taking into consideration the status of KRAS. Methods: We conducted a retrospective study within a cohort of patients with mPC that had a determination of the KRAS status. These patients were treated at Medical Oncology between January 2017 and December 2020. We performed a descriptive and survival analysis of our sample. We also studied the prevalence of VTE among the. Results: Our study cohort was 88 patients (pts), 63 (61, 2%) men and 40 (38, 8%) women. The median age was 63 years (32-84). 19 pts (18, 4%) were KRAS wild type (KRASwt), 69 pts (67%) KRASm. There was no statistically significant difference in gender, age, performance status, comorbidities, primary tumor/metastases location, disease control rate and toxicity between KRASwt and KRASm. Median serum levels of Ca 19.9 were higher in KRASm (39.847 U/ml vs 2026 U/ml). At the time of diagnosis, 78 pts (88, 6%) were metastatic and 10 pts (11, 4%) were localized/locally-advanced. Most of metastatic pts (62/78) were KRASm (p = 0, 015). Most common histology (86, 4%) was adenocarcinoma. This histology was more frequent in KRASm, 61, 8% (p = 0, 02). At time of analysis, 72 pts (69, 9%) were dead, most of them (54, 4%) were KRASm (p = 0, 001). 31 pts developed VTE: 4 were KRASwt and 27 KRASm. The prevalence of VTE was 36, 3%. It was greater in KRASm (39, 1%) than in KRASwt (26, 3%). There were 7 cases of rethrombosis instead of anticoagulant treatment (1 KRASwt and 6 KRASm). KRASwt seems to be a protective factor in the development of VTE (OR 0, 55; CI 95% 0, 18-1, 71). The most common entity were VTE of splenoportomensenteric axis (16 pts), followed by pulmonary embolism, EP, (7 pts), deep venous thrombosis, DVT, (4 pts) EP + DVP (3 pts), thrombosis associated with central venous catheter (3 pts) and other locations (2 pts). There were no differences in VTE location between KRASwt and KRASm. The median overall survival (OS) was 12, 82 months (CI 95%: 7, 87-17, 78). It was higher in KRASwt (26 months; CI 95%: 12, 21-40, 48) than in KRASm (9, 8 months; CI 95%: 6, 07-13, 65). This difference was statistically significant (p = 0, 001). Conclusions: In our cohort, the prevalence of VTE is higher than de prevalence described in the literature and was greater in KRASm population. OS was significantly larger in KRASwt.