The Spanish Society of Medical Oncology (SEOM) last published clinical guidelines on venous thromboembolism (VTE) and cancer in 2019, with a partial update in 2020. In this new update to the guidelines, SEOM seeks to incorporate recent evidence, based on a critical review of the literature, to provide practical current recommendations for the prophylactic and therapeutic management of VTE in patients with cancer. Special clinical situations whose management and/or choice of currently recommended therapeutic options (low-molecular-weight heparins [LMWHs] or direct-acting oral anticoagulants [DOACs]) is controversial are included.
12 April 2025 in European Journal of Internal Medicine
Cancer-associated thrombosis (CAT) remains a leading cause of morbidity and mortality among oncology patients, with an incidence influenced by tumor type, stage, treatment, and molecular characteristics. This review explores the molecular determinants of venous thromboembolism (VTE) in cancer, emphasizing its pathophysiology and association with specific oncogenic alterations. Certain molecular profiles exhibit heightened VTE risk. In lung cancer, due to hypercoagulability mechanisms linked to tissue factor overexpression, an increased incidence of VTE has been reported in populations with ALK (30-40 %) and ROS1 rearrangements (34.7-46.6 %). In gastrointestinal cancers, while pancreatic adenocarcinoma has the highest VTE rates (up to 22 %), KRAS mutations seem to be implicated but not conclusively validated. Similarly, colorectal cancer mutations (KRAS/BRAFV600E) and antiangiogenic therapies may elevate thrombotic risk, warranting further study. High-grade gliomas, particularly glioblastomas, present VTE rates up to 30 %, driven by podoplanin-induced platelet aggregation. IDH1 mutations inversely correlate with thrombosis, highlighting its protective role. Emerging evidence suggests that agnostic biomarkers such as STK11 mutations influence VTE risk across tumor types, while others like KRAS, MET and BRCA mutations show inconclusive results. Large-scale validation studies are imperative to integrate molecular profiles into clinical practice. Until then, management decisions should be individualized, balancing the thrombotic risks with oncologic considerations.
Background: Catheter – related thrombosis (CRT) is the most frequent non-infectious complication regarding central venous access devices (CVAD). Its incidence has been reported between 13% and 66% in symptomatic and asymptomatic patients, respectively, with several factors influencing its development. Methods: CRT events recorded in TESEO, an international, multicentric, and prospective cancer-associated thrombosis registry were assessed. Descriptive analyses were conducted. Results: Between July 2018 and December 2023, 2,567 patients were included in TESEO. Of them, 245 patients developed CRT and were included in this analysis. Mean age was 60.5 years (SD 12.3). Peripherally inserted central catheters (PICC) was present in 42.1%, totally implanted ports (PORT) in 40.9% while 17% had missing data. The most common reported comorbidities were arterial hypertension (28.6%) and dyslipidemia (28.2%). Other thromboembolism – associated risk factors were present in ≤10% of patients. Venous thromboembolism (VTE) – related symptoms occurred in 70.2% of cases at presentation. Pulmonary embolism (PE) was present in 6.5%, being clinically suspected in 56.2% of cases. The diagnosis was mainly unilateral (81.3%) and 50% were central. Arterial and venous rethrombosis were present in 0.8% and 4.9%, respectively. Minor bleeding episodes occurred in 2.5% of cases, while major/clinically relevant episodes were present in 3.6%. Conclusions: Usual VTE – associated risk factors were infrequent in the TESEO registry population. CRT was symptomatic in most cases, with reduced complication rates after treatment.
Colorectal liver metastases (CRLM) management remains a complex conundrum in the context of potential curable disease. The combination of systemic therapy and surgery, with overall survival outcomes up to 58% at five years, has become the gold standard. Locoregional therapies have gained evidence in complementing surgery or even substituting it in selected cases. Adequate patient selection is paramount, but prognostic models have certain limitations that prevent their full implementation in clinical practice. A plethora of prognostic factors exists, with variable evidence supporting their definitive role. Thus, CRLM management decisions frequently vary depending on multidisciplinary team experience and hospital access to systemic and locoregional treatments. Definition of resectability has evolved in recent years due to technical developments in surgical and non-surgical approaches. Complexity is added when trying to fully understand the integration between local and systemic treatment. Whereas evidence in the context of resectable disease has been attempted in several phase III trials, definitive conclusions regarding the best approach to potentially resectable disease cannot be drawn. In addition, liver transplantation has gained evidence and is proposed in selected patients, raising a challenge regarding its integration and wider implementation. In this review, current standards in the management of CRLM regarding patient selection, resectability, surgical and non-surgical locoregional strategies, as well as the best systemic approach are covered.
Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. CRC leads to increased activation of the clotting system. Since CRC patients present a higher rate of bleeding, careful evaluation of the risk/benefits of anticoagulant prophylaxis is necessary. To evaluate low molecular weight heparin (LMWH) for primary thromboprophylaxis in metastatic CRC outpatients receiving first-line systemic cancer therapy. PROTINCOL (NCT05625932) is a randomized, open-label (PROBE), multicenter study. Patients will receive tinzaparin (75 IU/kg) or no pharmacological prophylaxis for 4 months and will be stratified based on: BRAF/RAS mutation, primary resection tumor and antiangiogenic therapy. The study outcomes will be assessed by a blinded central independent adjudication committee. The primary efficacy endpoints will include the cumulative incidence of any venous thromboembolism (VTE) event (symptomatic or incidental) including symptomatic central venous catheter VTE. Secondary variables will be clinically relevant bleedings, health-related quality of life and the predictive value of validated risk assessment scales of VTE, including the genetic risk score (TIC-ONCO). Our hypothesis is that prophylactic LMWH will reduce the 55% relative risk to an estimated VTE incidence of 13.5%. A total of 526 patients will be required. Risk prediction of chemotherapy-associated VTE is a compelling challenge in oncology, as VTE may result in treatment delays, impaired quality of life, and increased mortality. Patients with a single type of metastatic cancer with a high risk of VTE will be selected for study inclusion. For the first time in ambulatory prophylaxis of cancer-associated thrombosis, a precision medicine approach will be used in a clinical trial. If the individualization of antithrombotic prophylaxis can reduce the complications of outpatient cancer treatment and be cost effective, it would be of great value in the future care of patients with metastatic CRC. NCT05625932. Registered on 15 Nov 2022. The trial started recruitment on March 2023.