Thrombosis rates and genetic thrombophilia risk among patients with advanced germ cell tumors treated with chemotherapy

Introduction Men with advanced germ cell tumors (GCT) treated with chemotherapy are at high risk of venous thromboembolism (VTE). Predictors of VTE may identify patients who would benefit from prophylactic anticoagulation. Patients and Methods Men with advanced GCT (Stage IS, II, III) treated with chemotherapy were identified at two centers. High genomic risk was defined from a 5 single nucleotide polymorphism (SNP) germline panel. Logistic regression was used to evaluate the impact of genomic risk on VTE within six months of chemotherapy initiation. Orthogonal Projection to Latent Structures Discriminant Analysis (OPLS-DA) was used to build models to predict VTE based on clinical variables and an 86 SNP panel. Results This 123-patient cohort experienced a VTE rate of 26% with an incidence of high genomic risk of 21%. Men with high genomic risk did not have a significantly higher VTE rate (31%, 8/26) than men with low genomic risk (25%, 24/97), unadjusted OR 1.4 (95% CI 0.5–3.5, p=0.54). Incorporation of clinical variables (Khorana score, N3 status and elevated LDH) resulted in adjusted OR 2.1 (95% CI 0.7–6.5, p=0.18). A combined model using clinical variables and 86 SNPs performed similarly (AUC 0.77) compared to clinical variables alone (AUC 0.72). Conclusions A previously established 5-SNP panel was not associated with VTE among patients with GCT receiving chemotherapy. However, multivariable models based on clinical variables alone warrant further validation to inform prophylactic anticoagulation strategies. MicroAbstract VTE occurs at a high rate in men with germ cell tumors treated with curative intent chemotherapy. A 5-SNP genetic risk panel was not significantly associated with VTE in a retrospective cohort of 123 patients. Clinical variables alone with or without a broad 86 SNP panel did successfully identify a high-risk population who warrant further study of prophylactic anticoagulation. Clinical Practice Points Men with advanced germ cell tumors (GCT) treated with chemotherapy are at high risk of venous thromboembolism (VTE). We analyzed 123 patients with advanced GCT treated with cisplatin-based chemotherapy to evaluate the association between VTE and a 5 gene single nucleotide polymorphism (SNP) panel that has previously been associated with VTE risk. While no significant association between VTE and the 5-SNP panel was found, we did show that clinical variables are a powerful predictor of VTE. Additionally, a broad 86 SNP panel did provide additional benefit when combined with clinical variables for VTE risk stratification using a novel machine learning model. These results emphasize that VTE is a common issue in this population and strategies to reduce the risk of VTE, such as with prophylactic anticoagulation, are urgently needed. We propose a prospective clinical trial of prophylactic anticoagulation in this high-risk group, which would be practice changing if it were shown to reduce the risk of VTE in this population of patients undergoing curative intent treatment.