Thrombosis Rates and Genetic Thrombophilia Risk Among Patients With Advanced Germ Cell Tumors Treated With...

Area of Science:

• Oncology
• Genetics
• Hematology

Background:

• Men with advanced germ cell tumors (GCT) undergoing chemotherapy face a significant risk of venous thromboembolism (VTE).
• Identifying reliable predictors for VTE is crucial for implementing effective prophylactic anticoagulation strategies in this patient population.

Purpose of the Study:

• To evaluate the predictive value of a 5-single nucleotide polymorphism (SNP) germline panel for VTE risk in men with advanced GCT.
• To assess the utility of clinical variables and a larger SNP panel in predicting VTE using multivariable models.

Main Methods:

• A cohort of 123 men with advanced GCT (Stage IS, II, III) treated with chemotherapy at two centers was analyzed.
• Genomic risk was determined using a 5-SNP panel, and logistic regression evaluated its association with VTE within six months of chemotherapy initiation.
• Orthogonal Projection to Latent Structures Discriminant Analysis (OPLS-DA) was employed to build predictive models incorporating clinical data and an 86-SNP panel.

Main Results:

• The overall VTE rate in the cohort was 26%, with a 21% incidence of high genomic risk.
• High genomic risk, as defined by the 5-SNP panel, was not significantly associated with an increased VTE rate (31% vs. 25%).
• Multivariable models incorporating clinical variables (Khorana score, N3 status, elevated LDH) showed improved, though not statistically significant, VTE prediction (OR 2.1, P = .18), with an AUC of 0.72. A combined model with clinical variables and 86 SNPs achieved a similar AUC of 0.77.

Conclusions:

• The previously established 5-SNP panel lacks predictive power for VTE in chemotherapy-treated GCT patients.
• Multivariable models integrating clinical variables show potential for VTE risk stratification and warrant further validation for guiding prophylactic anticoagulation decisions.