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April 12, 2026Circulation Genomic and Precision MedicineOpen Access

The prediction model combining clinical predictors, germline variants, and 14 somatic mutations achieved a concordance index of 0.77 (95% CI, 0.72–0.81), significantly higher than the Khorana VTE risk score (concordance index, 0.55 [95% CI, 0.51–0.59]; P <0.005).

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Why the study?

Does tumor whole-genome sequencing improve the prediction of venous thromboembolism in patients with metastasized solid cancer compared to standard clinical risk scores?

Population

3087 patients with metastasized solid cancer (pan-cancer cohort)

Comparison

Prediction model combining clinical predictors… vs Clinical predictors only or the currently…

Design

Cohort

Follow-up

12 months

Authors

FMFrits I. MulderPulmonary Hypertension AssociationNGNoori A.M. GumanPulmonary Hypertension AssociationJRJob van RietGerman Cancer Research Center

Discussion

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Overview

May better identify metastatic solid tumor patients for VTE prophylaxis; extends clinical risk scores but leaves open prospective validation.

Key Points

  • The study aims to determine whether tumor whole-genome sequencing can enhance the prediction of venous thromboembolism risk in cancer patients.
  • Analyzed a cohort of 3087 patients using tumor genomic data and clinical predictors.
  • Calculated associations between genetic risk factors and VTE using hazard ratios.
  • Developed predictive models incorporating various combinations of clinical predictors and genomic data.
  • 7.7% of patients developed VTE during the 12-month follow-up.
  • Germline variants and specific somatic mutations showed significant associations with VTE.
  • Predictive model utilizing both germline and somatic mutations outperformed traditional risk scores.

Structured PICO

Does tumor whole-genome sequencing improve the prediction of venous thromboembolism in patients with metastasized solid cancer compared to standard clinical risk scores?

P
Population
3087 patients with metastasized solid cancer (pan-cancer cohort)
I
Intervention
Prediction model combining clinical predictors, germline variants, and 14 top discriminating somatic mutations derived from tumor whole-genome sequencing
C
Comparator
Clinical predictors only (model 1) or the currently endorsed clinical Khorana VTE risk score
O
Outcome
Venous thromboembolism (VTE) during 12-month follow-uphard clinical

Tumor whole-genome sequencing significantly improves the prediction of venous thromboembolism in patients with metastasized solid cancer compared to standard clinical risk scores.

Limitations

  • Validation studies to confirm these findings are needed

Cite This Study

Mulder et al. (2026) studied this question.

synapsesocial.com/papers/69db37df4fe01fead37c5f13https://doi.org/10.1161/circgen.124.005182
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Prediction of venous thromboembolism in cancer patients2010 · 781 citations
  2. 2A Validated Risk Score for Venous Thromboembolism Is Predictive of Cancer Progression and Mortality2016 · 68 citations
  3. 3Genomic Profiling Identifies Somatic Mutations Predicting Thromboembolic Risk in Patients with Solid Tumors2020 · 5 citations
  4. 4Cancer‐associated thrombosis: The search for the holy grail continues2018 · 26 citations
  5. 5A nomogram for predicting the risk of venous thromboembolism in patients with solid cancers2023 · 9 citations