ctDNA and Venous Thromboembolism (MSK, 2024)

Overview

Pan-cancer liquid biopsy cohort from Memorial Sloan Kettering Cancer Center used to develop and validate a ctDNA-based prediction model for cancer-associated venous thromboembolism (VTE). Includes a discovery cohort (n=4,141) and a prospective validation cohort (n=1,426), all sequenced with MSK-ACCESS. A companion international generalizability cohort for NSCLC is available as nsclc_ctdx_msk_2022. PMID:39147831

Composition

  • Discovery cohort: 4,141 patients with any cancer type, plasma sequenced with MSK-ACCESS (129 genes) at MSK (June 2019–September 2022). 61% ctDNA-positive; 11% developed VTE after plasma draw. PMID:39147831
  • Prospective validation cohort: 1,426 patients with any cancer type (September 2022–September 2023). PMID:39147831
  • Cancer type breakdown (discovery): NSCLC 34%, breast 13%, pancreatic 10%, melanoma 7%, prostate 5%, bladder 5%, plus 53 other cancer types. PMID:39147831

Assays / panels (linked)

Papers using this cohort

  • PMID:39147831 — DNA liquid biopsy-based prediction of cancer-associated venous thromboembolism.

Notable findings derived from this cohort

  • ctDNA detection associated with higher VTE rates (HR=2.49, 95% CI: 1.99–3.11, P<0.001). Dose-dependent relationship: highest VAF quartile had greatest VTE risk. PMID:39147831
  • In multivariate analysis, ctDNA detection (HR=1.66), cfDNA concentration (HR=1.61), Khorana score, number of disease organ sites, and chemotherapy receipt were all independently associated with VTE. PMID:39147831
  • ctDNA-VTE association held across most cancer types with notable exceptions of bladder, hepatobiliary, and colorectal cancers. PMID:39147831
  • ctDNA detection remained significant for VTE prediction even after controlling for tissue-confirmed gene-level alterations including KRAS, STK11, and KEAP1. PMID:39147831

Sources

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