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Publications

Journal Article Ahead of print

PubMed: 42468056 DOI: 10.1016/j.ctarc.2026.101316

Circulating tumor DNA to predict the risk of venous thromboembolism in locally advanced rectal cancer.

Cancer Treat Res Commun 48:101316

Authors: Lorenzo Gervaso, Davide Ciardiello, Samuele Frassoni, Vincenzo Bagnardi, Giuliana Gregato, Chiara Alessandra Cella, Lavinia Benini, Darina Tamayo, Francesca Spada, Francesco Bertolini, Nicola Fazio, Maria Giulia Zampino

Affiliations

  • Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IRCCS, Milan, Italy.
  • Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IRCCS, Milan, Italy.
  • Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy; Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
  • Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy.
  • Laboratory of Hematology-Oncology, European Institute of Oncology, IRCCS, Milan, Italy.
  • Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IRCCS, Milan, Italy.

Abstract

BACKGROUND

Venous thromboembolism (VTE) is a common complication in cancer patients and negatively affects prognosis. Colorectal cancer (CRC) has the second highest incidence of VTE among the four most common cancers. In locally advanced rectal cancer (LARC), circulating tumor DNA (ctDNA) has emerged as a biomarker of residual disease and tumor burden, but its association with thrombotic risk remains unclear. We aimed to explore the association between baseline ctDNA levels and VTE occurrence in LARC.

METHODS

We conducted a prospective study of patients with LARC treated with chemoradiation at IEO. Plasma ctDNA was analyzed by droplet digital PCR for tumor-specific mutations identified in tissue samples, including KRAS, NRAS, BRAF, and PIK3CA. Baseline ctDNA, defined as variant allele frequency (VAF), was correlated with VTE occurrence using univariable and exploratory adjusted analyses.

RESULTS

Sixty-one patients underwent ctDNA assessment and were classified as VAF-low (n = 33) or VAF-high (n = 28) according to the median baseline value. Twenty-three patients (38%) were VAF-negative. After a median follow-up of 58 months, 9 VTE events (15%) were observed. Higher VTE cumulative incidence was observed in VAF-high versus VAF-low patients [HR 2.42, 95% CI 0.61-9.59; p = 0.21] and in ctDNA-positive versus ctDNA-negative patients [HR 5.70, 95% CI 0.70-46.1; p = 0.10]. In the KRAS-mutant subgroup, all VTE events occurred in patients with high baseline VAF (p = 0.001).

CONCLUSIONS

Higher baseline ctDNA levels may be associated with increased VTE occurrence in KRAS-mutant LARC. These exploratory findings require validation in larger prospective studies.

MeSH

Thromboembolism, Circulating Tumor Dna, Incidence, Neoplasms, Rectal Neoplasms, Venous Thromboembolism, Dna, Prospective Studies