Risk of Late Venous Thromboembolism in Survivors of Childhood Cancer

Key Points

  • Childhood survivors are at increased risk of late venous thromboembolism.
  • Late venous thromboembolism is associated with increased risk of mortality in these patients.

In a report from the Childhood Cancer Survivor Study published in the Journal of Clinical Oncology, Madenci et al found that survivors of childhood cancer are at increased risk of late venous thromboembolism, with several factors increasing such risk.

The study involved data from a multi-institutional cohort of 24,355 5-year childhood cancer survivors diagnosed between 1970 and 1999, with a median age at last follow-up of 28.7 years (range = 5.6–58.9 years) and a median follow-up since diagnosis of 21.3 years (range = 5.0–39.2 years). There were 5,051 sibling participants.

The primary endpoint was self-reported late (≥ 5 years after cancer diagnosis) venous thromboembolism. Rate ratios (RRs) were estimated in multivariable models adjusted for sex, race, body mass index (BMI), year of diagnosis, attained age, and socioeconomic status.

Risk and Risk Factors

Rates of late venous thromboembolism among survivors and siblings were 1.1 vs 0.5 events per 1,000 person-years (RR = 2.2, 95% confidence interval [CI] = 1.7–2.8), representing 2.5 excess events per 100 survivors over 35 years. Risk factors for venous thromboembolism among survivors were female vs male sex (RR = 1.3, 95% CI = 1.1–1.6), cisplatin exposures vs no exposure of 1 to 199 mg/m2 (RR = 3.0, 95% CI = 1.4–6.5), 200 to 399 mg/m2 (RR = 1.9, 95% CI = 1.0–3.6], and ≥ 400 mg/m2 (RR = 2.0, 95% CI = 1.2–3.3), L-asparaginase treatment (RR = 1.3, 95% CI = 1.0–1.7), obesity (RR = 1.6, 95% CI =1.2–2.0) and underweight (RR = 2.4, 95% CI = 1.7–3.4), and late cancer recurrence or subsequent malignant neoplasm (RR = 4.6, 95% CI = 3.6–5.8).

Among survivors of lower-extremity osteosarcoma, compared with amputation, limb salvage (RR = 3.1, 95% CI = 1.2–7.5) and cisplatin exposure 200 to 399 and ≥ 400 mg/m2 (RR = 4.0, 95% CI = 1.1–14.6, and 2.9, 95% CI =1.1–8.0) were independent risk factors for late venous thromboembolism. Venous thromboembolism was associated with an increased risk of nonexternal cause late mortality (RR = 1.9, 95% CI = 1.6–2.3).

The investigators concluded, “Childhood cancer survivors are at increased risk for [venous thromboembolism] across their lifespan and a diagnosis of [venous thromboembolism] increases mortality risk. Interventions that target potentially modifiable comorbidities, such as obesity, warrant consideration, with prophylaxis for high-risk survivors, including those treated with cisplatin and limb-sparing approaches.”

The study was supported by grants from the National Cancer Institute and by the American Lebanese Syrian Associated Charities.

Christopher B. Weldon, MD, PhD, of the Department of Surgery, Boston Children’s Hospital, is the corresponding author for the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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