AMSTERDAM – Children, adolescents, and young adults who survived a diagnosis and treatment of cancer had a greater than threefold higher rate of acute venous thromboembolism during roughly 10 years of follow-up, compared with matched controls from the general population, in a study that included more than 30,000 Canadians.
The increased rate of VTE appeared to be linked to the chemotherapy and radiation treatments that patients received, because patients who were managed only by surgery had a substantially reduced rate of VTE during follow-up.
"Our working hypothesis is that VTE that develops during [initial] treatment of childhood cancers then places these patients at an increased risk" for a second VTE later in their life, Dr. Ketan P. Kulkarni said at the congress of the International Society on Thrombosis and Haemostasis.
If a first episode of VTE during or soon after the initial therapy that young cancer patients receive can be clearly established as a major risk factor for a subsequent episode of VTE, the next step would be to test whether improved prophylaxis during initial therapy can prevent a first episode and thereby also cut patients’ risk for a second VTE several months or years later. Clinicians who manage children, adolescents, and young adults with cancer need increased awareness that VTE "is a major problem" during both initial treatment and follow-up, Dr. Kulkarni said in an interview. "We think the VTEs during follow-up are recurrences of clots that first formed during treatment." He and his associates have begun to review the medical records of each survivor to better determine how many of the VTEs seen during follow-up were recurrences.
Another major finding from this analysis of people who survived at least 5 years following cancer diagnosis at age 0-24 years was that the entire range of cancers posed a VTE risk to patients, not just leukemia as some had previously though. The VTE rate during follow-up of the survivors was roughly the same regardless of whether patients had leukemia, lymphoma, carcinoma, or some other type of cancer.
"We have clearly dispelled the myth that it’s only leukemias. It’s all cancers," said Dr. Kulkarni, a pediatric hematologist-oncologist at the University of Alberta in Edmonton.
The researchers used provincial health insurance records from British Columbia during 1981-1999 to identify 2,857 patients who were aged 0-24 years at the time of their initial cancer diagnosis and then lived for at least another 5 years. The survivors averaged about 14 years old at the time of their initial cancer diagnosis. The investigators also assembled a control group matched by age and sex from the general British Columbia population, taking 10 controls for each case for a total of 28,570 controls.
During follow-up that ranged from 5 to 21 years and averaged nearly 10 years, they found that 43 survivors had an episode of VTE, a 1.5% incidence rate, compared with a 0.5% rate among the controls. In a multivariate analysis that controlled for sex, socioeconomic status, and region of residence, patients who were cancer survivors had a statistically significant, 3.4-fold increased rate of VTE compared with the controls, Dr. Kulkarni reported. Among the survivors the incidence of deep vein thrombosis was roughly 0.8%, the incidence of pulmonary embolism was roughly 0.5%, and VTE in other locations occurred in about 0.3% of the survivors (the total is 1.6% because of rounding). The incidence of VTEs was highest during the first 6 months following cancer diagnosis.
Cancer survivors who had been treated by surgery alone, without chemotherapy or radiation, had a statistically significant, 81% lower rate of developing a VTE compared with the patients treated by chemotherapy alone, radiation alone, or both.
"This supports the hypothesis that treatment by radiation or by chemotherapy increases the VTE risk," Dr. Kulkarni said.
The VTE rate was also substantially higher in survivors who had a relapse of their cancer during follow-up. Patients with relapses had a 2.5-fold higher rate of VTE compared with survivors who did not have a relapse.
Dr. Kulkarni said that he had no disclosures.
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