年轻癌症存活患者的VTE发病率升高2倍

阿姆斯特丹——加拿大阿尔伯塔大学 的小儿血液-肿瘤专家Ketan P. Kulkarni博士在国际血栓症与止血学会(ISTH)大会上报告了一项涉及3万多名加拿大人的研究结果：被诊断为癌症并接受治疗后仍存活的儿童、青少年和年轻成人患者在大约10年随访期间发生急性静脉血栓栓塞(VTE)的几率，是一般人群中匹配的对照者的3倍。

VTE发病率的增高似乎与患者之前接受的化疗和放疗有关，原因是仅接受手术治疗的患者在随访期间发生VTE的几率明显下降。

Ketan P. Kulkarni博士

Kulkarni博士报告称：“我们的工作假说是，VTE是在最初的儿童期癌症治疗过程中发生的，患者在余生中便面临更高的再次发生VTE的风险。”假如能确定“年轻癌症患者在接受治疗期间或之后短期内发生首次VTE”是之后再次发生VTE的一个主要危险因素，那么下一步就应当检验在最初治疗期间改进预防措施能够避免首次VTE并且降低数月或数年后再次VTE风险。负责诊治年轻癌症患者的临床医生应当意识到，VTE在最初治疗和之后随访过程中都“是一个重要问题”。Kulkarni在接受采访时表示：“我们认为随访期间发生的VTE实际上是治疗期间形成的血栓的复发。”目前他正与同事一道回顾分析每例存活患者的病历，以更好地确定在随访期间发生的VTE中究竟有多少属于复发。

这项研究的另一大发现是，所有类型的癌症均增加VTE风险，而不仅是白血病。白血病、淋巴瘤及其他类型癌症患者的随访期间VTE发病率几乎相同。

研究者利用不列颠哥伦比亚省1981~1999年的健康保险记录开展了这项分析，共确认了2,857例在0~24岁时被诊断为癌症且在此后存活至少5年的患者。这些存活患者在初始诊断时的平均年龄约为14岁。研究者还从该省一般人群中选取了28,570名对照者，每例患者有10名年龄、性别匹配的对照者。

在5~21年(平均近10年)的随访过程中，研究者发现43例存活患者曾发生VTE，发病率为1.5%，而对照者的VTE发病率仅为0.5%。校正性别、社会经济状态及居住地的多变量分析显示，癌症存活患者的VTE发病率是对照者的3.4倍，具有统计学显著性。在存活患者中，深静脉血栓(DVT)发病率约为0.8%，肺栓塞(PE)发病率约为0.5%，约有0.3%的存活患者发生了其他部位VTE。诊断癌症后头6个月内的VTE发病率最高。

仅接受过手术治疗而未曾接受化疗或放疗的癌症存活患者的VTE发病率，比曾接受化疗和(或)放疗的存活患者显著降低81%。“这提示VTE风险升高是由化疗或放疗引起的。”

在随访期间癌症复发的患者的VTE发病率进一步显著升高，达到癌症未复发患者的2.5倍。

Kulkarni博士声称无相关利益冲突。

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By: MITCHEL L. ZOLER, Oncology Practice

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.