Verbruggen Lisanne C, Kok Judith L, Kremer Leontien C M, Janssens Geert O, Nederkoorn Paul J, Penson Adriaan, Versluijs A Birgitta, de Vries Andrica C H, Reedijk Ardine M J, Bresters Dorine, Hoving Eelco W, van Dulmen-den Broeder Eline, Loonen Jacqueline J, de Bont Judith, Wilbers Joyce, Louwerens Marloes, van der Heiden-van der Loo Margriet, van den Heuvel-Eibrink Marry M, Pluijm Saskia M F, Neggers Sebastian J C M M, Tissing Wim J E, Roos Yvo B W E M, Ronckers Cécile M, Teepen Jop C, van der Pal Helena J H
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Emma Children's Hospital, University of Amsterdam, Amsterdam, The Netherlands.
Int J Cancer. 2025 May 15;156(10):1858-1872. doi: 10.1002/ijc.35275. Epub 2024 Dec 16.
Cerebrovascular events (CVEs) are serious late adverse events among childhood cancer survivors. We estimated the incidence and risk factors of symptomatic CVEs and described the clinical characteristics among childhood cancer survivors after upper body radiotherapy. The Dutch Childhood Cancer Survivor Study LATER cohort study includes 5-year childhood cancer survivors diagnosed <age 18 years in the period 1963-2001. Data about CVEs were retrieved from medical records of survivors treated with upper body radiotherapy (n = 1633). Multivariable Cox and logistic regression models were used to identify potential risk factors for developing a symptomatic CVE. In 107 survivors with upper body radiotherapy, a CVE emerged, at a median age of 35.5 years. Cumulative incidence 40 years after diagnosis was 9.1% (95% CI: 7.2%-11.6%). A cranial radiotherapy prescription dose >50 Gy was associated with 6-fold increased risk, compared to upper body radiotherapy not involving the cranium (hazard ratio = 6.3, 95%CI: 3.3-12.1). In a subgroup with available data on lifestyle and comorbidities, hypertension (odds ratio[OR] = 6.2, 95%CI: 1.6-23.8) and obesity (BMI≥30 vs. <30 = 2.95, 95%CI: 1.1-8.0) significantly increased CVE risk. During CVE episode, 17 (16%) had a life-threatening situation, and two (2%) others died. In 28%, a second CVE developed during follow-up. At end of follow-up, 29% were deceased, and 40% of those alive were unable to carry out normal activities/active work. Childhood cancer survivors treated with higher doses of cranial radiotherapy are at highest risk for developing CVEs. CVEs occur at a young age and cause a high morbidity. Studies to investigate risk-reducing secondary preventive interventions are warranted.
脑血管事件（CVEs）是儿童癌症幸存者中严重的晚期不良事件。我们估计了有症状CVEs的发生率和风险因素，并描述了上半身放疗后儿童癌症幸存者的临床特征。荷兰儿童癌症幸存者研究LATER队列研究纳入了1963年至2001年期间确诊时年龄<18岁的5年儿童癌症幸存者。关于CVEs的数据从接受上半身放疗的幸存者（n = 1633）的医疗记录中获取。使用多变量Cox和逻辑回归模型来确定发生有症状CVEs的潜在风险因素。在107例接受上半身放疗的幸存者中，出现了CVEs，中位年龄为35.5岁。诊断后40年的累积发病率为9.1%（95%CI：7.2%-11.6%）。与未累及颅骨的上半身放疗相比，颅骨放疗处方剂量>50 Gy与风险增加6倍相关（风险比=6.3，95%CI：3.3-12.1）。在一个有生活方式和合并症可用数据的亚组中，高血压（优势比[OR]=6.2，95%CI：1.6-23.8）和肥胖（BMI≥30与<30相比=2.95，95%CI：1.1-8.0）显著增加了CVEs风险。在CVEs发作期间，17例（16%）出现危及生命的情况，另有2例（2%）死亡。在随访期间，28%发生了第二次CVEs。随访结束时，29%已死亡，40%存活者无法进行正常活动/积极工作。接受高剂量颅骨放疗的儿童癌症幸存者发生CVEs的风险最高。CVEs发生在年轻时，发病率高。有必要开展研究以调查降低风险的二级预防干预措施。
