Temming Petra, Viehmann Anja, Arendt Marina, Eisele Lewin, Spix Claudia, Bornfeld Norbert, Sauerwein Wolfgang, Jöckel Karl-Heinz, Lohmann Dietmar R
Department of Pediatric Hematology and Oncology, University Hospital Essen, Essen, Germany.
Eye Oncogenetics Research Group, University Hospital Essen, Essen, Germany.
Pediatr Blood Cancer. 2015 Oct;62(10):1799-804. doi: 10.1002/pbc.25576. Epub 2015 May 13.
Children with retinoblastoma carry a high risk to develop second primary malignancies in childhood and adolescence. This study characterizes the type of pediatric second primary malignancies after retinoblastoma treatment and investigates the impact of different treatment strategies and prognostic factors at presentation.
All national patients treated for retinoblastoma at the German referral center with a current age of 6-27 years were invited to participate in a study to characterize late effects.
Data on pediatric second primary malignancies were recorded from 488 patients. Ten developed a malignancy before the age of 18 years. For children with heterozygous oncogenic RB1 alteration (heritable retinoblastoma), the cumulative incidence to develop a second malignancy at the age of 10 years was 5.2% (95% CI 1.7; 8.7%). This results in an elevated risk for sarcoma (n = 4) (SIR 147.98; 95% CI 39.81; 378.87) and leukemia (n = 4) (SIR 41.38; 95% CI 11.13; 105.95). Neither the functional type of the RB1 alteration nor its origin showed a significant impact. Treatment modality influenced incidence, latency, and type of malignancy. Previous radiotherapy increased the risk for solid tumors and 3 of 91 children developed acute leukemia after chemotherapy. However, 2 of 10 malignancies were diagnosed in patients with heritable retinoblastoma but without previous chemotherapy or external beam radiotherapy.
Screening for second primary malignancy is an important part of pediatric oncological follow-up in patients with heritable retinoblastoma. For patients with sporadic unilateral retinoblastoma, genetic information influences treatment decisions and allows tailoring of follow-up schedules.
视网膜母细胞瘤患儿在儿童期和青少年期发生第二原发性恶性肿瘤的风险很高。本研究对视网膜母细胞瘤治疗后的小儿第二原发性恶性肿瘤类型进行了特征描述，并调查了不同治疗策略和就诊时预后因素的影响。
邀请德国转诊中心所有接受视网膜母细胞瘤治疗且当前年龄在6至27岁之间的全国患者参加一项研究，以确定晚期效应。
记录了488例患者小儿第二原发性恶性肿瘤的数据。10例在18岁之前发生了恶性肿瘤。对于具有杂合致癌性RB1改变（遗传性视网膜母细胞瘤）的儿童，10岁时发生第二种恶性肿瘤的累积发病率为5.2%（95%CI 1.7；8.7%）。这导致肉瘤（n = 4）（标准化发病比147.98；95%CI 39.81；378.87）和白血病（n = 4）（标准化发病比41.38；95%CI 11.13；105.95）的风险升高。RB1改变的功能类型及其起源均未显示出显著影响。治疗方式影响恶性肿瘤的发病率、潜伏期和类型。既往放疗增加了实体瘤的风险，91例儿童中有3例在化疗后发生急性白血病。然而，10例恶性肿瘤中有2例是在遗传性视网膜母细胞瘤患者中诊断出来的，但之前没有接受过化疗或外照射放疗。
筛查第二原发性恶性肿瘤是遗传性视网膜母细胞瘤患儿儿科肿瘤学随访的重要组成部分。对于散发性单侧视网膜母细胞瘤患者，基因信息会影响治疗决策，并有助于制定个性化的随访计划。
