van Hoefen Wijsard Milo, Schonfeld Sara J, van Leeuwen Flora E, Moll Annette C, Fabius Armida W, Abramson David H, Seddon Johanna M, Francis Jasmine H, Tucker Margaret A, Kleinerman Ruth A, Morton Lindsay M
Department of Ophthalmology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
Cancers (Basel). 2021 Apr 8;13(8):1773. doi: 10.3390/cancers13081773.
Hereditary retinoblastoma survivors have substantially increased risk of subsequent malignant neoplasms (SMNs). The risk of benign neoplasms, a substantial cause of morbidity, is unclear. We calculated the cumulative incidence of developing benign tumors at 60 years following retinoblastoma diagnosis among 1128 hereditary (i.e., bilateral retinoblastoma or unilateral with family history, mutation testing was not available) and 924 nonhereditary retinoblastoma survivors diagnosed during 1914-2006 at two US medical centers with follow-up through 2016. Using Cox proportional hazards regression, we compared benign tumor risk by hereditary status and evaluated the association between benign tumors and SMNs. There were 100 benign tumors among 73 hereditary survivors (cumulative incidence = 17.6%; 95% confidence interval [CI] = 12.9-22.8%) and 22 benign tumors among 16 nonhereditary survivors (cumulative incidence = 3.9%; 95%CI = 2.2-6.4%), corresponding to 4.9-fold (95%CI = 2.8-8.4) increased risk for hereditary survivors. The cumulative incidence after hereditary retinoblastoma was highest for lipoma among males (14.0%; 95%CI = 7.7-22.1%) and leiomyoma among females (8.9%; 95%CI = 5.2-13.8%). Among hereditary survivors, having a prior SMN was associated with 3.5-fold (95%CI = 2.0-6.1) increased risk of developing a benign tumor; the reciprocal risk for developing an SMN after a benign tumor was 1.8 (95%CI = 1.1-2.9). These large-scale, long-term data demonstrate an increased risk for benign tumors after hereditary versus nonhereditary retinoblastoma. If confirmed, the association between benign tumors and SMNs among hereditary patients may have implications for long-term surveillance.
遗传性视网膜母细胞瘤幸存者患后续恶性肿瘤（SMNs）的风险大幅增加。良性肿瘤作为发病的一个重要原因，其风险尚不清楚。我们计算了1128例遗传性（即双侧视网膜母细胞瘤或单侧且有家族史，无法进行突变检测）和924例非遗传性视网膜母细胞瘤幸存者在视网膜母细胞瘤诊断后60年发生良性肿瘤的累积发病率，这些患者于1914年至2006年期间在美国的两个医疗中心确诊，并随访至2016年。使用Cox比例风险回归，我们比较了遗传性状态下的良性肿瘤风险，并评估了良性肿瘤与SMNs之间的关联。73例遗传性幸存者中有100例良性肿瘤（累积发病率 = 17.6%；95%置信区间[CI] = 12.9 - 22.8%），16例非遗传性幸存者中有22例良性肿瘤（累积发病率 = 3.9%；95%CI = 2.2 - 6.4%），遗传性幸存者的风险增加了4.9倍（95%CI = 2.8 - 8.4）。遗传性视网膜母细胞瘤后，男性脂肪瘤的累积发病率最高（14.0%；95%CI = 7.7 - 22.1%），女性平滑肌瘤的累积发病率最高（8.9%；95%CI = 5.2 - 13.8%）。在遗传性幸存者中，既往有SMN与发生良性肿瘤的风险增加3.5倍（95%CI = 2.0 - 6.1）相关；良性肿瘤后发生SMN的反向风险为1.8（95%CI = 1.1 - 2.9）。这些大规模、长期的数据表明，遗传性视网膜母细胞瘤后发生良性肿瘤的风险高于非遗传性视网膜母细胞瘤。如果得到证实，遗传性患者中良性肿瘤与SMNs之间的关联可能对长期监测有影响。
