J Natl Cancer Inst. 2019 Sep 1;111(9):961-969. doi: 10.1093/jnci/djy227.
Previous studies of hereditary retinoblastoma survivors have reported elevated mortality, particularly for sarcomas, compared with the general population. However, cause-specific mortality patterns for long-term hereditary and nonhereditary retinoblastoma survivors are poorly understood.
Among 2053 retinoblastoma patients diagnosed during 1914-2006 at two major US treatment centers and followed to 2016, we estimated cumulative mortality, standardized mortality ratios (SMRs), and absolute excess risks (AERs) compared with the US general population.
Most deaths occurred in 1129 hereditary retinoblastoma patients (n = 518 deaths, cumulative mortality 70 years after retinoblastoma = 75.8%, 95% CI = 69.0% to 82.6%; SMR = 8.5, 95% CI = 7.7 to 9.2). Of these, 267 were due to subsequent cancers (SMR = 27.4, 95% CI = 24.2 to 30.9; AER = 72.3 deaths/10 000 person-years), for which SMRs were highest 15-29 years after diagnosis (n = 69, SMR = 89.9, 95% CI = 70.0 to 113.8) but remained statistically significantly elevated at 60 and more years (n = 14, SMR = 6.7, 95% CI = 3.6 to 11.2), whereas AERs increased with time (AER<15years = 38.0; AER60+years = 327.5). Increased risk of death due to cancers of pancreas, large intestines, and kidney were noted for the first time. Overall risk of subsequent cancers was greater for those treated with radiotherapy and chemotherapy compared to radiotherapy alone, although patterns varied by organ site. For 924 patients with nonhereditary retinoblastoma, we noted a modestly increased risk of death for subsequent cancers (n = 27, SMR = 1.8, 95% CI = 1.2 to 2.6) possibly due to treatment or misclassification of hereditary status. Risks of noncancer causes of death were not elevated for hereditary or nonhereditary patients.
Hereditary retinoblastoma survivors died mainly from an excess risk of subsequent cancers up to six decades later, highlighting the need to develop long-term clinical management guidelines for hereditary retinoblastoma survivors treated in the past.
先前的遗传性视网膜母细胞瘤幸存者研究报告显示，与普通人群相比，这些患者的死亡率尤其因肉瘤而升高。然而，对于长期遗传性和非遗传性视网膜母细胞瘤幸存者的特定原因死亡率模式，我们知之甚少。
在两个美国主要治疗中心于 1914 年至 2006 年间诊断的 2053 例视网膜母细胞瘤患者中，我们对这些患者进行了随访，直至 2016 年，以估计与美国普通人群相比的累积死亡率、标准化死亡率比 (SMR) 和绝对超额风险 (AER)。
大多数死亡发生在 1129 例遗传性视网膜母细胞瘤患者中（n=518 例死亡，视网膜母细胞瘤后 70 年的累积死亡率为 75.8%，95%CI=69.0%至 82.6%；SMR=8.5，95%CI=7.7 至 9.2）。其中，267 例是由随后的癌症导致的（SMR=27.4，95%CI=24.2 至 30.9；AER=72.3 例/10000 人年），这些癌症的 SMR 在诊断后 15-29 年最高（n=69，SMR=89.9，95%CI=70.0 至 113.8），但在 60 岁及以上时仍具有统计学显著升高（n=14，SMR=6.7，95%CI=3.6 至 11.2），而 AER 随时间增加（AER<15 年=38.0；AER60+年=327.5）。首次注意到胰腺癌、大肠和肾脏癌症死亡风险增加。与仅接受放疗相比，接受放疗和化疗的患者随后发生癌症的总体风险更高，尽管模式因器官部位而异。对于 924 例非遗传性视网膜母细胞瘤患者，我们注意到随后癌症的死亡风险适度增加（n=27，SMR=1.8，95%CI=1.2 至 2.6），这可能是由于治疗或遗传性状态的错误分类。遗传性或非遗传性患者的非癌症死亡原因风险并未升高。
遗传性视网膜母细胞瘤幸存者主要死于随后癌症的风险增加，这一风险高达六十年后才显现，这突出表明需要为过去接受治疗的遗传性视网膜母细胞瘤幸存者制定长期临床管理指南。
