Galvin Robert T, Chen Yan, Yuan Yan, Cooney Tabitha, Howell Rebecca, Smith Susan, Arnold Michael A, Conces Miriam, Leisenring Wendy, Armstrong Gregory T, Neglia Joseph P, Turcotte Lucie M
Division of Pediatric Hematology and Oncology, University of Minnesota, Minneapolis, MN 55455, United States.
Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
J Natl Cancer Inst. 2025 May 1;117(5):1036-1045. doi: 10.1093/jnci/djaf005.
It is not known whether temporal changes in childhood cancer therapy have reduced risk of subsequent malignant neoplasms of the central nervous system (CNS), a frequently fatal late effect of cancer therapy.
Five-year survivors of primary childhood cancers diagnosed between 1970 and 1999 in the Childhood Cancer Survivor Study with CNS subsequent malignant neoplasms were identified. Cumulative incidence rates and standardized incidence ratios were compared among survivors diagnosed between 1970-1979 (n = 6223), 1980-1989 (n = 9680), and 1990-1999 (n = 8999). Multivariable models assessed risk factors for CNS subsequent malignant neoplasms.
A total of 157 CNS subsequent malignant neoplasms (1970s, 52; 1980s, 63; 1990s, 42) were identified, excluding meningiomas, which were most often malignant gliomas. The proportion of survivors receiving any cranial radiotherapy exposure was reduced over time (1970s, 77.0%; 1980s, 54.3%; 1990s, 33.9%), while the proportion receiving more than 35 Gy cranial radiotherapy showed a smaller reduction (11.4%, 10.8%, and 8.5%, respectively). Twenty-year cumulative incidence and standardized incidence ratios for CNS subsequent malignant neoplasms by treatment decade were 0.32% (95% confidence interval = 0.18% to 0.46%) and 6.6 (95% CI = 5.0 to 8.7); 0.55% (95% CI = 0.41% to 0.70%) and 8.3 (95% CI = 6.6 to 10.4); and 0.43% (95% CI = 0.31% to 0.55%) and 9.2 (95% CI = 7.0 to 12.0), respectively, with no statistically significant decreases between eras. Multivariable analyses showed increased risk for cranial radiotherapy dose levels more than 10 Gy and for primary diagnoses of medulloblastoma and/or primitive neuro-ectodermal tumor (hazard ratio [HR] = 18.7, 95% CI = 9.2 to 37.9) and astrocytoma (HR = 10.1, 95% CI = 5.3 to 19.5). Three-year cumulative incidence of death after CNS subsequent malignant neoplasms, by treatment decade, were 76%, 74%, and 73%, respectively.
CNS subsequent malignant neoplasm incidence has not decreased despite fewer survivors exposed to CNS-directed radiotherapy. CNS subsequent malignant neoplasm remains a substantial source of mortality for affected patients.
儿童癌症治疗的时间变化是否降低了随后发生中枢神经系统（CNS）恶性肿瘤的风险尚不清楚，而CNS恶性肿瘤是癌症治疗常见的致命晚期效应。
在儿童癌症幸存者研究中，确定了1970年至1999年间诊断为原发性儿童癌症且随后发生CNS恶性肿瘤的5年幸存者。比较了1970 - 1979年（n = 6223）、1980 - 1989年（n = 9680）和1990 - 1999年（n = 8999）诊断的幸存者的累积发病率和标准化发病率。多变量模型评估了CNS随后发生恶性肿瘤的危险因素。
共确定了157例CNS随后发生的恶性肿瘤（20世纪70年代，52例；80年代，63例；90年代，42例），不包括脑膜瘤，其中最常见的是恶性胶质瘤。接受任何颅脑放疗的幸存者比例随时间减少（20世纪70年代，77.0%；80年代，54.3%；90年代，33.9%），而接受超过35 Gy颅脑放疗的比例下降幅度较小（分别为11.4%、10.8%和8.5%）。按治疗年代划分的CNS随后发生恶性肿瘤的20年累积发病率和标准化发病率分别为0.32%（95%置信区间 = 0.18%至0.46%）和6.6（95% CI = 5.0至8.7）；0.55%（95% CI = 0.41%至0.70%）和8.3（95% CI = 6.6至10.4）；以及0.43%（95% CI = 0.31%至0.55%）和9.2（95% CI = 7.0至12.0），各年代之间无统计学显著下降。多变量分析显示，颅脑放疗剂量超过10 Gy以及髓母细胞瘤和/或原始神经外胚层肿瘤（风险比[HR] = 18.7，95% CI = 9.2至37.9）和星形细胞瘤（HR = 10.1，95% CI = 5.3至19.5）的原发性诊断风险增加。按治疗年代划分，CNS随后发生恶性肿瘤后3年的累积死亡率分别为76%、74%和73%。
尽管接受CNS定向放疗的幸存者减少，但CNS随后发生恶性肿瘤的发病率并未降低。CNS随后发生恶性肿瘤仍然是受影响患者的主要死亡原因。
