Abstract：
BACKGROUND: Treatment of childhood medulloblastoma has evolved to reduce neurotoxicity while improving survival. However, the impact of evolving therapies on late neurocognitive outcomes and adult functional independence remains unknown.
METHODS: Adult survivors of childhood medulloblastoma (n=505; median[minimum-maximum] age, 29[18-46] years) and sibling controls (n=727; 32[18-58] years) from the Childhood Cancer Survivor Study completed surveys assessing neurocognitive problems and chronic health conditions (CHCs). Treatment exposures were categorized as historical (craniospinal irradiation [CSI]≥30 Gy, no chemotherapy), standard-risk (CSI>0 to <30 Gy +chemotherapy) and high-risk (CSI≥30 Gy +chemotherapy) therapy. Latent class analysis identified patterns of functional independence using employment, independent living, assistance with routine/personal care needs, driver\'s license, marital/partner status. Multivariable models estimated risk of neurocognitive impairment in survivors versus siblings and by treatment exposure group, and associations between neurocognitive impairment, CHCs, and functional independence.
RESULTS: Survivors in each treatment exposure group had 4- to 5-fold elevated risk of impaired memory and task efficiency compared to siblings. Contemporary risk-based therapies did not confer lower risk compared to historical therapy. Survivors treated in the 1990s had higher risk of memory impairment (relative risk [RR] 2.24, 95% confidence interval [CI] 1.39-3.60) compared to survivors treated in the 1970s. Sensorimotor, hearing problems and seizures were associated with 33%-34%, 25-26% and 21%-42% elevated risk of task efficiency and memory impairment, respectively. Treatment-related CHCs and neurocognitive impairment were associated with non-independence.
CONCLUSIONS: Despite treatment changes, long-term survivors of childhood medulloblastoma remain at risk for neurocognitive impairment, which was associated with CHCs. Neurocognitive surveillance after contemporary regimens is imperative.
METHODS: Adult survivors of childhood medulloblastoma (n=505; median[minimum-maximum] age, 29[18-46] years) and sibling controls (n=727; 32[18-58] years) from the Childhood Cancer Survivor Study completed surveys assessing neurocognitive problems and chronic health conditions (CHCs). Treatment exposures were categorized as historical (craniospinal irradiation [CSI]≥30 Gy, no chemotherapy), standard-risk (CSI>0 to <30 Gy +chemotherapy) and high-risk (CSI≥30 Gy +chemotherapy) therapy. Latent class analysis identified patterns of functional independence using employment, independent living, assistance with routine/personal care needs, driver\'s license, marital/partner status. Multivariable models estimated risk of neurocognitive impairment in survivors versus siblings and by treatment exposure group, and associations between neurocognitive impairment, CHCs, and functional independence.
RESULTS: Survivors in each treatment exposure group had 4- to 5-fold elevated risk of impaired memory and task efficiency compared to siblings. Contemporary risk-based therapies did not confer lower risk compared to historical therapy. Survivors treated in the 1990s had higher risk of memory impairment (relative risk [RR] 2.24, 95% confidence interval [CI] 1.39-3.60) compared to survivors treated in the 1970s. Sensorimotor, hearing problems and seizures were associated with 33%-34%, 25-26% and 21%-42% elevated risk of task efficiency and memory impairment, respectively. Treatment-related CHCs and neurocognitive impairment were associated with non-independence.
CONCLUSIONS: Despite treatment changes, long-term survivors of childhood medulloblastoma remain at risk for neurocognitive impairment, which was associated with CHCs. Neurocognitive surveillance after contemporary regimens is imperative.
摘要：
背景：儿童髓母细胞瘤的治疗已经发展到减少神经毒性，同时提高生存率。然而,不断发展的治疗方法对晚期神经认知结局和成人功能独立性的影响尚不清楚.
方法：儿童髓母细胞瘤的成年幸存者（n=505；中位[最小-最大]年龄，29[18-46]年）和兄弟姐妹对照（n=727;32[18-58]年）来自儿童癌症幸存者研究完成了评估神经认知问题和慢性健康状况（CHC）的调查。治疗暴露被归类为历史（颅骨脊髓照射[CSI]≥30Gy，没有化疗)，标准风险（CSI>0至<30Gy+化疗）和高风险（CSI≥30Gy+化疗）治疗。潜在类分析确定了使用雇佣的功能独立模式，独立生活,协助日常/个人护理需求，驾驶执照,婚姻/伴侣状态。多变量模型估计幸存者与兄弟姐妹以及治疗暴露组的神经认知障碍风险，和神经认知障碍之间的关联，CHC,功能独立。
结果：与兄弟姐妹相比，每个治疗暴露组的幸存者记忆力和任务效率受损的风险提高了4至5倍。与历史疗法相比，当代基于风险的疗法并未带来更低的风险。与1970年代接受治疗的幸存者相比，1990年代接受治疗的幸存者的记忆障碍风险更高（相对风险[RR]2.24，95％置信区间[CI]1.39-3.60）。感觉运动,听力问题和癫痫发作与33%-34%相关，25-26％和21-42％的任务效率和记忆障碍的风险升高，分别。治疗相关的CHCs和神经认知障碍与非独立性相关。
结论：尽管治疗有所改变，儿童髓母细胞瘤的长期幸存者仍然存在神经认知障碍的风险，与CHC相关。现代治疗方案后的神经认知监测势在必行。
方法：儿童髓母细胞瘤的成年幸存者（n=505；中位[最小-最大]年龄，29[18-46]年）和兄弟姐妹对照（n=727;32[18-58]年）来自儿童癌症幸存者研究完成了评估神经认知问题和慢性健康状况（CHC）的调查。治疗暴露被归类为历史（颅骨脊髓照射[CSI]≥30Gy，没有化疗)，标准风险（CSI>0至<30Gy+化疗）和高风险（CSI≥30Gy+化疗）治疗。潜在类分析确定了使用雇佣的功能独立模式，独立生活,协助日常/个人护理需求，驾驶执照,婚姻/伴侣状态。多变量模型估计幸存者与兄弟姐妹以及治疗暴露组的神经认知障碍风险，和神经认知障碍之间的关联，CHC,功能独立。
结果：与兄弟姐妹相比，每个治疗暴露组的幸存者记忆力和任务效率受损的风险提高了4至5倍。与历史疗法相比，当代基于风险的疗法并未带来更低的风险。与1970年代接受治疗的幸存者相比，1990年代接受治疗的幸存者的记忆障碍风险更高（相对风险[RR]2.24，95％置信区间[CI]1.39-3.60）。感觉运动,听力问题和癫痫发作与33%-34%相关，25-26％和21-42％的任务效率和记忆障碍的风险升高，分别。治疗相关的CHCs和神经认知障碍与非独立性相关。
结论：尽管治疗有所改变，儿童髓母细胞瘤的长期幸存者仍然存在神经认知障碍的风险，与CHC相关。现代治疗方案后的神经认知监测势在必行。
