Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, California.
Keck School of Medicine, University of Southern California, Los Angeles, California; Radiation Oncology Program, Children's Hospital Los Angeles, Los Angeles, California.
Int J Radiat Oncol Biol Phys. 2021 Aug 1;110(5):1488-1495. doi: 10.1016/j.ijrobp.2021.02.050. Epub 2021 Mar 4.
Cranial radiation therapy (RT) and cisplatin-based chemotherapy are essential to treating many pediatric cancers but cause significant ototoxicity. The objective of this study is to determine the relationship between the RT dose and the risk of subsequent hearing loss in pediatric patients treated with cisplatin.
This retrospective study of cisplatin-treated pediatric patients examined ototoxicity from cranial RT. Ototoxicity was graded for each ear according to the International Society of Pediatric Oncology (SIOP) consensus ototoxicity scale. The RT dose to the cochlea was calculated using the mean, median, maximum, and minimum dose received to determine the most predictive parameter for hearing loss. Multivariable logistic regression models then examined risk factors for hearing loss.
In 96 children (161 ears) treated with RT + cisplatin, the minimum cochlear RT dose was most predictive of hearing loss. A higher cochlear RT dose was associated with increased hearing loss (odds ratio per 10 Gy dose increase = 1.64; P = .043), with an added risk in those receiving an autologous bone marrow transplantation (hazard ratio = 10.47; P < .001).
This research supports further testing of the minimum cochlear RT dose as a more predictive dose parameter for risk of ototoxicity. The cochlear RT dose was additive to the risk of hearing loss from underlying cisplatin-based chemotherapy. Exposure to autologous bone marrow transplantation was the strongest predictor of developing hearing loss, placing these children at particularly high risk for hearing loss across all cochlear doses. Future prospective studies are crucial to further inform RT dose thresholds and minimize the risk of hearing loss in childhood cancer survivors.
颅放射治疗（RT）和基于顺铂的化疗对于治疗许多儿科癌症至关重要，但会导致严重的耳毒性。本研究的目的是确定接受顺铂治疗的儿科患者的 RT 剂量与随后发生听力损失风险之间的关系。
这项对接受顺铂治疗的儿科患者的回顾性研究检查了颅 RT 引起的耳毒性。根据国际儿科肿瘤学会（SIOP）共识耳毒性量表对每只耳朵的耳毒性进行分级。使用接受的平均、中位数、最大和最小剂量来计算耳蜗的 RT 剂量，以确定听力损失的最具预测性参数。然后使用多变量逻辑回归模型检查听力损失的危险因素。
在 96 例（161 只耳朵）接受 RT+顺铂治疗的儿童中，耳蜗 RT 剂量最低最能预测听力损失。耳蜗 RT 剂量越高，听力损失的风险越高（每增加 10 Gy 剂量的比值比=1.64；P=0.043），接受自体骨髓移植的患者风险增加（风险比=10.47；P<0.001）。
这项研究支持进一步测试耳蜗 RT 剂量最低作为耳毒性风险更具预测性的剂量参数。耳蜗 RT 剂量增加了基础顺铂化疗引起听力损失的风险。自体骨髓移植的暴露是发生听力损失的最强预测因素，使这些儿童在所有耳蜗剂量下都面临极高的听力损失风险。未来的前瞻性研究对于进一步告知 RT 剂量阈值和最大限度地降低儿童癌症幸存者听力损失的风险至关重要。
