Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, 262 Danny Thomas Place, MS 735, Memphis, TN 38105-3678, USA.
J Clin Oncol. 2012 Oct 10;30(29):3618-24. doi: 10.1200/JCO.2012.42.6841. Epub 2012 Sep 4.
Long-term survivors of childhood Hodgkin lymphoma (HL) are at risk for cardiopulmonary complications and CNS stroke, although neurocognitive function has not been previously examined. The aim of this study was to examine neurocognitive and brain imaging outcomes in adult survivors of childhood HL.
In all, 62 adult survivors (mean age, 42.2 years; standard deviation [SD], 4.77; mean age at diagnosis, 15.1 years; SD, 3.30) were identified by stratified random selection from a large cohort treated with either high-dose (≥ 30 Gy) thoracic radiation (n = 38) or lower-dose (< 30 Gy) thoracic radiation combined with anthracycline (n = 24). Patients underwent neurocognitive evaluations, brain magnetic resonance imaging (MRI), echocardiograms, pulmonary function tests, and physical examinations.
Compared with national age-adjusted norms, HL survivors demonstrated lower performance on sustained attention (P = .004), short-term memory (P = .001), long-term memory (P = .006), working memory (P < .001), naming speed (P < .001), and cognitive fluency (P = .007). MRI revealed leukoencephalopathy in 53% of survivors, and 37% had evidence of cerebrovascular injury. Higher thoracic radiation dose was associated with impaired cardiac diastolic function (E/E'; ratio of peak mitral flow velocity of early rapid filling [E] to early diastolic velocity of the mitral annulus [E']; P = .003), impaired pulmonary function (diffusing capacity of lungs for carbon monoxide [DL(co)(corr); P = .04), and leukoencephalopathy (P = .02). Survivors with leukoencephalopathy demonstrated reduced cognitive fluency (P = .001). Working memory impairment was associated with E/E', although impaired sustained attention and naming speed were associated with DL(co)(corr). Neurocognitive performance was associated with academic and vocational functioning.
These results suggest that adult long-term survivors of childhood HL are at risk for neurocognitive impairment, which is associated with radiologic indices suggestive of reduced brain integrity and which occurs in the presence of symptoms of cardiopulmonary dysfunction.
儿童霍奇金淋巴瘤(HL)的长期幸存者存在心肺并发症和中枢神经系统中风的风险,尽管神经认知功能尚未得到评估。本研究的目的是检查儿童 HL 成年幸存者的神经认知和脑成像结果。
通过分层随机选择,从接受大剂量(≥30Gy)胸部放射治疗(n=38)或低剂量(<30Gy)胸部放射治疗联合蒽环类药物(n=24)治疗的大型队列中确定了 62 名成年幸存者(平均年龄 42.2 岁;标准差[SD],4.77;平均诊断年龄为 15.1 岁;SD,3.30)。患者接受神经认知评估、脑磁共振成像(MRI)、超声心动图、肺功能检查和体格检查。
与全国年龄调整后的标准相比,HL 幸存者在持续注意力(P=0.004)、短期记忆(P=0.001)、长期记忆(P=0.006)、工作记忆(P<0.001)、命名速度(P<0.001)和认知流畅性(P=0.007)方面的表现较低。MRI 显示 53%的幸存者存在白质脑病,37%的幸存者存在脑血管损伤证据。较高的胸部放射剂量与舒张功能障碍(二尖瓣血流速度早期快速充盈[E]与二尖瓣环早期舒张速度[E ']的比值[E/E ']; P=0.003)、肺功能受损(一氧化碳弥散量[DL(corr); P=0.04)和白质脑病(P=0.02)相关。有白质脑病的幸存者认知流畅性降低(P=0.001)。工作记忆障碍与 E/E '相关,而注意力持续时间和命名速度障碍与 DL(corr)相关。神经认知表现与学业和职业功能相关。
这些结果表明,儿童 HL 的成年长期幸存者存在神经认知障碍的风险,这种障碍与提示脑完整性降低的影像学指数相关,并且在存在心肺功能障碍症状的情况下发生。