Redmond Kristin J, Hales Russell K, Anderson-Keightly Heather, Zhou Xian C, Kummerlowe Megan, Sair Haris I, Duhon Mario, Kleinberg Lawrence, Rosner Gary L, Vannorsdall Tracy
Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University, Baltimore, Maryland.
Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University, Baltimore, Maryland.
Int J Radiat Oncol Biol Phys. 2017 Jul 1;98(3):603-611. doi: 10.1016/j.ijrobp.2017.03.009. Epub 2017 Mar 14.
To prospectively evaluate cognitive function and intracranial failure patterns after hippocampal-sparing prophylactic cranial irradiation (PCI) for limited-stage small cell lung cancer (SCLC).
Adults with limited-stage SCLC, achieving a complete response to chemoradiotherapy and no brain metastases, were eligible. Patients received PCI 25 Gy/10 fractions, with a mean hippocampal dose limited to <8 Gy and ≥90% of the brain receiving 90% of the prescription. A diverse battery of neuropsychological testing was performed at baseline and 6 and 12 months after PCI. Brain MRI scans were performed at baseline and 6, 12, 18, and 24 months. The primary endpoint was memory measured by the Hopkins Verbal Learning Test-Revised Delayed Recall at 6 months after PCI. The 25-Gy arm of Radiation Therapy Oncology Group protocol 0212 was used as a reference of potential efficacy. Development of intracranial metastases was recorded. Overall survival and progression-free survival were estimated using the Kaplan-Meier method.
Eight men and 12 women with a median age of 61 years enrolled. Two-year overall survival was 88% (95% confidence interval 68%-100%). There was no significant decline in performance between baseline and 6 or 12 months for any of the tests. The association between baseline intelligence quotient and change in performance on testing was not significant. Magnetic resonance imaging revealed asymptomatic brain metastases at a cumulative rate of 20%, with no concurrent extracranial progression. Two patients developed a metastasis in the under-dosed region. Neither involved the dentate gyrus, but 1 involved the avoidance region. Both patients concurrently developed additional metastasis in fully treated brain regions. There were 2 neurologic deaths.
This prospective study suggests a potential benefit of hippocampal sparing in limiting the neuropsychological sequelae of brain radiation, but with a risk of failures in the spared region. These data strongly support continued enrollment on ongoing cooperative group randomized trials. Clinical Trials registration number: NCT01797159.
前瞻性评估局限性小细胞肺癌（SCLC）患者在保留海马体的预防性颅脑照射（PCI）后的认知功能和颅内失败模式。
符合条件的成年局限性SCLC患者，对放化疗取得完全缓解且无脑转移。患者接受25 Gy/10次分割的PCI，海马体平均剂量限制在<8 Gy，且≥90%的脑体积接受90%的处方剂量。在基线以及PCI后6个月和12个月进行了一系列多样的神经心理学测试。在基线以及6、12、18和24个月进行脑部MRI扫描。主要终点是PCI后6个月通过霍普金斯词语学习测试修订版延迟回忆测量的记忆力。放射肿瘤学组方案0212的25 Gy组被用作潜在疗效的参考。记录颅内转移的发生情况。使用Kaplan-Meier方法估计总生存期和无进展生存期。
纳入了8名男性和12名女性，中位年龄61岁。两年总生存率为88%（95%置信区间68%-100%）。任何测试在基线与6个月或12个月之间的表现均无显著下降。基线智商与测试表现变化之间的关联不显著。磁共振成像显示无症状脑转移的累积发生率为20%，无同时发生的颅外进展。2例患者在剂量不足区域发生转移。均未累及齿状回，但1例累及避让区域。两名患者在全脑治疗区域同时发生了额外转移。有2例神经学死亡。
这项前瞻性研究表明保留海马体在限制脑部放疗的神经心理学后遗症方面有潜在益处，但在保留区域有失败风险。这些数据有力支持继续纳入正在进行的合作组随机试验。临床试验注册号：NCT01797159。
