Gardner Melissa M, Winter Sebastian F, Stahl Franziska, Gerstner Elizabeth R, Shih Helen A, Sherman Janet, Dietrich Jorg, Parsons Michael W
Division of Neuro-Oncology, Mass General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Psychiatry, Psychology Assessment Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
J Neurooncol. 2025 Jan;171(2):351-363. doi: 10.1007/s11060-024-04850-9. Epub 2024 Oct 14.
Radiation therapy (RT) is an integral treatment component in patients with glioma but associated with neurotoxicity. Proton RT (PRT), as compared with photon RT (XRT), reduces excess radiation to nontarget tissue. We used a retrospective method to evaluate brain imaging metrics of neurotoxicity after treatment with PRT and XRT for glioma.
We analyzed brain volume change in thirty-four patients with WHO grade 2-3 gliomas treated with either PRT (n = 17) or XRT (n = 17). Both groups were carefully matched by demographic/clinical criteria and assessed longitudinally for two years post-radiotherapy. Brain volume change was measured as ventricular volume expansion in the tumor free hemisphere (contralateral to RT target) as a proxy indicator of brain volume loss. We further assessed the impact of volumetric changes on cognition in PRT patients, who completed neuropsychological testing as part of an outcome study.
We found significant ventricular volume increases in the contralesional hemisphere in both groups at two years post-RT (F(1, 31) = 18.45, p < 0.000, partial η2 = 0.373), with greater volume change observed in XRT (26.55%) vs. PRT (12.03%) (M = 12.03%, SD = 16.26; F(1,31) = 4.26, p = 0.048, partial η2 = 0.121). Although, there was no group-level change on any cognitive test in PRT treated patients, individual changes on cognitive screening, working memory, processing speed and visual memory tasks correlated with contralesional brain volume loss.
This study suggests progressive brain volume loss following cranial irradiation, with greater severity after XRT vs. PRT. Radiation-induced brain volume loss appears to be associated with measurable cognitive changes on an individual level. Prospective studies are warranted to validate these findings and their impacts on long-term cognitive function and quality of life. An improved understanding of the structural and functional consequences of cranial radiation is essential to develop neuroprotective strategies.
放射治疗（RT）是胶质瘤患者综合治疗的重要组成部分，但会产生神经毒性。与光子放疗（XRT）相比，质子放疗（PRT）可减少对非靶组织的过量辐射。我们采用回顾性方法评估PRT和XRT治疗胶质瘤后神经毒性的脑成像指标。
我们分析了34例WHO 2-3级胶质瘤患者的脑容量变化，其中17例接受PRT治疗，17例接受XRT治疗。两组在人口统计学/临床标准方面进行了仔细匹配，并在放疗后两年进行纵向评估。脑容量变化通过无肿瘤半球（与放疗靶区对侧）的脑室容积扩大来测量，作为脑容量损失的替代指标。我们进一步评估了PRT患者容积变化对认知的影响，这些患者作为一项结果研究的一部分完成了神经心理学测试。
我们发现两组在放疗后两年对侧半球的脑室容积均显著增加（F(1, 31) = 18.45，p < 0.000，偏η2 = 0.373），XRT组的容积变化（26.55%）大于PRT组（12.03%）（均值 = 12.03%，标准差 = 16.26；F(1,31) = 4.26，p = 0.048，偏η2 = 0.121）。虽然接受PRT治疗的患者在任何认知测试中均未出现组水平的变化，但在认知筛查、工作记忆、处理速度和视觉记忆任务上的个体变化与对侧脑容量损失相关。
本研究表明颅脑照射后会出现渐进性脑容量损失，XRT后的严重程度高于PRT。辐射引起的脑容量损失似乎与个体水平上可测量的认知变化相关。有必要进行前瞻性研究以验证这些发现及其对长期认知功能和生活质量的影响。更好地理解颅脑放疗的结构和功能后果对于制定神经保护策略至关重要。
