Kiss-Miki Renáta, Obeidat Mahmoud, Máté Vanda, Teutsch Brigitta, Agócs Gergely, Kiss-Dala Szilvia, Hegyi Péter, Kovács Janka, Párniczky Andrea, Tuboly Eszter, Garami Miklós
Centre for Translational Medicine, Semmelweis University, Budapest, Hungary.
Neurosurgery and Neurointerventional Clinic, Semmelweis University, Budapest, Hungary.
PLoS One. 2025 Feb 20;20(2):e0318194. doi: 10.1371/journal.pone.0318194. eCollection 2025.
With the introduction of new therapy modalities and the resulting increase in survival rates, childhood brain cancers have become a focal point of research in pediatric oncology. In current protocols, besides surgical resection and chemotherapy, radiotherapy is required to ensure optimal survival. Our aim was to determine which of the two major irradiation options, proton (PT) or photon (XRT), was the least harmful yet effective for children with brain tumors.
The protocol was registered on PROSPERO in advance (CRD42022374443). A systematic search was performed in four databases (MEDLINE via (PubMed), Embase, Cochrane Library, and Scopus) on 23 April 2024. Odd ratios (OR) and mean differences (MD) with 95% confidence intervals (CI) were calculated using a random-effects model. Survival and six major types of side effects were assessed based on data in the articles and reported using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Heterogeneity was assessed using Higgins and Thompson's I2 statistics.
Altogether, 5848 articles were screened, of which 33 were eligible for data extraction. The 5-year overall survival results showed statistically no significant difference between the two radiotherapy modalities (OR = 0.80, 95% CI: 0.51-1.23, p = 0.22, I2 = 0%). In terms of toxicity rates, an advantage was found for PT, particularly in terms of chronic endocrine side effects (hypothyroidism OR: 0.22, 95% CI: 0.10-0428, p = 0.002, I2 = 68%), neurocognitive decline (global IQ level MD: 13.06, 95% CI: 4.97-21.15, p = 0.009, I2 = 68%). As for hematological, acute side effects, neurological changes and ophthalmologic disorders PT can be beneficial for survivors in terms of reducing them.
In comparison with XRT, PT can reduce most side effects, without significantly decreasing the survival rate. There is considerable clinical relevance in the findings, even not all of them are statistically significant, which may facilitate the development of protocols regarding the usage of radiotherapy methods, and may encourage the establishment of more proton centers, where more studies can be done.
随着新治疗方式的引入以及生存率的提高，儿童脑癌已成为儿科肿瘤学研究的焦点。在当前的治疗方案中，除了手术切除和化疗外，还需要放疗以确保最佳生存率。我们的目的是确定质子治疗（PT）和光子放疗（XRT）这两种主要放疗方式中，哪一种对脑肿瘤儿童的危害最小且最有效。
该方案已提前在国际前瞻性系统评价注册库（PROSPERO）上注册（注册号：CRD42022374443）。于2024年4月23日在四个数据库（通过PubMed检索的MEDLINE、Embase、Cochrane图书馆和Scopus）中进行了系统检索。使用随机效应模型计算比值比（OR）和平均差（MD）以及95%置信区间（CI）。根据文章中的数据评估生存率和六种主要类型的副作用，并使用不良事件通用术语标准（CTCAE）第5.0版进行报告。使用希金斯和汤普森的I²统计量评估异质性。
共筛选了5848篇文章，其中33篇符合数据提取条件。5年总生存结果显示，两种放疗方式之间在统计学上无显著差异（OR = 0.80，95% CI：0.51 - 1.23，p = 0.22，I² = 0%）。在毒性率方面，发现质子治疗具有优势，特别是在慢性内分泌副作用方面（甲状腺功能减退症OR：0.22，95% CI：0.10 - 0.428，p = 0.002，I² = 68%）、神经认知功能下降方面（整体智商水平MD：13.06，95% CI：4.97 - 21.15，p = 0.009，I² = 68%）。至于血液学、急性副作用、神经系统变化和眼科疾病，质子治疗在减少这些方面对幸存者可能有益。
与光子放疗相比，质子治疗可以减少大多数副作用，而不会显著降低生存率。这些发现具有相当大的临床意义，即使并非所有结果在统计学上都具有显著性，这可能有助于制定关于放疗方法使用的方案，并可能鼓励建立更多的质子治疗中心，以便开展更多研究。
