Service de Neurologie, Hôpital du Val-de-Grâce, France.
Curr Opin Oncol. 2009 Nov;21(6):559-65. doi: 10.1097/CCO.0b013e328330c669.
Treatment-induced brain toxicity remains a major cause of morbidity in adult patients with cancer. Contrasting with the 40-year-old unresolved controversy about the primary damaging event (vascular versus parenchymal) in the physiopathology, numerous prospective clinical trials have recently addressed the question of brain toxicity. Despite remarkable efforts in methodological design, they often only partially answer the questions of which treatment modalities are responsible, which brain functions are mainly impaired, how long the impairment duration is and which characteristics make patients vulnerable.
Real advances in the design of safer radiation procedures have been counterbalanced by a wider use of combined radiotherapy-chemotherapy regimens, the development of radiosurgery and the increasing number of long-term survivors. Although classic radionecrosis or chemonecrosis has become less common, more subtle changes such as progressive cognitive dysfunction are increasingly reported after radiotherapy (radiation-induced leukoencephalopathy) or chemotherapy, administered alone or in combination as reviewed here. The methodological aspects of published studies are questioned and suggestions are provided that may improve the design of future trials.
The abovementioned issue is of clinical importance given the number of patients treated for brain tumors, including patients with brain metastases, and the number of patients who are at high risk for brain metastasis who could benefit from prophylactic cranial irradiation. Moreover, drugs used in nonbrain tumors are now recognized to impair brain normal functioning.
治疗相关的脑毒性仍然是成年癌症患者发病率的主要原因。与 40 年来关于发病生理机制中主要损伤事件(血管性还是实质损伤)的未决争议形成对比的是,最近有大量前瞻性临床试验探讨了脑毒性问题。尽管在方法学设计方面付出了巨大努力,但这些试验往往只能部分回答以下问题:哪些治疗方法会导致脑毒性,哪些脑功能受到主要损害,损害持续时间有多长,以及哪些特征会使患者易受影响。
在设计更安全的放疗方法方面取得了显著进展,但与此同时,联合放化疗方案的应用更为广泛,放射外科的发展,以及长期幸存者数量的增加,使得治疗相关脑毒性的问题更为突出。虽然经典的放射性坏死或化学性坏死已变得不那么常见,但越来越多的研究报告了放疗(放射性脑白质病)或化疗单独或联合应用后出现的更微妙的变化,如进行性认知功能障碍。本文对已发表研究的方法学方面提出了质疑,并提出了一些建议,以期改进未来试验的设计。
总之,鉴于治疗脑肿瘤(包括脑转移瘤患者)的患者数量,以及接受预防性颅脑照射以降低脑转移风险的患者数量众多,上述问题具有重要的临床意义。此外,目前已认识到用于治疗非脑部肿瘤的药物也会损害脑的正常功能。