Perry Arie, Schmidt Robert E
Division of Neuropathology, Washington University School of Medicine, St. Louis, MO 63110-1093, USA.
Acta Neuropathol. 2006 Mar;111(3):197-212. doi: 10.1007/s00401-005-0023-y. Epub 2006 Feb 4.
Standard therapeutic options for brain tumors include surgery, radiation, and chemotherapy. Unfortunately, these same therapies pose risks of neurotoxicity, the most common long-term complications being radiation necrosis, chemotherapy-associated leukoencephalopathy, and secondary neoplasms. These side effects remain difficult to predict, but are associated with risk factors that include patient age, therapeutic modality and dosage, genetic background, and idiosyncratic predispositions. Experimental treatments designed to enhance efficacy and to minimize neurotoxicity include molecularly targeted, genetic, stem cell, and immune therapies. Newer modifications in radiation and drug delivery include stereotactic radiosurgery, interstitial therapy such as intracavitary brachytherapy and gliadel wafer placement, 3D conformal radiation, boron neutron capture therapy, radiosensitizers, blood-brain barrier disrupting agents, and convection enhanced delivery. Toxicities associated with these newer modalities have yet to be fully investigated and documented. Additionally, a number of recently implemented radiographic techniques such as PET and SPECT imaging have enhanced the ability to distinguish recurrent tumor from radiation necrosis. Nevertheless, post-therapeutic brain biopsies and autopsies remain the gold standard for assessing neurotoxicity, therapeutic efficacy, tumor progression, and the development of secondary neoplasms. At the same time, treatment-associated changes such as tumor necrosis, vasculopathy, inflammation, and cytologic atypia can pose significant diagnostic pitfalls, particularly if the pathologist is not provided a detailed therapeutic history. Therefore, it is critical to recognize the full spectrum of cancer therapy-associated neuropathology, the topic of the current review.
脑肿瘤的标准治疗选择包括手术、放疗和化疗。不幸的是，这些相同的疗法存在神经毒性风险，最常见的长期并发症是放射性坏死、化疗相关的白质脑病和继发性肿瘤。这些副作用仍然难以预测，但与包括患者年龄、治疗方式和剂量、遗传背景以及特异体质倾向等风险因素相关。旨在提高疗效并将神经毒性降至最低的实验性治疗包括分子靶向治疗、基因治疗、干细胞治疗和免疫治疗。放疗和药物递送方面的新改进包括立体定向放射外科、腔内近距离放疗和胶质母细胞瘤缓释剂植入等间质治疗、三维适形放疗、硼中子俘获疗法、放射增敏剂、血脑屏障破坏剂以及对流增强递送。与这些新疗法相关的毒性尚未得到充分研究和记录。此外，一些最近应用的影像学技术，如正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT）成像，增强了区分复发性肿瘤与放射性坏死的能力。然而，治疗后脑活检和尸检仍然是评估神经毒性、治疗效果、肿瘤进展以及继发性肿瘤发生的金标准。同时，与治疗相关的变化，如肿瘤坏死、血管病变、炎症和细胞异型性，可能会造成重大的诊断陷阱，特别是如果病理学家没有得到详细的治疗史。因此，认识癌症治疗相关神经病理学的全貌至关重要，这也是本综述的主题。
