Chang Julie E, Khuntia Deepak, Robins H Ian, Mehta Minesh P
Department of Medicine, Section of Hematology and Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
Clin Adv Hematol Oncol. 2007 Nov;5(11):894-902, 907-15.
Effective treatment of glioblastoma multiforme (GBM) is complicated by multiple factors, including the diffusely infiltrative nature of the disease, which limits complete surgical resection; the difficulty in overcoming the blood-brain barrier with systemic therapies; and the challenge of identifying novel means of treating the residual hypoxic tumor cells that are relatively resistant to radiotherapy (RT) and chemotherapy. Clear survival advantages have been demonstrated with postresection RT to doses of 5,000-6,000 cGy, but further attempts at dose escalation over 6,000 cGy have resulted in increased toxicity without a survival benefit. In an effort to improve local control of tumor and limit toxicity to normal brain tissue, novel imaging techniques (eg, chemical shift imaging) are being explored in order to better define RT fields. Brachytherapy and stereotactic radiosurgery are effective therapies for relapsed GBM but have undefined roles outside of clinical trials in treating newly diagnosed GBM. Stereotactic RT may have a survival advantage in subgroups that have undergone a gross total resection and have favorable (recursive partitioning analysis class IV) disease. In contrast, experience with hyperfractionated RT in GBM has shown that survival outcomes may actually be unfavorable in certain patient subgroups. Novel means of delivering RT, including radioimmunotherapy, have demonstrated efficacy with acceptable toxicity. Systemic agents are being explored as potential radiosensitizers, with the recent emergence of temozolomide as a model radiosensitizing agent having a positive impact on survival. Ongoing investigations are evaluating temozolomide in combination with other systemic agents, and additional agents (eg, motexafin gadolinium, mammalian target of rapamycin inhibitors, farnesyltransferase inhibitors) have shown promising activity in combination with RT.
多形性胶质母细胞瘤（GBM）的有效治疗因多种因素而变得复杂，这些因素包括该疾病的弥漫浸润性，这限制了手术完全切除；全身治疗难以突破血脑屏障；以及识别治疗对放疗（RT）和化疗相对耐药的残留缺氧肿瘤细胞的新方法面临挑战。已证明切除术后给予5000 - 6000 cGy的放疗具有明显的生存优势，但进一步尝试将剂量提高到6000 cGy以上会导致毒性增加而无生存获益。为了改善肿瘤的局部控制并限制对正常脑组织的毒性，正在探索新型成像技术（如化学位移成像）以更好地界定放疗区域。近距离放疗和立体定向放射外科是复发性GBM的有效治疗方法，但在治疗新诊断的GBM方面，其在临床试验之外的作用尚不明确。立体定向RT在已进行大体全切且疾病预后良好（递归分区分析IV级）的亚组患者中可能具有生存优势。相比之下，GBM超分割RT的经验表明，在某些患者亚组中生存结果实际上可能不佳。包括放射免疫疗法在内的新型放疗递送方式已证明具有疗效且毒性可接受。正在探索全身药物作为潜在的放射增敏剂，最近出现的替莫唑胺作为一种放射增敏剂对生存有积极影响。正在进行的研究正在评估替莫唑胺与其他全身药物联合使用的情况，其他药物（如莫替沙芬钆、雷帕霉素哺乳动物靶点抑制剂、法尼基转移酶抑制剂）与RT联合使用已显示出有前景的活性。
