Glantz Michael, Kesari Santosh, Recht Lawrence, Fleischhack Gudrun, Van Horn Alexis
Department of Neurosurgery, Penn State Hershey Medical Center, Hershey, PA 17033-0859, USA.
Semin Oncol. 2009 Aug;36(4 Suppl 2):S17-24. doi: 10.1053/j.seminoncol.2009.05.003.
Glioblastoma multiforme (GBM), the most common malignant primary brain tumor in adults, carries a poor prognosis, with median survival generally less than 1 year. Although initial therapy often eradicates the bulk of the tumor, disease recurrence, usually within 2 cm of the original tumor, is almost inevitable. This may be due to a failure of current therapies to eradicate viable chemotherapy- and radiotherapy-resistant neoplastic progenitor cells, which may then repopulate tumors. An increasing body of preclinical data suggests that these cells may correspond to stem cells derived from the subventricular zone (SVZ), which migrate to tumor sites and contribute to glioma growth and recurrence. Therapeutic targeting of SVZ stem cell populations via cerebrospinal fluid (CSF)-directed therapy may provide a means for limiting tumor recurrence. This approach has proved successful in the treatment of medulloblastoma, another brain tumor thought to be derived from stem cells. We discuss the rationale and design considerations for a clinical trial to evaluate the efficacy of CSF-directed therapy for preventing GBM recurrence.
多形性胶质母细胞瘤（GBM）是成人中最常见的原发性恶性脑肿瘤，预后较差，中位生存期通常不到1年。尽管初始治疗常常能消除大部分肿瘤，但疾病复发几乎不可避免，通常发生在原发肿瘤2厘米范围内。这可能是由于当前治疗方法未能根除存活的对化疗和放疗耐药的肿瘤祖细胞，这些细胞随后可能重新填充肿瘤。越来越多的临床前数据表明，这些细胞可能对应于源自脑室下区（SVZ）的干细胞，它们迁移到肿瘤部位并促进胶质瘤的生长和复发。通过脑脊液（CSF）导向治疗对SVZ干细胞群体进行治疗靶向可能提供一种限制肿瘤复发的方法。这种方法已在髓母细胞瘤的治疗中证明是成功的，髓母细胞瘤是另一种被认为源自干细胞的脑肿瘤。我们讨论了一项临床试验的基本原理和设计考虑因素，以评估CSF导向治疗预防GBM复发的疗效。
