Neoadjuvant targeting of glioblastoma multiforme with radiolabeled DOTAGA-substance P-results from a phase I study
Neoadjuvant targeting of glioblastoma multiforme with radiolabeled DOTAGA-substance P-results from a phase I study
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DOI：
10.1007/s11060-010-0153-5
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发表时间：
2010-10-01
影响因子：
3.9
通讯作者：
Merlo, Adrian
中科院分区：
文献类型：
--
作者：
Cordier, Dominik;Forrer, Flavio;Merlo, Adrian
多形性胶质母细胞瘤（GBM）由于具有浸润性，无法实现肿瘤边缘以外的完全手术切除。在几种癌症中，已经实施了新辅助治疗以降低切除术期间肿瘤细胞扩散的风险。在GBM中，新辅助方法的目的是减少主要肿瘤块内和浸润区以外的肿瘤细胞。这种方法只能在颅内压升高可以通过医学控制的情况下进行。在先前对复发性胶质瘤的研究中，我们发现局部瘤内注射放射性标记的DOTAGA-P物质可显著抑制肿瘤进一步生长，并导致肿瘤放射性坏死转化（CCR 2006）。我们现在已经检查了这种方式作为新辅助治疗GBM，主要评估可行性，毒性，切除范围和功能结果。在确诊GBM后，17例患者被纳入前瞻性I期研究。重复瘤内注射放射性标记的DOTAGA-P物质，然后进行手术切除。先前描述了肽载体[90钇]-DOTAGA-P物质的化学合成、放射性标记和局部注射。新辅助注射[90 Y]-DOTAGA-P物质是可行的，不会导致颅内压失代偿。长期应用皮质类固醇被确定为副作用的主要危险因素。15例患者的功能状态稳定或改善。在随后的手术中，平均切除范围为96%。局部注射DOTAGA-P物质新辅助治疗GBM是可行的，且毒性低。浸润区肿瘤细胞的高切除程度和伴随的照射可能与病理学相关。
Complete surgical resection beyond tumor margins cannot be achieved in glioblastoma multiforme (GBM) because of infiltrative nature. In several cancers, neoadjuvant treatment has been implemented to reduce the risk of tumor cell spreading during resection. In GBM, the objective of a neoadjuvant approach is reduction of tumor cells within the main tumor mass and beyond in the infiltration zone. Such an approach can only be performed if elevated intracranial pressure can be medically controlled. In a previous study with recurrent gliomas, we showed that local intratumoral injection of radiolabeled DOTAGA-substance P substantially inhibited further growth and led to radionecrotic transformation of the tumor (CCR 2006). We have now examined this modality as neoadjuvant treatment for GBM, primarily assessing feasibility, toxicity, the extent of resection, and functional outcome. After diagnosis of GBM, 17 patients were included in a prospective phase I study. Repetitive intratumoral injections of radiolabeled DOTAGA-substance P were performed, followed by surgical resection. Chemical synthesis, radiolabeling, and local injection of the peptidic vector [90Yttrium]-DOTAGA-substance P were described previously. Neoadjuvant injection of [90Y]-DOTAGA-substance P was feasible without decompensation of intracranial pressure. Prolonged application of corticosteroids was identified as the main risk factor for side effects. Fifteen patients stabilized or improved their functional status. The mean extent of resection in subsequent surgery was 96%. Neoadjuvant therapy of GBM using locally injected radiolabeled DOTAGA-substance P was feasible and of low toxicity. The high extent of resection and concomitant irradiation of tumor cells in the infiltration zone may be prognostically relevant.