Parney Ian F, Kunwar Sandeep, McDermott Michael, Berger Mitchel, Prados Michael, Cha Soonmee, Croteau David, Puri Raj K, Chang Susan M
Department of Neurological Surgery, Brain Tumor Research Center, University of California at San Francisco, California 94143-0350, USA.
J Neurosurg. 2005 Feb;102(2):267-75. doi: 10.3171/jns.2005.102.2.0267.
Convection-enhanced delivery (CED) is a novel method for delivering therapeutic agents to infiltrative brain tumor cells. For agents administered by CED, changes on magnetic resonance (MR) imaging directly resulting from catheter placement, infusion, and the therapeutic compound may confound any interpretation of tumor progression. As part of an ongoing multiinstitutional Phase I study, 14 patients with recurrent malignant glioma underwent CED of interleukin (IL) 13-PE38QQR, a recombinant cytotoxin consisting of human IL-13 conjugated with a truncated Pseudomonas exotoxin. Serial neuroradiographic changes were assessed in this cohort of patients.
Patients were treated in two groups: Group 1 patients received IL13-PE38QQR before and after tumor resection; Group 2 patients received infusion only after tumor resection. Preoperative and postinfusion MR images were obtained prospectively at specified regular intervals. Changes were noted along catheter tracks on postresection MR images obtained in all patients. A simple grading system was developed to describe these changes. When MR imaging changes appeared to be related to IL1 3-PE38QQR, patients were followed up without instituting new antitumor therapy.
As CED of therapeutic agents becomes more common, clinicians and investigators must become aware of associated neuroimaging changes that should be incorporated into toxicity assessment. We have developed a simple grading system to facilitate communication about these changes among investigators. Biological imaging modalities that could possibly distinguish these changes from recurrent tumor should be evaluated. In this study the authors demonstrate the challenges in determining efficacy when surrogate end points such as time to tumor progression as defined by new or progressive contrast enhancement on MR imaging are used with this treatment modality.
对流增强递送（CED）是一种将治疗药物递送至浸润性脑肿瘤细胞的新方法。对于通过CED给药的药物，由导管置入、输注和治疗性化合物直接导致的磁共振（MR）成像变化可能会混淆对肿瘤进展的任何解读。作为一项正在进行的多机构I期研究的一部分，14例复发性恶性胶质瘤患者接受了白细胞介素（IL）13-PE38QQR的CED治疗，IL-13-PE38QQR是一种重组细胞毒素，由人IL-13与截短的铜绿假单胞菌外毒素缀合而成。对该队列患者的系列神经影像学变化进行了评估。
患者分为两组治疗：第1组患者在肿瘤切除前后接受IL13-PE38QQR治疗；第2组患者仅在肿瘤切除后接受输注。术前和输注后的MR图像在指定的固定间隔前瞻性获取。记录所有患者切除术后MR图像上沿导管轨迹的变化。开发了一个简单的分级系统来描述这些变化。当MR成像变化似乎与IL1 3-PE38QQR相关时，对患者进行随访，不采用新的抗肿瘤治疗。
随着治疗药物的CED变得越来越普遍，临床医生和研究人员必须意识到应纳入毒性评估的相关神经影像学变化。我们开发了一个简单的分级系统，以促进研究人员之间关于这些变化的交流。应评估可能将这些变化与复发性肿瘤区分开来的生物成像模式。在本研究中，作者展示了在使用这种治疗方式时，当使用诸如MR成像上新发或进行性对比增强所定义的肿瘤进展时间等替代终点来确定疗效时所面临的挑战。
