Convection-enhanced delivery of topotecan into diffuse intrinsic brainstem tumors in children.
Convection-enhanced delivery of topotecan into diffuse intrinsic brainstem tumors in children.
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DOI：
10.3171/2012.10.peds12142
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发表时间：
2013-03
期刊：
影响因子：
--
通讯作者：
Bruce JN
中科院分区：
文献类型：
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作者：
Anderson RC;Kennedy B;Yanes CL;Garvin J;Needle M;Canoll P;Feldstein NA;Bruce JN
对流增强输送(CED)治疗恶性胶质瘤是一种通过持续、低级别的正压输注将化疗药物直接输送到肿瘤及其周围间质的技术。这允许肿瘤内的高局部药物浓度，同时将通常导致剂量限制性毒性的全身水平降至最低。弥漫性桥脑胶质瘤(DIPGs)是儿童常见的致命肿瘤，目前尚无有效的治疗方法。在这篇报道中，作者描述了拓扑异构酶抑制剂拓扑替康的CED治疗2例儿童DIPG。作为先导可行性研究的一部分，作者治疗了2名患有DIPG的儿科患者。立体定向活检和冰冻切片证实胶质瘤后，在同一过程中放置双侧导管用于拓扑替康的CED。第一例患者在初诊后210d、放疗后和肿瘤复发时进行CED，总剂量为0.403 mg/6.04ml100h。治疗前卡诺夫斯基评分为60分，治疗后为50分。系列MRI最初显示肿瘤大小和水肿适度缩小，但肿瘤继续发展，患者在治疗49天后死亡。第二例患者在初步诊断后24天接受放射治疗，总剂量为0.284 mg，5.30ml，100h。治疗前KPS评分为70分，治疗后为50分。系列磁共振成像同样显示肿瘤大小在最初有适度的缩小。患者随后接受了分割放射治疗，但肿瘤继续发展，治疗120天后死亡。拓扑替康通过延长CED进入脑干治疗DIPG在技术上是可行的。在这两个患者中，高输液速率(>；0.12ml/小时)和高输液量(>；2.8ml)导致新的神经功能障碍和KPS评分降低，但较低的输液速率(<；0.04ml/小时)耐受性良好。虽然系列MRI显示治疗效果中等，但CED并未延长这2例患者的生存时间。需要更多的研究来改进患者选择和确定化疗药物进入DIPG的最佳CED流量，以最大限度地提高安全性和有效性。临床试验注册号：NCT00324844。
Convection-enhanced delivery (CED) for the treatment of malignant gliomas is a technique that can deliver chemotherapeutic agents directly into the tumor and the surrounding interstitium through sustained, low-grade positive-pressure infusion. This allows for high local concentrations of drug within the tumor while minimizing systemic levels that often lead to dose-limiting toxicity. Diffuse intrinsic pontine gliomas (DIPGs) are universally fatal childhood tumors for which there is currently no effective treatment. In this report the authors describe CED of the topoisomerase inhibitor topotecan for the treatment of DIPG in 2 children. As part of a pilot feasibility study, the authors treated 2 pediatric patients with DIPG. Stereotactic biopsy with frozen section confirmation of glial tumor was followed by placement of bilateral catheters for CED of topotecan during the same procedure. The first patient underwent CED 210 days after initial diagnosis, after radiation therapy and at the time of tumor recurrence, with a total dose of 0.403 mg in 6.04 ml over 100 hours. Her Karnofsky Performance Status (KPS) score was 60 before CED and 50 posttreatment. Serial MRI initially demonstrated a modest reduction in tumor size and edema, but the tumor progressed and the patient died 49 days after treatment. The second patient was treated 24 days after the initial diagnosis prior to radiation with a total dose of 0.284 mg in 5.30 ml over 100 hours. Her KPS score was 70 before CED and 50 posttreatment. Serial MRI similarly demonstrated an initial modest reduction in tumor size. The patient subsequently underwent fractionated radiation therapy, but the tumor progressed and she died 120 days after treatment. Topotecan delivered by prolonged CED into the brainstem in children with DIPG is technically feasible. In both patients, high infusion rates (> 0.12 ml/hr) and high infusion volumes (> 2.8 ml) resulted in new neurological deficits and reduction in the KPS score, but lower infusion rates (< 0.04 ml/hr) were well tolerated. While serial MRI showed moderate treatment effect, CED did not prolong survival in these 2 patients. More studies are needed to improve patient selection and determine the optimal flow rates for CED of chemotherapeutic agents into DIPG to maximize safety and efficacy. Clinical trial registration no.: NCT00324844.