Repeat convection-enhanced delivery for diffuse intrinsic pontine glioma
Repeat convection-enhanced delivery for diffuse intrinsic pontine glioma
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DOI：
10.3171/2020.6.peds20280
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发表时间：
2020-12-01
影响因子：
1.9
通讯作者：
Souweidane, Mark M.
中科院分区：
文献类型：
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作者：
Bander, Evan D.;Ramos, Alexander D.;Souweidane, Mark M.
目的虽然对流增强给药(CED)在接受单剂量药物输注的患者中的安全性和有效性已被研究，但用于肿瘤治疗的药物可能需要重复或长期输注才能维持治疗药物浓度。重复和慢性CED输注很少被描述为肿瘤学目的。目前可用的CED装置还没有被批准用于延长留置时间，目前唯一的可能性是通过多个程序进行连续治疗。作者报道了一组儿童患者接受脑干序贯CED治疗弥漫性内源性脑桥胶质瘤的安全性和经验。方法本研究的患者参加了一项I期单中心临床试验，使用124I-8H9单抗(124I-omburTamab)，CED(临床试验和政府标识NCT01502917)。回顾图表和影像回顾被用来评估人口统计学数据、CED输注数据以及术后神经学和手术结果。MRI扫描使用iPlan Flow软件进行体积测量分析。使用ClearPoint成像软件计算靶点和导管的坐标以及在MRI空间中的放射状、深度和绝对误差。没有患者经历临床术语标准的不良事件3级或更大的缺陷。一名患者在第二次输液后出现持续性的2级脑神经缺陷。术后无一例发生出血或中风。与第一次输液相比，第二次输液的径向误差(p=0.005)和绝对尖端误差(p=0.008)有统计学意义的降低。序贯输液在第一次和第二次输注之间没有显著差异(分布容量由PET信号/输注比体积[Mean+/-SD]决定：2.66+/-0.35 vs 2.42+/-0.75；p=0.45)。结论本系列显示了在儿童脑干内进行CED序贯灌注的能力。过去的治疗没有对程序工作流程、靶向接口的技术应用或分发能力产生负面影响。这一有限的经验为将重复CED用于肿瘤学目的提供了基础。
OBJECTIVE While the safety and efficacy of convection-enhanced delivery (CED) have been studied in patients receiving single-dose drug infusions, agents for oncological therapy may require repeated or chronic infusions to maintain therapeutic drug concentrations. Repeat and chronic CED infusions have rarely been described for oncological purposes. Currently available CED devices are not approved for extended indwelling use, and the only potential at this time is for sequential treatments through multiple procedures. The authors report on the safety and experience in a group of pediatric patients who received sequential CED into the brainstem for the treatment of diffuse intrinsic pontine glioma.METHODS Patients in this study were enrolled in a phase I single-center clinical trial using 124I-8H9 monoclonal antibody (124I-omburtamab) administered by CED (clinicaltrials.gov identifier NCT01502917). A retrospective chart and imaging review were used to assess demographic data, CED infusion data, and postoperative neurological and surgical outcomes. MRI scans were analyzed using iPlan Flow software for volumetric measurements. Target and catheter coordinates as well as radial, depth, and absolute error in MRI space were calculated with the ClearPoint imaging software.RESULTS Seven patients underwent 2 or more sequential CED infusions. No patients experienced Clinical Terminology Criteria for Adverse Events grade 3 or greater deficits. One patient had a persistent grade 2 cranial nerve deficit after a second infusion. No patient experienced hemorrhage or stroke postoperatively. There was a statistically significant decrease in radial error (p = 0.005) and absolute tip error (p = 0.008) for the second infusion compared with the initial infusion. Sequential infusions did not result in significantly different distribution capacities between the first and second infusions (volume of distribution determined by the PET signal/volume of infusion ratio [mean +/- SD]: 2.66 +/- 0.35 vs 2.42 +/- 0.75; p = 0.45).CONCLUSIONS This series demonstrates the ability to safely perform sequential CED infusions into the pediatric brainstem. Past treatments did not negatively influence the procedural workflow, technical application of the targeting interface, or distribution capacity. This limited experience provides a foundation for using repeat CED for oncological purposes.