PEDIATRIC LOW GRADE ASTROCYTOMA--TREATMENT GUIDANCE

儿童低度星形细胞瘤——治疗指南

• 批准号: 2461212
• 负责人: Jeffry R Alger
• 金额: $ 14.15万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-12 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2461212
• 关键词: apoptosis; astrocytoma; cell proliferation; child (0-11); choline; clinical research; clinical trials; electron spin resonance spectroscopy; human subject; human therapy evaluation; immunocytochemistry; neoplasm /cancer chemotherapy; neoplasm /cancer radiation therapy; outcomes research; pediatric neoplasm /cancer; pediatric pharmacology; prognosis; tissue /cell culture

DESCRIPTION: Clinical outcome in cases of pediatric low grade astrocytoma (LGA), the single most common type of solid tumor in children, is unpredictable. Although complete resection is often curative, this is not possible, in many instances, because LGA tends to invade midline brain structures having essential systemic physiological significance. After partial resection, LGA may remain stable, may continue to grown, or may undergo malignant transformation. Even modest postoperative growth can result in severe neurological deficits or death. After partial resection, several adjunctive management options are available for biologically aggressive tumors. Fractionated radiation therapy or chemotherapy may be used, but these options are often deferred as long as possible to avoid therapy-attributable developmental problems. Stereotactic radiation therapy may be used to ablate aggressive tumor foci ("pruning") as a means of controlling volumetric growth thereby permitting the child to develop to the point where global radiation therapy or chemotherapy can be considered. Conventional diagnostic neuroimaging methods are unable to identify biologically aggressive LGA so that adjunctive therapy may be offered nor are they capable of identifying the location of tumor subvolumes exhibiting aggressive characteristics for "pruning". We hypothesize that choline signal measures obtained from newly developed proton magnetic resonance spectroscopic imaging (1H-MRSI) technology will overcome these shortcomings. The hypothesis is based on studies which suggest that choline signal levels are related proliferative activity and on our own work which has shown that histopathologically homogeneous LGA cases exhibit heterogeneous patterns of tumoral choline signal. The hypothesis will be tested with clinical/laboratory correlation study and two pilot clinical trials. In the clinical/laboratory correlation study, pre-operative determination of metabolically relevant regions of interest with 1H-MRSI will be followed by intra-surgical excision of samples identified. These will be analyzed immunocytochemically for proliferative and apoptosis characteristics. In the clinical pilot trials, we will seek to establish that post-therapy choline measures are predictive of future growth and that 1H-MRSI may be used in target planning for focal therapies.

描述：儿童低级别星形细胞瘤病例的临床结局 (LGA)是儿童中最常见的一种实体瘤， 不可预测 尽管完全切除通常可以治愈，但事实并非如此 在许多情况下，这是可能的，因为LGA倾向于侵入中线脑 具有重要的全身生理意义的结构。 后 部分切除后，LGA可能保持稳定，可能继续生长，或者可能 经历恶性转化。 即使是适度的术后生长， 导致严重的神经功能缺损或死亡。 部分切除后， 有几种连续的管理方法可供生物学上使用， 侵袭性肿瘤 分次放疗或化疗可能 使用，但这些选项往往被推迟，只要可能，以避免 治疗引起的发育问题。 立体定向放射治疗 可用于消融侵袭性肿瘤病灶（“修剪”）， 控制体积生长，从而允许儿童发育到 可以考虑进行全身放疗或化疗。 传统的诊断神经成像方法无法识别 生物侵袭性LGA，以便可以提供连续治疗， 它们是否能够识别肿瘤亚体积的位置， “修剪”的侵略性特征。 我们假设胆碱 从新开发的质子磁共振获得的信号测量 光谱成像（1H-MRSI）技术将克服这些缺点。 这一假设是基于研究表明胆碱信号水平 与增殖活性有关，我们自己的研究表明， 组织病理学均质LGA病例表现出异质性模式， 肿瘤胆碱信号。 该假设将被测试， 临床/实验室相关性研究和两项试点临床试验。 在 临床/实验室相关性研究，术前确定 1H-MRSI的代谢相关感兴趣区域将随后进行 确定的样本的术中切除。 这些将被分析 免疫细胞化学检测增殖和凋亡特征。 在 临床试验，我们将寻求建立治疗后 胆碱测量可预测未来的生长，1H-MRSI可能是 用于局部治疗的目标规划。