PEDIATRIC BRAIN TUMOR CONSORTIUM--CHOP MEMBERSHIP

这项建议的总体目标是改善儿童原发性脑肿瘤的治疗结果。这将通过新成立的儿科脑肿瘤临床试验联盟（PBTC）进行的有前景的新治疗药物、递送技术、生物疗法和放射治疗策略的I期和II期临床评估来完成。该联盟将把八家优秀医疗机构的经验和资源结合在一个组织结构中，旨在促进对儿童脑肿瘤新疗法的快速和成功研究。第二个目标是利用联盟机制共享脑肿瘤标本以及其他临床和实验室数据，并开展有关神经影像学、药理学和儿童脑肿瘤生物学的研究。为了实现这些目标，PBTC必须依靠每个参与机构的特殊优势和资源。因此，我们提出以下具体目标来推进PBTC的目标：作为成员机构参与PBTC临床试验、实验室和神经影像学研究；目标2。开发儿童中枢神经系统肿瘤的新实验疗法，并为PTBC的I/II期临床试验提出这些策略；目标3。建议和促进鞘内治疗预防或治疗儿童中枢神经系统肿瘤的发展和研究；和Aim 4。提出并发展区域性肿瘤药代动力学和脑肿瘤生物学的神经影像学研究，供PBTC成员参与。费城儿童医院（CHOP）拥有一支由国际公认的儿科神经肿瘤学、放射肿瘤学、神经外科、神经放射学、药理学和新药开发领域的领导者组成的优秀多学科临床团队；(2)大量儿童原发性脑肿瘤患者可用于研究；(3)先进的神经影像学诊断和研究设施（MRI, MRSpectroscopy， PET， SPECT），神经外科（计算机图像引导手术）和放射治疗（立体定向放射手术，伽玛刀，近距离治疗）；(4)美国国立卫生研究院资助的脑肿瘤银行，存储来自CHOP、NYU和Beth Israel （NYC）的脑肿瘤活检；(5)国际公认的神经病理学专业知识；(6)在生物统计学和临床试验数据管理方面拥有广泛的机构资源，在临床护理和研究方面享有卓越声誉；(7)具有组织协调多机构临床试验的经验；(8)大量高质量、临床相关、同行评审和NIH资助的脑肿瘤研究。这些计划和制度优势支持我们具体目标的可行性，符合RFA规定的联盟参与标准，并大大提高了PBTC实现其长期目标的可能性。

The overall objective of this proposal is to improve therapeutic outcomes for children with primary brain tumors. This will be accomplished by Phase I and II clinical evaluations of promising new therapeutic drugs, delivery technologies, biological therapies, and radiation treatment strategies conducted by a newly-established Pediatric Brain Tumor Clinical Trials Consortium (PBTC). This consortium will combine the experience and resources of eight outstanding medical institutions in an organizational structure designed to facilitate a rapid and successful study of new therapies for childhood brain tumors. A second objective is to utilize the consortium mechanism to share brain tumor specimens as well as other clinical and laboratory data and to conduct research pertaining to neuroimaging, pharmacology, and the biology of childhood brain tumors. To achieve these objectives, the PBTC must rely on the special strengths and resources of each participating institution. Accordingly, we propose the following Specific Aims to advance PBTC goals: Aim 1. to participate as a Member Institution in PBTC clinical trials, laboratory, and neuroimaging studies; Aim 2. to develop new experimental therapies for CNS tumors in children and propose these strategies for phase I/II clinical trials by the PTBC; Aim 3. to propose and facilitate the development and study of intrathecal therapies for the prophylaxis or treatment of childhood CNS tumors; and Aim 4. to propose and develop neuroimaging studies of regional tumor pharmacokinetics and brain tumor biology for participation by PBTC members. The Children's Hospital of Philadelphia (CHOP) has: (1) an outstanding multi- disciplinary clinical team of internationally-recognized leaders in pediatric neuro-oncology, radiation oncology, neurosurgery, neuro-radiology, pharmacology, and new drug development; (2) a large number of patients with childhood primary brain tumors available for study; (3) state-of-the-art facilities for diagnostic and research neuroimaging (MRI, MRSpectroscopy, PET, SPECT), neurosurgery (computer image-guided surgery), and radiation therapy (stereotaxic radiosurgery, Gamma Knife, brachytherapy); (4) an NIH-funded brain tumor bank which stores brain tumor biopsies from CHOP, NYU, and Beth Israel (NYC) (5) internationally-recognized expertise in neuro-pathology; (6) extensive institutional resources for biostatistics and clinical trial data management and a reputation for excellence in clinical care and research; (7) experience in the organization and coordination of multi-institutional clinical trials; and (8) a large number of high quality, clinically relevant, peer reviewed and NIH funded brain tumor research studies. These programmatic and institutional strengths support the feasibility of our specific aims, are responsive to the criteria for consortium participation specified by the RFA, and substantially enhance the likelihood that the PBTC will achieve its long-term goals.