Brain Tumor Clinical and Clinical Research Program

NOB在建立必要的基础设施方面取得了重大进展，以履行其为患有脑髓和脊髓肿瘤的儿童和成人开发新的和改进的治疗方法的使命。以下是建立脑肿瘤临床和临床研究项目的部分成就：建立了一个NIH范围内的多学科脑肿瘤诊所，有三个不同的NCI分支机构（ROB， MOCRU， CCRLP），五个不同的NIH机构（NCI， NINDS， NEI， NHLBI， NIMH）和五个不同的临床中心项目（神经放射学，精神病学，疼痛和缓解，康复医学，社会工作）的积极参与。临床专家包括肿瘤内科、放射肿瘤学、神经外科、神经病学、眼科、心脏病学、精神病学、内分泌学、社会工作和康复医学；组建了一个初级神经肿瘤临床护理/研究团队，目前包括4名神经肿瘤学家，6名nob培训的神经肿瘤执业护士，3名研究护士，2名神经肿瘤研究员，2名患者协调员，2名临床试验专家和5名数据管理员；建立健全的神经肿瘤学咨询服务，本地/区域患者在NIH就诊并随访(所有患者均纳入中枢神经系统肿瘤自然病史协议；远端患者可能只需要检查放射学/医疗记录；作为搜索委员会主席，Howard Fine帮助为NINDS/NCI招募了两名新的终身任职临床医生/科学家脑肿瘤神经外科医生，导致NINDS外科神经病学分会共有5名临床活跃的脑肿瘤神经外科医生；启动了超过30个IRB批准的临床试验，另外4个预计将在未来几个月内获得批准，总共有30个方案，而当NOB于2000年成立时，NIH只有一个原发性脑肿瘤方案（一个先前的放射方案，累积了500个新的原发性脑肿瘤患者（几乎所有胶质瘤），在过去的12个月里，有2000-3000名随访患者）。而在NOB成立前一年（1999年），在NIH发现的恶性脑肿瘤患者为10例。此外，NOB每周审查2-6个新的邮寄患者咨询。为沃尔特里德医疗中心、朴茨茅斯海军医院和贝塞斯达海军医疗中心提供几乎所有的神经肿瘤学服务；与约翰霍普金斯医疗中心、乔治华盛顿医疗中心、费尔法克斯Inova和华盛顿医院中心以及当地和全国范围内广泛的私人神经外科、放射和肿瘤实践小组建立了密切的合作临床项目；创建了美国仅有的几个有组织的神经肿瘤学奖学金培训项目之一——美国国立卫生研究院、约翰霍普金斯医学中心和华盛顿特区的国家儿童医学中心的三机构联合研究培训项目；通过临床前筛选项目鉴定出5种化合物（CC8490、LY317615、Velcade + Tamoxifen、CC5013、Talampanel、MLN518、Sunitinib），这些化合物已在NIH提交临床试验。我们还启动了一项真正独特的研究，这项研究只能在美国国立卫生研究院和临床中心完成，用于所有实际目的。为了在功能性和肿瘤干细胞水平上试图了解恶性胶质瘤患者大脑内肿瘤内的异质性，有必要获得大脑所有区域的活的肿瘤和正常组织。显然，这样的取样不能在活着的病人身上进行，但不幸的是，我们发现离死亡12小时的尸体解剖标本太老了，无法生长出可存活的组织。因此，我们发起了一项独特的试验，希望将大脑捐献给脑肿瘤研究的患者和家属在死亡前不久被送入临床中心接受临终关怀/临终关怀。在心脏骤停时，病人的身体立即被带到手术室，在无菌的手术条件下，我们的一位神经外科医生从颅顶取出大脑，然后迅速解剖所有合适的组织样本，立即冷冻和/或放入培养中供肿瘤细胞生长。这项研究将给我们前所未有的机会来构建一个基于肿瘤细胞的人类大脑基因组微解剖图谱。该试验是NOB临床和基础科学研究工作紧密结合的典型。在神经肿瘤学实验室内，作为翻译工作的直接结果，启动了超过9项临床试验。

The NOB has made substantial progress towards building an infrastructure necessary for fulfilling its mission of developing new and improved therapies for children and adults with brain and spinal cord tumors. Below are partial lists of accomplishments in the building of the Brain Tumor Clinical and Clinical Research Program: Established an NIH-wide multidisciplinary Brain Tumor Clinic with active participation from three different NCI Branches (ROB, MOCRU, CCRLP), five different NIH Institutions (NCI, NINDS, NEI, NHLBI, NIMH), and five different Clinical Center Programs (Neuroradiology, Psychiatry, Pain and Palliation, Rehabilitation Medicine, Social Work). Expertise represented in the clinic includes Medical Oncology, Radiation Oncology, Neurosurgery, Neurology, Ophthalmology, Cardiology, Psychiatry, Endocrinology, Social Work, and Rehabilitation Medicine; Assembled a primary neuro-oncology clinical care/research team, which now consists of 4 neuro-oncologists, 6 NOB-trained neuro-oncology nurse practitioners, 3 research nurses, 2 neuro-oncology fellows, 2 patient coordinators, 2 clinical trials specialists and 5 data managers; Established a robust neuro-oncology consultation service, in which local/regional patients are seen and followed at the NIH (all patients are accrued to a CNS tumor natural history protocol; distant patients may just have radiology/medical records reviewed; Serving as Chair of the Search Committee, Howard Fine helped recruit two new tenure track clinician/scientist brain tumor neurosurgeons to NINDS/NCI leading to a total of 5 clinically active brain tumor neurosurgeons in the Surgical Neurology Branch, NINDS; Activated more than 30 IRB approved clinical trials with an additional 4 expected to be approved in the coming months, for a total of 30 protocols compared to just 1 protocol existing for primary brain tumors at the NIH when the NOB was formed in 2000 (a prior radiation protocol that had accrued 500 new primary brain tumor patients (almost all gliomas) and between 2000-3000 follow-up patients over the last 12 months, up from < 10 patients with malignant brain tumor seen at NIH in the year before the NOB was formed (1999). Additionally, the NOB reviews 2-6 new mail-in patient consults per week. Provides almost all neuro-oncology services for Walter Reed Medical Center, the Portsmouth Naval Hospital, and the Naval Medical Center in Bethesda; Established close collaborative clinical programs with Johns Hopkins Medical Center, George Washington Medical Center, Fairfax Inova and Washington Hospital Center and a wide array of private neurosurgical, radiation, and oncology practice groups locally and nationally; Created one of only a few organized neuro-oncology fellowship training programs in the United Statesa three-institution joint research training program between the NIH, Johns Hopkins Medical Center, and Childrens National Medical Center in Washington, D.C.; Identified five compounds through the preclinical screening program that have since been brought forward to clinical trials at the NIH (CC8490, LY317615, Velcade + Tamoxifen, CC5013, Talampanel, MLN518, Sunitinib). We have also initiated a truly unique study that could only be accomplished at the NIH and the Clinical Center for all practical purposes. In an effort to try and understand the intra-tumor heterogeneity found within the brain of a patient with malignant gliomas at a functional and tumor stem cell levels it is necessary to obtain viable tumor and normal tissue for all regions of the brain. Obviously such a sampling can not be done on alive patient but unfortunately, we have found that autopsy specimens that are as fresh as 12 hours from death are too old to grow viable tissue. Thus, we initiated a unique trial where patients and families who wish to donate their brains to brain tumor research are admitted to the Clinical Center shortly prior to death for hospice/end of life care. Immediately upon cardiac arrest the patients body is quickly brought down to the surgical suite and under sterile surgical conditions the brain is removed from the cranial vault by one of our neurosurgeons and then quickly dissected with all of the appropriate tissue samples immediate frozen and/or put into culture for tumor cell growth. This study will give us unprecedented opportunity to construct a tumor cell-based genomic microanatomical map of a human brain harboring a GBM. This trial typifies the close and intertwined functioning of the clinical and basic science research effort of the NOB. Activated more than 9 clinical trials as a direct result of translational work performed within the Neuro-Oncology Laboratory.