CONNECT: Comprehensive Oncology Network Evaluating Rare CNS Tumors - Cures

迄今为止，我们的进展包括建立了一个由致力于该项目的研究人员和机构组成的NCI-CONNECT网络。这个小组每两年开会一次。这包括与我们已经在NIH举行的脑肿瘤试验合作（BTTC）年会合作举行的为期两天的会议；本次会议将主要利益相关者和研究人员聚集在一起，讨论项目进展和更新以及新的临床试验设计和概念，使我们的BTTC网络正式加入NCI-CONNECT。第二次重点会议与每年11月的神经肿瘤学会年会同时举行。2020年4月，由于新型冠状病毒疾病（COVID-19），我们的第三届年会被推迟，但迄今为止，我们在全国拥有32个机构和站点的强大网络和基础设施，合作研究精选的罕见中枢神经系统肿瘤。我们的进展包括建立与患者权益团体的正式关系机制。我们与世界知名的国家和国际组织建立了九个倡导伙伴关系。根据与NCI的谅解备忘录（mou），这些组织与我们合作，分享教育内容并提高认识，目标是改善罕见中枢神经系统肿瘤患者的预后。他们还与我们合作举办研讨会和会议，重要的是，他们将患者的观点和关注点带到我们的研讨会上。这一观点有助于我们理解和开发有利于患者的临床试验。我们的合作伙伴包括美国脑肿瘤协会、脑肿瘤治疗、脑肿瘤网络、协作室管膜瘤研究网络基金会、结束脑癌倡议、波兰胶质瘤中心基金会、国际脑肿瘤联盟、国家脑肿瘤协会和Oligo Nation。此外，NCI-CONNECT正在与最大的国际专业组织神经肿瘤学协会合作，该协会正在帮助分发NCI-CONNECT的教育材料，并促进神经肿瘤学社区对这些努力的认识。我们的研究人员和倡导合作伙伴网络帮助我们成功地主办或共同主办了五次科学或临床结果研讨会，并在NIH举办了一次国际患者倡导峰会。科学研讨会汇集了世界各地的神经肿瘤学专家和患者倡导者，讨论选定的特定罕见中枢神经系统癌症类型的科学进展和挑战，并找到合作改善治疗和开发新的临床试验的方法。组蛋白突变胶质瘤研讨会，2018年9月27日少突胶质瘤研讨会，2018年11月19日临床结果评估会议，2018年11月20日第四届双年展室管膜瘤共识，2019年2月20日至22日第四届双年展脑肿瘤患者倡导者世界峰会，2019年10月9日至12日2019年髓母细胞瘤研讨会，2019年11月25日这些研讨会是开发基础设施的工具方法，以改善成人患者的结果。我们发表了这些研讨会的论文，并改变了癌症治疗指南，如下面的成就部分所示。我们在教育和外联方面的努力非常成功。自2018年9月NCI-CONNECT网站开发和推出以来，这已被证明是一个非常重要和受欢迎的在线目的地。目前，该网站每月约有2.2万名访客，其中1.9万名是独立访客。它每月的浏览量也超过3万。我们每月的NCI-CONNECT电子通讯或博客每月至少发布三篇新文章，并交付给超过4,000名订阅者。我们开发了第一个NCI私人Facebook小组，截至2020年4月，已有238名成员。我们也是唯一的NCI计划与专门的YouTube播放列表或频道。这些都是吸引患者参与临床试验的重大成就，一般来说，促进我们的项目将患者带到NIH。我们的进展包括2018年1月成立了NCI-CONNECT诊所，致力于将相似罕见中枢神经系统肿瘤类型的患者聚集在一起进行特殊服务。如下图所示，我们45%的临床病人患有罕见的中枢神经系统肿瘤。作为NCI-CONNECT诊所的一部分，我们已经接待了289名患者。这些患者接受基因检测和咨询，用先进的分子检测对他们的诊断进行评估，并参加一个名为CARES（应对、倡导、关系、教育、支持）的支持小组会议，由专门的健康和健康顾问负责。我们目前有7项正在进行的NCI-CONNECT临床研究和试验，在2.25年的时间里总共积累了350多名受试者（见下图）。这些研究包括：罕见中枢神经系统（CNS）癌症成人的自然史和标本库研究（16C0151）；成人中枢神经系统癌症患者结局和风险的在线调查（17CN141）；免疫检查点抑制剂nivolumab治疗罕见中枢神经系统癌症的一揽子试验（17C0102）；靶向治疗试验包括卡铂和贝伐单抗治疗室管膜瘤患者（16C0009），舒尼替尼治疗中枢神经系统肉瘤患者（18C0137），尼沃单抗治疗复发性IDH突变胶质瘤患者，包括少突胶质细胞瘤（19C0006）， marizomib治疗rela融合阳性室管膜瘤（19C0011）。此外，我们最近启动了一项研究，以创建一个罕见的中枢神经系统癌症肿瘤和数据库（P194734）。我们在实现目标和成果方面取得的主要成就包括启动我们的项目，与美国中央脑肿瘤登记处合作，确定我们项目重点关注的12种癌症的发病率和患病率。这些数据帮助我们了解这12种中枢神经系统癌症，开发教育内容，并确定对肿瘤特异性临床试验和研究、研讨会和诊所的需求。如上所述，我们的特定疾病科学研讨会和临床结果评估研讨会成功地将神经肿瘤学专家聚集在一起，合作推进研究和护理，这些研讨会发表的论文就是例证。两篇发表在《神经肿瘤学进展》（neurooncology Advances）杂志上的论文正在总结，并提供建议和行动计划，目标是发现新的治疗方法和方法，以改善成人患者的预后。《柳叶刀肿瘤学》（Lancet Oncology）上的第三篇论文使用会议输入来说明，在临床试验中纳入患者功能和症状的具体数据如何有助于确定试验的益处。此外，每个研讨会都有一个肿瘤委员会，重点讨论各自癌症患者的管理。这些都被记录下来，可以在神经肿瘤学会的教育中心网站上找到。由于我们的科学研讨会的合作，其他手稿正在开发中，包括一篇关于髓母细胞瘤的论文，以及描述一类新药在组蛋白突变胶质瘤（NCI-CONNECT癌症之一）中表现出独特活性的临床前工作。

Our progress to date includes the establishment of an NCI-CONNECT network of researchers and institutions committed to the program's mission. This group meets biannually. This includes a two-day meeting in partnership with our already existing Brain Tumor Trials Collaborative (BTTC) Annual Meeting at NIH; this meeting brings together key stakeholders and investigators to discuss program advances and updates and new clinical trials designs and concepts, enabled our BTTC network to formally join NCI-CONNECT. The second focused meeting is held in conjunction with the annual Society for Neuro-Oncology meeting each November. In April 2020, our third annual meeting was postponed due to the novel coronavirus disease (COVID-19), but to date we have a robust network and infrastructure of 32 institutions and sites across the nation partnering to study select rare CNS tumors. Our progress includes establishing a mechanism for formal relationships with patient advocacy groups. We have nine advocacy partnerships with world-renowned national and international organizations. Under Memorandum of Understandings (MOUs) with NCI, these organizations partner with us to share educational content and raise awareness with the goal of improving outcomes for people with rare CNS tumors. They also partner with us to host workshops and meetings, and importantly, they bring the patient perspective and concerns to our workshops. This perspective is instrumental in our understanding and ability to develop clinical trials that benefit patients. Our partners include the American Brain Tumor Association, Brains for the Cure, Brain Tumor Network, Collaborative Ependymoma Research Network Foundation, The EndBrainCancer Initiative, Glioma Center Foundation of Poland, the International Brain Tumour Alliance, the National Brain Tumor Society, and Oligo Nation. Additionally, NCI-CONNECT is working with the Society for Neuro-Oncology, the largest international professional organization that is helping to distribute NCI-CONNECT educational materials and promote awareness of these efforts to the neuro-oncology community. Our network of investigators and advocacy partners have helped us successfully host or co-host five scientific or clinical outcomes workshops and an international patient advocacy summit at NIH. The scientific workshops bring together neuro-oncology experts and patient advocates worldwide to discuss the scientific progress and challenges of a selected specific rare CNS cancer type and find ways to collaborate to improve therapies and develop new clinical trials. Histone Mutated Glioma Workshop, September 27, 2018 Oligodendroglioma Workshop, November 19, 2018 Clinical Outcomes Assessment Meeting, November 20, 2018 The Fourth Biennial Ependymoma Consensus, February 20 to 22, 2019 Fourth Biennial World Summit of Brain Tumor Patient Advocates, October 9 to 12, 2019 Medulloblastoma Workshop, November 25, 2019 These workshops are an instrumental method to develop an infrastructure to improve adult patient outcomes. We have published papers from these workshops and changed cancer care guidelines as highlighted in the accomplishments section below. Our efforts in education and outreach have been extremely successful. Since the development and launching of the NCI-CONNECT website in September 2018, this has proven to be a very important and popular online destination. Currently the website receives about 22,000 monthly visitors and of those 19,000 are unique. It also receives over 30,000 page views monthly. Our monthly NCI-CONNECT e-newsletter or blog publishes at least three new articles each month and is delivered to over 4,000 subscribers. We developed the first NCI private Facebook group and as of April 2020 have 238 members. We also are the only NCI program with a dedicated YouTube Playlist or Channel. These are substantial accomplishments to engage patients, enroll patients in clinical trials, and generally, promote our program to bring patients to NIH. Our progress includes the establishment of the NCI-CONNECT Clinic in January 2018, which is dedicated to bringing together patients with similar rare CNS tumor types for special services. As shown in the below graphic, 45 percent of our clinic patients have a rare CNS tumor. We have seen 289 patients as part of NCI-CONNECT Clinics. These patients receive genetic testing and counseling, a review of their diagnosis with advanced molecular testing, and participate in a support group meeting called CARES (Coping, Advocacy, Relationships, Education, Support) with a dedicated Health and Wellness Counselor. We currently have seven active NCI-CONNECT clinical studies and trials, which altogether have accrued over 350 subjects in 2.25 years (see figure below). These include: a natural history and specimen banking study for adults with rare central nervous system (CNS) cancers (16C0151); an online survey of outcomes and risk for patients with adult CNS cancers (17CN141); a basket trial testing the immune checkpoint inhibitor nivolumab for adults with rare CNS cancers (17C0102); and targeted treatment trials including carboplatin and bevacizumab for patients with ependymoma (16C0009), sunitinib for patients with sarcoma of the central nervous system (18C0137), nivolumab for patients with recurrent IDH mutant gliomas including oligodendrogliomas (19C0006), and marizomib for RELA-fusion positive ependymoma (19C0011). Additionally, we recently activated a study to create a rare CNS cancer tumor and data repository (P194734). Our key accomplishments towards our goals and outcomes include kicking off our program by partnering with the Central Brain Tumor Registry of the United States to determine the incidence and prevalence of the 12 cancers our program focuses on. The data helped us understand these 12 CNS cancers, develop educational content and establish the need for tumor specific clinical trials and studies, workshops, and clinics. Our disease-specific scientific workshops and clinical outcomes assessment workshop noted above have successfully brought together neuro-oncology experts to collaborate to advance research and care as exemplified by the publishing of papers resulting from these workshops. Two proceedings papers in Neuro-Oncology Advances, with two more in progress, are meeting summaries and provide recommendations and action plans with the goal to discover new therapies and methods to improve adult patient outcomes. A third paper in Lancet Oncology used meeting input to show how including specific data on how patients function and their symptoms on clinical trials can help determine the benefit of a trial. Furthermore, each workshop had a Tumor Board highlighting discussions of management of patients with the respective cancers. These were recorded and are available in the Educational Center on the Society for Neuro-Oncology website. Additional manuscripts are in development as a result of the collaborations fostered by our scientific workshops, including a paper on medulloblastoma, and preclinical work describing the mechanism of action of a new class of drugs showing unique activity in the histone mutated gliomas, one of the NCI-CONNECT cancers.