MyPART: My Pediatric and Adult Rare Tumor Network - Cures

通过与MyPART、美国癌症研究中心（CCR）罕见肿瘤倡议（RTI）和CCR儿科肿瘤学分会（POB）的合作，我们开发了一项罕见肿瘤自然史和生物标本试验，研究儿童、青少年和成人患者的罕见实体肿瘤。罕见实体瘤自然史研究（NCT03739827）自2019年1月开始开放招募，已经招募了超过469名患有各种非常罕见实体瘤的患者。患者可以通过在家中提供信息（实地队列）或到NIH临床中心由专家临床医生和其他医疗保健提供者（临床队列）进行更广泛的工作来注册。任何患有罕见实体瘤的人都可以参加现场队列，根据患者的病史细节，患者将被邀请到NIH临床中心加入临床队列。远程招募参与者的能力使我们能够在COVID大流行期间继续保持活跃，因为我们无法将大多数患者带到NIH临床中心进行评估。在自然史研究下建立的子协议允许MyPART和非MyPART研究人员使用主研究的基础设施对特定罕见肿瘤类型进行更深入的研究。一项针对脊索瘤的子方案已经开放，并招募了超过75名参与者。神经内分泌肿瘤（92例入组患者）和肾上腺皮质癌（65例入组患者）的附加子方案已经制定并开放入组。随着时间的推移，对主要研究和子方案的参与者进行纵向跟踪。该方案数据库已建立并拥有广泛的信息，包括患者报告的结果、病史、肿瘤标本、成像信息和在NIH临床中心进行的临床评估。血液和肿瘤样本的研究分析管道已经发展为核酸，免疫表征和细胞因子。对提供的所有信息进行审查，并在可行的情况下给出临床建议。此外，我们已经建立了一个分子肿瘤委员会，我们正在将分子肿瘤数据返回给患者。肿瘤测序研究正在进行中。对于因临床原因在NIH临床中心接受手术的患者，我们正在全面分析肿瘤，包括单细胞测序，我们正在建立临床前模型（患者来源的异种移植物和类器官系）。我们与NCI发育治疗诊所建立的合作是积极的，我们已经开展了5项治疗试验，包括PD-L1抑制剂atezolizumab的一项新试验，该试验已开放用于患有特定罕见肉瘤的儿童和青少年，此前该试验被FDA认定为突破性治疗肺泡软组织肉瘤。除了组织特异性试验外，发育治疗诊所还对许多不同类型的罕见肿瘤患者进行了早期临床试验。另外8项针对非常罕见肿瘤的临床试验正在进行中，包括针对患有SMARCB1-或smarca4缺陷肿瘤的儿童和成人的TIGIT抗体和PD-L1抑制剂的II期试验。该试验将是MyPART和NCI- ctep儿科早期临床试验网络的合作，MyPART研究者作为pi和NCI癌症研究中心（CCR）的几位研究者参与6个罕见实体肿瘤分层的入组。2019年和2020年，MyPART为“野生型”（sdh缺乏）胃肠道间质瘤、甲状腺髓样癌和小儿脊索瘤患者举办了专业罕见肿瘤门诊。这些诊所汇集了来自美国和世界各地的临床医生、研究人员、患者、家属和倡导者。患者和家属受益于接受世界肿瘤专家的医疗意见，同时也有机会与患有同样罕见肿瘤诊断的其他人见面，通常是第一次。临床医生和研究人员从分享他们关于一种特殊罕见肿瘤的知识中受益，这也导致了小组之间的合作增加。由于COVID大流行，我们无法在NIH临床中心亲自举办罕见肿瘤诊所，但我们有几个远程诊所。更多罕见肿瘤的新诊所也在计划中，希望能亲自去诊所。MyPART在临床前罕见肿瘤研究方面也取得了进展。目前正在进行的工作是设计一种具有sdh缺陷GIST的小鼠模型，该模型可用于更多地了解这种罕见肿瘤并测试潜在的治疗方法。MyPART以患者参与为重点，建立了一个强大的沟通计划。我们有一个网站（www.cancer.gov/mypart），每月有超过6万的独立访问者，提供一些罕见肿瘤的信息，罕见实体肿瘤的自然史研究，为患者和他们的护理人员提供支持，以及其他资源的链接。我们还每月发送一份时事通讯，并与POB共享一个Twitter账户。MyPART已与22个倡导组织建立了伙伴关系，以便与罕见肿瘤社区建立牢固的关系，了解对他们重要的是什么，并向罕见肿瘤患者及其家属提供教育和信息，说明参与罕见肿瘤研究的重要性，以加速开发新的有效疗法。我们进行并起草了一份关于国内和国际罕见肿瘤工作的景观分析的手稿，我们计划在2022年为特定罕见肿瘤工作小组举办罕见肿瘤研讨会。MyPART的努力与NCI儿童癌症数据倡议（CCDI）的目标保持一致，MyPART的成员积极参与CCDI的几个工作组。

Through collaboration between MyPART, the Center for Cancer Research (CCR) Rare Tumor Initiative (RTI), and the CCR Pediatric Oncology Branch (POB), we have developed a rare tumor natural history and biospecimen trial to study rare solid tumors in pediatric, adolescent, and adult patients. The Natural History Study of Rare Solid Tumors (NCT03739827) has been open for enrollment since January 2019 and has enrolled more than 469 patients with a variety of very rare solid tumors. Patients can enroll by providing information from their home (field cohort) or by coming to the NIH Clinical Center to be seen by expert clinicians and other healthcare providers (clinic cohort) for a more extensive work up. Anyone with a rare solid tumor can participate in the field cohort and patients will be invited to come the NIH Clinical Center to join the clinic cohort based on the details of their medical history. The ability to enroll participants remotely allowed us to continue to remain active during the COVID pandemic where we were not in the position to bring most patients to the NIH Clinical Center for evaluation. Sub-protocols established under the Natural History Study allow the infrastructure of the master study to be used by both MyPART and non-MyPART investigators to carry out more in-depth studies of specific rare tumor types. A sub-protocol for chordoma has opened and has enrolled over 75 participants. Additional sub-protocols for neuroendocrine tumors (92 patients enrolled) and adrenocortical carcinoma (65 patients enrolled) have been developed and are open to enrollment. Participants in the main study and sub-protocols are followed longitudinally over time. The protocol database is established and holds a wide range of information including patient reported outcomes, medical history, tumor specimens, imaging information, and clinical evaluations performed at the NIH Clinical Center. A research analysis pipeline for blood and tumor samples has been developed for nucleic acids, immune characterization, and cytokines. All information provided is reviewed and a clinical recommendation is given, when feasible. In addition, we have established a molecular tumor board and we are returning molecular tumor data to patients. Research tumor sequencing is ongoing. For patients who undergo surgery at the NIH Clinical Center for clinical reasons, we are comprehensively analyzing tumors including single cell sequencing and we are establishing preclinical models (patient derived xenografts and organoid lines). Our collaboration established with the NCI Developmental Therapeutics Clinic is active and we have 5 treatment trials opened, including a new trial of the PD-L1 inhibitor atezolizumab that has opened for children and adolescents with specific rare sarcomas, following its Breakthrough Therapy Designation by the FDA for alveolar soft part sarcoma. In addition to histology-specific trials, the Developmental Therapeutics Clinic has early clinical trials open to patients with many different types of rare tumors. Eight additional clinical trials for very rare tumors are in development including a phase II trial of a TIGIT antibody and a PD-L1 inhibitor for children and adults with SMARCB1- or SMARCA4-deficient tumors. This trial will be a collaboration between MyPART and the NCI-CTEP Pediatric Early Clinical Trials Network, with MyPART investigators serving as PIs and several NCI Center for Cancer Research (CCR) Investigators contributing to enrollment on 6 rare solid tumor strata. In 2019 and 2020 MyPART held specialty rare tumor clinics for patients with "wild-type" (SDH-deficient) GIST (gastrointestinal stromal tumor), medullary thyroid carcinoma, and pediatric chordoma. These clinics assemble clinicians, researchers, patients, families, and advocates from across the US and the world. Patients and families benefit from receiving medical opinions from world experts in their tumor while also having the opportunity to meet others with the same rare tumor diagnosis, often for the first time. Clinicians and researchers benefit from sharing their knowledge about a particular rare tumor, which has also led to increased collaboration between groups. Due to the COVID pandemic we have not been able to hold rare tumor clinics in person at the NIH Clinical Center, but we had several remote clinics. New, and hopefully in person clinics, for additional rare tumors are planned. MyPART has also made progress in pre-clinical rare tumor research. Work is ongoing to engineer a mouse model of SDH-deficient GIST that can be used to learn more about this rare tumor and test potential therapies. With its focus on patient engagement, MyPART has established a robust communications program. We have a website (www.cancer.gov/mypart) that receives over 60,000 unique visitors per month and provides information on a number of rare tumors, the Natural History Study of Rare Solid Tumors, support for patients and their caregivers, and links to additional resources. We also send out a monthly newsletter and have a Twitter account we share with the POB. MyPART has established partnerships with 22 advocacy organizations in order to build strong relationships with the rare tumor community, to learn what is important to them, and to provide education and information to rare tumor patients and their families about the importance of participating in rare tumor research to accelerate the development of new and effective therapies. We conducted and drafted a manuscript on a landscape analysis of rare tumor efforts nationally and internationally and we plan to host a rare tumor symposium for groups with specific rare tumor efforts workshop in 2022. MyPART efforts align well with the goals of the NCI Childhood Cancer Data Initiative (CCDI) and MyPART members are actively engaged with several CCDI working groups.