Clinical Cancer Genomics Program

临床癌症基因组学计划

• 批准号: 10926692
• 负责人: Kathleen Calzone
• 金额: $ 150.48万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10926692
• 关键词: Accreditation; Advisory Committees; Advocacy; Affect; Amendment; American; American Society of Clinical Oncology; Appointment; Bioethics; Budgets; CCR; CDH1 gene; CLIA certified; Charge; Childhood; Classification; Clinical; Clinical Management; Clinical Services; Collection; Communities; Complex; Consent; Consult; Consultations; Continuing Education; Contractor; Contracts; Counseling; Development; Disclosure; Doctor of Philosophy; Education; Education Gap; Educational Curriculum; Educational process of instructing; Electronic Mail; Enrollment; Environment; Ethics; Ethics Consultation; Extramural Activities; Family; Feedback; Funding; Genes; Genetic; Genetic Counseling; Genetic Enhancement; Genetic Research; Genetic Services; Genomics; Germ-Line Mutation; Goals; Guidelines; Healthcare; Hematologic Neoplasms; Hybrids; Incidental Findings; Individual; Infrastructure; Inherited; Interview; Justice; Kidney; Label; Laboratories; Leadership; Learning; Length; Letters; Longterm Follow-up; Lung; Lymphoma; Malignant Neoplasms; Malignant Pleural Mesothelioma; Medical; Medical Genetics; Mentors; Mesothelioma; National Human Genome Research Institute; National Institute of Allergy and Infectious Disease; Needs Assessment; Pathology; Patient Care; Patient Preferences; Patients; Persons; Positioning Attribute; Procedures; Process; Prostate; Protocols documentation; Provider; Public Health Schools; Questionnaires; Recording of previous events; Reporting; Research; Research Personnel; Resources; Role; Rotation; Saliva; Service delivery model; Services; Standardization; Students; Swab; Telemedicine; Telephone; Testing; Time; Training; Training Programs; Tumor Pathology; United States National Institutes of Health; Universities; Variant; Work; Workload; cancer genetics; cancer genomics; career; certificate program; clinical center; clinical infrastructure; clinical sequencing; clinical training; clinically relevant; cost; empowerment; equity, diversity, and inclusion; evidence base; exome; exome sequencing; experience; genetic counselor; genetic pedigree; genetic testing; genetic variant; instructor; interest; malignant stomach neoplasm; medical schools; meetings; member; multidisciplinary; neuro-oncology; novel; payment; programs; protocol development; racial diversity; research study; simulation; symposium; testing services; tool; tumor; variant of unknown significance; web portal; working group

The Genetic Counseling Training Program (GCTP) is staffed by one full-time PhD genetic counselor (GC) who also holds an appointment in the NIH Department of Bioethics. The Clinical Cancer Genetics Service (CCGS) is partially staffed with 1 part-time and 2 full-time clinical GCs and 1 full-time patient care coordinator (PCC) converted from a contactor to a GS position this year. CCR funded a 3rd full-time GC this year and our final candidate is being brought in as a contractor until she can be converted to a GS position given challenges as a direct GS hire. Our geneticist position remains open and continues to be advertised with the American College of Medical Genetics and Genomics and on the CCR Careers page. Dr. Chimene Kesserwan provides support for clinical, research, and T/N WES germline and somatic variant curation through her NIH Research Collaborator position. Dr. Sheila Rajagopal is available for urgent clinical issues and attends our weekly case conference to discuss complex patients, review testing decisions, result interpretations. The CCGP has achieved the following: 1) Genetic Counselor Training Program (GCTP): The MOU with the National Human Genome Research Institute (NHGRI) for the NIH GCTP in place through March 31, 2025. This year student stipends had a 15% increase and must cover the cost for our 6 students estimated at $16,853 for this fiscal year. This is a permanent increase that impacts the MOU annual budget MOU so the AO iworking on paperwork to amend the budget. NCI funded GCTP Assistant Director actively participates in weekly administrative meetings and Executive Committee tasks. This year she participated in a curriculum review with an outside consultant. She is involved in interviewing and ranking GCTP applicants. She is integral in student advising including independent and co-advising student thesis. She was the sole instructor for the Cancer Standardized Patient Rotation and developed, and taught the Advanced Topics in Cancer Genomics course. Dr. Jamal received the Johns Hopkins Bloomberg School of Public Health for Excellence in Teaching in 2023 associated with her work on three courses. In 8/2023, Dr. Jamal will complete a certificate program in Justice, Equity, Diversity, and Inclusion for Higher Educators at the UPenn with the aim of influencing the racial diversity of GCTP students. She contributed to the reaccreditation package and Drs. Meltzer and Calzone submitted a letter of support. CCGS GCs accept students for clinical experiences and mentoring. Students are provided a summary of cancer genetic research opportunities to consider for their Research Thesis and CCGS serves on committees as indicated. Dr. Jamal continues 50% effort in the NIH Clinical Center Department of Bioethics. This relationship benefits CCR by enhancing GC education with real ethical cases and facilitating CCR ethics consults. 2) Clinical Cancer Genetics Service (CCGS): CCGS provides investigator support in protocol development; manage genetic incidental findings; provide genetic counseling and testing as clinically or protocol indicated; and perform germline and/or somatic variant interpretation. CCGS continues not to be recognized by the Clinical Center as a formal consult service. We continue to maintain a central email and phone line for consult requests. From 7/10/2022-7/10/2023 CCGS saw 286 new consults up from 216. There were 65 requests for chart and/or genetic test report reviews. Chart reviews decreased as only 1 GC tracked this activity given time constraints. Most CCGS tests are conducted by outside laboratories. We have contracts with 2 laboratories and are establishing a 3rd. GCs complete the test request forms, PCC enters POTS information and reconciles when the laboratory invoice comes in to validate the test and charge. CAN 8036225 pays for all tests to avoid payment delinquency which affects laboratory contracts. Quarterly the AO reconciles with the PI CAN.This year CCGS worked with CCR to outline the process and assess need for a central payment mechanism. The final decison was to maintain the existing process and develop a SOP to cover the procedures and streamline the AO workload to reconcile test charges. PIs unable to pay will use the Outside Medical Services mechanism. Dr. Gulley began exploring options with Laboratory of Pathology (LP) to expand their testing platform to include CLIA approved germline testing. Dr. Aldape was provided with CCGS 2022-23 germline test volume/type to inform this effort. CCGS transitioned to a hybrid care delivery model seeing patients in person and telemedicine based on provider/patient preference. GCs are embedded as part of the team in 6 services: Kidney, Hematologic Malignancies, Mesothelioma; Prostate; Lung; and Inherited Gastric Cancer. DCRI developed a patient online portal family history questionnaire which pre-populates the CRIS Pedigree. DCRI demonstrated the tool to CCGS, allowed us to test and provide feedback, and on 7/26/2023 the developers demo'd the final product which now moves to the test environment. This may be deployed in CRIS within the next few months which could increase CCGS patient capacity. Tumor/Normal Whole Exome Sequencing (T/N WES) CCGS provides clinical support for the LP T/N WES test. CCGS roles involve: pretest genetic education and counseling; medical and family history collection; consent; germline variant curation, presentation of variant evidence at the weekly LP Exome Signout, and result disclosure. From 7/10/2022-7/10/2023 there were 182 T/N WES referrals, up from 49 in 2022. The CCGS PCC is the central contact for T/N WES consent requests for all NIH including NIAID GC (N=14 referrals) and Pediatric and Neuro Oncology Cases (N=76 referrals). For T/N WES cases not at the Clinical Center, saliva or buccal swab kits are mailed to the patient with a pre-paid return Fedex label. CCGS purchases the kits and covers mailing costs. The increase in T/N WES by the CCR Lymphoma team mentioned in last years' report has increased. CCGS supports student education including GCTP students for clinical experiences and research thesis. This year our concept for two post bacs from the Genetics Opportunities, Learning, Development, Empowerment and Networking (GOLDEN) Program was approved. One new post bac was approved with the second Vice slot coming from the existing CCGS CAN. We identified several GOLDEN students interested in pursuing a career in genetic counseling who were not accepted to a GCTP. Many are not local, but one is applying and a 2nd is considering the option. 3) Genomic Variant Curation and Clinical Management: Interpreting genomic variants is a challenge. ClinGen built a central resource to define the clinical relevance of genomic variants and convened several Working Groups, Task Forces, Gene Curation Expert Panels, and Variant Curation Expert Panels (VCEP). Grace Fasaye continues as a member on the CDH1 VCEP. Alex Lebensohn serves on the Expert Panel for the American Society of Clinical Oncology's Treatment of Malignant Pleural Mesothelioma Guidelines. She also participated in the FDA Advocacy Panel/Mesothelioma Listening Session. All team members participate in routine clinical work of verifying variant classifications from patients found to harbor a variant of uncertain significance, especially if a considerable length of time has passed since the patient was tested. Yi Liu leads the germline variant curation for the NIH T/N WES program with Dr. Calzone performing the Quality review of all variant classifications and accuracy of report content. Dr. Calzone leads the somatic variant curation for Dr. Apolo's protocol Olaparib protocol NCT04858334. Dr. Chimene Kesserwan provides the confirmation of these variant interpretations until a replacement geneticist is hired.

遗传咨询培训计划 (GCTP) 由一名全职博士遗传咨询师 (GC) 组成，该咨询师还在 NIH 生物伦理学部门任职。临床癌症遗传学服务 (CCGS) 的部分人员包括 1 名兼职和 2 名全职临床 GC，以及 1 名全职患者护理协调员 (PCC)，今年从接触员转为 GS 职位。 CCR 今年资助了第三个全职 GC，我们的最终候选人将以承包商的身份引入，直到她可以转换为 GS 职位，因为直接聘用 GS 面临着挑战。我们的遗传学家职位仍然开放，并继续在美国医学遗传学和基因组学院以及 CCR 职业页面上发布广告。 Chimene Kesserwan 博士通过她的 NIH 研究合作者职位为临床、研究和 T/N WES 种系和体细胞变异管理提供支持。 Sheila Rajagopal 医生可以处理紧急临床问题，并参加我们每周的病例会议，讨论复杂的患者、审查测试决策和结果解释。 CCGP 已实现以下目标： 1) 遗传咨询师培训计划 (GCTP)：与国家人类基因组研究所 (NHGRI) 就 NIH GCTP 签订的谅解备忘录将于 2025 年 3 月 31 日生效。今年学生津贴增加了 15%，必须涵盖本财年 6 名学生的费用，估计为 16,853 美元。这是永久性增加，会影响谅解备忘录年度预算谅解备忘录，因此 AO 正在处理文书工作以修改预算。 NCI 资助的 GCTP 助理主任积极参与每周的行政会议和执行委员会的任务。今年，她与外部顾问一起参加了课程审查。她参与 GCTP 申请人的面试和排名。她在学生咨询方面发挥着不可或缺的作用，包括独立和共同指导学生论文。她是癌症标准化患者轮换的唯一讲师，并开发并教授了癌症基因组学高级主题课程。 Jamal 博士因其在三门课程上的工作而于 2023 年获得约翰霍普金斯大学彭博公共卫生学院卓越教学奖。 8/2023 年，Jamal 博士将在宾夕法尼亚大学完成高等教育工作者正义、公平、多样性和包容性证书课程，旨在影响 GCTP 学生的种族多样性。她为重新认证计划和博士做出了贡献。 Meltzer 和 Calzone 提交了一封支持信。 CCGS GC 接受学生进行临床经验和指导。向学生提供癌症遗传学研究机会的摘要，以供他们的研究论文考虑，并且 CCGS 在指定的委员会中任职。 Jamal 博士在 NIH 临床中心生物伦理学部继续投入 50% 的精力。这种关系通过真实的道德案例加强 GC 教育并促进 CCR 道德咨询，从而使 CCR 受益。 2）临床癌症遗传学服务（CCGS）：CCGS为研究方案开发提供研究者支持；管理遗传偶然发现；根据临床或方案指示提供遗传咨询和测试；并进行种系和/或体细胞变异解释。 CCGS 仍然不被临床中心认可为正式咨询服务。我们继续维护中央电子邮件和电话线路以应对咨询请求。从 2022 年 7 月 10 日到 2023 年 7 月 10 日，CCGS 收到了 286 起新咨询，从 216 起增加到 286 起。有 65 起图表和/或基因检测报告审查请求。由于时间有限，只有 1 个 GC 跟踪了此活动，因此图表评论有所减少。大多数 CCGS 测试是由外部实验室进行的。我们与 2 个实验室签订了合同，并正在建立第三个实验室。 GC 填写测试申请表，PCC 输入 POTS 信息，并在收到实验室发票以验证测试和收费时进行核对。 CAN 8036225 支付所有测试费用，以避免拖欠付款而影响实验室合同。 AO 每季度与 PI CAN 进行一次协调。今年，CCGS 与 CCR 合作概述了流程并评估了中央支付机制的需求。最终决定是维持现有流程并制定 SOP 来涵盖程序并简化 AO 工作量以协调测试费用。无法支付费用的 PI 将使用外部医疗服务机制。 Gulley 博士开始与病理学实验室 (LP) 探索扩大其测试平台以包括 CLIA 批准的种系测试的选项。 Aldape 博士获得了 CCGS 2022-23 种系测试体积/类型，以告知这项工作。 CCGS 转变为混合护理服务模式，根据提供者/患者的偏好亲自看诊患者和远程医疗。 GC 作为团队的一部分融入 6 项服务：肾脏、血液恶性肿瘤、间皮瘤；前列腺;肺;和遗传性胃癌。 DCRI 开发了一个患者在线门户家族史调查问卷，该调查问卷预先填充了 CRIS 谱系。 DCRI 向 CCGS 演示了该工具，使我们能够进行测试并提供反馈，开发人员于 2023 年 7 月 26 日演示了最终产品，该产品现已转移到测试环境。这可能会在未来几个月内部署在 CRIS 中，从而增加 CCGS 患者的容量。肿瘤/正常全外显子组测序 (T/N WES) CCGS 为 LP T/N WES 测试提供临床支持。 CCGS 的作用包括： 预测试遗传教育和咨询；医疗和家族史收集；同意;种系变异管理、在每周 LP 外显子组签出时提供变异证据以及结果披露。从 2022 年 7 月 10 日到 2023 年 7 月 10 日，共有 182 起 T/N WES 转诊，高于 2022 年的 49 起。CCGS PCC 是所有 NIH 的 T/N WES 同意请求的中心联系人，包括 NIAID GC（N=14 转诊）和儿科和神经肿瘤学病例（N=76 转诊）。对于不在临床中心的 T/N WES 病例，唾液或口腔拭子套件将通过预付费退货联邦快递标签邮寄给患者。 CCGS 购买套件并承担邮寄费用。去年报告中提到的CCR淋巴瘤团队的T/N WES增加有所增加。 CCGS 支持学生教育，包括 GCTP 学生的临床经验和研究论文。今年，我们关于遗传学机会、学习、发展、赋权和网络（黄金）计划的两个博士后的概念获得了批准。一名新的岗位 bac 获得批准，第二个 Vice 插槽来自现有的 CCGS CAN。我们发现了几位有兴趣从事遗传咨询职业但未被 GCTP 录取的 GOLDEN 学生。许多人不是本地人，但其中一个正在申请，第二个正在考虑这一选择。 3) 基因组变异管理和临床管理：解释基因组变异是一个挑战。 ClinGen 建立了一个中心资源来定义基因组变异的临床相关性，并召集了多个工作组、任务组、基因管理专家小组和变异管理专家小组 (VCEP)。 Grace Fasaye 继续担任 CDH1 VCEP 成员。 Alex Lebensohn 是美国临床肿瘤学会恶性胸膜间皮瘤治疗指南专家小组的成员。她还参加了 FDA 倡导小组/间皮瘤聆听会议。所有团队成员都参与常规临床工作，验证发现携带不确定意义变异的患者的变异分类，特别是如果自患者接受测试以来已经过去了相当长的时间。 Yi Liu 领导 NIH T/N WES 项目的种系变异管理，Calzone 博士对所有变异分类和报告内容的准确性进行质量审查。 Calzone 博士领导了 Apolo 博士方案 Olaparib 方案 NCT04858334 的体细胞变异管理。 Chimene Kesserwan 博士对这些变异解释进行确认，直到聘请替代遗传学家。