Objective: To systematically summarize and comparatively analyze the development, establishment and usage of oncology drugs speedy review approaches in China and in the United States between 2012 and 2021. Methods: Based on National Medical Products Administration (NMPA) and Food and Drug Administration (FDA) websites, the development and current status of the speedy review approaches were consulted and summarized. Approved oncology drugs in China and in the United States (87 in China, 118 in the United States) over the past decade were analyzed using chi-square test for group comparison. Results: Five speedy approaches have been established in China and in the United States, three of which are the same, priority review, conditional approval or accelerated approval and breakthrough therapy. The rest two are special review and approval, special examination and approval in China, and fast track and real-time oncology review in the United States. Compared to the United States, speedy review approaches in China set up late (1992 vs. 2005). The overall utilization rates of the oncology drugs speedy review approaches were similar between the China and United States (90.8% vs. 92.4%, P=0.800) in the previous 10 years, and priority review have highest utilization rates in both China and the United States without significant group difference (77.0% vs. 82.2%, P=0.381); relatively low utilization rates of conditional approval (31.0% vs. 44.9%, P=0.041) and breakthrough therapy (2.3% vs. 50.0%, P＜0.001) were seen in China. 52.9% of new drugs applied for special examination and approval in China and 40.7% of new drugs applied for fast track in the United States. Overall, the priority review both in China and the United States are stable, with a similar average annual utilization rate (84.8% vs. 83.7%); accelerated approval and breakthrough therapies in the United States fluctuate wildly, but the situation is tending towards stability in the last 3 years. Conclusions: Both China and the United States have established a relatively complete accelerated review system, with an overall utilization rate over 90%; China's accelerated review started late, although the overall utilization rate is close to that of the United States. The utilization rates of conditional approval and breakthrough therapy are still relatively low. Flexible usage of speedy review approaches, gaining regulatory recognition to use alternative endpoints, achieving real-time review and guidance are keys to accelerate new drug development in China.

Background Conducting geriatric trials is the most feasible way to address the vast underrepresentation of older adults in clinical trials of cancer therapies. This study is a globally comprehensive examination of geriatric trials for solid tumor worldwide over the last decade. Methods Up-to-date information on cancer drug trials in older adults aged over 59 years from the beginning of 2012 to the end of 2021 was collected from Trialtrove and Pharmaprojects. The number of identified trials was the dependent variable and corresponding analysis was conducted from the perspective of time trend, status quo and comparisons by region and country, sponsor type and cancer type, study status and phase. Results A total of 292 geriatric cancer drug trials were identified, of which 287 were single-region studies, 219 were initiated by academic groups, and 55 (18.8%) were terminated. Decreasing trends in the annual number of all trials (−9.2% per year) and the annual number of trials by academic groups (−9.4%) were observed over time. Of the geriatric trials, 183 were conducted in Asia; this number was significantly higher than that in Europe (74), North America (37), Oceania (4), and South America (1). Similar difference was found in participation rate in trials by academic groups ranging from 71.7% in Asia to 0.5% in South America. Of the trials, 19 and 97 were initiated before drug and indication approval, respectively, and the remaining 176 were initiated after indication approval. Phase II trials accounted for the highest proportion of trials (213, 72.9%), while phase I trials accounted for the lowest proportion (14, 4.8%). Trials by academic groups had a higher termination rate (21.5% vs. 11.0%) and fewer were phase IV trials (8.2% vs. 21.9%). Treatment was explored for 16 different cancers, with lung, colorectal and breast cancers being the most common. Conclusion Geriatric trials of solid tumor drugs are scarce and partially prematurely terminated. Moreover, the number of geriatric trials has decreased and differs according to region. Global guidance and regulatory supervision are needed to facilitate the acquisition of adequate evidence on drug risk-benefit profiles in older adults, and thus to achieve high-quality care and safe medication.

Overall survival (OS) is considered the standard clinical endpoint to support effectiveness claims in new drug applications globally, particularly for lethal conditions such as cancer. However, the source and reliability of OS in the setting of clinical trials have seldom been doubted and discussed. This study first raised the common issue that data integrity and reliability are doubtful when we collect OS information or other time-to-event endpoints based solely on simple follow-up records by investigators without supporting material, especially since the 2019 COVID-19 pandemic. Then, two rounds of discussions with 30 Chinese experts were held and 12 potential source scenarios of three methods for obtaining the time of death of participants, including death certificate, death record and follow-up record, were sorted out and analysed. With a comprehensive assessment of the 12 scenarios by legitimacy, data reliability, data acquisition efficiency, difficulty of data acquisition, and coverage of participants, both short-term and long-term recommended sources, overall strategies and detailed measures for improving the integrity and reliability of death date are presented. In the short term, we suggest integrated sources such as public security systems made available to drug inspection centres appropriately as soon as possible to strengthen supervision. Death certificates provided by participants’ family members and detailed standard follow-up records are recommended to investigators as the two channels of mutual compensation, and the acquisition of supporting materials is encouraged as long as it is not prohibited legally. Moreover, we expect that the sharing of electronic medical records and the legal disclosure of death records in established health registries can be realized with the joint efforts of the whole industry in the long-term. The above proposed solutions are mainly based on the context of China and can also provide reference for other countries in the world.

2022年3月,随着新型冠状病毒肺炎(corona virus disease 2019,COVID-19)本土疫情再次蔓延,我国防疫工作仍面临严峻挑战,在事态变化的不断冲刷下,对临床试验应急手段显现出新的需求.本研究通过收集2022年4–6月期间,全国474家临床试验机构的医疗工作运行情况、机构伦理委员会日常工作、临床试验实施执行、来院防控管理要求等信息,分析疫情防控措施及临床试验开展所受到的影响,探讨建立有针对性的临床试验应急策略和构建各方应急协助体系的必要性,考量临床试验远程新模式的尝试需求.旨在为进一步优化临床试验管理和运行模式,最大程度地保障受试者权益,为更好地确保临床研究顺利开展提供新思路和理论依据.

背景与目的 临床研究协调员(clinical research coordinator,CRC)作为临床试验开展的关键一环,在试验管理,安全性保障,沟通等各方工作发挥重要作用.随着中国医药产业高质量发展,CRC队伍也在不断壮大,人员流动性大、离职率逐年增高的问题日益凸显.本研究旨在探讨中国临床研究协调员的离职原因及其影响因素,为临床试验现场管理组织(site management organization,SMO)和机构的科学规范化管理提供数据参考.方法 依托中国医学科学院肿瘤医院临床试验研究中心,收集2017年11月1日至2022年3月31日期间临床研究协调员基线信息,汇总分析并比较不同岗位(实习、一线和组长)CRC的总体离职率、离职原因、离职后去向及影响因素.结果 本研究共纳入518名CRC,其中实习、一线和组长CRC分别为124名、358名和36名.离职人数272名,总体离职率为52.5％,离职的实习、一线和组长CRC占比分别为29.0％、63.2％和7.7％.离职的主要原因包括:家庭原因(70名,28.1％)、工作内容(70名,28.1％)、晋升发展(46名,18.5％)与薪资原因(46名,18.5％).123(49.4％)名的CRC未变更职业,在变更职业的CRC中,47(69.0％)名选择从事临床监查员(clinical research associate,CRA)、4(1.6％)临床数据管理员(data management,DM)、2(0.8％)名药品警戒等其他临床试验职业,39(15.7％)名选择考研究生、考公务员、销售、医学大数据等非临床试验职业.165名(66.3％)CRC在离职后薪资得到提升.结论 本研究结果提示,中国临床研究协调员流动性较大,尤其是对于行业认知不足的实习CRC和拥有相关短暂工作经验的一线CRC,需要建立统一的CRC职业发展路径、定级标准及晋升依据,促进CRC行业的持续健康发展.

Rare tumor has a huge unmet medical need without standard regimens, calling for novel therapeutic interventions. The National Cancer Center of China identified a threshold of incidence for rare tumor as 2.5/100,000, based on the characteristics of Chinese population. Molecular profiles for rare tumor patients in China further provided prospects for precise and individualized targeted treatment. An ongoing phase II clinical trial, the PLATFORM study, is the first trial tailored for rare solid tumors in China, featured by molecule-guided therapeutics. With the promulgation of supportive policies to encourage the development of innovative drugs for rare tumors in China, opportunities will be provided for these patients and the gap will be filled in the treatment of rare tumors.

本文概述了数字化远程智能临床试验开展现状,重点介绍了电子源数据(eSource)到电子数据采集系统(EDC)的建设思路、应用情况以及成本效率、数据安全、流程合规等多维度价值.与传统模式相比,eSource to EDC(E2E)模式利用电子源数据平台、电子数据采集、远程监查等系统的有效融合,做到更小化人工干预,系统性地提升临床研究效率和数据质量.在保证数据安全与个人信息隐私的前提下,实现数据和操作的有效监管,达到国内外相关法律法规要求,为进一步探索临床研究信息化转型提供参考依据.

目的:了解并展示"十三五"期间中国肝癌药物临床试验发展状况及上市药物概况.方法:从药物临床试验登记与信息公示平台和国产药品及进口药品数据查询系统提取"十三五"期间肿瘤药物临床试验、涉及试验药品及上市药物信息,分析肝癌相关临床研究及上市药物的数量、年度增长情况及相关影响因素,并与其他癌种进行比较.结果:"十三五"期间共有110项肝癌药物临床试验进行了登记,年增长率为52％.其中,82项(75％)试验由国内制药企业发起.国内制药企业发起的I期临床试验和等效性试验所占比例高于国际制药企业(分别为27％和18％、33％和0,均P=0.0003).临床试验共涉及70种肿瘤试验药物,其中54种(77％)由国内制药企业开发.国内制药企业开发的药物中,原研药占比低于国际制药企业(54％和100％,P=0.0002).原研靶向药的作用靶点以程序性死亡蛋白-1及其配体(programmed cell death protein-1,PD-1/programmed cell death ligand 1,PD-L1)(19种,54％)和抗血管生成多靶点为主(9种,25％).共有6种肝癌原研药在中国获批上市.结论:"十三五"期间,中国肝癌药物临床试验蓬勃发展,本土制药企业已成为肝癌药物研发的中坚力量.PD-1/PD-L1和以VEGFR为代表的抗血管多靶点仍是当前研发的热门靶点.以临床为导向、探索新机制的创新性研发将是肝癌药物未来发展的重要方向.

本研究以药物临床试验机构备案管理信息系统和药物临床试验登记与信息公示平台数据为基础,从完成/新增备案机构、备案专业、备案主要研究者以及承担药物临床试验数量和区域分布情况等方面进行系统分析,以展示我国临床试验机构的发展情况,并分析内在因素.结果 显示,机构备案制的落地有助于促使医疗资源的释放和合理使用,对满足临床试验的需求起到重要作用,虽然仍存在各省份机构数量差异,研究者资源和临床试验承接能力分布不均衡的现象,但随着国内多地政策导向支持以及医药产业活跃发展,促使多区域的机构快速成长,呈现出逐渐趋向供求平衡的良好态势.

目的:总结分析我国药物临床试验机构在新版《药物临床试验质量管理规范》(GCP)实施后安全性报告要求现状.方法:对全国98家药物临床试验机构公开发布的药物临床试验安全性事件报告程序和管理要求进行数据处理和统计分析.结果:50家(51.0％)机构要求以研究者作为主要递交方向伦理委员会递交可疑且非预期严重不良反应(suspected unexpected serious adverse reaction,SUSAR)报告,未明确申办方SUSAR报告递交媒介和时限要求的机构比例较高;36家(36.7％)机构对申办者向研究者、伦理或试验管理部门至少一方递交本院和外院SUSAR报告的时限进行区分,本院SUSAR报告递交时限较外院更短,在有明确时限要求的机构中7或15 d是最常见的时限要求;42家(42.9％)机构要求研究者向伦理和/或试验管理部门至少一方上报严重不良事件(severe adverse event,SAE).结论:国内药物临床试验机构能够及时更新安全性报告要求,将SUSAR报告等本院安全性事件作为关注重点,现阶段有必要进一步提升安全性报告程序的清晰性、便利性,探索机构层面安全性事件管理机制.

Introduction Limited clinical studies have been conducted on rare solid tumours, and there are few guidelines on the diagnosis and treatment, including experiences with targeted therapy and immunotherapy, of rare solid tumours in China, resulting in limited treatment options and poor outcomes. This study first proposes a definition of rare tumours and is designed to test the preliminary efficacy of targeted and immunotherapy drugs for the treatment of rare tumours. Methods and analysis This is a phase II, open-label, non-randomised, multiarm, single-centre clinical trial in patients with advanced rare solid tumours who failed standard treatment; the study aims to evaluate the safety and efficacy of targeted drugs in patients with advanced rare solid tumours with corresponding actionable alterations, as well as the safety and efficacy of immune checkpoint (programmed death receptor inhibitor 1, PD-1) inhibitors in patients with advanced rare solid tumours without actionable alterations. Patients with advanced rare tumours who fail standardised treatment and carry actionable alterations (Epidermal growth factor receptor (EGFR) mutations, ALK gene fusions, ROS-1 gene fusions, C-MET gene amplifications/mutations, BRAF mutations, CDKN2A mutations, BRCA1/2 mutations, HER-2 mutations/overexpressions/amplifications or C-KIT mutations) will be enrolled in the targeted therapy arm and be given the corresponding targeted drugs. Patients without actionable alterations will be enrolled in the PD-1 inhibitor arm and be treated with sintilimab. After the patients treated with vemurafenib, niraparib and palbociclib acquire resistance, they will receive combination treatment with sintilimab or atezolizumab. With the use of Simon’s two-stage Minimax design, and the sample size was estimated to be 770. The primary endpoint of this study is the objective response rate. The secondary endpoints are progression-free survival in the targeted treatment group and single-agent immunotherapy group; the duration of response in the targeted therapy and single-agent immunotherapy groups; durable clinical benefit in the single-agent immunotherapy group; and the incidence of adverse events. Ethics and dissemination Ethics approval was obtained from the Chinese Academy of Medical Sciences (ID: 20/132-2328). The results from this study will be actively disseminated through manuscript publications and conference presentations. Trial registration numbers NCT04423185 ; ChiCTR2000039310.

Cell and gene therapies are being rapidly developed to treat solid tumors. Some have been approved, while the most of them are still under clinical investigation. Adoptive cell therapy (ACT) takes advantage of immune cells to eliminate tumors. ACT can be broadly classified as non-genetically and genetically engineered cell products or classified based on the cell type, such as T cell, natural killer (NK) cell, dendritic cell (DC), cytokine-induced killer (CIK), tumor-infiltrating lymphocyte (TIL), and mesenchymal stromal cell (MSC) (Stroncek et al., 2012Stroncek D.F. Berger C. Cheever M.A. Childs R.W. Dudley M.E. Flynn P. Gattinoni L. Heath J.R. Kalos M. Marincola F.M. et al.New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer.J. Transl. Med. 2012; 10: 48Crossref PubMed Scopus (39) Google Scholar). Both non-genetically and genetically engineered ACTs are either available or being actively investigated in clinical settings, including T cells (CAR-T, TCR-T, and γδ T cells as well as gene-edited T cells, respectively) (Stadtmauer et al., 2020Stadtmauer E.A. Fraietta J.A. Davis M.M. Cohen A.D. Weber K.L. Lancaster E. Mangan P.A. Kulikovskaya I. Gupta M. Chen F. et al.CRISPR-engineered T cells in patients with refractory cancer.Science. 2020; 367: eaba7365Crossref PubMed Scopus (328) Google Scholar), TILs, DCs, and macrophages. Genetically engineered cells also belong to the category of gene therapy, using extraneous genetic products (DNA or RNA) to treat diseases such as tumor. The gene introduction system can include viral and non-viral vector products. Oncolytic viruses (OVs) are a promising gene therapy because of their tumor lysis effect, their tumor selectivity, and their desirable immunogenic properties. Cell and gene therapies have shown great potential for treating solid tumors. Many have already been approved. From January 1, 2010, to December 31, 2019, 491 clinical trials on a total of 178 cell and gene therapies were carried out worldwide (INFORMA database). The number of trials increased by 16.1% on average annually and almost doubled in 2017 from the previous year. Phase 1 and 2 trials accounted for >90% of new trials each year (Figure S1A). These trials covered 26 solid tumor types, with melanoma, non-small cell lung cancer (NSCLC), and ovarian cancer as the top three most frequently tested (Figure S1B). In total, 318 ACT clinical trials have been carried out during the last decade, spanning all treatment stages from neoadjuvant to the last line treatment (Figure S1C) and mainly targeting advanced solid tumors (88.1%, Figure S1D). Cancer vaccines were the most popular in all treatment stages. In addition, 374 gene therapy (including genetically engineered ACT) clinical trials were registered in INFORMA. Although China was ranked second place by number of cell and gene therapy clinical trials, there was a large gap between China and the top country, the United States (39 versus 120 trials, Figure S1E). There were 14 and 5 investigational CAR-T and TCR-T trials in China, respectively, versus 22 and 16 in the rest of the world. The landscape of targets in those trials was also different between China and the other countries. The top three CAR-T targets were glypican-3, IL13Rα2/CEA/MUC1, and claudin 18.2/AFP in China and mesothelin, NKG2D, and IL13Rα2/CEA/MUC1 outside of China. The top three TCR-T targets were NY-ESO-1, HBV, and HPV E6 in China and NY-ESO-1, individualized tumor-specific neoantigen, and MAGE A4 outside of China. The higher representation of HBV and HPV E6 in China reflected higher incidences of HBV-related liver cancer and HPV-related cervical cancer in the Chinese population. In China, most trials were carried out in Shanghai, Guangzhou, and Beijing, followed by Shenzhen, Hangzhou, and Nanjing. Most cell and gene therapies didn’t move beyond phase 1 or 2 trials because of many remaining difficulties. First, few tumor-specific antigens have so far been identified on the cell surface in solid tumors (Leko and Rosenberg, 2020Leko V. Rosenberg S.A. Identifying and targeting human tumor antigens for T cell-based immunotherapy of solid tumors.Cancer Cell. 2020; 38: 454-472Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar). Second, solid tumors usually display substantial heterogeneity of antigens. Third, transferred T cells have limited tumor infiltration. Fourth, immunosuppressive tumor microenvironment is a common feature in late-stage cancer patients, leading to T cell exhaustion (Weigelin et al., 2011Weigelin B. Krause M. Friedl P. Cytotoxic T lymphocyte migration and effector function in the tumor microenvironment.Immunol. Lett. 2011; 138: 19-21Crossref PubMed Scopus (34) Google Scholar). Finally, clinical trials with biomarkers were limited, accounting for only 19.2% of ACT trials (61/318) and 14.7% gene therapy trials (55/374). In addition, operational challenges exist. For example, how can the preparation procedures of cell and gene therapies be simplified? How can more effective training be provided to all parties who are involved in cell and gene therapy trials? Various strategies have been developed to address those issues. For instance, better CAR design principles were utilized, and additional factors were included to promote antitumor efficacy, improve tumor infiltration, and overcome the immunosuppressive microenvironment (Hong et al., 2020Hong M. Clubb J.D. Chen Y.Y. Engineering CAR-T cells for next-generation cancer therapy.Cancer Cell. 2020; 38: 473-488Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar). Furthermore, different therapies can be combined in the clinics to improve efficacy. Finally, a new manufacturing process called Generation-2 has been developed for TIL generation, with only 22 days of completion instead of the original 6-week process. The Generation-2 TIL product for melanoma and cervical cancer might soon become commercialized in the United States. In conclusion, cell and gene therapies have been actively developed to treat solid tumors, and related clinical trials covering almost all solid tumor types increased quickly especially after 2017. Cell and gene therapies still face many challenges in solid tumors, and innovative solutions are required to move these therapies to the clinics. This work was supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (Platform Improvement of Clinical Trial Capability 2020-I2M-2-007 ), Chinese Academy of Medical Sciences (grant 2019XK320068 ), and Beijing Municipal Science and Technology Commission ( International Pharmaceutical Clinical Research and Development Platform 2015 ). Q.-J.L. is a co-founder and stockholder for TCRCure Biopharma. T.D. is the founder of Chengdu MedGenCell Co Ltd., Chengdu, Sichuan, China. Download .pdf (.36 MB) Help with pdf files Document S1. Figure S1

Immuno-oncology therapies have revolutionised the standard of care for many types of cancer. The advent of immune checkpoint inhibitors and chimeric antigen receptor T (CAR-T) cell immunotherapy in the past decade marks a new era of modern immunotherapy treatment for oncology. 1 Tang J Shalabi A Hubbard-Lucey VM Comprehensive analysis of the clinical immuno-oncology landscape. Ann Oncol. 2018; 29: 84-91 Summary Full Text Full Text PDF PubMed Scopus (260) Google Scholar The emergence of these immunotherapies, along with policies made by the Chinese government to strengthen medical innovations and drug research and development (R&D), 2 Li N Huang HY Wu DW et al. Changes in clinical trials of cancer drugs in mainland China over the decade 2009-18: a systematic review. Lancet Oncol. 2019; 20: e619-e626 Summary Full Text Full Text PDF PubMed Scopus (20) Google Scholar means that the immuno-oncology drug pipeline for oncology treatment has strengthened in China over the past 5 years. 3 Yu JX Hubbard-Lucey VM Tang J Immuno-oncology drug development goes global. Nat Rev Drug Discov. 2019; 18: 899-900 Crossref PubMed Scopus (80) Google Scholar The developments in immunotherapies for oncology in China led us to explore the data on the outlook and development of these drugs in this country, which can inform future targets for industry, policy makers, and other stakeholders.

Immune checkpoint inhibitors have been approved for clinical application in China. However, the increased immune-related adverse event (irAE) needs more attention. This review summarized the incidence, characteristic clinical manifestation and treatment of irAEs associated with programmed cell death protein-1(PD-1) and programmed cell death ligand-1(PD-L1) inhibitors. To have a deep insight into irAE, the potential mechanisms, the different incidences of cancer types, influencing factors and the direction of future research were also discussed here to provide guidance for clinical oncologist to identify and monitor irAE.

Abstract Background: Salivary adenoid cystic carcinoma (ACC) and oral tongue squamous cell carcinoma (OTSCC) are rare malignancies with low incidence and dismal prognosis. The molecular underpinnings of these remain poorly understood, particularly in Asian population. Methods: Through a whole-exome sequencing analysis of 13 OTSCC and 30 ACC patients, a systematic overview of the mutational features in single-nucleotide variations, copy number variations and chromosomal variations were illustrated. Results: In addition to the well-characterized alterations previously reported in Caucasian patients, such as TP53 mutations (11/13, 84.6%) in OTSCC and MYB-NFIB fusion in ACC (11/30, 36.7%), we also observed several novel genetic changes, including FOXP1-TEX261 fusion (1/13, 7.7%) and MYB-FMO5 fusion (1/30, 3.3%) in OTSCC and ACC respectively, which might play a role in facilitating tumor progression. The data exhibited promising translational value as numerous actionable genes were identified with mutations. 76.9% OTSCC and 20% salivary ACC harbored at least one alteration in actionable genes, mutations in CDKN2A (4/13, 30.8%), NTRK3 (3/13, 23.1%) in OTSCC and FGFR2 (2/30, 6.7%), BRAF (2/30, 6.7%) in salivary gland ACC, suggesting targeted immunotherapy might be an effective intervention. Instead of MYB-independent NFIB fusions previously reported in ACC, only NFIB-independent MYB fusions were found in our cohort, indicating that alterations in NFIB rather than MYB might be essential to ACC tumorigenesis. Conclusions: This study reveals the genetic underpinnings of two rare malignancies in Chinese population, illustrating consistent mutational features with published literature as well as demonstrating several distinct genetic alterations, warranting further investigations. Citation Format: Ning Li, Shuhang Wang, Yue Yu, Yuan Fang, Huiyao Huang, Dawei Wu, Hong Fang, Chao Sun, Anqi Yu, Qi Fan, Shi-Yuan Cheng. Whole-exome sequencing reveals genetic underpinnings of salivary adenoid cystic carcinoma and tongue carcinoma in Chinese population [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-310.

BACKGROUND:Early investigation suggested patients' level of awareness regarding clinical trials was related with willingness to participation. This study was intended to evaluate the level of awareness of cancer patients regarding clinical trials and related influencing factors, and to compare the differences of awareness between patients who attended clinical trials before and not. METHODS:From Jun, 2018 to April, 2019, standardized question-naires were gathered from cancer patients (attended clinical trials vs not attended clinical trials) in our hospital regarding basic information and 10 other questions about awareness. The level of awareness was evaluated and patients were classified into "low cognition" and "high cognition" groups. Logistic regression analysis was performed to determine whether certain characteristics would predict for awareness. RESULTS:Of the 617 participants, 38.6% have attended clinical trials before. 338 (54.6%) patients had a correct overall understanding of clinical trials, while 44 (7.1%) patients still thought participants were the victim of scientific research. Except for the compensation of medical expenses (51.5% vs 48.7%) and related laws of clinical trials (52.3% vs 45.5%), other parts of understanding were elevated in patients attended clinical trials before comparing with patients who didn't, including significance (86.2% vs 77.6%), risk disclosure (91.2% vs 71.6%), confidentiality (73.2% vs 59.7%), voluntariness (95.8% vs 76.3%), withdrawal (86.6% vs 68.2%) and expenses (62.8% vs 39.2%). The proportion of participants who understand these components did not increase even in 239 patients who had attended clinical trials before. Participants who attended clinical trials before (OR=1.83, 95%CI: 1.11-3.00), unmarried/divorced (OR=5.04, 95%CI: 1.73-14.66), retired (OR=2.53, 95%CI: 1.16-5.50) had a higher level of awareness, while patients who had bad impression with doctors (OR=0.43, 95%CI: 0.26-0.72) had lower awareness. CONCLUSIONS:The current level of awareness for clinical trials of cancer patients in our hospital was relatively low, even in patients who had attended clinical trials before. It's necessary to improve patients' awareness of clinical trial by promoting harmony relationship between patients and doctors, as well as by enhancing related propagation. Strengthening the adequacy and efficacy of informed consent in clinical trials also needs to be achieved in the future.

Comprehensive Genomic Profiling may be informative for novel treatment strategies and to improve outcomes for patients with rare tumors. This study aims to discover opportunities for use of targeted therapies already approved for routine use in patients with rare tumors. Solid tumors with an incidence lower than 2.5/100,000 per year was defined as rare tumors in China after comprehensive analysis based on epidemiological data and current availability of standardized treatment. Genomic data of rare tumors from the public database cBioPortal were compared with that of the Chinese population for targetable genomic alterations (TGAs). TGAs were defined as mutations of ALK, ATM, BRAF, BRCA1, BRCA2, CDKN2A, EGFR, ERBB2, FGFR1,2,3, KIT, MET, NF1, NTRK1,2,3, PIK3CA, PTEN, RET, and ROS1 with level 1 to 4 of evidence according to the OncoKB knowledge database. Genomic data of 4,901 patients covering 63 subtypes of rare tumor from cBioPortal were used as the western cohort. The Chinese cohort was comprised of next generation sequencing (NGS) data of 1,312 patients from across China covering 67 subtypes. Forty-one subtypes were common between the two cohorts. The accumulative prevalence of TGAs was 20.40% (1000/4901) in cBioPortal cohort, and 53.43% (701/1312) in Chinese cohort (p < 0.001). Among those 41 overlapping subtypes, it was still significantly higher in Chinese cohort compared with cBioPortal cohort (54.1%% vs. 26.1%, p < 0.001). Generally, targetable mutations in BRAF, BRCA2, CDKN2A, EGFR, ERBB2, KIT, MET, NF1, ROS1 were ≥3 times more frequent in Chinese cohort compared with that of the cBioPortal cohort. Cancer of unknown primary tumor type, gastrointestinal stromal tumor, gallbladder cancer, intrahepatic cholangiocarcinoma, and sarcomatoid carcinoma of the lung were the top 5 tumor types with the highest number of TGAs per tumor. The incidence of TGAs in rare tumors was substantial worldwide and was even higher in our Chinese rare tumor population. Comprehensive genomic profiling may offer novel treatment paradigms to address the limited options for patients with rare tumors.

BACKGROUND:The clinical trials of new anti-tumor drugs are prospering in China. The acceptance of clinical trials in patients is an important factor affecting the speed and quality of clinical trials. Previous studies have investigated the acceptance of clinical trials in those cancer patients, who have never participated in a trial. This study is designed to investigate and compare the acceptance and related causes of clinical trials in cancer patients who have once participated in a clinical trial or not.METHODS:From June 2018 to April 2019, a standardized questionnaire-based survey was conducted among two groups of cancer patients classified by history of clinical trial participation in Cancer hospital, Chinese Academy of Medical Science, mainly focusing on their overall acceptance of clinical trials and related considerations, including the role of attending doctors, as well as group differences between the two participants.RESULTS:A total of 538 patients were enrolled with an average age of 53.5 years old, 51.1% of whom were males, and 43.3% of whom have never participated in a clinical trial. Overall, 502 patients (93.3%) were willing to or recommend their relatives or friends to participate in clinical trials, and patients with history of clinical trial participation had higher willingness (96.6% vs 90.8%, P=0.008). Patients were most likely to be motivated by expectation of optimal treatment (100.0% vs 99.3%) for both those who had once participated in a clinical trial or those not, respectively followed by financial burden reduction (56.0%) and recommendation by attending doctor (43.7%). The main reasons for unwillingness-to-participate for those who had once participated in a clinical trial were abandoning other treatment options, divided into control group or additional visits, while for those who had never participated in a clinical trial, ineffective treatment or serious adverse reactions were their main concerns. In the decision-making of clinical trial participation, 88% patients highly valued the role of recommendation by attending doctors. Among patients without trial participation history, 60.9% of those had no unwillingness-to-participate expressed that recommendation by attending doctors would change their decisions. The study also reported patients' preferences for information and access to clinical trials.CONCLUSIONS:The acceptance of clinical trials in cancer patients in our hospital is generally high, especially in patients who had a history of trial participation. It's of substantial significance to give full play to the role of doctors in improving the acceptance of clinical trials of cancer patients in China.

Salivary gland carcinomas（SGCs） are rare malignancies that remain poorly understood owing to their low incidence（Matsuba et al., 1986 b; Liu et al., 2012）. As per GLOBOCAN 2018, 52,800 new cancers arising from salivary glands were estimated to be diagnosed across the world that year. Because of their high propensity to invade local and perineural structures, SGCs impose significant threat of local recurrence and distant metastasis to patients, leading to high mortality（Matsuba et al., 1986 b）. Among SGCs,

2020年初始新型冠状病毒肺炎(COVID-19)疫情爆发,国家经济和人民生活受到重创,临床试验行业深受影响,也给研究机构管理和试验项目实施带来前所未有的挑战.通过分析各大研究机构针对COVID-19防控要求下的应对措施,选取2020年1月23日至2020年4月8日,整理出本研究中心试验进展情况、处理方式、随访用药、脱落失访等情况,探讨疫情期间降低临床试验影响的可行性方法,旨在为今后探索临床试验的远程执行积累经验,为建立特殊时期临床试验应对策略提供参考依据.