Establishment of an infrastructure for rapid pandemic response at the Frederick National Laboratory

The sudden onset of the 2019 SARS-CoV-2 pandemic required agile development of standards and efficient validation of assays to assess prevalence of infection as well as immune responses to infection and vaccination. Leveraging their experience in HPV serology and standards, the Vaccine, Immunity and Cancer Directorate (VICD) at the Frederick National Laboratory for Cancer Research (FNCLR) pivoted to address this unmet need in SARS-Co-V2 serology clinical testing and research. This standardization effort required the collection and processing of large volumes of blood from SARS-Co-V2 infected and uninfected individuals into serum and peripheral blood mononuclear cells (PBMCs). Collaborations with specimen collection sites across the United States were established. Following qualification for anti-SARS-CoV-2 IgG and IgM levels in independent laboratories, VICD assembled reference evaluation panels, which were used to assist the FDA's performance evaluation of commercial assays submitted for EUA approval. To date, 185 different shipments of the standard or validation panel have been sent to both domestic and international labs. These materials are also available to the SARS-CoV-2 serology community for assay calibration and performance evaluation which greatly facilitates assay data harmonization. In addition, the NCI Serological Sciences Network (SeroNet) was born from this initiative and expertise, resulting in the establishment of Capacity Building Centers (CBCs) for sample collection from different healthy, cancer and immunocompromised cohorts at Mount Sinai, Arizona State University, the University of Minnesota, and Northwell Feinstein. The NCI and FNLCR simultaneously collaborated to develop a network of investigators focused on advancing research on the immune response to SARS-CoV-2 infection and vaccination among diverse and vulnerable populations, including cancer patients. Their research has resulted in over 326 peer-reviewed publications. The CBC's have enrolled patients in longitudinal studies, resulting in a centralized collection of annotated, well characterized serum, PBMCs and clinical data. Numerous cancer cohorts, but predominantly Multiple Myeloma, are included. Furthermore, technology development was supported at the CBC's. Based upon this success, the VICD in collaboration with NCI is pursuing an even more innovative effort in pandemic preparedness to establish a Center for Serology and Data Emergency Preparedness (CESDEP);a global network able to activate and pivot to address pandemic-level threats, while continuing to expand the development of immunological assays that can inform clinical decisions for cancer and other immunocompromised patients.

Impact of COVID-19 on longitudinal breast cancer research studies involving TNBC patients

Background Triple-negative breast cancer (TNBC) accounts for ~15% of breast cancer diagnoses but is linked to worse outcomes and comprises a disproportionate number of breast cancer deaths. The TNBC pilot study is a prospective longitudinal study to provide a critical resource for understanding TNBC disease. However, the pandemic impacted the collection of samples. Objective To highlight the impacts of COVID-19 on this longitudinal cancer translational research study including the patient's perspective and to develop recommendations to avoid future disruptions. Methods 389 participants were enrolled in the prospective longitudinal cohort, which collected serial blood samples for up to 5 years. Due to the pandemic, research was curtailed for 6 months due to concerns about patient safety, halting the collection of blood samples. Missed samples and data gaps were documented. To complement this, we initiated a survey capturing the patient perspective on their experience of the study disruption due to COVID. Results 217 enrolled participants missed a blood draw or had a collection outside the study window. 158 patients missed 1 time-point collection, and 59 patients missed >= 2 collections. Of the 217 participants who missed a collection, 6 disease recurrence diagnoses and 3 deaths occurred during research curtailment. The collection of survey responses from participants is ongoing and will be presented at the AACR Annual Meeting. Conclusion Missed samples resulted in irreplaceable data gaps critical to monitoring patient outcomes, and reduced cohort sampling during the pandemic. Our current knowledge of the risks suggests that with proper informed consent, collections could have continued. To mitigate disruption in future clinical studies, clear plans should be part of study design to provide continuity. The participants' experience to be reported will also help researchers understand their issues and help develop policies. (Table Presented).

Federated Learning for Healthcare Domain - Pipeline, Applications and Challenges

Federated learning is the process of developing machine learning models over datasets distributed across data centers such as hospitals, clinical research labs, and mobile devices while preventing data leakage. This survey examines previous research and studies on federated learning in the healthcare sector across a range of use cases and applications. Our survey shows what challenges, methods, and applications a practitioner should be aware of in the topic of federated learning. This paper aims to lay out existing research and list the possibilities of federated learning for healthcare industries.© 2022 Copyright held by the owner/author(s).

Developing a comorbidity score in cancer patients using healthcare utilization databases during the COVID-19 pandemic: An experience from Italy.

BACKGROUND: A strong relationship has been observed between comorbidities and the risk of severe/fatal COVID-19 manifestations, but no score is available to evaluate their association in cancer patients. To make up for this lacuna, we aimed to develop a comorbidity score for cancer patients, based on the Lombardy Region healthcare databases. METHODS: We used hospital discharge records to identify patients with a new diagnosis of solid cancer between February and December 2019; 61 comorbidities were retrieved within 2 years before cancer diagnosis. This cohort was split into training and validation sets. In the training set, we used a LASSO-logistic model to identify comorbidities associated with the risk of developing a severe/fatal form of COVID-19 during the first pandemic wave (March-May 2020). We used a logistic model to estimate comorbidity score weights and then we divided the score into five classes (<=-1, 0, 1, 2-4, >=5). In the validation set, we assessed score performance by areas under the receiver operating characteristic curve (AUC) and calibration plots. We repeated the process on second pandemic wave (October-December 2020) data. RESULTS: We identified 55,425 patients with an incident solid cancer. We selected 21 comorbidities as independent predictors. The first four score classes showed similar probability of experiencing the outcome (0.2% to 0.5%), while the last showed a probability equal to 5.8%. The score performed well in both the first and second pandemic waves: AUC 0.85 and 0.82, respectively. Our results were robust for major cancer sites too (i.e., colorectal, lung, female breast, and prostate). CONCLUSIONS: We developed a high performance comorbidity score for cancer patients and COVID-19. Being based on administrative databases, this score will be useful for adjusting for comorbidity confounding in epidemiological studies on COVID-19 and cancer impact.

Communication transforms the impact of the COVID-19 pandemic on children with cancer and their families.

BACKGROUND: The COVID-19 pandemic altered healthcare systems globally, causing delays in care delivery and increased anxiety among patients and families. This study examined how hospital stakeholders and clinicians perceived the global impact of the COVID-19 pandemic on children with cancer and their families. METHODS: This secondary analysis examined data from a qualitative study consisting of 19 focus groups conducted in 8 languages throughout 16 countries. A codebook was developed with novel codes derived inductively from transcript review. In-depth analysis focused on the impact of the COVID-19 pandemic on children with cancer and their families. RESULTS: Eight themes describing the impact of the pandemic on patients and their families were identified and classified into three domains: contributing factors (COVID-19 Policies, Cancer Treatment Modifications, COVID-19 Symptoms, Beliefs), patient-related impacts (Quality of Care, Psychosocial impacts, Treatment Reluctance), and the central transformer (Communication). Participants described the ability of communication to transform the effect of contributing factors on patient-related impacts. The valence of impacts depended on the quality and quantity of communication among clinicians and between clinicians and patients and families. CONCLUSIONS: Communication served as the central factor impacting whether the COVID-19 pandemic positively or negatively affected children with cancer and families. These findings emphasize the key role communication plays in delivering patient-centered care and can guide future development of communication-centered interventions globally.

How COVID-19 exposed pre-existing roadblocks for cancer control in Africa: strategies, lessons and recommendations from the 2019-2020 Africa Cancer Research and Control ECHO

Background: The COVID-19 related mitigation measures adversely affected various cancer control activities in Africa, with cancer prevention and screening activities amongst the most significantly impacted. When the COVID-19 pandemic struck, the Africa Cancer Research and Control ECHO utilised their virtual platform to share experiences and knowledge of how to continue cancer service delivery during the pandemic. This analysis describes the evolved strategies, dilemmas, and recommendations to strengthen the health systems for cancer control in Africa. Method(s): Eleven 1-hour-long sessions about the then newly emerging coronavirus infection and its impact on cancer control in Africa were held from April 2020 to August 2020, using Zoom. An average of 39 participants attended the sessions including scientists, clinicians, policymakers and global partners. Sessions were analysed thematically. Result(s): Most strategies to maintain cancer services during the COVID-19 pandemic centred around cancer treatment, with few strategies on maintaining cancer prevention services, early detection, palliative care and research services. The most mentioned challenge during the pandemic was fear of exposure to COVID-19 infection at the health facility during diagnosis, treatment or follow-up for cancer care. Other challenges were disruptions to service delivery, inaccessibility of cancer treatment, disruption of research activities and a lack of psychosocial support for COVID-19 related fear/anxiety. Significantly, this analysis shows that the COVID-19 related mitigation measures exacerbated existing predicaments in Africa, such as inadequate attention to cancer prevention strategies, psychosocial and palliative services and cancer research. The Africa Cancer ECHO recommends African countries to leverage the infrastructure developed in response to COVID-19 pandemic to strengthen the health system along the entire cancer control continuum. This calls for urgent action to develop and implement evidence-based frameworks and comprehensive National Cancer Control Plans that will withstand any future disruptions.Copyright © the authors;licensee ecancermedicalscience. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http:// creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Patient centred care: filling in the gaps

Research by Courtney Davis and colleagues on new cancer drugs approved by the European Medicines Agency is concerning on this front (doi:10.1136/bmj-2022-073711).1 The study found that important information about the benefits of cancer drugs was not included in patient leaflets and that concerns about the reliability of evidence for these benefits were omitted in communication to clinicians and patients. Isabelle Munyangaju and colleagues discuss falling global vaccination rates in light of the covid-19 pandemic (doi:10.1136/bmj.p627).6 Vaccination campaigns stalled because of disruption to primary healthcare services, "a failure to deliver services to the hardest to reach, ‘last mile' populations,” and rising vaccine hesitancy caused by the spread of misinformation. The ongoing success of vaccination campaigns will rely on healthcare communities working with local populations to develop a mutual understanding and to fill knowledge gaps where good sources of information are missing, and poor evidence is shared.

Biobanking: Paving Way For Medical Research

Biobank is a place where biosamples and associated data are collected and stored. The concept of biobanks may spark little excitement for most people. Biobanks are more developed in economically reach countries while it is a new for LMICs. As the advancement of science and technology, completion of human genome project, the treatment of patients are transformed from conventional to personalised. Human Genome project has advanced science through its application in microbiology, virology and pathology. In parallel to Human Genome project, Biobank has become a vital infrastructure for research, new drug discovery, it is also leading to the development of novel technologies, analytical tools and advancement of patient treatment through medical research. Biobanks are a key component of personalized medicine built on the three pillars of cancer research: proteomics, metabolomics, and epigenomics.lt has the potential to advance personalised medicine. Biobank aided in intense development in cancer research from the diagnostic, prognostic and therapeutic aspects. In recent pandemic Biobank have played and proved its role in fight against Covid-19 by allowing researches to study the disease and develop vaccines and treatment in short time. Without involvement of biobank and good quality of samples from patients infected with Covid-19, it would have been unachievable to sequence SARS-COV-2 virus and develop effective vaccines in record times.

Reasons for Reduced Willingness to Participate in Clinical Trials During the COVID-19 Pandemic: The Translational Breast Cancer Research Consortium (TBCRC) 057 Survey

Background: Historically, less than 10% of adult patients with cancer enroll in clinical trials, however, enrollment dropped further at the onset of the COVID-19 pandemic. Barriers to trial participation during the pandemic have not been reported. As part of the TBCRC 057 survey on the impact of the pandemic on willingness to participate in breast cancer trials, we assessed reasons for reluctance to participate in trials during the pandemic. Method(s): US residents who self-reported a breast cancer diagnosis were eligible to complete the online survey 8/6/21-9/30/21. Respondents indicated whether they were current trial participants and, if not, their willingness to consider participating in a trial during the pandemic using a 5-point scale (0-not at all willing to 4-definitely willing). Respondents who were not current trial participants and who were not "definitely willing" to consider participation during the pandemic were characterized as "reluctant" and asked to select reasons for their reluctance from a checklist. Pandemic-related anxiety was assessed on an 11-point scale (0-no anxiety to 10-worst anxiety possible). Respondents indicated how the option to conduct trial activities online would affect their decision to participate in a trial (much less likely, somewhat less likely, would not affect my decision, somewhat more likely, or much more likely). In exploratory analyses, we evaluated whether pandemic-related anxiety and favorable reactions towards opportunities to conduct trial activities online were associated with reluctance to consider trial participation during the pandemic due to fear of SARS-CoV-2 exposure. Means were compared with two sample t-tests and proportions with Fisher's exact tests. Result(s): Of 385 survey respondents, 185 (48%) were characterized as reluctant to consider trial participation during the pandemic. Among these 185, median age was 55 (range 25-80), 85.7% were non-Hispanic White, 48.1% had metastatic disease and 44.2% received care at academic centers. Reasons for reluctance to consider trial participation during the pandemic cited by >=15% of the 185 reluctant respondents are shown in the Table. Respondents who selected fear of exposure to SARS-CoV-2 as a reason for their reluctance to consider participating in a trial during the pandemic had higher mean pandemic-related anxiety (7.0 vs 5.2, p< 0.001). These respondents were more likely to indicate telemedicine doctor visits (p=0.01), virtual consents (p=0.001) and online study questionnaires (p=0.001) would make them somewhat or much more likely to participate in trials than respondents who did not select fear of exposure to SARS-CoV-2 as a reason for their reluctance. Conclusion(s): Reasons for reluctance of patients with breast cancer to consider participation in clinical trials during the pandemic are multifactorial. Although concerns about safety and efficacy remain prominent, fear of exposure to SARS-CoV-2 drives unwillingness to participate in >25% of reluctant patients. Trial accrual may benefit from incorporation of electronic activities when possible.

A preregistered vignette experiment on determinants of health data sharing behavior Willingness to donate sensor data, medical records, and biomarkers.

The COVID-19 pandemic has spotlighted the importance of high-quality data for empirical health research and evidence-based political decision-making. To leverage the full potential of these data, a better understanding of the determinants and conditions under which people are willing to share their health data is critical. Building on the privacy theory of contextual integrity, the privacy calculus, and previous findings regarding different data types and recipients, we argue that established social norms shape the acceptance of novel practices of data collection and use. To investigate the willingness to share health data, we conducted a preregistered vignette experiment. The scenarios experimentally varied the vignette dimensions by data type, recipient, and research purpose. While some findings contradict our hypotheses, the results indicate that all three dimensions affected respondents' data sharing decisions. Additional analyses suggest that institutional and social trust, privacy concerns, technical affinity, altruism, age, and device ownership influence the willingness to share health data.

Pivot to SPARCC diversity in the clinical cancer research workforce, implementation and evaluation of an academic enrichment pathway before, during, and after the COVID-19 global pandemic

Academic pipeline programs are designed to mitigate systemic barriers that have historically excluded individuals due to deep-rooted, structural inequities. The Student-centered Pipeline to Advance Research in Cancer Careers (SPARCC) was developed in 2018 to diversify the clinical research health professions workforce and has graduated three cohorts of scholars from 20192021. Due to COVID-19 and safety concerns, SPARCC evolved, pivoting to establish effective learning environments virtually and in-person to ensure the original curriculum of academic, research, and professional identity development were upheld. The program aims to a.) immerse students in the clinical cancer research environment, supporting immediate employment as a clinical research professional (CRP) and b.) to provide structured support and guidance for individuals intending to pursue advanced professional degrees. SPARCC programmatic evaluations included a multifactorial strategy utilizing the same three evaluative instruments each year. These included a 17-item knowledge, attitudes, and practices (KAP) survey specific to clinical cancer research, daily workshop evaluations, and clinical practicum rotation evaluations. The SPARCC KAP was distributed immediately prior to the start of the program, upon graduation from the program, and six months later. After exploratory factor analysis, items were grouped into three factors: knowledge of clinical research practice, knowledge of research practice, and knowledge of culturally responsive cancer care. Mixed ANOVAS were used to assess changes in factors based on time (pre-, post-, and 6-month follow up;within) and cohort (year of participation;between). Over three years 156 students applied, 65% of whom identified belonging to an underrepresented ace or ethnicity. Thirty-six scholars matriculated through the program: 14(39%) White;13(36%) Black;3(8%) Asian;3(8%) Native American;1 3%) Native American/Black;1(3%) Black/Asian;1(3%) Pacific Islander. Forty-four percent (16 scholars) identified as Hispanic/Latino/a. Six scholars (17%) entered the clinical research workforce within six months of graduating from the SPARCC program, all who identified as belonging to underrepresented groups. The KAP evaluations revealed that scholars' knowledge increased significantly after participation in the program in each of the three factors: knowledge of clinical research practice (p < .007);knowledge of research practice (p < .007);and knowledge of culturally responsive cancer care (p < .007). Within six months of graduation from SPARCC, 17% of scholars entered the clinical research workforce, and nearly 60% were enrolled in graduate-research degree programs or medical school. SPARCC demonstrated curricular flexibility and ingenuity when pivoting from entirely in-person to entirely virtual, and finally to a hybrid program over the first three years of the program. Through didactic, clinical, research, and career professional identity exploration, robust learning experiences engaged scholars despite limitations on in-person contact.

Student-initiated seminars in the undergraduate medical training program "interdisciplinary oncology" of the Medical Faculty of Heidelberg

Introduction: Longitudinal electives ("tracks") were introduced within the Heidelberg Curriculum Medicinale (HeiCuMed) in 2017. Participation in one of the 11 tracks is obligatory. Within the track "Interdisciplinary Oncology" (IO), > 150 participants can choose from > 170 courses each semester. Since students of all terms are allowed, previous knowledge and research experience are heterogeneous. Tus, medical students and participants have initiated a lecture series entitled "Insights in Research" to facilitate the entry of medical students into scientifc research. In addition, a student-led cofee meet-up ("DoktorandenCafe") was set up. Here we report on those student initiatives. Method(s): To allow medical students with a strong interest in oncology to get into contact with basic scientifc research groups at the University Hospital Heidelberg, the German Cancer Research Center (DKFZ), the Hopp Childrens' Cancer Center (KiTZ) and the National Cancer for Tumor Diseases (NCT), a seminar entitled "Insights in Research" is organized on a monthly basis by student representatives. Guest lecturers who are first or co-author of a respective paper are invited and their research work is discussed with all participants. To increase exchange between current and future medical doctoral students, the "DoktorandenCafe" was initiated by student representatives. Result(s): Since February 2020, > 70 students enrolled in the IO elective have participated in the seminars "Insights in Research" and "DoktorandenCafe". The seminar "Insights in Research" enables students to gain basic knowledge of scientifc research processes, facilitating the first contact of medical students with cancer research. Moreover, this seminar enables students to discuss scientifc topics in the field of oncology together with other participants of the course and with a researcher that actively participated in the presented research project. Additionally, the newly initiated cofee meet-up enables students who are writing or planning to write their doctoral thesis in the field of oncology to get in touch with each other and to discuss thesis-related issues. Due to the COVID-19 pandemic, both seminars were held virtually during the summer term 2020. Conclusion(s): The student-initiated seminars have a high participation rate. This indicates that student-initiated teaching initiatives should be encouraged and implemented into medical education to strengthen interest in basic and translational research.

Precision public health approaches to health equity

Since President Barack Obama announced the Precision Medicine Initiative during his state of the union address in January 2015, the sciences of precision medicine and health equity have largely grown in parallel, though there have been some efforts to bring the two together. As research on health equity has evolved to name and consider structural racism, the penultimate goal of research in this area also as moved from efforts to identify and describe gaps between racial and ethnic groups to characterizing the context creates and perpetuates racial inequities and how best to mitigate them. In this presentation, I will briefly describe how syndemics, intersectionality, and individual tailoring may complement downstream efforts to characterize epigenetic and genomic efforts to develop biomedical interventions to achieve healthcare equity and health equity. After noting how the principles of precision medicine may be applied more broadly than the most common way it is operationalized through genomic medicine, I argue that that creating racial justice in health will require defining health equity more clearly and precisely. Consequently, I utilize the example of Black men and the context of COVID-19 to highlight how more precisely defining the structural context of the population of interest by using tools such as intersectionality and syndemics is fundamental to achieving equity. I highlight how achieving health equity will require creating, resisting, undoing, and mitigating structural racism and note what that means for cancer research. Precision medicine may help to mitigate the health effects of structural racism, and it will remain an important tool to promote population health;however, efforts to achieve health equity and racial justice will require interventions that change the contexts and conditions that create, exacerbate, and perpetuate structural inequities and the racial inequities in health outcomes that they produce and maintain.

The Use of Virtual Research Experiences for Appalachian Career Training in Oncology (ACTION) Program High School Participants During the COVID-19 Pandemic.

Objective: Kentucky has the highest cancer incidence and mortality rates in the nation, with rates greatest in the Appalachian region due to poor health behaviors and inequities in social determinants of health. The Appalachian Career Training in Oncology (ACTION) Program at the University of Kentucky Markey Cancer Center engages 20 Appalachian-native high school students annually in cancer education, research, and outreach activities. During the COVID-19 pandemic, programming was disrupted, and alternative activities were implemented, including virtual research experiences. Methods: The program's goals were to improve students' biology and cancer content knowledge and research skills and help students make career decisions. Virtual laboratories were used to help accomplish these goals. This study aimed to evaluate the use of virtual laboratories embedded in the program and determine if such experiences helped reach the program's goals. A survey was used to measure students' perceptions of the virtual labs. Results: Results indicated that students perceived they gained content knowledge, obtained research skills, and considered entering science and cancer-related careers. Conclusion: The decision to incorporate virtual laboratories into the ACTION programming during the COVID-19 pandemic was a sound instructional choice. Evidence provided herein gives researchers and program developers information necessary to consider using virtual labs in their programs.

Therapeutic delivery: industry update covering January 2022

This industry update covers the period from January 1 through January 31, 2022, and is based on information sourced from company press releases, scientific literature, patents and news websites. January 2022 saw Janssen and Midatech expand their collaboration on bioresorbable polymer microsphere technology for drug delivery. Takeda announced its plans to acquire UK-based Adaptate Biotherapeutics and Gandeeva raised further investment funds to support its drug discovery and development platform focused on the evaluation of protein-drug interactions. Biogen announced that it will sell its stake in a biosimilars joint venture and ABL Bio and Sanofi announced a collaboration around a novel treatment for Parkinson's disease. New regulatory announcements this month included US FDA approvals of a new insomnia treatment for Idorsia and a treatment for atopic dermatitis developed by Pfizer. Insulet gained FDA clearance for a closed-loop insulin pump and Ascendis Pharma followed up its United States approval last year for a once-weekly treatment for growth hormone deficiency with European approval. Pfizer and Ionis announced the discontinuation of the clinical development of a novel cardiovascular drug. In terms of collaborations, Novartis and Alnylam announced they will work together to explore targeted therapies to restore liver function;Scorpion Therapeutics partnered with AstraZeneca to develop novel cancer treatments and Nutriband Inc. and Kindeva Drug Delivery will work together to develop a transdermal fentanyl patch. Collaborations were also announced between Century Therapeutics and Bristol Myers Squibb and Lilly and Entos Pharmaceuticals in the areas of stem cell therapies for cancer treatment and neurology, respectively. A team from the Massachusetts Institute of Technology reported progress in developing oral mRNA treatments and West Pharmaceutical Services published a blog describing the development of a proof-of-principle system for a closed-loop feedback system targeting opioid overdose. A report on the BBC website highlighted the benefits of more sustainable inhalers.

NCRI's Consumer Forum: Patients promoting evidence-based medicine and evidence-based policy

Background: Since its inception in 2000 the UK’s National Cancer Research Institute (‘NCRI’) has committed to involve Consumers (patents and public) representatives in all aspects of its work. Methods: Consumers are recruited in open competition, trained for specific NCRI roles, and supported to work beyond those roles. The NCRI Consumer Forum contains 140 members from all four UK nations, providing a pool of experienced advocates working in all areas of cancer research. The membership reflects the geographic diversity of the four UK nations. Results: 75% of Consumers work with research funders or organisations outside the NCRI Partners. In the 2021 census, more than 50 such organisations were identified, including local, national and international organisations, charities, NHS Trusts, online communities and patient groups. Consumers work or have worked with industry including Big Pharma, biotechs and medical device manufacturers. They serve on Trial Management/Steering Groups, sit on research funding committees and hold governance or accountability posts, eg Board members, Charity Trustees, NHS Commissioners. All have worked on patient information, including websites, videos and audio. During the COVID-19 pandemic in 2020-21 the Consumer Forum worked collaboratively with the UK Coronavirus Cancer Monitoring Project to create, distribute and analyse a survey asking cancer patients what was important to them for COVID-19 and cancer research. Results informed the direction of Covid-19 and cancer research in the UK. This collaboration continued with regular discussion around new research areas and collaboration on peer-reviewed journal articles. Consumers work/have worked with strategic bodies in the UK and beyond eg NICE, MHRA, HRA, BBMRI-ERIC, EORTC. Consumers have provided responses to two recent UK Government consultations, inputting into the strategy of the UK regulatory environment via the MHRA clinical trials regulation and shaping the future strategy for cancer care and research via the national 10-year cancer plan. Conclusions: The NCRI Consumer Forum is a group of Patients and Carers promoting evidence-based medicine and evidence-based policy in the UK and beyond. Legal entity responsible for the study: NCRI. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Progression-free survival (PFS) and overall survival (OS) in advanced/recurrent (AR) mismatch repair deficient/microsatellite instability–high or proficient/stable (dMMR/MSI-H or MMRp/MSS) endometrial cancer (EC) treated with dostarlimab in the GARNET study

Background: Dostarlimab is a programmed death 1 (PD-1) inhibitor approved in the EU as a monotherapy in patients (pts) with dMMR/MSI-H AR EC that has progressed on or after platinum-based chemotherapy;and in the US as a monotherapy in pts with dMMR AR EC that has progressed on or after platinum-based chemotherapy or dMMR solid tumors that have progressed on or after prior treatment, with no satisfactory alternative treatment options. We report on PFS and OS in 2 expansion cohorts of the GARNET trial that enrolled pts with EC. Methods: GARNET is a multicenter, open-label, single-arm phase 1 study. Pts were assigned to cohort A1 (dMMR/MSI-H EC) or A2 (MMRp/MSS EC) based on local immunohistochemistry assessment. Pts received 500 mg of dostarlimab IV every 3 weeks for 4 cycles, then 1000 mg every 6 weeks until disease progression, discontinuation, or withdrawal. PFS and OS are secondary efficacy endpoints. Results: 153 pts with dMMR/MSI-H and 161 pts with MMRp/MSS EC were enrolled and treated. The efficacy-evaluable population included 143 pts with dMMR/MSI-H EC and 156 pts with MMRp/MSS EC with measurable disease at baseline and ≥6 mo of follow-up. Median follow-up was 27.6 mo for dMMR/MSI-H and 33.0 mo for MMRp/MSS EC (Table). For pts with dMMR/MSI-H EC, median PFS (mPFS) was 6.0 mo, with 3-year estimated PFS rate of 40.1%. With 37.3% of pts experiencing an event, mOS was not reached;estimated 3-year OS was >50%. For pts with MMRp/MSS EC, mPFS was 2.7 mo. mOS was 16.9 mo with 68.9% of pts experiencing an event. Safety has been previously reported. [Formula presented] Conclusions: Dostarlimab demonstrated durable antitumor activity in dMMR/MSI-H and MMRp/MSS AR EC. dMMR/MSI-H was associated with longer PFS and OS than MMRp/MSS as expected. Clinical trial identification: NCT02715284. Editorial acknowledgement: Writing and editorial support, funded by GlaxoSmithKline (Waltham, MA, USA) and coordinated by Heather Ostendorff-Bach, PhD, of GlaxoSmithKline, was provided by Shannon Morgan-Pelosi, PhD, and Jennifer Robertson, PhD, of Ashfield MedComms, an Ashfield Health company (Middletown, CT, USA). Legal entity responsible for the study: GlaxoSmithKline. Funding: GlaxoSmithKline. Disclosure: A.V. Tinker: Financial Interests, Institutional, Sponsor/Funding: AstraZeneca;Financial Interests, Personal, Other: AstraZeneca, Eisai, GlaxoSmithKline. B. Pothuri: Financial Interests, Institutional, Funding: AstraZeneca, Celsion, Clovis Oncology, Eisai, Genentech/Roche, Karyopharm, Merck, Mersana, Takeda Pharmaceuticals, Tesaro/GSK;Financial Interests, Personal, Other: Arquer Diagnostics, AstraZeneca, Atossa, Clovis Oncology, Deciphera, Elevar Therapeutics, Imab, Mersana, Tesaro/GSK, Merck, Sutro Biopharma, Tora, GOG Partners;Financial Interests, Personal, Advisory Board: Arquer Diagnostics, AstraZeneca, Atossa, Deciphera, Clovis Oncology, Eisai, Elevar Therapeutics, Imab, Merck, Mersana, Sutro Biopharma, Tesaro/GSK, Toray;Financial Interests, Personal, Leadership Role: GOG Partners, NYOB Society Secretary, SGO Clinical Practice Committee Chair, SGO COVID-19 Taskforce Co-Chair. L. Gilbert: Financial Interests, Institutional, Funding: Alkermes, AstraZeneca, Clovis, Esperas, IMV, ImmunoGen Inc, Karyopharm, Merck Sharp & Dohme, Mersana, Novocure GmbH, OncoQuest Pharmaceuticals, Pfizer, Roche, Tesaro;Financial Interests, Personal, Other: Merck, Alkermes, AstraZeneca, Eisai, Eisai-Merck, GlaxoSmithKline. R. Sabatier: Financial Interests, Institutional, Funding: AstraZeneca, Eisai;Financial Interests, Personal, Other: AstraZeneca, GlaxoSmithKline, Novartis, Pfizer, Roche;Non-Financial Interests, Personal, Other: AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Pfizer, Roche. J. Brown: Financial Interests, Personal, Advisory Role: Caris, Clovis, Eisai, GlaxoSmithKline;Financial Interests, Personal, Funding: GlaxoSmithKline, Genentech. S. Ghamande: Financial Interests, Personal, Advisory Role: Seattle Genetics;Financial Interests, Personal, Speaker’s Bureau: GlaxoSmithKline;Financial Interests, Institutional, Funding: Abbv e, Advaxis, Bristol Myers Squibb, Clovis, Genentech, GlaxoSmithKline, Merck, Roche, Seattle Genetics, Takeda. C. Mathews: Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Deciphera, Moderna, GSK, Regeneron, Seattle Genetics;Financial Interests, Personal, Advisory Board: IMAB biopharma. D. O'Malley: Financial Interests, Personal, Advisory Board: AstraZeneca, Tesaro/GSK, Immunogen, Ambry, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, GOGFoundation, Iovance, Eisai, Agenus, Merck, SeaGen, Novartis, Mersana, Clovis, Elevar, Takeda, Toray, INXMED, SDP Oncology (BBI), Arquer Diagnostics, Roche Diagnostics MSA, Sorrento, Corcept Therapeutics, Celsion Corp;Financial Interests, Personal, Funding: AstraZeneca, Tesaro/GSK, Immunogen, Janssen/J&J, Abbvie, Regeneron, Amgen, Novocure, Genentech/Roche, VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto Inc, Ludwig Cancer Research, Stemcentrx, Inc, Cerulean Pharma, GOGFoundation, Bristol-Myers Squibb Co, Serono Inc, TRACON Pharmaceuticals, Yale University, New Mexico Cancer Care Alliance, INC Research, Inc, inVentiv Health Clinical, Iovance, PRA Intl, Eisai, Agenus, Merck, GenMab, SeaGen, Mersana, Clovis, SDP Oncology (BBI);Financial Interests, Personal, Other: Myriad Genetics, Tarveda. V. Boni: Financial Interests, Personal, Advisory Board: OncoArt, Guidepoint Global;Financial Interests, Personal, Speaker’s Bureau: Solti;Financial Interests, Personal, Other: START, Loxo, IDEAYA Biosciences;Financial Interests, Institutional, Research Grant: Sanofi, Seattle Genetics, Loxo, Novartis, CytomX Therapeutics, Pumo Biotechnology, Kura Oncology, GlaxoSmithKline, Roche/Genentech, Bristol-Myers Squibb, Menarini, Synthon, Janssen Oncology, Merck, Lilly, Merus, Pfizer, Bayer, Incyte, Merus, Zenith Epigenetics, Genmab, AstraZeneca, Seattle Genetics, Adaptimmune, Alkermes, Amgen, Array BioPharma, Boehringer Ingelheim, BioNTech AG, Boston Biomedical. A. Gravina: Financial Interests, Personal, Other: Gentili, Pfizer. S. Banerjee: Financial Interests, Personal, Advisory Board: Amgen, Genmab, Immunogen, Mersana, Merck Sereno, MSD, Roche, Tesaro, AstraZeneca, GSK, Oncxerna;Financial Interests, Personal, Invited Speaker: Clovis, Pfizer, Tesaro, AstraZeneca, GSK, Takeda, Amgen, Medscape, Research to Practice, Peerview;Financial Interests, Personal, Stocks/Shares: PerciHealth;Financial Interests, Institutional, Research Grant: AstraZeneca, GSK, Tesaro;Non-Financial Interests, Principal Investigator, Phase II clinical trial Global lead, ENGOTov60/GOG3052/RAMP201: Verastem;Non-Financial Interests, Principal Investigator, ENGOT-GYN1/ATARI phase II international trial (academic sponsored): Astrazeneca;Non-Financial Interests, Advisory Role: Epsilogen;Non-Financial Interests, Other, Member of membership committee: ESGO;Non-Financial Interests, Advisory Role, Medical advisor to UK ovarian cancer charity: Ovacome Charity;Non-Financial Interests, Other, Received research funding from UK based charity I have provided medical advice (non-remunerated): Lady GardenFoundation Charity. R. Miller: Financial Interests, Personal, Other: AZD, Clovis Oncology, Ellipses, GlaxoSmithKline, MSD, Shionogi, AZD, GlaxoSmithKline;Financial Interests, Personal, Speaker’s Bureau: AZD, Clovis Oncology, GSK, Roche. J. Pikiel: Financial Interests, Personal, Other: Amgen, Clovis Oncology, GlaxoSmithKline, Incyte, Novartis, Odonate Therapeutics, Pfizer, Regeneron, Roche. M.R. Mirza: Financial Interests, Personal, Advisory Board: AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, Zailab;Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK, Karyopharm;Financial Interests, Personal, Stocks/Shares: Karyopharm;Financial Interests, Institutional, Research Grant: GSK, AstraZeneca, ultimovacs, Apexigen;Financial Interests, Institutional, Invited Speaker: Deciphera;Non-Financial Interests, Advisory Role: Ultimovacs, Apexigen. T. Duan: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. G. Antony: Financial Interests, Personal, Fu l or part-time Employment: GlaxoSmithKline. S. Zildjian: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. E. Zografos: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. J. Veneris: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. A. Oaknin: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Deciphera Pharmaceuticals, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, Roche, Tesaro, Merck Sharps & Dohme de España, SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, prIME Oncology, Sattucklabs, Itheos, Eisai, F. Hoffmann-La Roche,;Financial Interests, Personal, Other, Travel and accomodation: AstraZeneca, PharmaMar, Roche;Financial Interests, Institutional, Funding: Abbvie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc, EISAI limited LTD, F. Hoffmann –La Roche LTD, Regeneron Pharmaceuticals, Immunogen Inc, Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb;Non-Financial Interests, Leadership Role, Executive Board member as a Co-Chair: GEICO;Non-Financial Interests, Leadership Role, Phase II Committee and Cervix Cancer Committee Representative on behalf of GEICO: GCIG;Non-Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019. Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022. Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines.: ESMO;Non-Financial Interests, Member: ESMO, ASCO, GCIG, SEOM, GOG.

National impact of the COVID-19 pandemic on clinical trial staff attrition: Results of the SWOG Cancer Research Network Survey of Oncology Research Professionals

Background: Severe shortages in clinical trial staffing across the United States and internationally has been anecdotally noted, but data are lacking. To better assess the scope and impact of staffing shortages, SWOG conducted a Cooperative Group-wide survey of Oncology Research Professionals (ORP). Methods: The survey was developed by SWOG leadership and was granted an IRB exemption by Lifespan IRB (Providence, RI). The survey was disseminated by email in January 2022 to Head Clinical Research Associates (CRAs, n = 100) using an inclusive distribution list that goes to the site-identified administrative leader of each SWOG Member and National Community Oncology Research Program institution. The data were collected and managed using REDCap electronic data capture tools hosted at Lifespan. Descriptive statistics were performed and qualitative analysis conducted to identify major themes. Results: The response rate was 87% and 41 of 87 respondents completed the full survey (47%). The majority of respondents were female (89.6%), not Hispanic (87.8%) and White (85.1%). The proportion that identified as Hispanic or Asian was 12.8 and 6.9%, respectively. One participant identified as Black and another as American Indian/Alaskan native. The most common work setting was within an academic medical center (47.9%) and 57.8% held a management or leadership role at their institutions. The majority (79%) used an Institutional IRB for trials not overseen as part of the National Clinical Trials Network. Over 80% of respondents reported their institution is experiencing a personnel shortage due to COVID-19. Proportion who reported this negatively impacted IRB processes was 50%, financial review was 42%, and legal review was 26.9%. On a scale of 0 (none) to 6 (significant), the impact was most significant on audit activities and accrual to trials (both rated 5), transfer of data to sponsors and sponsor visits (both rated 4.5);all other aspects rated a 4, including screening procedures, regulatory activities, and data collection. Ranked reasons for attrition were desire for better pay, seeking better opportunities, and seeking more flexible working conditions. General burn out was ranked as the fourth most common cause. Important themes included increasing trial complexity, morale, lack of support (due to staff shortages), lack of opportunities for promotion, unfilled positions, and the lack of experience of new hires. Conclusions: Over 80% of research programs affiliated with SWOG report staffing shortages due to the COVID-19 pandemic and the impact of these shortages touch every aspect of clinical research. Initiatives to recruit, train, and retain staff are urgently needed. As in other areas of medicine (e.g. hospital nursing), the potential for post-pandemic persistence of this issue requires an immediate national response.

Adapting a medical school cancer research education program to the virtual environment

Background: As the number of patients with a cancer diagnosis grows in the United States, there is an increasing need for physician scientists with oncology-related research training to develop new approaches to screening, diagnosis, therapy, and survivorship. A single US medical school developed the National Cancer Institute-funded Scholars in Oncology-Associated Research (SOAR) cancer research education program. Due to the COVID-19 pandemic, SOAR transitioned from fully in-person in 2019 to virtual in 2020 and hybrid in 2021. This study examines whether the in-person, virtual, or hybrid formats provide better educational experiences as rated by participants. Methods: SOAR includes a seminar series, an 11-week full-time cancer research experience, weekly research cluster group meetings, and tumor board and interprofessional shadowing experiences. In 2019 all program activities were in-person. In 2020 all activities were virtual with the shadowing suspended. In 2021, seminars and tumor boards were virtual, shadowing was in-person, and all other activities were hybrid. Pre- and post-surveys were collected from all participants to assess understanding of oncology and associated medical specialties. How participant understanding of oncology and related specialties changed within each year's program was analyzed with a Wilcoxon rank-sum test. The Kruskal-Wallis test was used to examine change in understanding between the cohorts. Results: 37 students participated in SOAR (2019 n = 11, 2020 n = 14, 2021 n = 12). Self-reported understanding of oncology as a clinical (p < 0.01 for all) and research discipline (p < 0.01 for all) improved within all three cohorts. There was no significant difference between each cohort's improvement in research understanding (p = 0.6158). However, there was a trend towards more of an improvement in the in-person cohort (p = 0.0796) for clinical understanding. There was no significant difference between each cohort's improvement in understanding of oncology-related disciplines such as medical oncology, radiation oncology, pediatric oncology, surgical oncology, and survivorship as both clinical and research disciplines (p > 0.1 for all). Conclusions: A virtual cancer research education program can be as effective as an in-person or hybrid program for research education although it may be suboptimal for learning about clinical oncology. Given the ongoing challenges presented by the COVID-19 pandemic, flexibility is needed in delivering cancer research education programs such as SOAR. With modern research methodology and communications technology, cancer research is becoming increasingly diverse and flexible in terms of research environment. If program leaders are steadfast in their adaptation of research education programs to a virtual or hybrid environment, participant understanding of oncology as a clinical and research discipline remains robust.