Translational Research Program Research Articles

126 20 YEARS SHAPING A NEW GENERATION OF HISPANIC CLINICAL AND TRANSLATIONAL RESEARCHERS: UPR-MSC POSTDOCTORAL MASTER IN CLINICAL & TRANSLATIONAL RESEARCH PROGRAM

OBJECTIVES/GOALS: This project presents the Post-doctoral Master of Science in Clinical and Translational Research (MSc) program’s outcomes in 20 years of its implementation. This program is a joint offering between the Schools of Health Professions and School of Medicine of the University of Puerto Rico. METHODS/STUDY POPULATION: This study consists of secondary data analysis of academic and administrative documents. It also includes data from the Annual Evaluation retreats reports and an Alumni Follow-up Survey using an electronic questionnaire. All 121 Scholars admitted to the program from academic years 2003 to 2023 were included in the sample. Data analysis included descriptive statistical analysis of quantitative data and qualitative content analysis regarding recruitment/admissions, faculty composition, curriculum design, Scholars’ outcomes, and program’s financial support sources. Quantitative data were analyzed using the statistical software SPSS. RESULTS/ANTICIPATED RESULTS: Scholars of the program had been recruited from the UPR-MSC and several partner institutions with diverse backgrounds, disciplines, and research areas. Faculty and committee members have representation from the six MSC-Schools and partner institutions. The academic Program structure has changed over the years, and currently, more than 65% of the courses are offered online. Several financial sources have been identified to support the scholars. The Scholars’ portfolios of grant submission and publication productivity evidence the program’s success. Graduates have also been successful in advancing to positions that foster research impacting Hispanics. DISCUSSION/SIGNIFICANCE: The Post-doctoral Master’s in Clinical and Translational Research program (MSc) has contributed to the formation of committed Hispanic clinical and translational researchers impacting minorities and contributing to diversity in the research workforce.

122 Evaluating the impact of the Translational Research Program at the University of Toronto

OBJECTIVES/GOALS: There is a need to develop a workforce of translational research professionals with the skills to innovate, mobilize, and commercialize research for unmet needs in the Canadian health system. The objective of this study is to evaluate the impact and value of the master’s degree on the Translational Research Program (TRP) alumni. METHODS/STUDY POPULATION: This study will use a cross-sectional approach and an electronic survey will be administered to alumni. The TRP was established in 2015 and has graduated over 150 students since its inception. Participants will be recruited through convenience sampling via email, social media platforms, and personal communication. Eligible participants must have a conferred Master of Health Science in Translational Research from the University of Toronto. All collected data will remain anonymous and include demographic information about graduation year, race, ethnicity, gender, and employment status. Descriptive statistics will be used to analyze and report the findings. RESULTS/ANTICIPATED RESULTS: The results of this survey will be used to evaluate how the TRP graduate degree helps alumni contribute to healthcare, learn to think differently, and establish their professional networks. The findings will also be used to inform curriculum improvements, enhance competency-based assessments, and understand demographic differences in student cohorts to promote equity, diversity, and inclusion. Investigating the perspectives of alumni reflecting on their degree will support validating the program’s objectives and advance the integration of translational science principles in the healthcare workforce and community. DISCUSSION/SIGNIFICANCE: This research addresses the need to evaluate health sciences education to ensure the program’s novel pedagogical approaches are equipping the next generation of health professionals with the skills to accelerate the transformation of discoveries into interventions that benefit human health, improve clinical medicine, and enhance patient care.

Abstract 1852: NCI’s Clinical Proteomic Tumor Analysis Consortium: A proteogenomic cancer analysis program

Abstract The National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (NCI’s CPTAC) is a national effort to accelerate the understanding of cancer biology through the integration of large-scale proteome and genome analysis, or proteogenomics. The program which is composed of a Tumor Characterization Program and a Translational Research Program (proteomics.cancer.gov) aims to leverage the investments made in cancer research by understanding the molecular changes by proteogenomically characterizing cancers and accelerating the basic discovery toward clinical impact. All data and analytical tools are made broadly available to the research community through public databases to maximize utility and public benefit.CPTAC teams have characterized a plethora of treatment-naïve tumor types, including colorectal, ovarian, breast, clear cell renal cell carcinoma, uterine corpus endometrial carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, brain (including adult, pediatric, and adolescent and young adult), head and neck squamous cell carcinoma, and pancreatic ductal adenocarcinoma (proteomics.cancer.gov/resources/milestones-and-publications). Ongoing projects include acute myeloid leukemia (AML), cutaneous melanoma, sarcoma, oligodendroglioma, gastric, prostate, liver, and thyroid cancers. In the PTRC Program, CPTAC is partnering with NCI-sponsored clinical trials to support clinically relevant research projects that would elucidate biological mechanisms of therapeutic response, resistance, and/or toxicity in cancers including AML, multiple myeloma, melanoma, and lung cancers. All mass spectrometry-based proteomic, genomic, and imaging data (histopathology and radiology) are made publicly available at the CPTAC Proteomic Data Commons (pdc.cancer.gov), Genomic Data Commons (gdc.cancer.gov), and the Cancer Imaging Archive (cancerimagingarchive.net)/Imaging Data Commons (imaging.datacommons.cancer.gov) respectively. CPTAC is also supporting development of new proteogenomic data analysis tools (proteomics.cancer.gov/resources/computational-tools). In addition, the CPTAC Assay Portal (assays.cancer.gov) is a public resource populated with mass spectrometry-based targeted proteomic assays developed by the consortium for quantitatively measuring proteins of interest, including those discovered through comprehensive tumor characterization. Lastly, well-characterized monoclonal antibodies targeting cancer-specific proteins and peptides are also made available at CPTAC’s Antibody Portal (antibodies.cancer.gov). Citation Format: Mehdi Mesri, Eunkyung An, Xu Zhang, Jasmin Bavarva, Ana I. Robles, Tara Hiltke, Henry Rodriguez. NCI’s Clinical Proteomic Tumor Analysis Consortium: A proteogenomic cancer analysis program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1852.

BIOSKIN: A Protocol for the Copenhagen Translational Skin Immunology Biobank and Research Programme

IntroductionPsoriasis, atopic dermatitis and contact dermatitis are common chronic inflammatory skin diseases that have a significant impact on individuals and society.Methods and analysisThe Copenhagen Translational Skin Immunology Biobank and Research...

Multicenter randomized trial of deferred cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma receiving checkpoint inhibitors: the NORDIC-SUN-Trial

BackgroundPrimary tumor removal by cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma patients has been investigated in the context of various treatment regimens. Two randomized controlled trials investigated the role and timing of cytoreductive nephrectomy in the era of targeted therapy and demonstrated that upfront nephrectomy should no longer be performed when patients require systemic therapy. Superiority of checkpoint immunotherapy agents has led to a paradigm change from targeted therapies to immunotherapy-based first-line treatment in patients with primary metastatic disease; thus, deferred cytoreductive nephrectomy needs to be verified in the immunotherapy setting. Furthermore, a need exists for personalizing treatment choices for the individual patient to avoid unnecessary overtreatment.Methods/designTo explore the impact of cytoreductive nephrectomy in this patient group receiving checkpoint immunotherapy, we initiated a randomized, controlled trial comparing deferred cytoreductive nephrectomy with no surgery. The trial integrates a comprehensive translational research program with specimen sampling for biomarker analysis.DiscussionThe trial aims to show that deferred cytoreductive nephrectomy improves overall survival in patients with synchronous metastatic renal cell carcinoma, and furthermore, to identify relevant biomarkers for personalized renal cancer management.Trial registrationClinicalTrials.gov NCT03977571 June 6, 2019.

Machine Learning-assisted immunophenotyping of peripheral blood identifies innate immune cells as best predictor of response to induction chemo-immunotherapy in head and neck squamous cell carcinoma – knowledge obtained from the CheckRad-CD8 trial

PurposeIndividual prediction of treatment response is crucial for personalized treatment in multimodal approaches against head-and-neck squamous cell carcinoma (HNSCC). So far, no reliable predictive parameters for treatment schemes containing immunotherapy have been identified. This study aims to predict treatment response to induction chemo-immunotherapy based on the peripheral blood immune status in patients with locally advanced HNSCC. MethodsThe peripheral blood immune phenotype was assessed in whole blood samples in patients treated in the phase II CheckRad-CD8 trial as part of the pre-planned translational research program. Blood samples were analyzed by multicolor flow cytometry before (T1) and after (T2) induction chemo-immunotherapy with cisplatin/docetaxel/durvalumab/tremelimumab. Machine Learning techniques were used to predict pathological complete response (pCR) after induction therapy. ResultsThe tested classifier methods (LDA, SVM, LR, RF, DT, and XGBoost) allowed a distinct prediction of pCR. Highest accuracy was achieved with a low number of features represented as principal components. Immune parameters obtained from the absolute difference (lT2-T1l) allowed the best prediction of pCR. In general, less than 30 parameters and at most 10 principal components were needed for highly accurate predictions. Across several datasets, cells of the innate immune system such as polymorphonuclear cells, monocytes, and plasmacytoid dendritic cells are most prominent. ConclusionsOur analyses imply that alterations of the innate immune cell distribution in the peripheral blood following induction chemo-immuno-therapy is highly predictive for pCR in HNSCC.

Building our research administrator workforce as our clinical and translational research programs become increasingly complex.

Introduction: Research administrators (RA's) are critical members of the research workforce. For purposes of this article, research administrators are personnel who support the development, compliance, management, and financial oversight of sponsored research. There are currently very few institutional career development and mentoring programs available to research administrators. Recruitment and retention of quality research administrators has been especially challenging across the country in recent years. Methods: In an effort to address this gap in training and to increase recruitment and retention, the integrated Translational Health Research Institute of Virginia (iTHRIV), a collaborative NIH-NCATS funded Clinical Translational Science Award (CTSA) hub, has developed an innovative program of workforce development and mentoring for research administrators. This article provides an overview of one institutional training and development initiative, the Research Administration Program for Training and Resources (RAPTR). RAPTR provides training, resources and mentoring to develop a Community of Practice. Results: The program provides a forum where research administrators can share ideas, practices, and challenges. Discussion: This manuscript describes the benefits and lessons learned from our early experience in this program. We highlight selected components that may be generalizable to other institutions and describe individualized components, which require local policies and processes.

Evaluating Collaboration in a Translational Research Ecosystem

A core challenge of a multidisciplinary and multi-organizational translational research program is to set up and promote collaboration between researchers, labs, and organizations. Although the literature has studied and provided guidelines for collaboration, little has been written on how to evaluate it in large research projects and in a practical way. This study aims to identify dimensions and barriers to evaluating and leveraging collaboration in a large translational research ecosystem related to developing phytotherapy-based cancer treatments. By applying the Collaboration Evaluation and Improvement Framework (CEIF), our paper adds value by developing a methodological design for evaluation, incorporating mixed data in a real research ecosystem. Empirical findings provide support for applying the assessment approach and show that a research project’s sustainability depends on several collaboration factors and barriers at the socio-technical, management, operational, and institutional levels. Research results provide valuable insights for managing and improving collaborative efforts in large research groups, by anticipating collaboration issues with actionable and opportune strategies that can enhance the planning process, ecosystem performance, sustainability, research outcomes, and the program’s overall success. As a result, monitoring governance, management, leadership, and social relationships throughout the different phases of a translational research program is crucial in assessing and promoting collaboration.

Autres cibles addictives (KRAS, RET, HER2, NTRK…): Other addictive targets (KRAS, RET, HER2, NTRK…)

The prognosis of advanced Non-Small Cell Lung Cancer (NSCLC) has been significantly improving ever since the discovery of oncogenic driver alterations and the implementation of targeted therapies. Today, molecular profiling, preferably by using next-generation sequencing panels as well as liquid biopsies is crucial before starting treatment in patients with non-squamous NSCLC independent of their smoking status, as well as in those with squamous NSCLC who are little or non-smokers. In this review, we present the latest evidence on the most detected driver alterations in advanced NSCLC apart from EGFR, BRAF, ALK and ROS1. A few of the novel therapies have been approved in Europe in specific settings, and many are still not reimbursed by third-party payers. This highlights the importance of encouraging patients to participate in clinical trials to gain access to innovative treatments. Translational research programs are also important to uncover mechanisms of resistance to targeted therapies and how to overcome them.1877-1203/© 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.

The International Society for Biological and Environmental Repositories Presents Abstracts from Its Annual Meeting

The International Society for Biological and Environmental Repositories Presents Abstracts from Its Annual Meeting

The FOxTROT platform: Clinical trials and exploratory research for personalization of neoadjuvant (NA) therapy in locally advanced colon cancer (LACC)—ISRCTN83842641.

TPS3636 Background: The FOxTROT1 trial demonstrated a significant reduction in 2-year (yr) recurrence with 6 weeks (wks) of oxaliplatin and fluoropyrimidine (OxFp) NA chemotherapy (NAC) in patients (pts) with LACC, establishing NAC as a new therapeutic option. The ongoing FOxTROT platform will refine and personalize NA therapy in LACC. FOxTROT2 is testing NAC in older pts and those with frailty, who are poorly represented in clinical trials. FOxTROT3 is assessing intensified NAC with modified FOLFOXIRI (mFOLFOXIRI; 5-fluorouracil, oxaliplatin, irinotecan) in fit pts. The FOxTROT platform will also test targeted treatments with established safety and efficacy in defined molecular subgroups. FOxTROT4 is investigating the efficacy and safety of NA encorafenib and cetuximab in BRAF-mutant pMMR LACC. Other arms in setup are shown in Table. Methods: FOxTROT platform trials are international, multicenter, open-label, phase II/III RCTs. Pts with resectable, cT3-4 N0-2 M0, biopsy-proven colon adenocarcinoma are eligible for recruitment. Pts whose age or frailty precludes mFOLFOXIRI can be considered for FOxTROT2. Pts suitable for mFOLFOXIRI can be considered for FOxTROT3. BRAF-mutant pMMR pts can be considered for FOxTROT4. Pts are randomized 2:1 between intervention and control arms. FOxTROT2 randomizes between 6 wks OxFp NAC (choice of 100% or 80% dose) vs proceeding straight to surgery. Adjuvant chemotherapy (AC) is per physician choice. Primary outcome is 3-yr DFS. 759 pts will be recruited over 5 yrs. FOxTROT3: 6 wks mFOLFOXIRI NAC vs 6 wks OxFp NAC. All pts receive AC but physicians may de-escalate mFOLFOXIRI to OxFp. Hierarchical co-primary endpoints: tumor regression grade (TRG) (blinded central assessment) and 3-yr DFS. 873 pts over 5 yrs. FOxTROT4: 6 wks NA encorafenib and cetuximab vs 6 wks OxFp NAC. AC is per physician choice. Primary outcome: TRG. 45 pts over 3 yrs. Secondary outcomes include: histopathological endpoints, downstaging, minimal residual disease by ctDNA, safety, toxicity, OS, surgical outcomes and patient-reported outcomes; and DFS in FOxTROT4. The FOxTROT platform opened 7th Feb 2022, funded by Yorkshire Cancer Research. At submission, 50 pts had been randomized at 23 centers. Trial design and management is conducted in partnership with patient representatives. A program of translational and radiomics research is running in parallel. International recruitment in France and India will commence in 2023 with additional international partners joining from 2024. Clinical trial information: ISRCTN83842641 . [Table: see text]

Editorial introductions.

Current Opinion in Organ Transplantation was launched in 1996. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of organ transplantation is divided into 18 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Editors-in-Chief, Associate Editor and Section Editors for this issue. SECTION EDITORS Matthew HartwigMatthew HartwigDr. Hartwig is a thoracic surgeon with a clinical focus in robotic assisted minimally invasive thoracic surgery for the treatment of diseases of the chest. He serves as the Surgical Director of the Esophageal Center at Duke. He is also the Director of the Minimally Invasive Thoracic Surgery Fellowship at Duke, while providing advanced instruction in robotic surgery to surgeons around the world. He also leads a successful program of clinical, basic and translational research in thoracic surgery and lung transplantation. He currently directs the Duke Ex Vivo Organ Laboratory (DEVOL), is the Chief of Lung Transplant Research, and is a faculty member at the Duke Clinical Research Institute (DCRI). John L.R. ForsytheJohn L.R. ForsytheProfessor John Forsythe was first appointed as a Consultant Transplant Surgeon at the Royal Infirmary of Edinburgh, UK in 1995. Prior to this, he was a Consultant Surgeon with special interest in renal transplantation at the Royal Victoria Infirmary, Newcastle upon Tyne, UK. He is currently an Organ Utilisation Consultant for NHSBT, working with all departments of health for the UK. Professor Forsythe has held many professional committee appointments, among them Lead Clinician for Organ Donation and Transplantation in Scotland, Chairman of the Scottish Donation and Transplant Group and Chairman of the Safety of Blood, Tissues and Organs Advisory Committee to all four UK health ministers. He is a Past President of the British Transplantation Society and remains Honorary President of the British Society for Histocompatibility and Immunogenetics. Shunji NagaiShunji NagaiDr. Shunji Nagai is a general surgeon in Detroit, Michigan and is affiliated with Henry Ford Hospital. He received his medical degree from Nagoya University- School of Medicine and has been in practice for more than 20 years.

Initial results from the phase 2A trial of visugromab (CTL-002) + nivolumab in advanced/metastatic anti-PD1/-L1 relapsed/refractory solid tumors (The GDFATHER-TRIAL).

2501 Background: Increasing evidence has emerged that Growth and Differentiation Factor 15 (GDF-15) plays a critical role in tumoral immunosuppression. Apart from blocking immune-cell entry into the tumor microenvironment, GDF-15 also has a major impact on the formation of the immune synapse. Many tumors overexpress GDF-15 and have hijacked this mechanism to block immunotherapy success. Here we report initial results of the phase 2a part of the GDF-15 neutralizing antibody visugromab (CTL-002) in combination with nivolumab. Methods: At cut-off date (06-Feb-2023), a total of 79 pts with advanced/metastatic solid tumors have been enrolled and were treated with visugromab 10 mg/kg Q2W in combination with nivolumab 240 mg Q2W in the phase 2a expansion part of the CTL-002-001 phase 1/2 trial (NCT04725474). The primary endpoint of the phase 2a expansion is the Objective Response Rate (ORR) according to RECIST v1.1. Tumor assessments were performed every 8 weeks and patients had to be relapsed/refractory to a minimum of 12 weeks continuous prior anti-PD1/-PD-L1-containing therapy, with relapse or progression after initial response to have occurred on continued anti-PD1/PDL1 therapy. Phase 2a contained several indication-specific expansion cohorts (e.g. NSCLC, Bladder Cancer, HCC, Melanoma), following a Simon 2-stage design, and two cohorts were already expanded to stage 2 in light of initial responses observed. An additional expansion cohort is a pan-tumor basket cohort with sequential tumor biopsies for biomarker analyses. A key component of this multi-arm trial is an extensive translational research program to identify response-predictive tumor and immunologic marker and pattern. Results: Across several expansion cohorts, durable tumor regressions were observed, including several partial responses (PR) and one complete response (CR) in heavily pretreated patients with a median of 3 prior lines of systemic therapy for advanced/metastatic cancer, including at least one prior line of anti-PD1/-PD-L1 therapy and being relapsed/refractory to it. In NSCLC, so far 13 pts underwent at least one tumor assessment. Of these, two experienced a PR (one confirmed), three additional tumor shrinkage > 5% (TS) and one longer-term SD (LT-SD) were seen. In bladder cancer, 7 patients underwent at least one tumor assessment with 1 confirmed CR, 1 TS and 1 LT-SD. The treatment was overall well tolerated. Conclusions: These initial phase 2a results demonstrate promising clinical activity for the combination of visugromab and nivolumab in heavily pretreated anti-PD1/-PD-L1 refractory/relapsed solid tumor patients across various indications, including induction of confirmed partial and complete responses. Extensive biomarker evaluations are ongoing to further evaluate potential response-predictive markers identified during phase 1 development. Clinical trial information: NCT04725474 .

Study protocol of an open-label, single arm phase II trial investigating the efficacy and safety of Trifluridine/Tipiracil combined with irinotecan as a second line therapy in patients with cholangiocarcinoma (TRITICC)

BackgroundThe prognosis of patients with advanced biliary tract cancer (BTC) who have progressed on gemcitabine plus cisplatin is dismal. Trifluridine/tipiracil (FTD/TPI) and irinotecan have proven efficacy in different gastrointestinal malignancies. We therefore hypothesized that this combination might improve the therapeutic outcome in patients with BTC after failure of first line treatment.MethodsTRITICC is an interventional, prospective, open-label, non-randomised, exploratory, multicentre, single-arm phase IIA clinical trial done in 6 sites with expertise in managing biliary tract cancer across Germany. A total of 28 adult patients (aged ≥ 18 years) with histologically verified locally advanced or metastatic biliary tract cancer (including cholangiocarcinoma and gallbladder or ampullary carcinoma) with documented radiological disease progression to first-line gemcitabine based chemotherapy will be included to receive a combination of FTD/TPI plus irinotecan according to previously published protocols. Study treatment will be continued until disease progression according to RECIST 1.1 criteria or occurrence of unacceptable toxicity. The effect of FTD/TPI plus irinotecan on progression-free survival will be analyzed as primary endpoint. Safety (according to NCI-CTCAE), response rates and overall survival are secondary endpoints. In addition, a comprehensive translational research program is part of the study and might provide findings about predictive markers with regard to response, survival periods and resistance to treatment.DiscussionThe aim of TRITICC is to evaluate the safety and efficacy of FTD/TPI plus irinotecan in patients with biliary tract cancer refractory to previous Gemcitabine based treatment.Trial registrationEudraCT 2018–002936-26; NCT04059562

The Changing Environment in Postgraduate Education in Orthopedic Surgery and Neurosurgery and Its Impact on Technology-Driven Targeted Interventional and Surgical Pain Management: Perspectives from Europe, Latin America, Asia, and The United States.

Personalized care models are dominating modern medicine. These models are rooted in teaching future physicians the skill set to keep up with innovation. In orthopedic surgery and neurosurgery, education is increasingly influenced by augmented reality, simulation, navigation, robotics, and in some cases, artificial intelligence. The postpandemic learning environment has also changed, emphasizing online learning and skill- and competency-based teaching models incorporating clinical and bench-top research. Attempts to improve work-life balance and minimize physician burnout have led to work-hour restrictions in postgraduate training programs. These restrictions have made it particularly challenging for orthopedic and neurosurgery residents to acquire the knowledge and skill set to meet the requirements for certification. The fast-paced flow of information and the rapid implementation of innovation require higher efficiencies in the modern postgraduate training environment. However, what is taught typically lags several years behind. Examples include minimally invasive tissue-sparing techniques through tubular small-bladed retractor systems, robotic and navigation, endoscopic, patient-specific implants made possible by advances in imaging technology and 3D printing, and regenerative strategies. Currently, the traditional roles of mentee and mentor are being redefined. The future orthopedic surgeons and neurosurgeons involved in personalized surgical pain management will need to be versed in several disciplines ranging from bioengineering, basic research, computer, social and health sciences, clinical study, trial design, public health policy development, and economic accountability. Solutions to the fast-paced innovation cycle in orthopedic surgery and neurosurgery include adaptive learning skills to seize opportunities for innovation with execution and implementation by facilitating translational research and clinical program development across traditional boundaries between clinical and nonclinical specialties. Preparing the future generation of surgeons to have the aptitude to keep up with the rapid technological advances is challenging for postgraduate residency programs and accreditation agencies. However, implementing clinical protocol change when the entrepreneur-investigator surgeon substantiates it with high-grade clinical evidence is at the heart of personalized surgical pain management.

Need for a Dedicated Ophthalmic Malignancy Clinico-Biological Biobank: The Nice Ocular MAlignancy (NOMA) Biobank

Ophthalmic malignancies include various rare neoplasms involving the conjunctiva, the uvea, or the periocular area. These tumors are characterized by their scarcity as well as their histological, and sometimes genetic, diversity. Uveal melanoma (UM) is the most common primary intraocular malignancy. UM raises three main challenges highlighting the specificity of ophthalmic malignancies. First, UM is a very rare malignancy with an estimated incidence of 6 cases per million inhabitants. Second, tissue biopsy is not routinely recommended due to the risk of extraocular dissemination. Third, UM is an aggressive cancer because it is estimated that about 50% of patients will experience metastatic spread without any curative treatment available at this stage. These challenges better explain the two main objectives in the creation of a dedicated UM biobank. First, collecting UM samples is essential due to tissue scarcity. Second, large-scale translational research programs based on stored human samples will help to better determine UM pathogenesis with the aim of identifying new biomarkers, allowing for early diagnosis and new targeted treatment modalities. Other periocular malignancies, such as conjunctival melanomas or orbital malignancies, also raise specific concerns. In this context, the number of biobanks worldwide dedicated to ocular malignancies is very limited. The aims of this article were (i) to describe the specific challenges raised by a dedicated ocular malignancy biobank, (ii) to report our experience in setting up such a biobank, and (iii) to discuss future perspectives in this field.

Abstract 2019: NCI’s clinical proteomic tumor analysis consortium analysis tools and resources

Abstract The National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (NCI’s CPTAC) is an integrative proteogenomic program composed of a Tumor Characterization Program and a Translational Research Program (PTRC) (https://proteomics.cancer.gov). The CPTAC aims to leverage the investments made in cancer research by understanding the molecular changes by proteogenomically characterizing cancers and accelerating the basic discovery toward clinical impact. This goal is achieved through the application of large-scale proteome and genome analyses, followed by proteogenomic integration of genome, transcriptome, and proteome data sets. Together, it enables the correlation analysis of mRNA and protein, mutations, post-translational modifications, and signaling pathways. All data and analytical tools are made broadly available to the research community through public databases to maximize utility and public benefit. CPTAC teams have characterized a multitude of treatment-naïve tumor types, including colorectal, ovarian, breast, clear cell renal cell carcinoma, uterine corpus endometrial carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, brain (including adult, pediatric, and adolescent and young adult), head and neck squamous cell carcinoma, and pancreatic ductal adenocarcinoma (https://proteomics.cancer.gov/resources/milestones-and-publications). Ongoing projects include acute myeloid leukemia (AML), cutaneous melanoma, sarcoma, oligodendroglioma, and stomach cancers. In the PTRC Program, CPTAC is partnering with NCI-sponsored clinical trials to support clinically relevant research projects that would elucidate biological mechanisms of therapeutic response, resistance, and/or toxicity. The PTRC Program currently explores breast, ovarian, AML, multiple myeloma, melanoma, and lung cancers. All mass spectrometry-based proteomic, genomic, and imaging data (histopathology and radiology) are made publicly available at the CPTAC Proteomic Data Commons (https://pdc.cancer.gov), Genomic Data Commons (https://gdc.cancer.gov), and the Cancer Imaging Archive (https://cancerimagingarchive.net) respectively. CPTAC is also supporting development of new proteogenomic data analysis tools (https://proteomics.cancer.gov/resources/computational-tools). In addition, the CPTAC Assay Portal (http://assays.cancer.gov) is a public resource populated with mass spectrometry-based targeted proteomic assays developed by the consortium for quantitatively measuring proteins of interest, including those discovered through comprehensive tumor characterization. Lastly, well-characterized monoclonal antibodies targeting cancer-specific proteins and peptides are also made available at CPTAC’s Antibody Portal (http://antibodies.cancer.gov). Citation Format: Mehdi Mesri, Eunkyung An, Xu Zhang, Jasmin Bavarva, Ana I. Robles, Tara Hiltke, Henry Rodriguez. NCI’s clinical proteomic tumor analysis consortium analysis tools and resources [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2019.

96 Evidence to impact: Developing a workforce of translational research professionals

OBJECTIVES/GOALS: The goal of the Translational Research Program (TRP) at the University of Toronto is to provide structured and adaptive competency-based training around the translation, mobilization, implementation, and commercialization of research for the current and future Canadian healthcare workforce. METHODS/STUDY POPULATION: Guided by the Toronto Translational Framework, the TRP is a two-year hybrid master’s degree program that integrates courses, case-studies, mentorship, and experiential learning to facilitate real-world student-led translational projects. Focusing on skills development and competency-based assessment, the curriculum emphasizes ongoing reflection, interprofessional collaboration, and multidisciplinary problem-solving using human-centered principles. Learners identify problems using contextual inquiry to define unmet needs and frame design requirements. Systematic ideation is used to generate, select, and validate promising concepts for further iterative prototyping and evaluation. RESULTS/ANTICIPATED RESULTS: Throughout the program, students demonstrate a range of collaborative skills and activities around developing, assessing, and implementing new health interventions. Learners apply the Toronto Translational Framework and refine their professional competencies during the final year of the program in a student-led Capstone project. The unconventional combination of a guided framework and a learner-driven curriculum has produced over 120 graduates in a variety of careers within government, industry, clinical settings, and start-ups. The program’s focus on problem-solving and lifelong learning is growing Canada’s translational workforce and advancing translational health science education. DISCUSSION/SIGNIFICANCE: The TRP addresses the need to educate healthcare professionals in Canada about translational research and accelerate the transformation of scientific discoveries into tangible interventions that benefit human health, improve clinical medicine, and enhance patient care.

131 Beyond the Case Study: Advancing Development and Use of the Translational Science Benefits Model (TSBM) Framework through Application Across Diverse CTSA Contexts

OBJECTIVES/GOALS: This project has two linked aims. (1) It seeks to integrate the TSBM into specific practices and processes to advance its integration into translational research and translational science processes. (2) Via this integration, it aims to determine ways to expand the TSBM as a conceptual model. Ultimately, we aim to advance the TSBM framework and use. METHODS/STUDY POPULATION: We developed a process that implemented and integrated the TSBM within three intentionally-distinct processes. First, we expanded the use of the TSBM case study from a focus on research studies to a focus on translational research programs, and specifically workforce development programs. Second, we integrated TSBM domains and indicators into a new Duke CTSA-wide database used to track, monitor, and assess activities and achievements across the CTSA. Third, we embedded TSBM and its indicators into our Pilots projects application and review process as well as ongoing reporting. RESULTS/ANTICIPATED RESULTS: We were able to successfully integrate the TSBM model into the processes indicated in methods, yet this integration identified opportunity to improve the model to enhance its applicability and value. We found the TSBM applies in distinct ways to translational science programs compared to research studies, with added indicators better accommodating TSBM application to programs. To properly integrate TSBM into progress monitoring systems, we found added needs to ensure comprehensibility for a wide array of researchers and program implementers. Across uses, we identified challenge distinguishing between TSBM benefits as demonstrated versus potential and ambiguity in potential as based on time to benefit realization, likelihood of realization, or centrality of a specific project to realization. DISCUSSION/SIGNIFICANCE: Our session contributes significantly to the field of translational research and science through its focus on advancement and implementation of an innovated model in its early stages, including how researchers and translation science entities can incorporate this model into their own work beyond the traditional use of case studies.

Natural history and treatment efficacy in an ambispective case series of NTRK-rearranged mesenchymal tumors

Apart for infantile fibrosarcoma (IFS), very little is known about NTRK-rearranged mesenchymal tumors (NMTs). The objective of this study is to describe the distribution, characteristics, natural history, and prognosis of NMT. This study was carried out as a translational research program, retrospectively from a cohort of 500 soft tissue sarcoma (STS; excluding IFS) and prospectively both in routine practice and from the RNASARC molecular screening program (N= 188; NCT03375437). Using RNA-sequencing, NTRK fusion was detected in 16 patient tumors diagnosed as STS: 8 samples of sarcoma with simple genomics (4 NTRK-rearranged spindle cell neoplasm, 3 ALK/ROS wild-type inflammatory myofibroblastic tumor, and 1 quadruple Wild-type gastrointestinal stromal tumor) and 8 samples of sarcomas with complex genomics (dedifferentiated liposarcoma, intimal sarcoma, leiomyosarcoma, undifferentiated pleomorphic sarcoma, high-grade uterine sarcoma, malignant peripheral nerve sheath tumor). Among the eight patients with simple genomics, four were treated with tyrosine receptor kinase inhibitor (TRKi) at different stages of the disease and all benefited from the treatment, including one complete response. Among the eight other patients, six evolved with metastatic spreading and the median metastatic survival was 21.9 months, as classically reported in these tumor types. Two of them received a first-generation TRKi without objective response. Our study confirms low frequency and histotype diversity of NTRK fusion in STS. While the activity of TRKi in simple genomics NMT is confirmed, our clinical data encourage subsequent studies focusing on the biological relevance of NTRK fusions in sarcomas with complex genomics together with the efficacy of TRKi in this population.