Our recent publication, “Quantitative Intravital Imaging for Real-time Monitoring of Pancreatic Tumor Cell Hypoxia and Stroma in an Orthotopic Mouse Model” was chosen to be the cover of Science Advances! Pancreatic cancer is a lethal disease with few successful treatment options. Recent evidence demonstrates that tumor hypoxia promotes pancreatic tumor invasion, metastasis, and therapy resistance. However, little is known about the complex relationship between hypoxia and the pancreatic tumor microenvironment (TME). In this study, we developed a novel intravital fluorescence microscopy platform with an orthotopic mouse model of pancreatic cancer to study tumor cell hypoxia within the TME in vivo, at cellular resolution, over time. Using a fluorescent BxPC3-DsRed tumor cell line with a hypoxia-response element (HRE)/green fluorescent protein (GFP) reporter, we showed that HRE/GFP is a reliable biomarker of pancreatic tumor hypoxia, responding dynamically and reversibly to changing oxygen concentrations within the TME. We also characterized the spatial relationships between tumor hypoxia, microvasculature, and tumor-associated collagen structures using in vivo second harmonic generation microscopy. This quantitative multimodal imaging platform enables the unprecedented study of hypoxia within the pancreatic TME in vivo. A representative image of an in vivo orthotopic BxPC3-DsRed-5xHRE/GFP tumor foci, taken using intravital fluorescence and SHG microscopy.BxPC3 cells (DsRed) are shown in red, HIF activity (5xHRE/GFP) in green, blood vessels (APC-CD31) in cyan, and fibrillar collagen (SHG) in white. Scale bars, 100 μm

An advisory group at UHN applied an evidence- and consensus-based process to derive measures from published research, and national and international best practices, then engaged researchers and research leaders across all of the institutes through a two-round Delphi survey.  This approach identified measures that reflect the relevance of the research program, funding, innovative outputs, publications, collaboration, recognition, and challenges to research productivity. The group also examined current assessment rubrics at the institutes for these measures to identify gaps and areas for improvement. The resulting publication: “Exploring the merits of research performance measures that comply with the San Francisco Declaration on Research Assessment and strategies to overcome barriers of adoption: qualitative interviews with administrators and researchers.” In prior research, we identified and prioritized ten measures to assess research performance that comply with the San Francisco Declaration on Research Assessment, a principle adopted worldwide that discourages metrics-based assessment. Given the shift away from assessment based on Journal Impact Factor, we explored potential barriers to implementing and adopting the prioritized measures. We identified administrators and researchers across six research institutes, conducted telephone interviews with consenting participants, and used qualitative description and inductive content analysis to derive themes. We interviewed 18 participants: 6 administrators (research institute business managers and directors) and 12 researchers (7 on appointment committees) who varied by career stage (2 early, 5 mid, 5 late). Participants appreciated that the measures were similar to those currently in use, comprehensive, relevant across disciplines, and generated using a rigorous process. They also said the reporting template was easy to understand and use. In contrast, a few administrators thought the measures were not relevant across disciplines. A few participants said it would be time-consuming and difficult to prepare narratives when reporting the measures, and several thought that it would be difficult to objectively evaluate researchers from a different discipline without considerable effort to read their work. Strategies viewed as necessary to overcome barriers and support implementation of the measures included high-level endorsement of the measures, an official launch accompanied by a multi-pronged communication strategy, training for both researchers and evaluators, administrative support or automated reporting for researchers, guidance for evaluators, and sharing of approaches across research institutes. While participants identified many strengths of the measures, they also identified a few limitations and offered corresponding strategies to address the barriers that we will apply at our organization. Ongoing work is needed to develop a framework to help evaluators translate the measures into an overall assessment. Given little prior research that identified research assessment measures and strategies to support adoption of those measures, this research may be of interest to other organizations that assess the quality and impact of research.

Shortly before the pandemic, the research institutes at UHN signed the San Francisco Declaration on Research Assessment (DORA)—a set of principles aimed at enhancing and modernizing research assessment. DORA promotes the evaluation of the quality and impact of research, and the elimination of using journal-based metrics (e.g., Journal Impact Factor) for decisions related to hiring, appointment, annual review, and promotion. An advisory group at UHN developed measures by which to report and assess research activity, outputs, and impact in a recent publication, “DORA-compliant measures of research quality and impact to assess the performance of researchers in biomedical institutions: Review of published research, international best practice and Delphi survey.” The San Francisco Declaration on Research Assessment (DORA) advocates for assessing biomedical research quality and impact, yet academic organizations continue to employ traditional measures such as Journal Impact Factor. We aimed to identify and prioritize measures for assessing research quality and impact. We conducted a review of published and grey literature to identify measures of research quality and impact, which we included in an online survey. We assembled a panel of researchers and research leaders, and conducted a two-round Delphi survey to prioritize measures rated as high (rated 6 or 7 by ≥ 80% of respondents) or moderate (rated 6 or 7 by ≥ 50% of respondents) importance. We identified 50 measures organized in 8 domains: relevance of the research program, challenges to research program, or productivity, team/open science, funding, innovations, publications, other dissemination, and impact. Rating of measures by 44 panelists (60%) in Round One and 24 (55%) in Round Two of a Delphi survey resulted in consensus on the high importance of 5 measures: research advances existing knowledge, research plan is innovative, an independent body of research (or fundamental role) supported by peer-reviewed research funding, research outputs relevant to discipline, and quality of the content of publications. Five measures achieved consensus on moderate importance: challenges to research productivity, potential to improve health or healthcare, team science, collaboration, and recognition by professional societies or academic bodies. There was high congruence between researchers and research leaders across disciplines. Our work contributes to the field by identifying 10 DORA-compliant measures of research quality and impact, a more comprehensive and explicit set of measures than prior efforts. Research is needed to identify strategies to overcome barriers of use of DORA-compliant measures, and to “de-implement” traditional measures that do not uphold DORA principles yet are still in use.

After a lengthy journey, our paper “Intraoperative fluorescence imaging with aminolevulinic acid detects grossly occult breast cancer: a phase II randomized controlled trial” has been published in Breast Cancer Research as an open access article. The journal is widely read globally by general surgeons and breast cancer clinicians, so we are pleased it will receive broad clinical exposure and impact specifically in (breast) surgical oncology. This trial, led by Dr. DaCosta, was conducted at The Princess Margaret Cancer Center (Toronto, Canada) and demonstrates the importance of strong collaborations between our (imaging) scientists and clinicians at the Princess Margaret Cancer Center.  For example, without the commitment and support of our surgeons (Drs. Wey Leong, Alexandra Easson and others) and our pathologist (Dr. Susan Done), we could never have reached this important result. Indeed, they and other Princess Margaret clinicians will soon join our large ongoing North American FDA IND-approved Pivotal Phase 3 RCT as we add PMCC to our growing list of Phase 3 trial sites. Future plans are in progress to expand this line of research to other cancers e.g. head & neck, cervical and lung where real-time intraoperative margin assessment is important.