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Supplementary Companion Paper from Quantitative Spatiotemporal Analysis of Antibody Fragment Diffusion and Endocytic Consumption in Tumor Spheroids

The goals of this research were to: 1) utilize geographic and geostatistical methods available in geographic information systems (GIS) software to gain an in-depth understanding of the spatial distribution of ovarian cancer incidence rates, at national, state and county levels; and2) based on patterns identified from the first goal, conduct a preliminary assessment of the hypothesized association between ovarian cancer occurrence and pulp and paper manufacturing. We used the following approaches: 1) exploratory spatial data analysis of 2008-2012 ovarian cancer incidence at the county level – choropleth mapping, trend surface analysis, spatial autocorrelation and hot spot analysis;2) exploratory spatial data analysis of pulp and paper production sites, using EPA's Toxic Release Inventory data from 1988-2012;3) geographically weighted regression analysis to examine the relationship between ovarian cancer incidence and toxic emissions to air and surface water; and4) preliminary fate and transport modeling of a case study area (Wisconsin) to examine river effluent and atmospheric dispersion of chemical by-products. Results indicate that there is a strong north-to-south trend (i.e. higher rates in the north) in ovarian cancer incidence at both state and county levels. This coincides with historically higher numbers of pulp and paper mills in northern states. Exceptions to this overall trend are statistically significant multi-county clusters of high rates in Georgia and Alabama, both of which have high levels of pulp and paper production. The hypothesis is weakly supported by geographically weighted regression, when migration patterns are taken into account. In conclusion, this research indicates that there is some support, at an ecological level, for the hypothesized association between ovarian cancer incidence rates and pulp and paper production. Citation Format: Carol L. Hanchette, PhD. OVARIAN CANCER AND PULP AND PAPER MANUFACTURING IN THE US: A GEOSPATIAL ANALYSIS [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr AP03.

Introduction: There is an increased need to monitor and intervene to assist breast cancer (BC) survivors overcome the long-term and late effects of treatment. Many institutions are moving toward computerized assessments (CA) of PROs such as symptoms and concerns in place of more traditional paper and pencil administration, but little work has been performed to demonstrate that these very different methods of administration produce comparable results. Our goal was to evaluate the outcomes produced by these methods by comparing two similar samples of breast cancer survivors, one of which completed a PROs assessment using paper and pencil (PP), the other of which was assessed using a computerized system that links to the patient portal in use at our facility. Data collection of the CA of PROs is ongoing. Method: Women were eligible if they had a confirmed diagnosis of Stage 0-III BC, were within one year of completion of primary therapy, and were scheduled for a survivorship-focused end of treatment visit. As this was a naturalistic cohort study, no randomization was undertaken. The PRO assessment covered 19 common long-term or late effects of treatment, inquiring about their occurrence and severity in the previous month. On the day of the visit, participants in the PP cohort were provided with the questionnaire packet to complete prior to meeting with their provider. The women who completed the CA were either already enrolled in the patient portal or enrolled at the time of recruitment and sent an online version of the same questionnaire. Reminder calls and/or emails were sent to the CA participants to improve compliance. Results: 164 BC survivors completed the PP questionnaire, and 62 women completed the CA. Racial make-up, marital status, and education, were similar between groups. Women in the PP group were older than those in the CA group (55.45 vs. 51.23 yrs, p < 0/05) and those in the PP group were marginally more likely than those in the CA group to have been menopausal prior to treatment (50% vs. 35%, p = 0.05). With respect to PROs, there were no significant differences between groups in either the proportion of women endorsing a given symptom/concern or in the mean severity rating for any symptom/concern. The five most commonly reported concerns did differ somewhat between groups, with PP reporting Fatigue, Insomnia, Hot Flashes, Aching Joints, and Memory Difficulties, respectively, and CA reporting Fatigue, Anxiety, Body Image Problems, Memory Difficulties, and a tie between Insomnia and Depression, respectively. Conclusion: The results of the PRO assessment can be assumed to be comparable whether the method of administration is either PP or computerized. Differences found between groups in the most commonly endorsed symptoms likely reflected differences in age and menopausal status. Citation Format: Palmer SC, DeMichele A, Glanz K, Schapira M, Pucci DA, Blauch AN, Jacobs LA. Comparability of computerized and paper-pencil patient reported outcome (PRO) assessments – Does it matter how they are administered?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-10-11.

Adoptive T-cell therapy (ACT) using expanded autologous tumor-infiltrating lymphocytes (TIL) and tumor antigen-specific T cell expanded from peripheral blood are complex but powerful immunotherapies directed against metastatic melanoma. A number of nonrandomized clinical trials using TIL combined with high-dose interleukin-2 (IL-2) have consistently found clinical response rates of 50% or more in metastatic melanoma patients accompanied by long progression-free survival. Recent studies have also established practical methods for the expansion of TIL from melanoma tumors with high success rates. These results have set the stage for randomized phase II/III clinical trials to determine whether ACT provides benefit in stage IV melanoma. Here, we provide an overview of the current state-of-the art in T-cell–based therapies for melanoma focusing on ACT using expanded TIL and address some of the key unanswered biological and clinical questions in the field. Different phase II/III randomized clinical trial scenarios comparing the efficacy of TIL therapy to high-dose IL-2 alone are described. Finally, we provide a roadmap describing the critical steps required to test TIL therapy in a randomized multicenter setting. We suggest an approach using centralized cell expansion facilities that will receive specimens and ship expanded TIL infusion products to participating centers to ensure maximal yield and product consistency. If successful, this approach will definitively answer the question of whether ACT can enter mainstream treatment for cancer. Clin Cancer Res; 17(7); 1664–73. ©2011 AACR.

The lack of reproducibility of preclinical research is a significant and growing problem which slows basic research and leads to fruitless clinical trials. An increasing number of reports have found discrepancies in published preclinical studies across scientific disciplines. For example: * Amgen found that 47 of 53 “landmark” oncology publications could not be reproduced. * Bayer found that their internal results contradicted academic publications in 43 of 67 oncology and cardiovascular projects. * Dr. John Ioannidis and his colleagues found that of 432 publications purporting sex differences in hypertension, multiple sclerosis, or lung cancer, only one data set was reproducible. These studies, and the many others that report similar results, highlight a significant problem in the development of new therapies to treat disease. With increasing reports of discrepancies in preclinical publications, pharmaceutical companies are being forced to re-evaluate their reliance on academic research. In fact, Bayer recently decided to halt nearly two-thirds of target-validation projects.In this session, we'll report the work we have done to address this issue. We will bring together researchers and representatives from funders and publishers to discuss the issue of reproducibility. We will share funder and publisher initiatives to promote reproducibility and also discuss research practices that lead to more reproducible research such as using proper statistical tests, reporting all experimental data, experimental blinding, and identification and validation of research reagents. We'll also share preliminary results from an Arnold Foundation-funded study to replicate the 50 most high impact cancer biology studies from 2010-1012. Reproducibility ResearchAmgen47 of 53 “landmark” oncology publications could not be reproducedBayerinternal results contradicted academic publications in 43 of 67 oncology and cardiovascular projectsDr. John Ioannidis and colleagues432 publications purporting sex differences in hypertension, multiple sclerosis, or lung cancer, only one data set was reproducible Note: This abstract was not presented at the meeting. Citation Format: Gunn William, Elizabeth Iorns, Elizabeth Silva, Brian Nosek. Preliminary results from the Reproducibility Project: Cancer Biology - a replication of 50 high-impact cancer cell biology papers from 2010-2012. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5053. doi:10.1158/1538-7445.AM2014-5053

Background: The healthcare system has extremely large volumes of patients' paper medical records (PMRs) scattered throughout various medical facilities. Currently the industry is transitioning to Electronic Medical Records (EMR). Although each source of information is equally important, a complete longitudinal health record is rarely available or currently attainable. The goal of this effort is to convert the existing PMRs into searchable electronic equivalents and merge them with existing EMRs to create a more complete longitudinal health record to support clinical care and biomedical research.Method: Using a subset of PMRs for subjects enrolled in the Clinical Breast Care Project at Walter Reed Army Medical Center, (WRAMC), we are developing an automated method to digitize and index the records, extract the biomedical information and prepare the data for delivery to clinicians and researchers. The electronic records were loaded into a database for immediate access by clinicians. To support translational research, MRs need to be de-identified, and information extracted and loaded into a research database; we used ten MRs to develop the operational method. Several methods were tested in the de-identification process: 1) manually, by striking out the protected health information (PHI) on paper before it was digitized and 2) “electronically”, by redacting the record electronically on the computer after it was digitized. We are in the process of testing automated data extraction tools and natural language processors to automatically de-identify and extract data from the EMR.Result: We quickly realized that only 10% of PMRs existed onsite at WRAMC; remaining MRs were held by the patients or other medical facilities. Approximately 300 PMRs, containing 66,600 pages, were scanned and digitized for this project. We have created a successful digitization process, which includes creating PDFs with hidden and searchable information. We have compared the effort and accuracy of various redaction methods. To de-identify 10 records, it took ∼10 hours manually and ∼20 hours electronically. It took longer electronically because of the preparations to ensure the removed information could not be retrieved. We expect that automated redaction tools will greatly reduce that effort. We also found that the electronic method had a 99% accuracy compared to 96% for the paper method. A portal prototype to allow access to medical records by clinicians and researchers is currently being tested and evaluated.Discussion: Conversion of non-searchable data into an explorable and computable format will enable clinicians to acquire needed information more conveniently in their clinical care including treatment plan development. Similarly, properly de-identified, complete MRs will serve as a rich source of clinical information to support translational research. Although the method we are developing will initially satisfy the CBCP need for clinical service and research, it will be further developed into a full solution to expand into other disease condition fields. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5123.

Several years ago, a prominent NIH intramural physician-scientist wanted to translate basic science observations to clinical medicine, but the paperwork involved in taking a protocol from concept to conduct was overwhelming. “It was easier to get a paper published in Nature, Science , or The New

Background Each year, approximately 13,110 women under age 40 are diagnosed with breast cancer, with 1,200 dying of the disease. There are approximately 250,000 breast cancer survivors living in the US today who were diagnosed under 40. Compared to older women, young women generally face more aggressive cancers, lower survival rates, and unique psychosocial concerns. Breast cancer in women under 40 is rarely studied. Young Survival Coalition (YSC) is the premier global organization dedicated to the critical issues unique to young women and breast cancer. It is a strategic goal of YSC to increase the amount of quality research on young women, to define the greatest research needs for young women with breast cancer, and to advocate these needs to doctors and researchers. In 2001, YSC convened the “Medical Research Symposium on Young Women and Breast Cancer,” consisting of seven researchers from the New York City area from all of the major cancer disciplines. The resulting white paper set an initial YSC agenda on both the current state and future direction for research in young women. In 2012, YSC decided to revisit this agenda, review what progress has been made and what priority research areas remain. Methods In 2012, work on the YSC Research Think Tank (RTT) began. Our goal was to identify the most pressing research questions that would improve the quality and quantity of life for young women diagnosed with breast cancer. YSC assembled doctors, researchers and advocates to focus on six areas of particular importance to its young constituents: risk factors; treatment; metastasis; quality of life; fertility; and pregnancy. Each participant was assigned to a workgroup based on their stated interest and expertise. A young survivor advocate led and coordinated each workgroup. In mid- 2012, these groups met remotely to review the state of the research in each of their assigned areas. They compiled detailed reports summarizing their work and listed the research gaps pertinent to young women. In February, 2013, all RTT participants met in Arlington, Virginia for a two day in-person meeting. Each workgroup briefly presented their work to date and displayed a large poster reflecting what they believed to be the most pressing research questions. During day two of the RTT, attendees rotated through the assigned rooms of three workgroups (other than their own), discussing more fully each of the items that workgroup identified as a research priority. Participants placed each priority on a graph, reflecting how that priority would impact quality and quantity of life for young women. Each workgroup re-assembled and discussed the feedback they received, selecting their top three research priorities. Results Young women with breast cancer remain an understudied population. Taking the knowledge gained and recommendations received at the RTT meeting, YSC is currently drafting a white paper and updated research agenda to be finalized by spring, 2014. These documents will be published and promoted in an effort to focus the research community on the unique issues of young women with breast cancer to extend their quantity and improve their quality of life. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-10-02.

Academic cancer research in the UK is structured around key organizations. The National Cancer Research Institute (NCRI) is a ‘virtual institute’ that brings together government and charitable funders to set priorities and co-ordinate funding of cancer research. NCRI Clinical Studies Groups (CSGs), which provide the site-specific leadership to develop studies, will be adopted into the national portfolio of cancer studies as part of the National Institute for Health Research (NIHR) if the funding is available. The NIHR National Cancer Research Network leads the delivery of research through research networks throughout the UK. Related groups and initiatives facilitate or carry out specific tasks in research development, management and monitoring. Patients have input at all levels and their voice has, throughout the history of NCRI & NCRN, been considered critically important in developing research. The key principles from researchers and clinicians include working together with consumers as partners in the research effort, involving consumers in developing strategy as well as specific initiatives and studies, listening to the consumer voice on research needs and the experience of participating in research, and learning from experience to develop and increase the impact of the consumer role in cancer research. The NCRI Consumer Liaison Group brings together patient and caregiver members to support research development at all levels from the NCRI Board through CSGs to membership of individual Trial and Study Management groups. Impact has been captured in many narratives from researchers, clinicians and patients. Working together in a robust partnership is a particular strength of UK Cancer Research and forms the ideal platform to truly achieve research intended for patient betterment. This is recognized in the recent White Paper: ‘Equity and excellence: Liberating the NHS’. The organization's first decade of patient and public involvement is captured in the NCRI report: Patient, Carer & Public Involvement in Cancer Research. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-73. doi:10.1158/1538-7445.AM2011-LB-73

The aim of my PhD project is the analysis of the ethical and regulatory issues of Phase 0 oncological trials. In 2003, the European Agency for the Evaluation of Medicinal Products (EMEA) published a concept note followed by a Position Paper on the nonclinical safety studies needed to support human clinical trials with a single microdose of a pharmacologically active compound. In 2004, the American FDA published a draft guidance regulating early human screening studies, and in 2006 new industry guidelines for early exploratory drug studies in humans have been issued. After the publication of the US FDA guidelines, the NCI in Bethesda started the' Phase 0 program' and launched the first Phase 0 trial. Given the recent development of such trials, there are few empirical data available on which to evaluate the ethical concerns they raise. I will pursue my analysis on the data of the NCI Phase 0 program, and by performing a comparison with the ethical concerns raised by other early cancer trials. I will also compare FDA to EMEA guidelines. The ‘therapeutic misconception’, which is a widespread ethical problem for participants to Phase 1 cancer trials, should not be an issue of Phase 0 trials, as they declare their lack of therapeutic intent. Another ethical issue appears controversial, though, as in Phase 0 studies the interests of society seem to play a greater role than the interests of the subjects, who contribute to the progression of medical knowledge, without receiving any direct benefit from their participation. Some ethicists suggest that paragraph # 6 of Helsinki Declaration, according to which the ‘interests’ of human subjects must always take precedence over the interests of science and society, is being violated. It is time to reflect upon the nature of statements contained in Helsinki Declaration, as recently scholars such as the British bioethicist John Harris and the US Rosamund Rhodes have argued. I will discuss how the concept of ‘interest’ in participating to research should be understood, and contribute to the debate about who should be entitled to decide regarding participation to clinical trials. On the basis of my preliminary analysis, I will conclude that Phase 0 trials appear ethically less problematic than Phase 1 cancer trials. I will also argue that the widespread presumption, that participation to clinical research is super-erogatory, needs to be changed, in favor of an approach with considers participation to research within the broadly conceived interests of the participants. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C40.

Supplementary Material and Methods includes search terms; excluded papers; study characteristics; risk of bias; forest plots; funnel plots. Supplementary Table 1: Search terms used for each component of the systematic review. Supplementary Table 2: Papers Excluded at Full Text Screen.* Supplementary Table 3A: Study characteristics of Mendelian randomisation studies. Supplementary Table 3B: Study characteristics of prospective cohort studies. Supplementary Table 4. Risk of Bias: Prospective Cohort Studies. Figure 1: Funnel plots. Figure 2: IGF-1 and breast cancer risk in models that adjust for IGFBP-3. Figure 3: IGF-1 and breast cancer risk by menopause status at blood draw. Figure 4: IGFBP-3 and breast cancer risk by menopause status at blood draw

All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.

Radiotherapy has proven efficacy in a wide range of cancers. There is growing interest in evaluating radiotherapy–novel agent combinations and a drive to initiate this earlier in the clinical development of the novel agent, where the scientific rationale and preclinical evidence for a radiotherapy combination approach are high. Optimal design, delivery, and interpretation of studies are essential. In particular, the design of phase I studies to determine safety and dosing is critical to an efficient development strategy. There is significant interest in early-phase research among scientific and clinical communities over recent years, at a time when the scrutiny of the trial methodology has significantly increased. To enhance trial design, optimize safety, and promote efficient trial conduct, this position paper reviews the current phase I trial design landscape. Key design characteristics extracted from 37 methodology papers were used to define a road map and a design selection process for phase I radiotherapy–novel agent trials. Design selection is based on single- or dual-therapy dose escalation, dose-limiting toxicity categorization, maximum tolerated dose determination, subgroup evaluation, software availability, and design performance. Fifteen of the 37 designs were identified as being immediately accessible and relevant to radiotherapy–novel agent phase I trials. Applied examples of using the road map are presented. Developing these studies is intensive, highlighting the need for funding and statistical input early in the trial development to ensure appropriate design and implementation from the outset. The application of this road map will improve the design of phase I radiotherapy–novel agent combination trials, enabling a more efficient development pathway.

PDF - 121KB, Exclusion Criteria for Scoring by Scientific Area and Translational Stage, Comparison of Translational Stage of CEC versus non-CEC associated cancer genetics papers, Acknowledgement of CEC contributions in associated papers. Table 1: Scientific areas, their definitions, and examples from the literature analysis. Table 2: Acknowledgment CEC contributions in 472 papers, associated with 4 established CEC, by acknowledgement type.

There is growing interest in early detection of colorectal cancer as current screening modalities lack compliance and specificity. This study systematically reviewed the literature to identify biomarkers for early detection of colorectal cancer and polyps. Literature searches were conducted for relevant papers since 2007. Human studies reporting on early detection of colorectal cancer and polyps using biomarkers were included. Methodologic quality was evaluated, and sensitivity, specificity, and the positive predictive value (PPV) were reported. The search strategy identified 3,348 abstracts. A total of 44 papers, examining 67 different tumor markers, were included. Overall sensitivities for colorectal cancer detection by fecal DNA markers ranged from 53% to 87%. Combining fecal DNA markers increased the sensitivity of colorectal cancer and adenoma detection. Canine scent detection had a sensitivity of detecting colorectal cancer of 99% and specificity of 97%. The PPV of immunochemical fecal occult blood test (iFOBT) is 1.26%, compared with 0.31% for the current screening method of guaiac fecal occult blood test (gFOBT). A panel of serum protein biomarkers provides a sensitivity and specificity above 85% for all stages of colorectal cancer, and a PPV of 0.72%. Combinations of fecal and serum biomarkers produce higher sensitivities, specificities, and PPVs for early detection of colorectal cancer and adenomas. Further research is required to validate these biomarkers in a well-structured population-based study. Cancer Epidemiol Biomarkers Prev; 23(9); 1712–28. ©2014 AACR.

This files contains detailed methods on procedures used in this study, which complements the method described in the main paper. It also expands on the methods described in the main paper. Specifically, it contains method on Microfluidic 3D cell migration assay; 2D Cell Migration Assay; Immunofluorescent staining, confocal microscopy, and DQ-Collagen I Release Assay; ELISA; Cancer cell-macrophage co-culture for western blot analysis; Treatment of cancer cells for western blot analysis; Protein isolation and western blot analysis; Total RNA extraction and mRNA detection; In vivo metastasis assay

Introduction: Advances in technology and internet capability have provided an opportunity for efficient collection of Patient Reported Outcomes (PRO) during medical treatment. Here we describe the development and implementation of a system for monitoring patient reported adverse events (AEs) and quality of life (QoL) using electronic PRO (ePRO) instruments for patients enrolled on the Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular analysis (I-SPY 2 TRIAL), a phase II adaptive platform clinical trial for locally advanced breast cancer. Methods: We designed an ePRO system to increase the accuracy of patient-reported QoL and AE data collection with the intent to act on symptoms in real time. Using the OpenClinica electronic data capture system, we developed rules-based logic to build automated ePRO surveys, customized to the I-SPY 2 treatment schedule. Weekly surveys contained a maximum of 126 validated, branching logic questions from the Patient Reported Outcomes Measurement Information System (PROMIS®) Health Measures and the National Cancer Institute’s Patient Reported Outcomes - Common Terminology Criteria for Adverse Events (PRO-CTCAE™) instruments. We piloted ePROs at the University of California, San Francisco (UCSF) to evaluate compatibility with a variety of I-SPY 2 patient scenarios (e.g., dose delays). We then staggered rollout of the ePRO system to 22 I-SPY 2 sites to ensure technological feasibility. In order to improve accuracy of data collection, we utilized real-time tracking and developed a Clinical Research Coordinator (CRC) training manual, which integrated workflow diagrams with technical solutions. CRCs were trained using remote video sessions. Results: The UCSF ePRO pilot began in September of 2020. Over 9-months, we accrued 43 I-SPY 2 patients (average age of 43.8 years), whose interactions with the ePRO system informed design improvements. Of the patients who received a baseline ePRO survey, the completion rate was 75.9% (average age of 44.2 years). This represents an increase from the 15-20% baseline completion rate for the 360 UCSF I-SPY 2 patients who received paper-based PRO surveys between May 2012 - January 2019. As of June 2021, the ePRO system was operational at all 22 I-SPY 2 sites. The UCSF pilot revealed that engagement with patients at critical timepoints improved survey completion. CRCs facilitated patient participation by sending instructional emails and communicating with patients weekly. We tracked data completeness using a Patient Tracking report, which displayed each patient’s survey completion history. This real-time tool enabled CRCs to identify patients who had not completed ePRO surveys prior to their visit, so they could be provided a tablet computer to complete the survey in the clinic. After introducing tablets into the workflow at UCSF, patient completion of the baseline survey increased from 75.9% to 80%. Conclusion: The transition from paper to electronic QOL and AE data collection improves the ability of patients to complete PRO surveys, but the process must also be optimized and integrated into clinical workflow and trial conduct. In the future, we will present additional results highlighting the feasibility of multilingual ePRO integration into I-SPY 2. ePRO also provides a new opportunity for data analysis, as well as the potential to reduce high grade toxicity through early intervention. It will allow us to assess QoL and AE data by drug regimen, site, provider, and study treatment. The creation of clinician-facing reports also enables access to patient responses in real-time. By implementing ePRO within I-SPY 2, we not only increase efficiency and accuracy of patient-reported data collection, but also improve quality of care and patient safety. Citation Format: Anna Northrop, Anika Christofferson, Michelle Melisko, Laura Sit, Ebunoluwa Olunuga, Ananya Mittal, Adi Goldman, Thelma Brown, Diane Heditsian, Bev Parker, Susie Brain, Carol Simmons, Alessandra Taboada, Kathryn J Ruddy, Tina Hieken, Mara Piltin, Kiri Cook, Carolina Salvador, Candace Mainor, Anosheh Afghahi, Sarah Tevis, Anne Blaes, Irene Kang, Susan Melin, Laura Esserman, Adam Asare, Dawn L Hershman, Amrita Basu. Improving patient-reported outcome data capture for clinical research: ePRO in ISPY 2, a phase 2 breast cancer study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-12-02.

The landmark paper by Kane and colleagues was the first report of DNA methylation in the promoter of the human MLH1 gene in sporadic colon cancers with mismatch repair (MMR) deficiency. In both cell lines and primary tumors, promoter methylation was associated with loss of MLH1 protein expression and with a lack of mutations in the MLH1 coding region. Together with subsequent papers that showed that this methylation was directly responsible for loss of MLH1 expression and MMR deficiency, the observation expanded the two-hit hypothesis of tumor suppressor gene loss in cancer to include both genetic and epigenetic mechanisms of gene inactivation. More broadly, the paper contributed to normalization of the hypothesis of an epigenetic basis for cancer development. See related article by Kane and colleagues, Cancer Res 1997;57:808–11

While rational drug combination design seeks to improve patient outcomes by leveraging biological synergy, outcomes from combination trials often fail. Only 12.4% of phase 1 trials eventually achieve regulatory approval. In vitro evidence has provided the rationale for the drug combinations in 36.6% of phase 1 combination trials, but none of those trials progressed past phase 3 (from a study by Paller CJ et al., 2019). A review of DrugCombDB, a publicly available database of experimental synergy results, supports the idea that such outcomes are mirrored in preclinical data. Analysis of the similarity of synergy scores within indication-specific subsets of cell lines from data in a 2022 paper by Douglass, et al. show that in both breast and lung cancer, combinations predicted to be synergistic in at least one cell line from that indication failed to be synergistic in the majority of indication cell lines more than half of the time. SHEPHERD’s Gene Cluster Voting Algorithm (GCVA) was adapted to improve upon current drug combination design and anticipate transcriptome changes as the result of drug treatment. GCVA relates drug sensitivity to the transcriptome by calculating a list of biomarkers that contribute to sensitivity and resistance for specific drugs, enabling the prediction of drug sensitivity on patient transcriptomic data captured via bulk RNAseq. Via this method, 15,137 publically available synergy data points in the Douglass paper were compared to predictions by our computational approach. For all synergy metrics contained within the dataset (ZIP, Bliss, Loewe, and HSA), the synergistic predictions made by application of GCVA have significantly higher synergy scores compared to the antagonistic predictions made by GCVA (p < .001). These test results support the potential for the application of GCVA to intelligent combination design with the ultimate goal of deployment on a patient-by-patient basis.In addition, analysis of GCVA’s drug efficacy predictions for the cell line DU145 showed that treatment with 9 kinase inhibitors consistently potentiated the predicted efficacy of between 5 and 11 additional drugs. Dasatinib, temsirolimus, and cabozantinib were newly predicted effective after treatment with each and every kinase inhibitor. This data suggests an avenue for the design of intelligent drug combinations based on anticipated transcriptomic changes that may improve on existing synergy prediction methods. Citation Format: Christina Gavazzi, Mikhail G. Grushko, Jeremy M. Goldstein, Mahta Samizadeh, Zakary Y. ElSeht, Katherine Arline. Transcriptome-driven combination design: A computational approach. [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 4278.

Background Breast conserving surgery with adjuvant radiotherapy (BCS+RT) and mastectomy are currently offered as oncologically equivalent options for the surgical management of early breast cancer based on findings from randomised controlled trials (RCTs) conducted over four decades ago. Since then, locoregional and systemic breast cancer treatments have improved significantly and several recent observational studies suggest a survival advantage in patients receiving BCS+RT compared to those having mastectomy. If BCS+RT is oncologically superior to mastectomy, this may dramatically impact surgical treatment recommendations. The aim of this systematic review was to identify, critically appraise and summarise the contemporary literature comparing survival following BCS+RT and mastectomy to inform surgical decision-making for patients with early breast cancer. Methods A systemic search of MEDLINE, Cochrane Central Register of Controlled Trials and Embase identified studies published between 1st January 2000 to 22nd September 2021. Included were primary research studies published in English comparing overall survival in women undergoing primary surgery with either BCS+RT or mastectomy for unilateral stage I to III breast cancer. Excluded were studies evaluating neoadjuvant chemotherapy; rare breast cancer subtypes (e.g. mucinous) or in specific patient populations (e.g. pregnancy associated breast cancer) and those that completed recruitment before 1st January 1990. We used the ROBINS-I tool to assess the risk of bias in study results and GRADE to assess the overall certainty of evidence. All papers without critical risk of bias were included in a quantitative meta-analysis. Where more than one study reported outcomes in overlapping population-based registry cohorts, the study with the most recent data on the largest cohort was selected for analysis. The primary analysis was a random effects meta-analysis with a fixed effect model undertaken as sensitivity analysis. A secondary meta-analysis was performed for studies only including triple negative breast cancers. All analyses were conducted using STATA17. Results 10,876 abstracts were screened and 157 full-text papers assessed for eligibility, of which 93 (17 multi-centre observational studies, 30 were single-centre observational studies and 46 registry-based studies) met the inclusion criteria for the review. 25 papers were excluded from meta-analysis due to an overall critical risk of confounder bias and 27 were excluded due overlapping study populations. 36 studies (34 with serious risk of bias and 2 with moderate risk of bias) reporting survival outcomes on 1,321,291 patients (729,789 undergoing BCS+RT and 591,502 undergoing mastectomy) were included in the meta-analysis. The pooled hazard ratio was 0.72 (95% CI 0.64– 0.81, p< 0.001, I2 97.6%) demonstrating improved overall survival for patients undergoing BCS+RT compared with those receiving mastectomy. The sensitivity analysis, using a fixed effect model, showed a hazard ratio of 0.88 (95% CI 0.87 – 0.89, p< 0.001, I2 97.6%) for survival in women undergoing BCS+RT compared with mastectomy. Meta-analysis of 8 studies reporting survival in 17,181 patients with triple negative breast cancer showed a hazard ratio of 0.73 (95% CI 0.68 – 0.79), p< 0.001, I2 34.7%) for those receiving BCS+RT versus mastectomy. Discussion This meta-analysis provides further, albeit very low certainty evidence, that overall survival is improved following BCS+RT compared with mastectomy in a contemporary cohort of patients treated for early-stage breast cancer. These results should be interpreted with caution due to the heterogeneity of included studies and the high risk of bias associated with observational data. As future RCTs will not be feasible, well-designed large-scale prospective observational studies are needed to provide better evidence to support surgical decision-making in early-stage breast cancer. Citation Format: Kiran Kasper Rajan, Katherine Fairhurst, Beth Birkbeck, Rebecca Wilson, Jelena savovic, Chris Holcombe, Shelley Potter. PD15-04 Overall survival following breast conserving surgery and adjuvant radiotherapy compared with mastectomy for early stage breast cancer: a systematic review and meta-analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD15-04.

Objective: The aim of this study was to conduct a bibliometric and visual analysis of breast reconstruction related research at China and abroad published in the past five years, to understand the research status and development trend in this field, to discuss the focus of research in different countries and different disciplines, and to provide reference for other researchers. Methods: Relevant literatures about breast reconstruction were retrieved from the Web of Science Core Collection. The VOS viewer 1.6.15 software was used to extract the authors, countries, institutions and keywords to generate network maps of high-yield authors, institutions and high-frequency keywords clustering network. Results: 4,815 documents meeting the requirements were retrieved, which showed an upward trend in the past five years. Regarding the discipline, 838 documents (17.40%) were published by breast surgery and Cancer Surgery, 3308 (68.70%) were published by plastic surgery, and 669 (13.90%) were jointly published by both types of researchers. A total of 161 clinical trials were registered in the US clinical trial registry (ClinicalTrial.gov), of which intervention trials accounted for the highest proportion (107, 66.46%), followed by observational trials (54, 33.54%) and patient registry (4, 2.48%). Regarding country distribution, the United States conducted the largest number of breast reconstruction-related clinical trials (45, 27.95%), followed by China (22, 13.66%), Italy (12, 7.45%), France (11, 6.83%), the Netherlands (9, 5.59%). The top ten institutions contributed 983 articles (20.41%), and the institution with the highest number of publications was MD Anderson Cancer Center (144, 2.99%), followed by Harvard Medical School (139, 2.89%), Sloan-Kettering Cancer Center (125, 2.60%), Stanford University (113, 2.35%) and University of Michigan (102, 2.12%). The author with the largest number of documents was Bernard T. Lee of Beth Israel Deaconess Medical Center (BIDMC), with 56 papers and 540 citations. The most cited author was Andrea L. Pusic of Brigham and Women’s Hospital, with 48 papers and 1,332 citations. Chinese authors published 310 documents, accounting for 6.44%. There were differences in the disciplines of the main authors between China and abroad. In China, authors from breast surgery published a larger proportion of documents (138, 44.52%), while the number of documents published by authors of plastic surgery (129, 44.52%) and the joint publication of both types of authors (43, 13.87%) was relatively small. However, foreign documents mainly came from authors of plastic surgery (74.74%). There were more cooperative groups (155) formed by major foreign authors, and joint publishing between groups was more frequent; while Chinese author formed only 16 cooperative groups with less cooperation. Keyword cluster analysis showed that top five keywords were flap, implant, breast cancer, immediate breast reconstruction, tissue. In breast surgery publications, top five keywords were breast cancer, breast reconstruction, complications, implant, immediate breast reconstruction, while in plastic surgery publications top five keywords were flap, implant, tissue, breast cancer, infection. Authors from breast surgery focus more on oncology-related issues in breast reconstruction, while in plastic surgery, more attentions were paid on autologous tissue reconstruction. Conclusion: Breast reconstruction had gradually attracted the attention of Chinese and foreign researchers. Compared with foreign countries, there were problems such as lack of high-quality research and less cooperative research in China. There were differences in the research focus of breast reconstruction between China and abroad, which is mainly related to the differences in the disciplines of researchers. Citation Format: Hengyu Ren, Shuang Hao, Jiajian Chen, Zhimin Shao, guangyu liu, A-Yong Cao, Jiong Wu. Current Status and Focus of Breast Reconstruction Research in China and Abroad-A Bibliometric Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-56.

Introduction Due to improvements in breast cancer (BC) diagnostics and treatment, the population of BC survivors is growing. BC treatments may have adverse effects that lead to an increased risk of developing type 2 diabetes mellitus (T2D). It is therefore important to investigate the risk of T2D in patients with BC in general and according to type of adjuvant BC treatment. Objectives To conduct a systematic review and meta-analysis investigating the association between early BC and the risk of subsequent T2D diagnosis. A secondary aim was to examine this association according to type of adjuvant BC treatment––chemotherapy and endocrine therapy (ET). Methods We searched PubMed and Embase using variations of the search terms breast cancer (population), ET, tamoxifen, aromatase inhibitors (AIs) and chemotherapy (exposures), and diabetes mellitus (outcome). Two authors screened papers for eligibility by title and abstract using Covidence and reviewed full texts of eligible papers. Guided by the Meta-analysis of Observational Studies in Epidemiology (MOOSE) checklist, study data were extracted. Using random-effects models, we calculated relative risks (RRs) and associated 95% confidence intervals (CIs) for the association between BC, adjuvant BC treatment (ET overall, tamoxifen, and AIs), and subsequent T2D. We used funnel plots to assess publication bias in the analyses. Results Among 16 eligible studies, 11 reported on T2D risk after BC, chemotherapy, or ET; five studies investigated more than one association. Compared with patients without BC, those with BC had elevated risk of T2D overall (RR=1.27, 95%CI=1.15-1.41), particularly those who received any ET (RR=1.23, 95% CI=1.16-1.32). Among BC patients only, risk of T2D was higher for those who received tamoxifen compared with those who did not receive tamoxifen (RR=1.19, 95% CI=1.13-1.25). Due to few studies, analyses investigating T2D risk after treatment with AIs and chemotherapy were inconclusive. Conclusion Our findings support an association between BC and subsequently elevated risk of T2D, particularly after tamoxifen use. Further research is needed to determine the impact of ET overall, AIs and chemotherapy on the incidence of T2D in patients with early BC. Funding This project was funded from the following source: The Novo Nordisk Foundation (NNF20OC0065928) Citation Format: Nanna Jordt, Kasper Kjærgaard, Signe Borgquist, Reimar W. Thomsen, Deirdre Cronin-Fenton. Breast Cancer and Subsequent Risk of Type 2 Diabetes Mellitus: A systematic review and Meta-Analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-23.

Background: Large-scale prospective cohorts traditionally use English, paper-based, mailed surveys, but Web-based surveys can lower costs and increase data quality, and multi-language surveys may aid in capturing diverse populations. Little evidence exists examining item response for multiple survey modalities or languages in epidemiologic cohorts. Methods: A total of 254,475 men and women completed a comprehensive lifestyle and medical survey at enrollment (2006–2013) for the Cancer Prevention Study-3, a U.S.-based prospective cohort. Web-based (English only) or paper (Spanish or English) surveys were offered. Using generalized linear models, differences in item response rates overall and by topical areas (e.g., reproductive history) by modality and language were examined. We further examined whether differences in response quality by sociodemographic characteristics within each survey modality existed. Results: Overall, English Web-based surveys had the highest average item response rate (97.6%), followed by English paper (95.5%) and Spanish paper (83.1%). Lower item response rates were seen among nonwhite, lower income, or less-educated participants. When examining individual survey sections by topic, results varied the most for residential history, with the lowest item response rate among Spanish language respondents (women, 62.7% and men, 64.3%) and the highest in English language Web-based, followed by paper respondents (women, 94.6% and men, 95.3%; and women, 92.8% and men, 92.1%, respectively). Conclusions: This study supports that utilizing multimodal survey approaches in epidemiologic studies does not differentially affect data quality. However, for some topic areas, further analysis should be considered for assessing data quality differences in Spanish language surveys. Impact: Multimodal survey administration is effective in nondifferentially capturing high-quality data. See all articles in this CEBP Focus section, “Modernizing Population Science.”

Rationale: Breast cancer diagnosis at a young age is associated with higher risk of recurrence, mortality, morbidity, and impact on quality of life. Long-term effects of treatment may include early menopause, fertility impairment, neuropathy, cardiovascular disease, lowered bone density, and risk of second malignancies. Young women with or at-risk for breast cancer often seek health information through mainstream print and digital media. However, they often find it does not address their unique concerns, is difficult to interpret, or even misleading. Media reports of breast cancer research are often unreliable, misleading, or confusing regarding which information is clinically relevant. Young women with or at-risk for breast cancer, need accurate, clearly presented information based on sound evidence to help them make informed decisions about their specific health needs. To help women better understand media coverage about new research, Facing Our Risk of Cancer Empowered (FORCE) developed the CDC-funded XRAYS (eXamining Relevance of Articles to Young Survivors) program. XRAYS is an online resource that provides brief articles summarizing recent research relevant to young women with or at-risk for breast cancer. XRAYS articles rate the quality and relevance of research, the quality of media reporting, and suggest questions users may be useful to address with health care providers. One critical aim of XRAYS is to improve users’ understanding of the information presented in media reports related to breast cancer. Objective: The objective of this study was to assess whether XRAYS improves readers’ knowledge about information presented in media reports relevant to breast cancer more than reading media reports alone. Methods: To assess XRAYS’ impact on users’ knowledge of information presented in media reports, an evaluator conducted a study with 36 volunteer participants who were attending a FORCE conference. Participants were randomly assigned to treatment or control groups. Both groups completed pre-test paper and pencil multiple choice assessments of knowledge regarding information presented in the article they read, in order to assess baseline knowledge. Then, the treatment group read a media report and the corresponding XRAYS article and the control group read only the media report. After reading the materials, participants answered the same paper and pencil multiple choice questions, so that changes in knowledge could be assessed. Results: A between groups t-test indicated that the groups had comparable baseline knowledge about the material they were assigned to read. A within group comparison showed that the control group’s knowledge did not significantly change between pre- and post-test, while the XRAYS group’s knowledge increased significantly (t(18)=-2.67, p (t(34)=-3.01, p Conclusion: Results indicate that XRAYS is effective in supporting users in learning more factual content from media reports on cancer research than people who read media reports alone, and that it may be useful to develop similar resources to meet other audiences’ needs for information about cancer research. Citation Format: Robin Hilary Pugh Yi, Piri Welcsch, Lisa Rezende, Craig Dearfield, Kelly Owens, Susan J. Friedman. Effectiveness of an online educational resource in increasing lay users' understanding of information in media reports on breast cancer research [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-15-07.

Introduction Patients referred for genetic counseling do not consistently complete a family history questionnaires (FHQ), which is required before scheduling a genetic counseling appointment (GCA). A paper survey has traditionally been used to collect this FHQ data. This requires the genetic counselor to manually input the patient's FHQ information into a pedigree generator prior to scheduling their GCA, thereby delaying the genetic screening process. Some genetic counseling centers have switched from using this paper survey to a web-based pedigree-generator, like PROGENY, for collecting patient's FHQ data. No literature to date has evaluated the impact of this change on patient compliance with completing the required FHQ, the genetic screening process, or patient outcomes. This study assesses changes in patient compliance and genetic screening efficiency with the implementation of PROGENY compared to traditional surveying as a means of collecting FHQ data. Hypothesis More patients will complete the FHQ and GCA and there will be reduced time between patient referral and completion of the FHQ and GCA with the use of PROGENY compared to the traditional paper survey. Methods This is a retrospective chart review of patients referred for genetic counseling six months before and after implementation of PROGENY. Independent t-tests assuming unequal variances were conducted using JMP to compare genetic screening efficiency with and without the use of PROGENY. Results This study found that 41% more patients completed the FHQ and 25% more patients completed a GCA when using PROGENY. Further, there was a statistically significant reduction in the time between referral and completion of the FHQ (t(311)=9.14, p Conclusions These results support our hypothesis and suggest that utilizing PROGENY in collecting patient FHQ data correlates with improved patient compliance and genetic screening efficiency. Future work should investigate how quality improvement such as this impacts patient outcomes, such as the timeliness of finding an actionable genetic mutation and detecting cancerous and precancerous lesions. Some limitations of this study include high variability. This is likely due to factors such as appointment cancellations, geneticist availability and workload, and patient age, ethnicity, gender, and socioeconomic status. Future work should assess the impact of these factors on variables such as patient compliance and efficiency of the genetic screening process. Citation Format: Hennick TM, Khan T, Moroose R, Bisson R. Improved patient compliance and genetic screening efficiency following implementation of an electronic pedigree survey (PROGENY) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-09-20.

Background: Almost a quarter of older adults in the United States will identify themselves as Hispanic/Latino by 2060. Our group has previously developed and validated a self-administered geriatric assessment tool which can be used to identify functional, psychological, social and cognitive impairments among older patients with various types of cancer. Among English-speaking older adults, completing this tool using paper/pencil or a tablet takes a median of 15-21 minutes (min), with < 10% needing assistance to answer it (Hurria, JOP 2016). However, the utilization of this tool among Spanish-speaking older adults has not been tested. We assessed the feasibility of administering a translated and validated Spanish version of our geriatric assessment tool for older Hispanic women with breast cancer, and identified their preferred format (tablet or paper/pencil). Methods: Spanish-speaking women aged ≥ 65 years with a diagnosis of breast cancer completed the geriatric assessment twice on the same day. Patients were randomized into 3 groups: paper/pencil twice; tablet and paper/pencil in random order; and tablet twice. We assessed the proportion of patients requiring assistance to complete the geriatric assessment, the time needed to complete it, and the proportion of patients who thought the geriatric assessment was difficult/very difficult. Results: 140 older women with breast cancer completed the geriatric assessment twice and were evaluable. Mean age was 71.6 years (SD 5.8), 53% had ≤ 8th grade education, 43% were married, 45% were retired, 32% were homemakers, and 6% were employed. The participants came from 13 different Spanish-speaking countries, although 70% were born in Mexico. For 90%, Spanish was their primary language, and 75% spoke only in Spanish at home. Regarding computer skills, 64% of the patients said they had none. 39% (n = 54) were unable to complete the geriatric assessment on their own; mean time to complete the geriatric assessment was 29 min (range 8-90); and 28% (n = 39) thought the geriatric assessment was difficult/very difficult. The most common reasons for needing assistance were difficulty understanding questions (39%) and visual problems (31%). Patients with ≤ 8th grade education took longer to complete the geriatric assessment (mean 37.2 vs 29.4 min, p < 0.01), and more often needed help completing the assessment (51% vs 19%, p < 0.01) than those with ≥9th grade education. 53% of the participants preferred using a tablet to answer the geriatric assessment, while 47% preferred paper/pencil. Conclusions: A substantial proportion of Spanish-speaking older women with breast cancer required assistance to complete our self-administered geriatric assessment tool. This may be a consequence of the low educational level we found among this patient population. Tailoring assessments for diverse populations with particular attention to educational level is needed in multicultural settings. Citation Format: Soto-Perez-de-Celis E, Vazquez J, Kim H, Sun C-L, Somlo G, Yuan Y, Waisman JR, Mortimer JE, Kruper L, Taylor L, Patel NH, Moreno J, Charles K, Roberts E, Uranga C, Levi A, Katheria V, Paredero-Perez I, Mitani D, Hurria A. A self-administered geriatric assessment tool for Spanish-speaking older women with breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-16-04.

Purpose: Collecting patient reported outcome (PRO) data in a systematic way enables an objective evaluation of treatments and its related outcomes. By using the disease specific questionnaires developed by the International Consortium of Health Outcome Measurement (ICHOM) this allows for comparison between physicians, hospitals and even different countries. Methods In November 2016 we implemented a web-based system to collect PRO data at the breast center at Charité University hospital using the ICHOM data set. All new patients who are seen at the breast center are enrolled and are answering a predefined set of questions using a tablet computer. Once they start their treatment at Charité automated emails are sent to the patient at predefined treatment points. Those emails contain a web-based link through which they can access their questionnaires. Results Until now we have enrolled 834 patients and initiated 2470 questionnaires. 9.44% of patients were under 40 years of age, 49.7% between 40 and 60, 39.6% between 60-80 and 1.3% over the age of 80 years. The average return rate of questionnaires is 72% without any additional intervention. When asked about preference regarding paper versus online 7.9% of the patients 50 to 60 years of age would prefer paper, 18% in the 60-70 years of age group and 21.2 % in the age group over 70 years. Conclusion Measuring PRO in breast cancer patients in an automated electronic version is possible across all age ranges while simultaneously achieving a high return rate. Citation Format: Karsten MM, Speiser D, Hartmann C, Lippold K, Kirchberger V, Blohmer J-U. First implementation of the International Consortium of Health Outcomes Measurement standard for breast cancer at a major German university hospital using a web-based tool to measure patient reported outcomes [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-12-05.

Tumorigenesis begins with cells that have normal mutation rates. As the cells become immortal and accumulate different numbers of mutations along the way, current literature splits in two describing if and how mutation rates increase as the cancer progresses. Some argue that as the mutation rates are small (mutation rate in healthy cells is per nucleotide site per cell division) and malignant cells are loaded with thousands of different types of mutations, they must have acquired a mutator phenotype early in their development. Others argue that immortality of malignant cells, and their rate of proliferation is responsible for their genetic instability and number of mutations observed in their genome. We conduct a review of the literature with the key words “mutation rate” and “cancer” in their title. We review 123 papers and found that description of mutation rates varied in the published work. This leads to estimates of mutation rates in cancer from per nucleotide site per cell division. Some of this variation in mutational rates arises across different organs of the body, for instance liver cells have a higher mutation rate than heart and brain. Cancer treatments such as chemotherapy influence mutation rate, and mutation rate of drug and multidrug resistance cancer cell is higher than newly diagnosed cancer cells. Further, mutation rate is defined differently in different literature, some papers measure the mutation rate in a population or a gene, some calculate it per base pair, genome, or mitosis. Here we provide a comprehensive picture of published mutation rates across different cancer types in order to inform cancer models and treatment plans for individual patients. We propose a unified framework for discussing and reporting mutation rate of cancer cells and formulations on how to switch between definitions. Citation Format: Fargam Neinavaie, Andrew Kramer. Does mutation rate of cancer cells change as the stage of the disease advances? [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A038.

Background: Liver cancer is one of the most important cancers in the United States, and hepatocellular carcinoma (HCC) is its most common form. In addition, health disparities can impact cancer-related outcomes in racial/ethnic minorities. Therefore, the aim of this study was to conduct a systematic review to analyze the hepatocellular carcinoma disparities among Latinos. Methods: A systematic review was conducted following the PRISMA guidelines. Papers were selected searching PubMed/Medline, SciELO, and LILACS databases in July 2021 using the search terms [Latin Americans] OR [Latinos] OR [Hispanics] OR [Racial Disparity] AND [Hepatocellular carcinoma]. The inclusion criteria was limited to observational studies published in the last five years that evaluated hepatocellular carcinoma disparities among Hispanics/Latinos. The language was restricted to English, Spanish or Portuguese. Results: Among the 179 papers initially identified, 44 were eligible for this review after full texts were read. Although there is a constant evolution in screening, diagnosis, and treatment strategies to improve the prognosis of HCC; racial and ethnic minorities are reported to have higher mortality related to HCC. In the United States, the age-adjusted incidence of HCC in Hispanics has surpassed those of HCC in Asians. From a public health perspective, active hepatitis C and B continue to drive most of the global burden of HCC, and there is a high prevalence of these infections in Latin America. In addition, non-alcoholic fatty liver disease (NAFLD) is one of the main risk factors for HCC in the USA, followed by alcoholic liver disease, and hepatitis C and B infections. Latin Americans have a higher prevalence of NAFLD, whereas African Americans have a lower prevalence of NAFLD. The exact contribution of genetic and environmental factors on these differences in prevalence has not been determined. While one in five HCC patients in the USA is of Hispanic ethnicity, only 38% meet the criteria for liver transplantation at the time of diagnosis. Acculturation, insurance status, and access to health care may further contribute to the observed HCC disparities among Latinos. Conclusions: The data indicates that HCC disparities in early diagnosis, treatment, and outcomes among Latinos are an important issue and need more attention. We suggest that interventions are necessary to reduce HCC disparities among Latinos in order to improve cancer-related outcomes. Citation Format: Tulio L. Correa, Mariana S.T.C. Guelli. Hepatocellular carcinoma disparities among Latinos: A systematic literature review [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-194.

Objective: In the Caribbean region, research has been limited, making it challenging to find. In order for the region to optimally access and utilize present research and identify gaps, we developed the Repository for Caribbean Cancer Publications (ReCCaP) to home publications on cancer in the Caribbean population and diaspora and report on publication trends. Methods: A systematic PubMed literature search for the period 2004-2019 (15 years) was developed using keywords related to “cancer” and “Caribbean.” Three independent investigators verified included publications. The final database was formatted and hosted in an online database management software. Publication trends over time, by country, cancer type, and income classification were investigated. Results: Of the 4935 publications found, 1194 papers met the inclusion criteria with 803 publications (67.25 %) being on the Caribbean population, 139 publications (11.64%) including multiple Caribbean countries and 252 publications (21.11%) on the diaspora. Between 2004-2019 there was an overall 0.20 increase in publications regionally. Overall, most publications were on breast (n = 168, 14.07%), prostate (n = 156, 13.07%), cervical (n = 152, 12.73%), colorectal (n = 80, 6.70%), and lung cancer (n = 36, 3.02%). The highest number of papers were published by Puerto Rico (22.80 pubs/year), Cuba (8.27 pubs/year), Jamaica (6.27 pubs/year), Trinidad and Tobago (3.53 pubs/year), and Martinique (2.27 pubs/year). The high-income countries (n=10) collectively lead in publications over the 15-year period. Conclusion: ReCCaP provides an easily searchable database highlighting published work and gaps in knowledge on cancer in the Caribbean and diaspora. Citation Format: Kimberly Badal, Moesha Moore, Mikhail Thomas. The repository for Caribbean cancer publications (ReCCaP): Database development and publication trends 2004-2019 [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-001.

Background: Despite increasing utilization of patient-derived xenografts (PDXs) in early drug development, there are no agreed upon metrics for assessment of PDX growth inhibition for agents given alone or in combination. In the present study, we aim to investigate what metrics are being used in the literature, as well as among the National Cancer Institute PDX Development and Trial Centers Research Network (PDXNet) investigators. Methods: Relevant PDX literature was identified and retrieved using an information retrieval tool, RetriLite, to search for articles that met following criteria: 1) Published between 01/2018 through 12/2019; 2) Published in a journal with impact factor of 10 or above; 3) Search terms included: Cancer, PDX(s), patient derived xenograft(s), and patient-derived xenograft(s). Exclusion criteria included: 1) Brain tumors; 2) Immune-oncology/non-solid tumors; 3) Studies with no detailed information; 4) studies from PDXNet investigators. In addition, a questionnaire regarding PDX analysis practices was distributed to NCI PDXNet investigators and responses were analyzed. Results: Sixty-five studies with relevant information were included in this systematic literature review and 15 NCI PDXNet PIs from all six centers responded to the survey representing the general practice in the network. The most commonly used tumor growth assessment metric was comparisons in tumor volumes in different treatment arms, used by 33 (51%) of 65 PDX papers and 13 (87%) of 15 PDXNet investigators. Thirteen different growth metrics were reported in the PDX literature and ten different metrics were used by PDXNet investigators. PDXNet investigators were more likely to use growth metrics analogous to clinical endpoints compared to the PDX literature, including percent change of tumor volume (80% vs 17%), event-free survival (EFS: 40% vs 11%), and overall survival (33% vs 8%). PDXNet investigators were also more likely to assess objective response rate (ORR) compared to the PDX literature (60% vs 12%); several different cutoffs were used for defining response and progression. For combination therapy, most investigators and literature compared tumor volumes across treatment arms, with few looking at measures of synergy or dynamic effects and with variable utilization of other metrics such as OR and EFS. In PDX literature, of the 40 papers with combination therapies presented, at least one monotherapy control arm was missing in 7 (18%), and four (10%) only compared growth with the no treatment control arm. Conclusions: In summary, there is great variability in growth metrics used in the PDX community. To better use PDXs as preclinical models and increase the reproducibility of treatment effect on PDXs, a joint effort is needed to harmonize approaches in PDX growth assessment. Citation Format: Dali Li, Min Jin Ha, Yvonne A. Evrard, Huiqin Chen, Lisa M. McShane, Jeffrey Grover, Jing Wang, Bingliang Fang, Timothy DiPeri, Michael T. Lewis, Lawrence Rubinstein, Jack A. Roth, Jeffrey H. Chuang, James H. Doroshow, Jeffrey A. Moscow, Funda Meric-Bernstam. A systematic review of the tumor growth metrics of patient-derived xenograft (PDX) models in the literature and in NCI PDXNet centers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3009.

PubMed is the most widely used database and search-engine in biomedical and healthcare field. It has evolved more powerfully using Best Match algorithm. However, users still have several difficulties to ‘catch' their target papers in limited time, which fundamentally originates from the conventional two-dimensional ‘top-down' display method of search results. We conducted a survey for 76 medical experts (including oncologists, surgeons, gastroenterologists, psychiatrists, et al) about their behaviors and difficulties in using PubMed. The most common ‘unmet needs' of users were (1) the rank of citation counts or impact factors, (2) more three-dimensional and interactive display of search results, and (3) author rank and network. Reflecting the results above, we developed a novel PubMed visualizing program, EEEvis version 1.0 (medical and healthcare evidence visualizer), and launched it on www.EEEvis.com. The basic operating principle of EEEvis version 1.0 is to visualize the metadata of PubMed and PubTator (a web-based text mining-tool) using (1) advanced filter tools, (2) a scatter & box plot using citation counts over years, (3) an author map reflecting the ranks and networks, and (4) a reinforced search list (Table 1). All the data crawling is based on the API (application programming interface) of PubMed and PubTator. To computing and visualizing the crawled metadata, we constructed two servers; a hidden station server and an open UI (user interface) server. In the interim result of our ongoing pilot study in searching oncology-related literatures, the two quantitative factors including (1) time to ‘catch' the target paper and (2) success rate finding the required paper showed significant improvement. Other qualitative factors including (3) user convenience, (4) interactivity, and (5) willingness to use EEEvis next time showed good results. Now we are developing EEEvis version 2.0 using text-mining technology and applying multiple patents for this program. Comparison between EEEvis and PubMedProgramsEEEvisPubMedFilter sectionBy article typeYesYesBy publication yearYesYesBy citation count of paperYesNoBy impact factor of journalYesNoInteraction section using Brushing & Linking techniqueScatter plot of citation counts by yearYesNo(with box plot of citation counts by year)YesNoMap of author networkYesNoList sectionSort by best matchYesYesSort by most recentYesYesSort by citation countYesNoSort by author or journalNoYesCitation count of each paperYesNoImpact factor of each journalYesNoPubTator informationYesNoData crawlingHow to crawl results from Pubmed serverIndirect using APIDirectLimit of result numbers10,000 (best matched)NoneUser experience in searching cancer-related keywords in pilot study (ongoing)Time to display results after entering keywordsNot inferiorPromptTime from visualizing results to finding the required paperSuperior(= faster)InferiorSuccess rate of finding the required paper after visualizing the resultsSuperiorInferior Citation Format: Jong-chan Lee, Brian J. Lee, Hyunjoo Song, Changhee Park, Chan-Young Ock, Yuna Youn, Hyojae Sung, Sungjin Woo, Jaihwan Kim, Jin-Hyeok Hwang. A novel PubMed visualizer using human-computer interaction technology: EEEvis.com [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 248.

Introduction: The use of 3D models to study pancreatic ductal adenocarcinoma (PDAC) has evolved in the last years. There are several described models all of which may seem to be equally relevant. However, which of these methodologies is preferred in pancreatic cancer research has not been clarified. There is no head-to-head comparison described so far and no data to prove which may better reflect the full spectrum of a patient's tumor and exhibit disease stage-specific characteristics. Our hypothesis is that if a model is useful it should be adopted and therefore referenced in the literature. Although there may be some concerns to this approach, we tried to show the most referenced models of 3D cultures in PDAC by different methodologies. Material and Methods: We performed a PubMed search using the following mesh terms ‘pancreatic ductal organoids', ‘human pancreatic ductal cancer organoids', ‘mouse pancreatic ductal cancer organoids' and ‘pancreatic ductal cancer organoids'. Using PubMed and Web Of Science we analyzed the citation network with regards to number of citations, impact factor and where in the article was the reference included. If it was included in the material and methods section, we confirmed they used that model for the article and not for other reasons. In that way, we tried to define the use of the model based on published literature. We defined this as the MM references. Results: According to our mesh terms, we identified 4 organoid models: Skala (Pancreas, July 2016), Muthuswamy (Nature, November 2015), Kuo (Nature, July 2014) and Tuveson (Cell, January 2015). They were cited 1062 times from the date of publication to October 5, 2020. Skala's methodology had the lowest number of citations (43), while Kuo ranked third (161), followed by Muthuswamy (217) and Tuveson (641). While examining the citation network of each model, we excluded reviews and book chapters and found that Skala's citations included 19 articles, Kuo's 62, Muthuswamy's 101 and Tuveson's 348. After analyzing the MM references we found that Skala's methodology had 5, Kuo's 8, Muthuswamy's 6 and Tuveson's had 79. We then identified the papers in which the authors were part of the original contributors for the purpose of identifying how extended the use of the method was. Taking this into consideration, Skala accounted for 1 out of 5 MM references (16.7% ), Kuo for 7 out of 8 (87.5%), Muthuswamy for 2 out of 6 (33.3%) and Tuveson for 58 out of 79 (73.4%). One caveat from our work is that not every published paper includes the original methodological reference in their publication and, if that is the case, it will not be reflected in our data. Conclusion: Tuveson's methodology is widely adopted, not only by the Tuveson Lab but also by the rest of the PDAC research community. Citation Format: Mariano Ponz-Sarvise, Carmen de Carvajal. 3D systems to study pancreatic ductal adenocarcinoma (PDAC). Comparison of the most referenced models using a bibliometric approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2979.

Introduction Especially in oncology patients, Patient Reported Outcomes (PRO) play an increasingly important role to measure subjectively perceived health status and treatment effects. At the moment, paper-based surveys of PRO still predominate (pPRO); in recent years, data on patient-relevant endpoints is being increasingly collected electronically (ePRO). The aim of the study was to analyze the acceptance of an ePRO-survey tool in breast cancer patients within the PRAEGNANT multicenter trial. Furthermore, it should be considered, whether differences in response behavior between pPRO and ePRO can be identified (reliability check). Materials and Methods ePROCOM (Patient Reported Outcomes and Compliance Anaysis) was conceptualized as a monocenter, randomized, parallel-group, cross-over study. Female patients with diagnosis breast cancer aged more than 18 years were included.We randomized the patients into one of two study arms. In study arm A the patients are first asked to use the electronic, web-based tool to document the patient questionnaire (EORTC QLQ C-30 and FACT-B). Afterwards the patients were asked to fill and evaluate the paper-based questionnaires accordingly, followed by evaluation of usability, acceptance and capability. In study arm B the course varies by meaning that paper-based evaluation will be followed by the assessment of electronic data capture. Results N=110 patients with breast cancer in adjuvant or neoadjuvant situation completing the study during an outpatient visit at the University Hospitals in Tuebingen and the National Cancer Centre Heidelberg (average age: 52.4). In most patients, there were no differences in terms of acceptance between pPRO and ePRO. Only in some older patients with a lower quality of life hurdles for ePRO could be identified, because of lower acceptance rates. We could not find significant differences in response behavior between pPRO and ePRO. Discussion Because no differences in response behavior could be identified, the tool can be define as reliable possibility to measure patient reported outcomes. E-PRO surveys appear to be suitable for use in breast cancer patients. However, there is a need of support in older and more ill patients, to participate form the technical capabilities of ePRO. Citation Format: Wallwiener M, Simoes E, Hartkopf AD, Taran F-A, Keilmann L, Sickenberger N, Stevanovic S, Belleville E, Ladra C, Schneeweiss A, Wallwiener D, Brucker SY, Graf J. Reliability and acceptance of e-based survey instruments for measuring patient reported outcomes (PRO) in breast cancer patients: First results of the ePROCOM study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-11-05.

Introduction Over the last 2 decades, an increasing number of primary breast cancer (PBC) patients opted for a risk reducing contralateral mastectomy, to minimize risk of subsequent contralateral breast cancer (CBC). Therefore, accurate risk estimates of CBC are important for patient tailored counseling and decision making regarding treatment. Currently, CBC risk estimates are determined by BRCA1/2 mutation status, age at PBC diagnosis and family history. For other risk factors, results are inconclusive. We therefore aimed to quantify the association with CBC risk for patient, tumor and treatment related factors as reported in the literature. Methods Medline was searched for publications on CBC risk by one reviewer (DA). We focused on associations between CBC risk and BRCA1/2 and CHEK2*1100delC mutations, SNPs, risk-reducing salpingo-oophorectomy and various factors at PBC diagnosis: family history of breast cancer (BC), age, BMI, menopausal status, mammographic density, TNM-stage, receptor status, morphology, administered radiotherapy and adjuvant systemic treatment. Eligible papers were published in English between 01-01-1990 and 01-04-2015, investigated female patients with invasive early BC and reported relative risk (RR) estimates (i.e., hazard ratios, relative risks or odds ratios). We combined RR estimates using a random effects model. Heterogeneity was assessed using the I2 statistic. Forest plots for crude and adjusted estimates were generated stratifying for mutation status (i.e., BRCA1, BRCA2, CHEK2*1100delC), non-carriers and unselected patients (i.e., population/hospital based cohorts). Results After screening of 1,423 papers for title and abstract, 173 eligible papers were fully read, and 96 papers fulfilled the inclusion criteria. Both in the unselected group and in the BRCA1 and BRCA2 groups, administration of adjuvant endocrine therapy (vs. not), was associated with decreased CBC risk (RR, 0.62 (95% CI 0.55-0.69), 0.55 (95% CI 0.39-0.77), and 0.62 (95% CI 0.40-0.95), respectively). Adjuvant chemotherapy was associated with reduced CBC risk in unselected patients (RR 0.73; 95% CI 0.62-0.86). CBC risk was increased in unselected patients who received radiotherapy at age30 (vs. For CHEK2*1100delC mutation carriers and non-carriers, information on factors affecting CBC risk was scarce. In non-carriers, the RR for adjuvant chemotherapy was 0.60 (95% CI 0.53-0.68). Conclusions In unselected patients, adjuvant systemic treatment for PBC decreases CBC risk while a lobular morphology of PBC, high BMI, and a family history of BC increase the risk of CBC. Data is scarce for carriers of a BRCA1/2 or CHEK2*1100delC mutation and non-carriers. This review identifies prognostic factors to consider for individualized CBC risk estimation which may support medical decision making in BC patients. Citation Format: Akdeniz D, Schmidt MK, McCool D, van den Broek AJ, Hauptmann M, Seynaeve CM, Steyerberg EW, Hooning MJ. Risk of metachronous contralateral breast cancer: Systematic review and meta-analysis [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-07-05.

The SUM breast cancer cell lines were developed in the 1990s and since that time, one or more of these cell lines have been distributed to over 500 laboratories world-wide. As a result, there are currently nearly 4000 papers in the peer-reviewed literature that contain data obtained with one or more of these cell lines. In addition, over the years, our laboratory and others have developed a number of complex genomic data sets for these cell lines, most of which are unavailable to the research community. The genomic data that have been developed for the SUM lines include: copy number/gene amplification data, gene expression profiling data using multiple platforms, whole exome sequencing data with cancer specific point mutation data, proteomic profiling data, and most recently, genome-scale shRNA screening data for each of the lines. The shRNA screening data functionalizes the other genomic data sets, adding significant power to these analyses. To make these genomic data sets available to the research community, we developed the SUM Breast Cancer Cell Line Knowledge Base (www.sumlineknowledgebase.com). This web-based resource provides information about each cell line, such as information on the patient from which the line was derived, a narrative summary of each cell line with a focus on the genomic drivers that are important for each line, a bibliography of published papers using each cell line and much more. To make the genomic data accessible to all breast cancer researchers, we have developed a number of data mining tools that allow researchers to rapidly and easily identify the key functional genes and pathways operative for each cell line. The tools developed so far include: a series of KEGG Pathway Engines, an Oncogene Signature tool, a Gene Query tool, a Proteomics tool and a Functional Druggable Signature tool. The KEGG Pathway Engines allows users to map shRNA screen data or gene expression data onto any KEGG pathway for any cell line and rank order pathways based on essentialness and druggability. The Oncogene Signature tool identifies all genes in each line that are genomically altered in each line, the status of each of those genes in the shRNA screen, and the druggability of each potential oncogene. The Gene Query tool allows researchers to search for any gene and obtain data on the status of that gene in any of the cell lines. The tool also generates a rank-ordered list of the cell lines based on the essentialness of the gene in each cell line., and provides data on copy number, expression level, hit status in the shRNA screen and the potential druggability of each gene. Thus, this SUM Breast Cancer Cell Line Knowledge Base and the tools contained within this web-based resource, allow researchers using any of the SUM lines to rapidly probe the deep biology of any cell line, identify the driving genomic alterations, most important KEGG pathways, and the most effective drug strategies for each cell line line. Work currently in progress is aimed at expanding this Knowledge Base to include all breast cancer cell lines, which will make this resource useful to all breast cancer researchers who use cell lines in their work. Citation Format: Stephen Paul Ethier, Kathryn Duchinsky, Daniel Couch. The SUM breast cancer cell line knowledge base (SLKBase): A knowledge base and functional genomics platform for breast cancer cell lines [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-05-13.

What is known about the impact of PACHE can be assessed through varied evaluative methods. Describing the scope of center publications offers one type of insight. Using document review, 963 publicly accessible NIH RePORT publications across the 16 funded U54 Partnerships to Advance Cancer Health Equity (PACHE) center programs were identified. The authors read each study and determined if it they met inclusion criteria: an evidence-based study that presented quantitative or qualitative results, a statement of purpose, overview of methods, presentation of results, and a discussion or conclusion section. Position papers and duplications were excluded from this review. Using the remaining 868 publications, the authors determined the frequency of publications across programs by longevity; reported the frequency of studies focused on cancer health disparities; determined the proportion of institutions serving underserved health disparity populations, underrepresented students (ISUPS) co- and lead-authored works; and categorized the scope of studies by commonalities in their reported purposes. Findings showed that: (1) center longevity was not necessarily related to the number of publications, (2) less than 20% of studies focused on cancer health disparities (CHD), (3) ISUPU co-authors appeared in 72% of publications while lead authors were 48%, (4) 6.07% publications focused on cancer diagnosis, screening, treatment, and risk factors; 57.50% studies were mechanistic; 21.53% focused on the impact of interventions on health promotion, prevention, and quality of life; 5.62% studies were related to educational outcomes; and 9.28% studies were classified as epidemiological/survey outcomes. One of the primary purposes of PACHE centers is CHD research. Thus, we advocate increasing the frequency of CHD-focused publications. We also suggest increasing the number of ISUPU lead-authored papers. To align with the PACHE mission, we also recommend increasing the number of studies focused on cancer diagnosis, screening, treatment, and risk factors, and the impact of interventions on health promotion, prevention, and quality of life. To demonstrate the effectiveness and impact of training, increasing the number educational outcome studies is also proposed. Citation Format: Linda S. Behar-Horenstein, Max D. Horenstein, Joyce M. Richey. Gauging U54 PACHE effectiveness through an analysis of publications [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-065.

Background: The NCI added Community Outreach and Engagement (COE) requirements for NCI-designated cancer centers in 2017, including the charge of characterizing the cancer burden in the geographic area served by their center (i.e., catchment area). Doing so helps cancer centers better identify needs and areas of inequality in their populations to guide research and outreach. To accomplish this, current and comprehensive data must be gathered from multiple sources and analyzed by the COE—a task that is tedious and inefficient. In this paper we present an efficient solution, known as Cancer InFocus, to collecting and visualizing quantitative data that we have generalized for use by other cancer centers on their catchment areas. Methods: Cancer InFocus utilizes open source programming languages and modern data collection techniques to gather and transform publicly-available data from various sources for use in specific geographic contexts. Results: Cancer InFocus delivers a choice of two routes for creating interactive online mapping applications that visualize cancer incidence and mortality rates, along with relevant social determinant and risk factor variables, at various geographic levels for a defined cancer center catchment area. Conclusions: Generalized software has been produced to collect and visualize data on any set of U.S. counties, which can be automated to continue providing the most up-to-date data. Impact: Cancer InFocus provides tools for cancer centers to accomplish the critical task of maintaining current and comprehensive catchment area data. The open source format will facilitate future enhancements through user collaboration.

Cancer is one of the leading causes of human death. As metabolomics techniques become more and more widely used in cancer research, metabolites are increasingly recognized as crucial factors in both cancer diagnosis and treatment. In this study, we developed MACdb (https://ngdc.cncb.ac.cn/macdb), a curated knowledgebase to recruit the metabolic associations between metabolites and cancers. Unlike conventional data-driven resources, MACdb integrates cancer-metabolic knowledge from extensive publications, providing high quality metabolite associations and tools to support multiple research purposes. In the current implementation, MACdb has integrated 40,710 cancer-metabolite associations, covering 267 traits from 17 categories of cancers with high incidence or mortality, based entirely on manual curation from 1,127 studies reported in 462 publications (screened from 5,153 research papers). MACdb offers intuitive browsing functions to explore associations at multi-dimensions (metabolite, trait, study, and publication), and constructs knowledge graph to provide overall landscape among cancer, trait, and metabolite. Furthermore, NameToCid (map metabolite name to PubChem Cid) and Enrichment tools are developed to help users enrich the association of metabolites with various cancer types and traits. Implication: MACdb paves an informative and practical way to evaluate cancer-metabolite associations and has a great potential to help researchers identify key predictive metabolic markers in cancers.