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Aim: Stakeholder engagement is central to comparative effectiveness research yet there are gaps in definitions of success. We used a framework developed by Lavallee et al. defining effective engagement criteria to evaluate stakeholder engagement during a pragmatic cluster-randomized trial. Methods: Semi-structured interviews were developed from the framework and completed to learn about members' experiences. Interviews were analyzed in a deductive approach for themes related to the effective engagement criteria. Results: Thirteen members participated and described: respect for ideas, time to achieve consensus, access to information and continuous feedback as areas of effective engagement. The primary criticism was lack of diversity. Discussion: Feedback was positive, particularly among themes of respect, trust and competence, and led to development of a list of best practices for engagement. The framework was successful for evaluating engagement. Conclusion: Standardized frameworks allow studies to formally evaluate their stakeholder engagement approach and develop best practices for future research.

PURPOSE: The discovery of driver oncogenes, such as ROS1, has led to the development of targeted therapies. Despite clinical advancements, gaps remain in our understanding of characteristics of patients with ROS1-positive ( ROS1+) cancers. The purpose of this study was to comprehensively assess demographic, clinical, and environmental characteristics associated with ROS1+ cancers worldwide. METHODS: In collaboration with a panel of patients with ROS1+ cancer, we designed and conducted a 204-question online assessment regarding the demographic, clinical, and environmental factors of patients with ROS1+ cancers. We invited patients with ROS1+ cancers to participate in the study from May 2016 to December 2018. RESULTS: A total of 277 patients from 18 countries worldwide responded and completed at least 90% of the survey. The majority of respondents were female (n = 191; 69%), non-Hispanic white (n = 202; 73%), never-smokers (n = 180/240; 75%). Most were diagnosed with lung cancer (n = 261/277; 94%) and stage IV disease (n = 201/277; 76%). The majority received chemotherapy in first (n = 137/199; 69%) and second (n = 103/199; 52%) lines of therapy. For patients diagnosed with lung cancer after the availability of crizotinib (n = 199), only a minority (n = 55/199; 28%) reported receiving crizotinib in the first line of therapy. CONCLUSION: This study is the first global, patient-designed approach, to our knowledge, to comprehensively assess demographic, clinical, and environmental characteristics associated with ROS1+ cancers. Future efforts include assessing these characteristics as well as patient-reported outcomes and treatment responses longitudinally.

Comprehensive genomic profiling (CGP) of circulating tumor DNA (ctDNA) provides an opportunity to noninvasively monitor a patient’s tumor burden via liquid biopsy. Liquid biopsies can assess a patient’s mutational landscape through time and provide information on treatment response and relapse. It has become increasingly common to have paired genomic data analysis between liquid and tissue biopsies from the same patient. However, the impact of clinical, temporal, and biologic factors on percentage of positive agreement (PPA) of variant detection between these biopsies is unclear. For our study, we leveraged two databases containing CGP data from paired liquid and tissue biopsy specimens tested by Foundation Medicine (FMI): the FMI database (>1700 paired samples) and the Flatiron Health-Foundation Medicine Clinico-Genomic Database (CGDB). The CGDB is a subset of the FMI database linked with the Flatiron Health nationwide de-identified EHR-derived database, which includes demographic, treatment, and clinical outcomes information (>500 paired samples). We report pan-solid tumor and per-indication prevalence and PPA for variants commonly assayed in both liquid and tissue tests. We found that PPA depended on the tumor DNA concentration in plasma and tissue biopsies, as well as the amount of time between tests. We also investigated the effect of treatments administered in the time between liquid and tissue tests on the detected variants and observed some well-described resistance alterations at a higher frequency in liquid samples, including a higher prevalence of ESR1 point mutations in breast cancer, more EGFR T790M alterations in lung cancer, and frequent KRAS Q61H alterations in colorectal cancer. Liquid biopsies can also contain DNA shed from multiple metastatic sites. We observed evidence of this in the form of polyclonal resistance alterations, which may also account for differences in PPA over time. Our findings indicate that while PPA is generally high between samples, it may be influenced by factors such as intervening therapies, resistance, therapy efficacy, and polyclonality of liquid samples. Citation Format: Zoe June F. Assaf, Smruthy Sivakumar, Dexter X. Jin, Sophia L. Maund, Svetlana Lyalina, Guneet Walia, Ethan S. Sokol, Sally E. Trabucco. Pan-solid tumor comparison of variant detection in paired liquid and tissue biopsies [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A17.

TPS2087 Background: Making personalized diagnostics and treatments a reality for every cancer patient necessitates comprehensively capturing the patient journey. Real-world data has shown promise for the future of clinical research and advancing precision medicine. However, certain limitations exist such as data quality management as well as bias and confounding factors associated with retrospective analyses. We present a multi-stakeholder platform to prospectively collect and link real-world clinico-genomic, imaging, and outcomes data to longitudinal blood genomic profiling for lung cancer. Methods: This study is enrolling approximately 1000 patients with metastatic non-small cell lung cancer or extensive-stage small cell lung cancer who will initiate standard-of-care systemic anti-neoplastic treatment, regardless of line of therapy, at 20 community oncology and academic practices within the Flatiron Health network. Relevant clinical data points from both structured and unstructured fields will be collected through the electronic health records via technology-enabled abstraction, eliminating the need for case report forms. Digital pathology and clinical images at standard-of-care visits will be collected. Blood samples for circulating tumor DNA (ctDNA) profiling using FoundationOne Liquid will be collected at three timepoints: enrollment, first tumor assessment, and end of treatment. Tumor tissue samples may be submitted at baseline for genomic profiling using FoundationOne CDx. Overall survival follow-up will occur until death, withdrawal of consent, loss to follow-up, or end of study. The objectives are to evaluate 1) the feasibility of building a scalable, prospective platform and 2) the associations between ctDNA and real-world clinical outcomes, including overall survival. Enrollment is ongoing. Clinical trial information: NCT04180176.

Background The Fred Hutchinson Cancer Research Center has engaged an External Stakeholder Advisory Group (ESAG) in the planning and implementation of the TrACER Study (S1415CD), a five-year pragmatic clinical trial assessing the effectiveness of a guideline-based colony stimulating factor standing order intervention. The trial is being conducted by SWOG through the National Cancer Institute Community Oncology Research Program in 45 clinics. The ESAG includes ten patient partners, two payers, two pharmacists, two guideline experts, four providers and one medical ethicist. This manuscript describes the ESAG’s role and impact on the trial. Methods During early trial development, the research team assembled the ESAG to inform plans for each phase of the trial. ESAG members provide feedback and engage in problem solving to improve trial implementation. Each year, members participate in one in-person meeting, web conferences and targeted email discussion. Additionally, they complete a survey that assesses their satisfaction with communication and collaboration. The research team collected and reviewed stakeholder input from 2014 to 2018 for impact on the trial. Results The ESAG has informed trial design, implementation and dissemination planning. The group advised the trial’s endpoints, regimen list and development of cohort and usual care arms. Based on ESAG input, the research team enhanced patient surveys and added pharmacy-related questions to the component application to assess order entry systems. ESAG patient partners collaborated with the research team to develop a patient brochure and study summary for clinic staff. In addition to identifying recruitment strategies and patient-oriented platforms for publicly sharing results, ESAG members participated as co-authors on this manuscript and a conference poster presentation highlighting stakeholder influence on the trial. The annual satisfaction survey results suggest that ESAG members were satisfied with the methods, frequency and target areas of their engagement in the trial during project years 1–3. Conclusions Diverse stakeholder engagement has been essential in optimizing the design, implementation and planned dissemination of the TrACER Study. The lessons described in the manuscript may assist others to effectively partner with stakeholders on clinical research.

Prostate Cancer Foundation (PCF) convened its 19th Annual Scientific Retreat October 25–27, 2012, in Carlsbad, CA. Each year, this event brings together diverse researchers in a collaborative forum to present and discuss new and largely unpublished findings for prostate cancer diagnosis, prognosis, and treatment and defines the challenges to ending this disease as a threat to life and well-being. Several themes resonated at the multidisciplinary meeting, notably (i) the roles of field cancerization, tumor microenvironment, epithelial plasticity, signal transduction pathways in cancer progression, and disease resistance; (ii) intratumoral heterogeneity and consequences for precision medicine; (iii) resistance mechanisms to androgen axis inhibitors; and (iv) advances in molecular imaging and therapeutics for better detection and treatment. Cancer Res; 73(16); 4988–91. ©2013 AACR.

223 Background: We have engaged 10 patient partners in the development and implementation of S1415CD, a five-year pragmatic clinical trial currently in year 3 assessing the effectiveness of a guideline-based colony stimulating factor standing order intervention (NCT02728596). Patient partners serve as part of a 21-person External Stakeholder Advisory Group (ESAG), which also includes providers, payers and guidelines experts. This abstract explores the influence of patient partners on the design, tools and implementation of S1415CD Methods: Patient partners advise the study team on protocol development, patient-facing materials and implementation challenges over four teleconferences each year, annual in-person meetings and targeted email communication. All patient partner input from 2014-2017 was tracked, collected and reviewed for impact on the trial. Results: Input from patient partners led to the refinement of the study’s patient-reported outcome (PRO) survey questions, the creation of a highly utilized patient brochure, and the formation of talking points for clinic staff to help explain the study. Patient partners in conjunction with high performing sites helped develop strategies for sites with lower patient accrual to optimize the approach and consent of study participants. Conclusions: The sustained engagement of patient partners in S1415CD ensured patient-centeredness in trial design and guided the development of PRO surveys and relevant, high quality patient-facing materials. Drawing on experiential knowledge and insights from their roles as caregivers and advocates, patient partners provided valuable feedback that influenced patient approach and engagement in the study. Embedding patient partners in the research continuum has catalyzed critical discussions and problem solving among the patient partners and study team, which has led to patient-centered solutions to study challenges. Clinical trial information: NCT02728596.

Background: Genomic fusions between ROS proto-oncogene 1 receptor tyrosine kinase (ROS1) and more than 20 genes drive many types of cancer. Only a handful of ROS1-positive (ROS1+) cancer models exist to use in research and developing new treatments. Few research facilities encounter ROS1+ patients–the incidence of ROS1+ cancer is only 1% to 2% in non-small cell lung cancer (NSCLC) and ROS1 testing is rarely done in other cancers. To address this, a group of ROS1+ patients and caregivers (“the ROS1ders") collaborated with advocacy organizations, researchers and industry to form the Global ROS1 Initiative. Methods: The ROS1ders and partners informed patients, caregivers, and clinicians of the initiative through social media, patient blogs, websites, distribution of fliers in several languages at cancer conferences, and contacts with their clinicians. The ROS1der online community shared ROS1+ information about treatment options and side effects, expert clinicians, clinical trials, research and general support. An epidemiologic survey captured data about ROS1 patient histories and treatments. When a member in the ROS1der community shared news of an upcoming surgery, biopsy or thoracentesis, a ROS1der leader told them of an opportunity to donate excess fresh specimens to create cancer models. Tumor samples and resulting cell lines underwent drug testing and sequencing for mechanisms of resistance. Results: The ROS1ders members include 166 patients (more than twice the largest ROS1 clinical trial cohort to date) from 16 countries representing 6 types of ROS1+ cancer. Four attempted fresh specimen donations resulted in 2 new ROS1+ cells lines, CUTO27 (CD74-ROS1) and CUTO28 (TPM3-ROS1). These cell lines have already been distributed to academic and industry partners to increase the value of these rare resources. The ROS1ders shared study results within their online group. The Initiative is now working to continue the longitudinal epidemiologic survey and create clinical studies that will generate ROS1+ cell lines and/or patient-derived xenograft (PDX) mouse models. We will conduct genomic analysis of the models to determine the presence of resistance mutations as well as ROS1 pairing partner genes. The resultant renewable tissue resources of PDX models and cell lines, when linked to the clinically annotated genomic database, will be broadly shared to help clinical and translational research understand mechanisms of response and resistance to therapies, and assist in drug development. Conclusions: This project demonstrates that partnerships between patient-caregiver groups, advocacy groups, researchers and industry, combined with social media outreach, can increase the available oncogene-driven patient data, specimens, and cancer models in small, geographically distributed patient populations. Citation Format: Janet Freeman-Daily, Lisa Goldman, Tori Tomalia, The ROS1ders, Christine M. Lovly, Manali I. Patel, Alice T. Shaw, Bonne J. Addario, Guneet Walia, Steven W. Young, Robert C. Doebele. The Global ROS1 Initiative: A patient-researcher partnership generating open-source, oncogene-driven cancer models and data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4766.

e20506Background: Immune checkpoint inhibitors have generated excitement for their ability to significantly prolong survival in cancers with poor prognoses. Success in slowing disease progression c...

e20552Background: CT scans have been shown to detect lung cancer, but suffer from high false positive rates. Approaches in artificial intelligence allow radiologists to interpret scans more precise...

INTRODUCTION The Prouts Neck Meetings on Prostate Cancer began in 1985 through the efforts of the Organ Systems Branch of the National Cancer Institute to stimulate new research and focused around specific questions in prostate tumorigenesis and therapy. METHODS These meetings were think tanks, composed of around 75 individuals, and divided equally between young investigators and senior investigators. Over the years, many new concepts related to prostate cancer resulted from these meetings and the prostate cancer community has sorely missed them since the last one in 2007. RESULTS We report here the first of a new series of meetings. The 2013 meeting focused on defining how the field of treatment for metastatic prostate cancer needs to evolve to impact survival and was entitled: “Beyond AR: New Approaches to Treating Metastatic Prostate Cancer.” As castrate resistant prostate cancers escape second generation anti-androgen agents, three phenotypes/genotypes of CRPC appear to be increasing in prevalence and remain resistant to treatment: NeuroEndocrine Prostate Cancer, Persistent AR—Dependent Prostate Cancer, and Androgen Receptor Pathway Independent Prostate Cancer. DISCUSSION It is clear that new treatment paradigms need to be developed for this diverse group of diseases. The Prouts Neck 2013 Meeting on Prostate Cancer helped to frame the current state of the field and jumpstart ideas for new avenues of treatment. Prostate 74:314–320, 2014. © 2013 Wiley Periodicals, Inc.

Being vastly different from the human counterpart, we suggest that the last enzyme of the Mycobacterium tuberculosis Coenzyme A biosynthetic pathway, dephosphocoenzyme A kinase (CoaE) could be a good anti-tubercular target. Here we describe detailed investigations into the regulatory features of the enzyme, affected via two mechanisms. Enzymatic activity is regulated by CTP which strongly binds the enzyme at a site overlapping that of the leading substrate, dephosphocoenzyme A (DCoA), thereby obscuring the binding site and limiting catalysis. The organism has evolved a second layer of regulation by employing a dynamic equilibrium between the trimeric and monomeric forms of CoaE as a means of regulating the effective concentration of active enzyme. We show that the monomer is the active form of the enzyme and the interplay between the regulator, CTP and the substrate, DCoA, affects enzymatic activity. Detailed kinetic data have been corroborated by size exclusion chromatography, dynamic light scattering, glutaraldehyde crosslinking, limited proteolysis and fluorescence investigations on the enzyme all of which corroborate the effects of the ligands on the enzyme oligomeric status and activity. Cysteine mutagenesis and the effects of reducing agents on mycobacterial CoaE oligomerization further validate that the latter is not cysteine-mediated or reduction-sensitive. These studies thus shed light on the novel regulatory features employed to regulate metabolite flow through the last step of a critical biosynthetic pathway by keeping the latter catalytically dormant till the need arises, the transition to the active form affected by a delicate crosstalk between an essential cellular metabolite (CTP) and the precursor to the pathway end-product (DCoA).

There is a lot to learn from transnational research collaboration, and the Prostate Cancer Foundation (PCF) is dedicated to building bridges around the world to address complex scientific and clinical issues related to the development of improved diagnostics and therapeutics for metastatic prostate cancer. With the goal of improving patient care for men with prostate cancer globally, the multidisciplinary Sixth Annual Forum of Prostate Disease was convened during 8–9 June 2012 in Shanghai, China. This conference provided an opportunity for scientists and clinicians from major medical centers in the United States and China to share data and forge new professional relationships. This special issue of the AJA provides an overview of the major presentations at the FPD, which highlighted prostate cancer biology, genetics, new clinical therapies, imaging technologies and the biotechnology of new diagnostic tests capable of identifying patients destined for unfavorable outcomes.