MatchMiner: an open-source platform for cancer precision medicine

Background: Despite improved outcomes for patients with metastatic breast cancer (MBC), attributed in part to advancements in precision therapeutics, clinical trial enrollment and genomic testing are relatively underutilized in the community oncology setting. To address this need, we launched a virtual molecular and precision medicine (vMAP) clinic to improve access for patients in our community network. Here we describe the initial results from the virtual clinic initiative. Methods: In 2020, the vMAP clinic was launched to provide real-time access to precision medicine expertise through virtual, email-based consultation directed to a multidisciplinary team. As part of the service, providers contacted vMAP regarding patients with MBC at the time of initial presentation or disease progression. Upon receipt, the vMAP team (including breast medical oncologists, a breast oncology research nurse, a research assistant, and ad hoc consultation from cancer genetics and molecular pathology representatives) engaged in discussion to identify potential clinical trials with slot availability or standard of care (SOC) options and provided recommendations to the referring provider within 72 hours. Relevant patient data and vMAP referral outcomes were recorded. Providers across the community network were surveyed at project onset and after seventeen months. Results: In its first 14-month period (June 2020-July 2021), 47 cases from 16 providers across seven community oncology sites and one academic site were referred to vMAP. A majority (88.6%) of patients had undergone somatic genomic testing (tissue-based, plasma-based, or both) to inform treatment guidance. All cases were screened for available clinical trials as well as SOC options at the time of referral. The average response time to the referring provider with a finalized recommendation was 1.77 days (range 0-5). Forty cases (85.1%) had clinical trial options identified on vMAP pre-screen. Subsequently, 22 patients (46.8%) screened for vMAP recommended clinical trials with 18 (38.3%) initiating enrollment. Of the remaining patients that did not pursue clinical trial screening, 17 (36.2%) started vMAP-recommended SOC treatment, five (10.6%) pursued a different treatment, one (2.1%) was not a candidate for further treatment, and two (4.3%) opted to receive care at a non-affiliated institution, and subsequent treatment information was not available. Reasons that patients did not enroll on trials included trial ineligibility, formal clinical trial screening failure, and patient/provider preference. At project onset, network provider survey results confirmed a previously suggested demand for improvements in processes surrounding genomic testing interpretation and clinical trial enrollment. Post-referral survey results indicated vMAP recommendations and pre-screenings improved the processes surrounding interpretation of genomic testing and clinical trial screening and enrollment, with high rates of referring provider satisfaction. Conclusion: A precision medicine virtual clinic demonstrated an efficient and flexible means to offer real-time interpretation of genomic and molecular test results and identification of appropriate treatment options, including clinical trials when applicable, for patients with MBC. The service highlights an example of an academic-community collaboration model to expand precision medicine and clinical trial access for patients with metastatic breast cancer. Citation Format: Lindsey Mortensen, Jennifer C. Keenan, Elizabeth Abraham, Sarah Padden, Annie Ma, Elyssa Denault, Lianne Ryan, Arielle J. Medford, Leif Ellisen, Joel H. Schwartz, Aditya Bardia, Laura M. Spring. Virtual molecular and precision medicine (vMAP) clinic to improve access to clinical trials for patients with metastatic breast cancer: an academic-community collaboration [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 P1-08-01.

BackgroundPaediatric precision oncology aims to match therapeutic agents to driver gene targets. We investigated whether parents and patients regret participation in precision medicine trials, particularly when their hopes are unfulfilled.MethodsParents and adolescent patients completed questionnaires at trial enrolment (T0) and after receiving results (T1). Parents opted-in to an interview at T1. Bereaved parents completed a questionnaire 6-months post-bereavement (T1B). We analysed quantitative data with R and qualitative data thematically with NVivo, before integrating all data for interpretation.Results182 parents and 23 patients completed T0; 108/182 parents and 8/23 patients completed T1; 27/98 bereaved parents completed T1B; and 45/108 parents were interviewed. At enrolment, participants held concurrent hopes that precision medicine would benefit future children and their child. Participants expressed concern regarding wait-times for receipt of results. Most participants found the trial beneficial and not burdensome, including bereaved parents. Participants reported high trial satisfaction (median scores: parents: 93/100; patients: 80/100). Participants expressed few regrets (parent median scores: parents: 10/100; bereaved parents: 15/100; patient regret: 2/8 expressed minimal regret).ConclusionsEven when trial outcomes did not match their hopes, parents and patients rarely regretted participating in a childhood cancer precision medicine trial. These data are critical for integrating participants’ views into future precision medicine delivery.

Previous research shows that families find concepts underpinning childhood cancer precision medicine challenging to understand. We developed three animated videos and then evaluated these videos' acceptability, accessibility, emotional impact, and impact on participants' understanding of precision medicine. Eligible participants included adolescents and young adults with cancer (12-25years) and parents of a child (< 25years) with cancer who recently enrolled in a precision medicine trial. Participants evaluated the videos using a questionnaire containing validated and purpose-designed quantitative and qualitative items. Twenty-three parents and five patients participated. Over 70% of participants rated each video as 'just right' in length, pace, and amount of information. Almost all felt the videos provided useful information about the precision medicine process (nparents = 19/20, 95%; npatients = 4/4, 100%) and would recommend the videos to other families (nparents = 18/20, 90%; npatients = 4/4, 100%). After watching the videos, parents' perceived understanding of key precision medicine concepts increased (p ≤ 0.011 for all items, e.g. possible risks and discomforts). Similarly, watching the videos increased parents' self-rated knowledge of all precision medicine-related terms that were initially poorly understood (p ≤ 0.016 for terms including 'precision medicine' and 'germline variant'). Qualitatively, participants reported valuing the videos and provided constructive feedback to improve the concision and quality of the videos. Parents and patients responded positively to the videos about precision medicine for childhood cancer and felt they would benefit other families. The videos are a potentially useful complement to written consent information and clinical discussions to support understanding of complex precision medicine concepts.

Precision medicine programs aim to utilize novel technologies to identify personalized treatments for children with cancer. Delivering these programs requires interdisciplinary efforts, yet the many groups involved are understudied. This study explored the experiences of a broad range of professionals delivering Australia's first precision medicine trial for children with poor-prognosis cancer: the PRecISion Medicine for Children with Cancer (PRISM) national clinical trial of the Zero Childhood Cancer Program. We conducted semi-structured interviews with 85 PRISM professionals from eight professional groups, including oncologists, surgeons, clinical research associates, scientists, genetic professionals, pathologists, animal care technicians, and nurses. We analyzed interviews thematically. Professionals shared that precision medicine can add complexity to their role and result in less certain outcomes for families. Although many participants described experiencing a greater emotional impact from their work, most expressed very positive views about the impact of precision medicine on their profession and its future potential. Most reported navigating precision medicine without formal training. Each group described unique challenges involved in adapting to precision medicine in their profession. Addressing training gaps and meeting the specific needs of many professional groups involved in precision medicine will be essential to ensure the successful implementation of standard care.

Distance to Care Predicts Clinical Trial Enrollment on COG ALL Clinical Trials: A Report from the Children's Oncology Group

Precision medicine is changing the treatment of childhood cancer globally, however little is known about quality of life (QoL) in children and adolescents participating in precision medicine trials. We examined QoL among patients enrolled in PRISM, the Zero Childhood Cancer Program's precision medicine trial for high-risk childhood cancer. We assessed patient QoL via self-report (aged 12-17 years) and parent-proxy (aged 4-17 years) completion of the EQ-5D-Y. We analysed data using descriptive statistics and regression models. Patients (n = 23) and parents (n = 136) provided data after trial enrolment and following receipt of trial results and treatment recommendations (n = 8 patients, n = 84 parents). At enrolment, most patients were experiencing at least some difficulty across more than one QoL domain (81% patient self-report, 83% parent report). We did not find strong evidence of a change in QoL between timepoints, or of demographic or disease factors that predicted parent-reported patient QoL (EQ-VAS) at enrolment. There was strong evidence that receiving a treatment recommendation but not a change in cancer therapy was associated with poorer parent-reported patient QoL (EQ-VAS; Mdiff = -22.5, 95% CI: -36.5 to -8.5, p = 0.006). Future research needs to better understand the relationship between treatment decisions and QoL and would benefit from integrating assessment of QoL into routine clinical care.

Precision medicine is changing cancer care and placing new demands on oncology professionals. Precision medicine trials for high-risk childhood cancer exemplify these complexities. We assessed clinicians’ (n = 39) and scientists’ (n = 15) experiences in the first year of the PRecISion Medicine for Children with Cancer (PRISM) trial for children and adolescents with high-risk cancers, through an in-depth semi-structured interview. We thematically analysed participants’ responses regarding their professional challenges, and measured oncologists’ knowledge of genetics and confidence with somatic and germline molecular test results. Both groups described positive early experiences with PRISM but were cognisant of managing parents’ expectations. Key challenges for clinicians included understanding and communicating genomic results, balancing biopsy risks, and drug access. Most oncologists rated ‘good’ knowledge of genetics, but a minority were ‘very confident’ in interpreting (25%), explaining (34.4%) and making treatment recommendations (18.8%) based on somatic genetic test results. Challenges for scientists included greater emotional impact of their work and balancing translational outputs with academic productivity. Continued tracking of these challenges across the course of the trial, while assessing the perspectives of a wider range of stakeholders, is critical to drive the ongoing development of a workforce equipped to manage the demands of paediatric precision medicine.

Clinical Trial Inclusion of Therapy-Related Myelodysplastic Syndromes (MDS) over the Past 20 Years

Background: Increasing Black patients' participation in cancer clinical trials is important because of the population's lower survival rate. Accrual for Blacks is the lowest of all groups at 0.5-1.5%. Our study aims to increase trial participation rates among Black breast cancer patients by testing the effectiveness of a culturally tailored video intervention on the decision to participate in a clinical trial. Methods: We hypothesized that the intervention would increase clinical trial enrollment by 6 percentage points compared to our 2012 enrollment baseline of 6% (22/384). Self- identified Black patients with invasive breast cancer at 5 MedStar Hospitals watched a 15' video about clinical trials, targeting six cultural and attitudinal barriers to participation. The Attitudes and Intention to Enroll in therapeutic clinical Trials (AIET) pre-/post-/follow-up tests with 31 items was used to determine the impact of the video on three domains: actual trial enrollment; likely participation in trials; and attitudes toward trials. The pre-test was conducted at baseline; post-test immediately after video; and follow-up 7-21 days after the intervention. Participants were followed for 6 months to assess trial enrollment status. Descriptive statistics were used to describe study subjects with respect to basic characteristics; means and standard deviations for continuous variables; and frequencies and percentages for categorical variables. Repeated measures analysis of variance was used to examine whether the changes in attitudinal barriers were statistically significant over time. The primary outcome measure was the proportion of Black breast cancer patients who signed consent and/or enrolled in a therapeutic clinical trial. Results: From Mar/2014 to Sept/2015, 279 patients were approached to join INSPIRE-BrC prior to discussion about therapeutic clinical trials; 52 declined participation. 208 signed consent and 200 completed it. Average age was 59 yrs (SD=12), 75% were stage I-III; 29% were married; 85% had 1 or more children; 29% attended some college or technical school; 53% had private insurance, 31% Medicare, 16% Medicaid; and 53% had a household income &amp;lt;$40,000/yr. A total of 41 INSPIRE-BrC participants (20.5%) signed consent and 29 (14.5%) enrolled onto a therapeutic study (one-sided p=0.027 vs H0: P=0.06). Pre-video, 52% of patients expressed that it was likely they would participate in a hypothetical therapeutic clinical trial; immediately post-video, 67% (p=&amp;lt;0.001) and 7-21 days after the intervention, 64% (p=0.003). Among 31 AIET items, 25 (81%) showed statistically significant and positive change after the intervention. Specifically, trust in the doctor increased and, suspicion in trials decreased (p&amp;lt;0.001). Further, patient views on fairness for treatment of poor people and Blacks became significantly more positive (p&amp;lt;0.001). Conclusion: Study findings show that the video is a promising tool for rapid dissemination of a theory-driven, evidence-based model to enhance clinical trial accrual among Black cancer patients. The video also has the potential to positively change attitudes about clinical trial participation. The study was supported by the Breast Cancer Research Foundation. Citation Format: Swain S, Robinson BN, Newman AF, Tefera E, Herbolsheimer P, Nunes R, Gallagher C, Randolph-Jackson P, Omogbehin A, Dilawari A, Pohlmann P, Mohebtash M, Ottaviano Y, Mohapatra A, Lynce F, Mete M. Increasing participation in research - breast cancer (Inspire-BrC) [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 P3-10-02.

Precision Medicine has major implications not only for clinical practice but also for drug development and clinical trials. The implementation and conduct of a precision medicine clinical trial involves a complex coordination between multiple teams including clinical staff, laboratory staff, pharmacies, biostatisticians, regulatory experts, and bioinformatics. This real-time coordination offers an opportunity for advanced informatics solutions to facilitate the conduct of the clinical trial. This chapter will present an overview of how clinical trials within oncology are adapting to the precision medicine framework. Oncology provides a focused area where we have numerous examples of precision medicine trials, but most of the informatics solutions readily apply to other clinical domains. Following a description of the various clinical trial designs, we present a focused evaluation of the NCI-MPACT clinical trial and the GeneMed informatics system that was developed for the study.

53 Background: Increasing black patients’ participation in cancer clinical trials is particularly important because of the population’s lower survival rate. Accrual to clinical trials remains low among the general population (1 to 3%), with recruitment of blacks the lowest of all groups at 0.5 to 1.5%. Clinical trials are key to developing new methods to prevent, detect, and treat cancer. INSPIRE-BrC aims to increase trial participation rates among black patients with breast cancer and examine the relationship between the intervention and attitudes/beliefs on the decision to participate. Methods: A sample size of 123 black patients with breast cancer at five MedStar sites will view a 15 minute, culturally tailored video about clinical trials, which targets six cultural and attitudinal barriers to participation. A pre-test/post-test method is used to determine the impact of the video on three variables — likely participation in therapeutic clinical trials; attitudes toward therapeutic clinical trials (assessed based on the 6 barriers); and actual trial enrollment. Expected Findings: We hypothesize that the intervention will increase clinical trial enrollment compared to our 2012 clinical trial enrollment baseline rate of 6% (22/384) for black patients with breast cancer in five MedStar hospitals. The primary outcome measure is the proportion of black patients with breast cancer who agree to participate in a therapeutic clinical trial among those who sign consent to INSPIRE-BrC. Study findings have the potential to increase patient recruitment as a promising tool for rapid dissemination of a theory-driven, evidence-based model to enhance clinical trial accrual among black patients with cancer. [Table: see text]

ABSTRACTIntroduction: The National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) is a multicenter phase II tissue agnostic trial with 39 treatment arms, that matches a targeted drug to an actionable genetic alteration identified by next-generation sequencing (NGS). It is unique in use of a bioinformatics tool MATCHBox to make patient treatment assignments. The purpose of this review is to offer an update on the current status of NCI-MATCH, and also to discuss the impact of this precision medicine trial on future studies.Areas covered: This review discusses how NCI-MATCH has evolved over time to address the challenges in enrollment as well as to better answer the needs of the wider cancer community. The interim results from the available arms are described, together with a discussion on the future direction of NCI-MATCH.Expert opinion: The NCI-MATCH is generating a unique genetic mutation landscape of relapsed/refractory malignancies, on top of which the future of precision medicine will be built upon. Real-time updates to public databases with new genetic alterations can further optimize treatment assignments for cancer patients. Formation of more definitive trials can study any promising treatments discovered.

&lt;div&gt;Abstract&lt;p&gt;Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers.&lt;/p&gt;Significance:&lt;p&gt;This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer.&lt;/p&gt;&lt;p&gt;&lt;i&gt;&lt;a href="https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-21-1498" target="_blank"&gt;See related commentary by Letai, p. 290&lt;/a&gt;.&lt;/i&gt;&lt;/p&gt;&lt;p&gt;&lt;i&gt;&lt;a href="https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-12-2-ITI" target="_blank"&gt;This article is highlighted in the In This Issue feature, p. 275&lt;/a&gt;&lt;/i&gt;&lt;/p&gt;&lt;/div&gt;

BackgroundTo address the heterogeneity of response to therapies, the oncology field is moving toward precision medicine (PM), with therapy tailored to a patient‘s disease. Biomarker assessment is now critical when...

3073 Background: Widespread integration of systematized next generation sequencing (NGS)-based precision oncology is hindered by numerous barriers. Hence, we developed the Strata trial (NCT03061305), a screening protocol to determine the impact of scaled precision oncology. Methods: We implemented no-cost NGS on formalin fixed paraffin embedded (FFPE) clinical samples for all patients with advanced tumors, a common portfolio of partnered therapeutic clinical trials, and robust infrastructure development across the Strata Precision Oncology Network. Results: Across the network of 17 centers, specimens from 8673/9222 (94%) patients were successfully tested in the Strata CLIA/CAP/NCI-MATCH accredited laboratory using comprehensive amplicon-based DNA and RNA NGS. Patients were tested with one of three StrataNGS test versions; the most recent panel assesses all classes of actionable alterations (mutations, copy number alterations, gene fusions, microsatellite instability, tumor mutation burden and PD-L1 expression). Median surface area of received FFPE tumor samples was 25mm2 (interquartile range 9-95mm2), and the median turnaround time from sample receipt to report was 6 business days. 2577 (27.9%) patients had highly actionable alterations, defined as alterations associated with within-cancer type FDA approved or NCCN guideline recommended therapies (1072 patients), NCI-MATCH trial arms (1467 patients), Strata-partnered therapeutic trials (327 patients), or specific alteration-matched FDA approved therapies in patients with cancers of unknown primary (71 patients). Of the 1467 patients matched to an NCI-MATCH trial arm, 15 enrolled. Of the 327 patients matched to one of nine Strata-partnered clinical trials, 77 (24%) were screen failures, while 250 (76%) have either enrolled or are being actively followed for enrollment upon progression. Conclusions: Through streamlined consent methods, electronic medical record queries, and high throughput laboratory testing at no cost to patients, we demonstrate that scaled precision oncology is feasible across a diverse network of healthcare systems when paired with access to relevant clinical trials. Clinical trial information: NCT03061305.