Widespread, comprehensive sequencing of patient tumors has facilitated the usage of precision medicine (PM) drugs to target specific genomic alterations. Therapeutic clinical trials are necessary to test new PM drugs to advance precision medicine, however, the abundance of patient sequencing data coupled with complex clinical trial eligibility has made it challenging to match patients to PM trials. To facilitate enrollment onto PM trials, we developed MatchMiner, an open-source platform to computationally match genomically profiled cancer patients to PM trials. Here, we describe MatchMiner’s capabilities, outline its deployment at Dana-Farber Cancer Institute (DFCI), and characterize its impact on PM trial enrollment. MatchMiner’s primary goals are to facilitate PM trial options for all patients and accelerate trial enrollment onto PM trials. MatchMiner can help clinicians find trial options for an individual patient or provide trial teams with candidate patients matching their trial’s eligibility criteria. From March 2016 through March 2021, we curated 354 PM trials containing a broad range of genomic and clinical eligibility criteria and MatchMiner facilitated 166 trial consents (MatchMiner consents, MMC) for 159 patients. To quantify MatchMiner’s impact on trial consent, we measured time from genomic sequencing report date to trial consent date for the 166 MMC compared to trial consents not facilitated by MatchMiner (non-MMC). We found MMC consented to trials 55 days (22%) earlier than non-MMC. MatchMiner has enabled our clinicians to match patients to PM trials and accelerated the trial enrollment process.

PURPOSE With the growing number of available targeted therapeutics and molecular biomarkers, the optimal care of patients with cancer now depends on a comprehensive understanding of the rapidly evolving landscape of precision oncology, which can be challenging for oncologists to navigate alone. METHODS We developed and implemented a precision oncology decision support system, GI TARGET, (Gastrointestinal Treatment Assistance Regarding Genomic Evaluation of Tumors) within the Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute. With a multidisciplinary team, we systematically reviewed tumor molecular profiling for GI tumors and provided molecularly informed clinical recommendations, which included identifying appropriate clinical trials aided by the computational matching platform MatchMiner, suggesting targeted therapy options on or off the US Food and Drug Administration–approved label, and consideration of additional or orthogonal molecular testing. RESULTS We reviewed genomic data and provided clinical recommendations for 506 patients with GI cancer who underwent tumor molecular profiling between January and June 2019 and determined follow-up using the electronic health record. Summary reports were provided to 19 medical oncologists for patients with colorectal (n = 198, 39%), pancreatic (n = 124, 24%), esophagogastric (n = 67, 13%), biliary (n = 40, 8%), and other GI cancers. We recommended ≥ 1 precision medicine clinical trial for 80% (406 of 506) of patients, leading to 24 enrollments. We recommended on-label and off-label targeted therapies for 6% (28 of 506) and 25% (125 of 506) of patients, respectively. Recommendations for additional or orthogonal testing were made for 42% (211 of 506) of patients. CONCLUSION The integration of precision medicine in routine cancer care through a dedicated multidisciplinary molecular tumor board is scalable and sustainable, and implementation of precision oncology recommendations has clinical utility for patients with cancer.

With the advent of next generation sequencing in cancer care, patients' tumors can be genomically profiled and specific genetic alterations can be targeted with precision medicine drugs. However, the abundance of patient sequencing data coupled with complex clinical trial eligibility has made it challenging to match patients to precision medicine trials. To facilitate interpretation of complex tumor sequencing data and clinical trial genomic eligibility criteria, we developed MatchMiner, an open-source platform to computationally match cancer patients to precision medicine clinical trials. MatchMiner supports two distinct workflows: (1) patient-centric mode, in which an oncologist can find clinical trial matches for a specific patient, and (2) trial-centric mode, in which a clinical trial investigator can identify and recruit patients for a specific trial. In MatchMiner at DFCI, there are currently 330+ precision medicine trials and genomic and genomic and clinical data from 39,000+ patients. Although MatchMiner has been operational at Dana-Farber Cancer Institute since early 2017, its impact on patient care has not yet been extensively studied. In this study, we analyzed temporal trends of 170 MatchMiner-driven trial enrollments. We compared these 170 MatchMiner-driven trial enrollments to non-MatchMiner-driven trial enrollments to determine how MatchMiner has impacted patient enrollments. To compare MatchMiner-driven trial enrollments to non-MatchMiner-driven enrollments, we limited the non-MatchMiner group by choosing patients who enrolled on the same trials. We also ensured that all patients in both enrollment groups had a genomic report present in MatchMiner before their consent date. We then analyzed temporal trends between genomic report dates, patient consent and on-study dates, and patient views in MatchMiner. MatchMiner-driven enrollments had a significant decrease in time from genomic report date to consent date compared to non-MatchMiner-driven enrollments. Thus, clinical use of MatchMiner decreased time to enroll in a precision medicine study, and suggests that use of precision medicine trial matching tools such as MatchMiner are important for the future of patient care. The MatchMiner open-source software package is available through GitHub (https://github.com/dfci/matchminer). We are committed to supporting MatchMiner as an open-source software; to our knowledge, at least five cancer centers are implementing MatchMiner. Citation Format: Harry Klein, Tali Mazor, Priti Kumari, James Lindsay, Andrea Ovalle, Ethan Siegel, Pavel Trukhanov, Joyce Yu, Michael Hassett, Ethan Cerami. MatchMiner: An open-source computational platform that accelerates patient enrollment on to precision medicine trials [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 1198.

With the advent of next generation sequencing in cancer care, patients’ tumors can be genomically profiled and specific genetic alterations can be targeted with precision medicine drugs. However, the abundance of patient sequencing data coupled with complex clinical trial eligibility has made it challenging to match patients to precision medicine trials. To facilitate interpretation of complex tumor sequencing data and clinical trial genomic eligibility criteria, we developed MatchMiner, an open-source platform to computationally match cancer patients to precision medicine clinical trials. MatchMiner has several modes of clinical use: (1) patient-centric, where clinicians look up trial matches for their patient, (2) trial-centric, where clinical trial investigators identify patients for their clinical trials, and (3) trial search, where clinicians identify available trials based on any criteria, including external genomic reports. To support users in all three modes, MatchMiner also displays full genomic reports for patients and detailed trial information in user-friendly formats. MatchMiner trial matching is performed via the MatchEngine, an algorithm that computes matches based on patient genomic and clinical data and trial eligibility criteria. The MatchEngine accepts many different data inputs for patient-trial matching, and is easily customized to work with data available at any institution. At Dana-Farber Cancer Institute (DFCI), MatchMiner supports the following data: 1) patient-specific genomic sequencing data, including mutations, copy number alterations, structural variants, tumor mutational burden and mutational signatures including mismatch repair deficiency or microsatellite instability, 2) patient-specific clinical data, including primary cancer type, gender, age, and vital status, and 3) trial eligibility criteria including genomic targets, cancer type, and age. Unique to MatchMiner, each trial’s eligibility criteria is encoded in clinical trial markup language (CTML), a structured format that encodes detailed information about a trial and utilizes boolean logic to encode inclusion and exclusion criteria. Although MatchMiner has been operational at DFCI since early 2017, its impact on patient care has not yet been extensively studied. Thus far, MatchMiner has facilitated 181 precision medicine trial consents (MatchMiner consents, MMC) for 159 patients. To quantify MatchMiner’s impact on trial consent, we retrospectively measured time from genomic sequencing report date to trial consent date for a subset of the 181 MMC (166 MMC). We compared time to trial consent date for the 166 MMC to a group of 353 consents for the same trials not facilitated by MatchMiner (non-MatchMiner consents, non-MMC). MMC consented to trials 22% faster (P=0.004, median=195 days, IQR=85-34) than non-MMC (median=250 days; IQR=99-491). Thus, clinical use of MatchMiner decreased time to enroll in a precision medicine study, and suggests that use of precision medicine trial matching tools such as MatchMiner are important for the future of patient care. Citation Format: Harry Klein, Tali Mazor, Priti Kumari, James Lindsay, Andrea Ovalle, Pavel Trukhanov, Joyce Yu, Michael Hassett, Ethan Cerami. MatchMiner: An open-source platform for cancer precision medicine [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P160.

The paper presents a mechanical and mathematical model for estimating the wear of rails in the form of a generalized indicator called the wear factor, which includes the total relative sliding caused by turning the truck when entering the curve and rotating the wheel. The wear factor also includes the normal pressure at the point of contact between the wheel flange and rail, the contact area, the friction coefficient, and the coefficient that takes into account the wobble of wheel sets.