Harmonization of cancer variant representation, efficient communication, and free distribution of clinical variant-associated knowledge are central problems that arise with increased usage of clinical next-generation sequencing. The Clinical Genome Resource (ClinGen) Somatic Working Group (WG) developed a minimal variant level data (MVLD) representation of cancer variants, and has an ongoing collaboration with Clinical Interpretations of Variants in Cancer (CIViC), an open-source platform supporting crowdsourced and expert-moderated cancer variant curation. Harmonization between MVLD and CIViC variant formats was assessed by formal field-by-field analysis. Adjustments to the CIViC format were made to harmonize with MVLD and support ClinGen Somatic WG curation activities, including four new features in CIViC: (1) introduction of an assertions feature for clinical variant assessment following the Association of Molecular Pathologists (AMP) guidelines, (2) group-level curation tracking for organizations, enabling member transparency, and curation effort summaries, (3) introduction of ClinGen Allele Registry IDs to CIViC, and (4) mapping of CIViC assertions into ClinVar submission with automated submissions. A generalizable workflow utilizing MVLD and new CIViC features is outlined for use by ClinGen Somatic WG task teams for curation and submission to ClinVar, and provides a model for promoting harmonization of cancer variant representation and efficient distribution of this information.

To truly achieve personalized medicine in oncology, it is critical to catalog and curate cancer sequence variants for their clinical relevance. The Somatic Working Group (WG) of the Clinical Genome Resource (ClinGen), in cooperation with ClinVar and multiple cancer variant curation stakeholders, has developed a consensus set of minimal variant level data (MVLD). MVLD is a framework of standardized data elements to curate cancer variants for clinical utility. With implementation of MVLD standards, and in a working partnership with ClinVar, we aim to streamline the somatic variant curation efforts in the community and reduce redundancy and time burden for the interpretation of cancer variants in clinical practice.

The My Cancer Genome (MCG) knowledgebase and resulting website were launched in 2011 with the purpose of guiding clinicians in the application of genomic testing results for treatment of patients with cancer. Both knowledgebase and website were originally developed using a wiki-style approach that relied on manual evidence curation and synthesis of that evidence into cancer-related biomarker, disease, and pathway pages on the website that summarized the literature for a clinical audience. This approach required significant time investment for each page, which limited website scalability as the field advanced. To address this challenge, we designed and used an assertion-based data model that allows the knowledgebase and website to expand with the field of precision oncology.

In this work, we present a conceptual framework to support clinical trial optimization and enrollment workflows and review the current state, limitations, and future trends in this space. This framework includes knowledge representation of clinical trials, clinical trial optimization, clinical trial design, enrollment workflows for prospective clinical trial matching, waitlist management, and, finally, evaluation strategies for assessing improvement.

In the last 3-5 years, there has been a rapid increase in clinical use of next generation sequencing (NGS) based cancer molecular diagnostic (MolDx) testing to develop better treatment plans with targeted therapies. To truly achieve precision oncology, it is critical to catalog cancer sequence variants from MolDx testing for their clinical relevance along with treatment information and patient outcomes, and to do so in a way that supports large-scale data aggregation and new hypothesis generation. Through the NIH-funded Clinical Genome Resource (ClinGen), in collaboration with NLM's ClinVar database and >50 academic and industry based cancer research organizations, a Minimal Variant Level Data (MVLD) framework to standardize reporting and interpretation of drug associated alterations was developed. Methodological and technology development to standardize and map MolDx data to the MVLD standard are presented here. Also described is a novel community engagement effort through disease-focused taskforces to provide usecases for technology development.

The field of oncology is expanding rapidly. New trials are opening as an increasing number of therapeutic agents are being investigated before they can become approved therapies. Aggregate views of these data, particularly data associated with diseases, biomarkers, and drugs, can be helpful in understanding the trends in current research as well as existing gaps in cancer care.

As clinical trials evolve in complexity, clinical trial data models that can capture relevant trial data in meaningful, structured annotations and computable forms are needed to support accrual.

We describe the clinical and genomic landscape of the non-small cell lung cancer (NSCLC) cohort of the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) Biopharma Collaborative (BPC).