Genomic Oncology Research Articles

ONCOLINER: A new solution for monitoring, improving, and harmonizing somatic variant calling across genomic oncology centers

The characterization of somatic genomic variation associated with the biology of tumors is fundamental for cancer research and personalized medicine, as it guides the reliability and impact of cancer studies and genomic-based decisions in clinical oncology. However, the quality and scope of tumor genome analysis across cancer research centers and hospitals are currently highly heterogeneous, limiting the consistency of tumor diagnoses across hospitals and the possibilities of data sharing and data integration across studies. With the aim of providing users with actionable and personalized recommendations for the overall enhancement and harmonization of somatic variant identification across research and clinical environments, we have developed ONCOLINER. Using specifically designed mosaic and tumorized genomes for the analysis of recall and precision across somatic SNVs, insertions or deletions (indels), and structural variants (SVs), we demonstrate that ONCOLINER is capable of improving and harmonizing genome analysis across three state-of-the-art variant discovery pipelines in genomic oncology.

Histology agnosticism: Infra-molecularizing disease?

The term “molecularization” has been used by historians and sociologists of science to describe the transition from an anatomic view of the body to a submicroscopic one, where health and illness, indeed life itself, are increasingly defined in terms of an individual’s “genetic landscape.” Here we introduce the notion of the infra-molecular as a way of extending and nuancing the molecularization trope as it applies to the domain of (post)genomic oncology. In particular we look at how infra-molecularity is enacted in practice as part of the so-called “histology-agnostic” turn in clinical cancer research and care. Drawing on fieldwork in North American oncology settings, we analyze how histology agnosticism partially reconfigures knowledge and practice across the linked domains of drug development and clinical trials, therapeutic decision making, and regulation, and the implications of this for an ongoing revision of how we understand the biopathology and temporality of cancer. We show how, in practice, the inframolecular gaze entails a “return” of histology as a modulator of histology-agnostic drugs and background for interpretation of mutational complexity.

Evaluation of OMOP CDM, i2b2 and ICGC ARGO for supporting data harmonization in a breast cancer use case of a multicentric European AI project

ObjectiveObservational research in cancer poses great challenges regarding adequate data sharing and consolidation based on a homogeneous data semantic base. Common Data Models (CDMs) can help consolidate health data repositories from different institutions minimizing loss of meaning by organizing data into a standard structure. This study aims to evaluate the performance of the Observational Medical Outcomes Partnership (OMOP) CDM, Informatics for Integrating Biology & the Bedside (i2b2) and International Cancer Genome Consortium, Accelerating Research in Genomic Oncology (ICGC ARGO) for representing non-imaging data in a breast cancer use case of EuCanImage. MethodsWe used ontologies to represent metamodels of OMOP, i2b2, and ICGC ARGO and variables used in a cancer use case of a European AI project. We selected four evaluation criteria for the CDMs adapted from previous research: content coverage, simplicity, integration, implementability. Resultsi2b2 and OMOP exhibited higher element completeness (100% each) than ICGC ARGO (58.1%), while the three achieved 100% domain completeness. ICGC ARGO normalizes only one of our variables with a standard terminology, while i2b2 and OMOP use standardized vocabularies for all of them. In terms of simplicity, ICGC ARGO and i2b2 proved to be simpler both in terms of ontological model (276 and 175 elements, respectively) and in the queries (7 and 20 lines of code, respectively), while OMOP required a much more complex ontological model (615 elements) and queries similar to those of i2b2 (20 lines). Regarding implementability, OMOP had the highest number of mentions in articles in PubMed (130) and Google Scholar (1,810), ICGC ARGO had the highest number of updates to the CDM since 2020 (4), and i2b2 is the model with more tools specifically developed for the CDM (26). ConclusionICGC ARGO proved to be rigid and very limited in the representation of oncologic concepts, while i2b2 and OMOP showed a very good performance. i2b2′s lack of a common dictionary hinders its scalability, requiring sites that will share data to explicitly define a conceptual framework, and suggesting that OMOP and its Oncology extension could be the more suitable choice. Future research employing these CDMs with actual datasets is needed.

ICGC-ARGO precision medicine: an update on targeted therapy based on longitudinal analysis of tumour heterogeneity and evolution in colorectal cancer

We previously reported two patients with metastatic colorectal adenocarcinoma who, after referral to the precision medicine tumour board, had tissue and longitudinal liquid biopsies and responded to targeted therapy based on their molecular profile. These patients are from the SCRUM-MONSTAR programme, a nationwide genome-screening project in Japan that is part of the International Cancer Genome Consortium–Accelerating Research in Genomic Oncology. Here, we summarise the clinical history of the two patients and report an update on clinical course and longitudinal molecular assessment using circulating-tumour DNA (ctDNA) sequencing.

ICGC-ARGO precision medicine: an update on familial matters in pancreatic cancer.

We previously described a case of two sisters (M and A) diagnosed with pancreatic ductal adenocarcinoma. M and A had somatic and germline tumour molecular profiling as part of the International Cancer Genome Consortium-Accelerating Research in Genomic Oncology (ICGC ARGO) programme, the results of which informed treatment for M and A and risk management for a third sister (Ma), who did not have pancreatic ductal adenocarcinoma but was diagnosed with thyroid cancer at age 36 years and meningioma at age 50 years. Here, we report an update on the treatment history and the clinical course of M and A.

Teaching cancer imaging in the era of precision medicine: Looking at the big picture

The role of imaging in cancer diagnosis and treatment has evolved at the same rapid pace as cancer management. Over the last twenty years, with the advancement of technology, oncology has become a multidisciplinary field that allows for researchers and clinicians not only to create individualized treatment options for cancer patients, but also to evaluate patients’ response to therapy with increasing precision. Familiarity with these concepts is a requisite for current and future radiologists, as cancer imaging studies represent a significant and growing component of any radiology practice, from tertiary cancer centers to community hospitals.In this review we provide the framework to teach cancer imaging in the era of genomic oncology. After reading this article, readers should be able to illustrate the basics cancer genomics, modern cancer genomics, to summarize the types of systemic oncologic therapies available, their patterns of response and their adverse events, to discuss the role of imaging in oncologic clinical trials and the role of tumor response criteria and to display the future directions of oncologic imaging.

Abstract IA-12: Precision oncology for pancreatic cancer

Abstract Pancreatic cancer presents distinct challenges in advancing more contemporary therapeutic approaches that target specific molecular aberrations within subgroups of patients. This “precision oncology” approach requires: 1. The ability to define targetable molecular pathology and the characteristics of molecular subtypes which harbour vulnerabilities and build preclinical platforms of evidence that support the testing of therapeutic strategies in clinical trials.2. The capability and capacity to accurately select subgroups of participants and provide feasible opportunities for clinical trials of novel therapeutic strategies in the real world.3. The ability to robustly aggregate data from clinical trials and cohorts to inform the evolution of novel therapeutic approaches. To achieve these goals, the Glasgow Precision Oncology Laboratory has endeavoured to define molecular vulnerabilities and build the systems that enable the above 3 requirements. The Glasgow Cancer Test The GPOL team have created a new suite of tests that not only covers what is already known about cancer, but also allows for new information to be assimilated. The content of the GCTs is carefully curated to include genomic features for which there is high-quality objective evidence for a biological role in cancer. These genomic features are tiered by clinical actionability and confidence to generate a nested set of cancer assays to accommodate different clinical or scientific requirements and financial and infrastructure constraints so as to meet increasing demand, especially in cancers of unmet need. Precision-panc Precision-Panc was designed to be the evolution of clinical trial platforms that involved molecular profiling for difficult to treat cancers, typically not a priority for commercial therapeutic development. It was developed in partnership with, and has significant funding support from industry. In order to institute a step change for pancreatic cancer, it was necessary to transform pancreatic cancer therapeutic development into a more competitive arena so as to secure greater investment from pharmaceutical companies. Essential to this strategy is the concept that molecular profiling of all cancer patients should be performed for clinical trials (Reasons to be testing: the dawn of complex molecular profiling in routine oncology practice. Beer et al. Ann Oncol. 2019 30:1691-1694). In the area of human data science, extremely accurate information from digital pathology and digital imaging necessitates the molecular profiling of cancer coupled with accurate clinical data at scale and is the long-term goal of the processes developed through Precision-Panc. From commencement of funding, the first site was open within 8 months, with the first randomisation a month after that. From first randomisation, after 2 years, 26 sites have been opened, 277 participants have entered the platform, 216 registered for studies and 113 proceeded to a trial. Current rate of participant entry into Precision-Panc is 15 - 20 per month. Of the 6 specific trials currently on the platform, one has completed, 5 continue with more in development in order to accommodate all therapeutic opportunities (eg:metastatic, 2nd-line, local advanced, resectable disease). ICGC-ARGO The International Cancer Genome Consortium’s new initiative called ARGO (Accelerating Research in Genomic Oncology) designed and led by GPOL aims to deliver a Million patient years of precision oncology knowledge. Platforms such as Precision-panc will contribute data to ICGC-ARGO to enable pooled analysis of granular standardised datasets across and between different cancer types. Citation Format: Andrew V. Biankin. Precision oncology for pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr IA-12.

Development of a Validated Exam to Assess Pathologist Knowledge of Genomic Oncology.

There is a clear need to educate health professionals in genomic medicine. Pathologists, given their critical role in cancer diagnostics, must understand core concepts in genomic oncology. Although high-quality evaluation is a cornerstone of medical education, to our knowledge a rigorously validated genomic oncology assessment tool has not been published. To develop and validate a genomic oncology exam. A previously developed exam was updated and validated using 3 approaches: pretesting/posttesting in relation to a live genomic pathology workshop; comparison of scores of individuals at a priori defined knowledge levels; and use of Rasch analysis. This last approach is used in high-stakes testing, such as licensing exams. The exam included both knowledge-based as well as skills-based questions related to the use of online genomics tools. There was a significant difference in exam scores preworkshop and postworkshop (37.5% to 75%; P < .001). Individuals at a priori defined beginner, intermediate, and expert levels scored 35%, 58%, and 89%, respectively (P < .001). Rasch analysis demonstrated excellent fit and reliability and led to further exam refinement with the removal of 2 questions deemed unnecessary for assessment. A rigorously validated exam has now been created to assess pathologist genomic oncology knowledge and skills. The exam can be used to assess both individual learners as well as educational interventions. The exam may also be applicable to other specialties involved in genomic-based cancer care.

Advanced Cancer Patient Knowledge of and Attitudes towards Tumor Molecular Profiling

Limited research has indicated that despite their overwhelming interest in tumor molecular profiling (MP),11Abbreviations: Accessibility and Remoteness Index of Australia (ARIA): an indication of the proximity of service centers relative to where the participant lives. Eastern Cooperative Oncology Group (ECOG): A performance status measure to quantify cancer patients' general well-being and activities of daily life. Molecular Therapeutics (MoST) Program: A research program which forms a component of the Australian Genomic Cancer Medicine Program. The Psychosocial Issues in Genomic Oncology (PiGeOn) Project: a longitudinal, mixed methods psychosocial sub-study of the MoST Program which aims to examine the psychosocial, behavioral and ethical impact of MP. Tumor molecular profiling (MP): a form of genomic testing, that involves characterization of tumor-derived DNA and RNA. cancer patients have poor knowledge about MP. The current study aimed to investigate demographic and psychological predictors of knowledge and perceived importance of MP in an advanced cancer patient cohort. Eligible participants had advanced solid cancers of any histological type with sufficient accessible tissue for MP and were enrolled in the Molecular Screening and Therapeutics (MoST) Program. A questionnaire was completed by 1074 participants (91% response rate) after consent, prior to undergoing MP. Overall, participants had poor to moderate knowledge of MP, yet perceived MP to have high importance. Higher education, speaking English at home, and greater satisfaction with the decision to undergo MP were associated with higher knowledge scores. More negative attitudes towards uncertainty, greater self-efficacy to cope with results, and lower perceived likelihood of cancer progression were associated with greater perceived importance of MP. Less educated participants and those who do not speak English at home will need clear explanations, visual aids and ample opportunity to ask questions about MP at the time of their decision-making. Clinicians also need to consider psychological factors relevant to patients' decision to pursue MP. Given the increased awareness of and demand for cancer genomic information and the rapidly changing nature of the actionability of MP, these findings will help inform an important ongoing debate on how to facilitate ethical and informed consent and manage patient expectations about personalized treatments.

Implementing a genomic oncology program in an integrated health care network with large scale genomic Next Generation Sequencing (NGS) testing of advanced cancers in a community setting.

e19185 Background: The importance of NGS testing to help guide oncologic therapy decisions has grown over time, presenting a unique challenge for community oncologists to properly translate the NGS test results to treatment (Tx) recommendations for patients. Kaiser Permanente Northern California (KPNC) is a large, integrated health care system providing comprehensive primary and specialty care to 4.4 million members, with over 4000 patients (pts) diagnosed with advanced cancer each year. NGS testing at KPNC is performed in a collaboration with Strata Oncology, that provides systematized comprehensive NGS testing (StrataNGS) paired with a portfolio of genomically guided clinical trials. Methods: KPNC has established workflows for upfront empiric review of all NGS results by our KPNC Genomic Oncology Committee (GOC), that includes representatives from medical oncology subspecialists, genetics, pathology, and clinical trials. KPNC GOC reviews all StrataNGS test results in our KPNC network to identify patients that might benefit from either a clinical trial, appropriate on or off-label drug options and/or genetic counseling. In addition, GOC conducts an in-depth case review per request of the treating oncologist. A study nurse pre-screens all pts whose results match to a trial for eligibility. Results: The numbers of pts tested with StrataNGS has increased over time with around 300 pts tested monthly and 4,977 NGS tests performed since Nov 2017. Median age was 65.2 (Range 18.5-96.0). About 42.4% of Pts were non-white. Approximately, 39% of Pts had an actionable mutation including 21.7% eligible for a promising in or out of network trial. 1.6% and 10.9% pts were potentially eligible for off- or on-label approved drugs, respectively. 4.9% were recommended to receive genetic counseling. The 3 most frequently sequenced cancers were: lung, colon and breast. Conclusions: KPNC is providing systematic subspecialty review and management of NGS results for pts in a community setting. Our approach has allowed for greater adoption of routine NGS testing, especially for rare cancer types with less effective standard Tx options available. This model also helps accrual to genomic-based drug trials that have been a challenge for the field. Workflows to streamline automated centralized acquisition of prior Tx history and analysis of response to therapy are in development.

The impact of tumor NGS testing on hereditary cancer risk assessment and population management in an integrated community health care system.

1517 Background: Next-generation sequencing (NGS) for tumor molecular profiling is used in Oncology to identify ‘actionable alterations’ for clinical trials or on/ off-label therapy. Tumor NGS can also reveal potentially heritable germline mutations. The frequency of such incidental germline mutations has been estimated to be 4-15%. The 2015 ASCO Statement supports communication of medically relevant incidental germline findings from somatic mutation profiling to patients (PTS). The impact of tumor NGS testing on hereditary cancer risk assessment programs in the context of a wider population management strategy is unknown. We sought to evaluate this within our Kaiser Permanente Northern California (KPNC) population with ready access to tumor NGS and an ongoing hereditary cancer risk assessment program. Methods: Kaiser Permanente Northern California (KPNC) is part of a large, integrated health care system. NGS at KPNC is performed in collaboration with STRATA Oncology, a precision oncology partnership. All NGS results are reviewed by a multidisciplinary KPNC Genomic Oncology Committee (GOC)which also includes genetic counselors and pathologists. We examined all NGS reports between November 2017 through December 2019 to determine the types of cancers tested, number with a possible germline mutation and number referred for genetic counseling and testing (GCT). Results: 4,825 PTS with advanced cancer underwent STRATA NGS testing. A total of 207 PTS (4.3%) were identified as potential germline mutation carriers, all 207 were recommended for GCT referral. Of these, 92 (45.0%) separately met 2020 NCCN Criteria for Genetic/Familial High-Risk Assessment (2020NG/FA), prior to tumor NGS; 115 (53.6%) did not and 3 (1.4%) had insufficient information. The cancers most frequently meeting NCCN criteria were pancreatic, breast and colon. Of the 92 PTS who met 2020NG/FA, 60 (65%) underwent GCT and 34 (57%) were confirmed to have a germline mutation. Of the 115 PTS that did not meet 2020NG/FA, 47 (41%) underwent GCT and 19 (40%) were confirmed to have a germline mutation. Overall germline mutations were confirmed in 16.5% of patients who did not meet 2020NG/FA and 37% who did. Conclusions: In our community-based integrated healthcare system, systematic review of next-generation sequencing results by an expert GOC led to more robust identification of germline mutation carriers and navigated them to appropriate GCT. Ongoing work will clarify data on cascade testing. We are currently developing automated workflows for GCT.

Cancer patients’ views and understanding of genome sequencing: a qualitative study

BackgroundLittle is known about knowledge of, and attitudes towards, genome sequencing (GS) among individuals with a personal history of cancer who decide to undergo GS. This qualitative study aimed to...

S5-KL-1 CANCER GENOMIC MEDICINE: FROM BENCH TO CLINIC

Over the last two decades, genomic technology such as microarray and next generation sequencing (NGS) enabled comprehensive analysis of cancer genome. International cancer genome consortium, established in 2007, completed the analysis of 25,000 cases and has brought discovery of novel cancer driver genes and improved our understanding cancer biology. For example, discovery of IDH1/2 mutation in various cancers created a new concept, 2-hydroxyglutarate as Oncometabolite. The mutational signature patterns allow us to predict how the individual cancer was developed. Anti-cancer drugs, such as alkylating agents, occasionally modify the bases and introduce mutations through mispairing in replication.Currently we are aware that cancer is a genetic disease, where accumulation of genetic and epigenetic alterations in the genome leads to cellular transformation, and that mutation in each patient is unique. To realize the personalized oncology, clinical sequencing test was developed. This year a couple of NGS-based cancer panel tests have been approved for reimbursement by nation-wide healthcare system in Japan.In this seminar I will discuss the future improvement in genomic oncology.

Abstract 1698: A million years of precision oncology knowledge for the world

Abstract Introduction: The most valuable information for someone with the diagnosis of cancer is the ability to predict which treatment will be most effective for them, and their prognosis. The most effective way to generate the knowledge required to do this for all people affected by cancer is to amass large datasets of deep molecular and detailed phenotypic data through health systems as part of routine care. However, the pathways and processes are not in place and require development, with the paramount challenge being the acquisition and application of rich, reliable clinical data including treatment and response parameters. Although multiple regional platforms have been established to generate cancer genomics data, no platform exists that can capture, aggregate, harmonize and appropriately share data globally to enable analysis of pooled individual participant data. Method: The International Cancer Genome Consortium1, established in 2007, aimed to define the genomes of 25,000 primary untreated cancers. The ICGC solved numerous data governance, ethical and logistical challenges and provided the international community with comprehensive genomic data for many cancer types. The ICGC’s next Initiative -ARGO aims to Accelerate Research in Genomic Oncology to provide a million patient-years of precision oncology knowledge to the world. To achieve this, ICGC-ARGO will acquire detailed treatment and response information mostly from participants in clinical trials along with genomic, transcriptomic and proteomic data from their tumors and healthy tissues. Results: ICGC membership already spans 28 countries, with new commitments to ARGO from 10 programmes investigating a range cancer types, comprising an estimate of 200,000 patient years of data. Regional Data Processing Centres are in operation in 4 countries to coordinate ICGC-ARGO data and to validate and process sequencing data through a standardized series of data analysis pipelines. A central site will integrate the various ICGC-ARGO data sets and disseminate to the community through the ICGC Data Portal. Policies and guidelines have been established that address the global challenges of clinical cancer genomics such as standardisation of clinical data parameters, data access structures, data composition and management and jurisdictional issues that impact global data sharing. Conclusion: The data generated by ICGC ARGO member programmes will allow for precise correlation of molecular attributes with clinical features, allowing for the discovery of molecular markers of response, resistance and adverse events, as well as novel therapeutic targets. This knowledge will translate into new approaches to improve outcomes for people affected by cancer. The ICGC ARGO project will also address the challenges of generating and sharing genomic data matched with clinical and patient information on a global scale. Citation Format: Amber Johns, International Cancer Genome Consortium (ARGO Initiative). A million years of precision oncology knowledge for the world [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1698.

Applying precision medicine approach to metastatic castration-resistant prostate cancer: urgent education need on genomic oncology

Metastatic castration-resistant prostate cancer (mCRPC) remains a therapeutic challenge. As a result of advances in genomic sequencing technology, “next-generation sequencing” (NGS) is increasingly incorporated into clinical trials and routine oncology clinical practice. Molecular profiling of mCRPC can be a valuable way of defining molecular alterations that might contribute to optimal treatments while reduce risk of adverse effects. To effectively apply cutting edge research to daily patient care, oncologists must grasp the fundamentals of genomic oncology, molecular testing and interpretation. There is an urgent need for health professional education to allow implementation of these novel precision medicine tools.

Abstract PL03-01: NCI-MATCH: A new paradigm in the era of genomic oncology

Abstract PL03-01: NCI-MATCH: A new paradigm in the era of genomic oncology

Resources for Interpreting Variants in Precision Genomic Oncology Applications.

Precision genomic oncology—applying high throughput sequencing (HTS) at the point-of-care to inform clinical decisions—is a developing precision medicine paradigm that is seeing increasing adoption. Simultaneously, new developments in targeted agents and immunotherapy, when informed by rich genomic characterization, offer potential benefit to a growing subset of patients. Multiple previous studies have commented on methods for identifying both germline and somatic variants. However, interpreting individual variants remains a significant challenge, relying in large part on the integration of observed variants with biological knowledge. A number of data and software resources have been developed to assist in interpreting observed variants, determining their potential clinical actionability, and augmenting them with ancillary information that can inform clinical decisions and even generate new hypotheses for exploration in the laboratory. Here, we review available variant catalogs, variant and functional annotation software and tools, and databases of clinically actionable variants that can be used in an ad hoc approach with research samples or incorporated into a data platform for interpreting and formally reporting clinical results.

Precision medicine in oncology: New practice models and roles for oncology pharmacists.

Three different precision medicine practice models developed by oncology pharmacists are described, including strategies for implementation and recommendations for educating the next generation of oncology pharmacy practitioners. Oncology is unique in that somatic mutations can both drive the development of a tumor and serve as a therapeutic target for treating the cancer. Precision medicine practice models are a forum through which interprofessional teams, including pharmacists, discuss tumor somatic mutations to guide patient-specific treatment. The University of Wisconsin, Indiana University, and Moffit Cancer Center have implemented precision medicine practice models developed and led by oncology pharmacists. Different practice models, including a clinic, a clinical consultation service, and a molecular tumor board (MTB), were adopted to enhance integration into health systems and payment structures. Although the practice models vary, commonalities of three models include leadership by the clinical pharmacist, specific therapeutic recommendations, procurement of medications for off-label use, and a research component. These three practice models function as interprofessional training sites for pharmacy and medical students and residents, providing an important training resource at these institutions. Key implementation strategies include interprofessional involvement, institutional support, integration into clinical workflow, and selection of model by payer mix. MTBs are a pathway for clinical implementation of genomic medicine in oncology and are an emerging practice model for oncology pharmacists. Because pharmacists must be prepared to participate fully in contemporary practice, oncology pharmacy residents must be trained in genomic oncology, schools of pharmacy should expand precision medicine and genomics education, and opportunities for continuing education in precision medicine should be made available to practicing pharmacists.

Clinical Validation of a Next-Generation Sequencing Genomic Oncology Panel via Cross-Platform Benchmarking against Established Amplicon Sequencing Assays

Next-generation sequencing (NGS) genomic oncology profiling assays have emerged as key drivers of personalized cancer care and translational research. However, validation of these assays to meet strict clinical standards has been historically problematic because of both significant assay complexity and a scarcity of optimal validation samples. Herein, we present the clinical validation of 76 genes from a novel 1212-gene large-scale hybrid capture cancer sequencing assay (University of Chicago Medicine OncoPlus) using full-data comparisons against multiple clinical NGS amplicon-based assays to yield dramatic increases in per-sample data comparison efficiency compared with previously published validations. Using a sample set of 104 normal, solid tumor, and hematopoietic malignancy specimens, head-to-head NGS data analyses allowed for 6.8 million individual clinical base call comparisons, including 2729 previously confirmed variants, with 100% sensitivity and specificity. University of Chicago Medicine OncoPlus showed excellent performance for detection of single-nucleotide variants, insertions/deletions up to 52 bp, and FLT3 internal tandem duplications of up to 102 bp or larger. Highly concordant copy number variant and ALK/RET/ROS1 gene fusion detection were also observed. In addition to underlining the efficiency of NGS validation via full-data benchmarking against existing clinical NGS assays, this study also highlights the degree of performance similarity between hybrid capture and amplicon assays that is attainable with the application of strict quality control parameters and optimized computational analytics.

Precision Medicine in Gastrointestinal Pathology

-Precision medicine is the promise of individualized therapy and management of patients based on their personal biology. There are now multiple global initiatives to perform whole-genome sequencing on millions of individuals. In the United States, an early program was the Million Veteran Program, and a more recent proposal in 2015 by the president of the United States is the Precision Medicine Initiative. To implement precision medicine in routine oncology care, genetic variants present in tumors need to be matched with effective clinical therapeutics. When we focus on the current state of precision medicine for gastrointestinal malignancies, it becomes apparent that there is a mixed history of success and failure. -To present the current state of precision medicine using gastrointestinal oncology as a model. We will present currently available targeted therapeutics, promising new findings in clinical genomic oncology, remaining quality issues in genomic testing, and emerging oncology clinical trial designs. -Review of the literature including clinical genomic studies on gastrointestinal malignancies, clinical oncology trials on therapeutics targeted to molecular alterations, and emerging clinical oncology study designs. -Translating our ability to sequence thousands of genes into meaningful improvements in patient survival will be the challenge for the next decade.