A recently discovered communication system used by cells to send messages across the human body promises to revolutionize our understanding of disease and how we treat it. Technologies based on this discovery promise to become important tools for our understanding, monitoring and treatment of some of man's most insidious diseases such as cancer. The key elements comprising this communication system are nano and micron sized vesicles often called exosomes or extracellular vesicles (EVs), which are the carriers of the molecular information.
 
Exosomes and EVs are produced by most if not all cell types, under normal conditions and especially in response to disease.  Exosomes and EVs are expelled from affected cells and circulate in various bodily fluids including blood, urine and saliva. Importantly, circulating exosomes share certain molecular structures and components in common with their parental cells, including DNA, RNA and Proteins. Exosomes shuttle this molecularly encoded information between cells and across distances, effectively acting as the body's molecular internet. 
                                       
By gathering exosomes via a simple blood draw, information can be accessed representing distant cells, tissues and organs, including information originating from a multitude of diverse diseases such as cancer, Alzheimer's, arteriosclerosis, arthritis, diabetes, and multiple sclerosis (MS) among many others. Unlike invasive tissue biopsies exosomes can be easily collected and interrogated serially. This dynamic accessibility would allow for screening and early detection of disease, monitoring of progression, drug response, recurrence and resistance. Not merely a blue sky technology, exosome and EVs are contributing to personalized and precision medicine today as research tools and may be available for first clinical applications as early as this year.  
 
Learning objectives:
1) understand the origins of exosomes and EVs  
2) understand the application of exosomes and EV for disease monitoring.
 
 

Healthcare-associated infections (HAIs) continue to be a considerable problem for hospitals and healthcare institutions that can adversely affect patient outcomes and impact the financial bottom lines. There are a number of strategies hospitals may implement for combating and controlling HAIs. Methicillin Resistant Staphylococcus aureus (MRSA) is one of those HAIs that can cause significant morbidity and mortality. Minimizing or eliminating the potential for infection is one main driver for a hospital to consider and develop a screening/surveillance program. Other factors include pressures from states passing legislation requiring a MRSA program to be implemented and CMS’s initiatives to prevent HAIs in general. The scope and clinical utility of a MRSA screening or active surveillance program is institution dependent and an assessment of the MRSA prevalence will help drive the decision to implement a formal Infection Control program. The identification of MRSA colonized patients is critical in directing Infection Control efforts towards limiting the risk of infection, and decreasing the likelihood that MRSA colonized patients become reservoirs of infection that could potentially be transmitted to other patients via the healthcare worker. In this presentation, we describe our successes and other lessons learned during our experiences in developing and implementing an active surveillance MRSA program in a large community healthcare system.

Cervical cancer screening has been the 20th century poster child for preventative screening.  This presentation is a gynecologist’s perspective on its continuing evolution –both as a great success and an opportunity for improvement.    Dr Baker will focus on the transition from experience based to data driven development of guidelines for physicians.  He will also reflect on the challenges for molecular laboratories.   Their anticipation of changes in screening practice and potential impact to their range of services including consultative role to OB/Gyn physicians.  
 
Learning objectives:
1) The attendee will understand how and why the approach to cervical cancer screening is evolving.
2) The attendee will understand how these changes might impact the molecular lab and it's relationship with OB/GYNs.
 
 

The Personalized Medicine Initiative (PMI) is a non-profit enterprise based in Vancouver, Canada that is focused on introducing personalized, molecularly-based medicine into the front lines of healthcare. The PMI is taking advantage of new technologies that increasingly allow individuals to be analyzed at the molecular level in a rapid and cost-effective manner. These analyses  enables both effective preventive medicine as more precise diagnostics to accurately match therapy to disease. The PMI is pursuing an “end-to-end” approach. First, the PMI has developed the resources necessary to construct the genomic, proteomic, metabolomic and microbiomic “data clouds” around individuals to determine their risks of disease, diagnose overt disease and monitor response to therapy. These “molecular you” profiles are now being generated by a PMI company called the Molecular You Corporation (MYCO). Second, in order to use molecular level information clinicians require clinical decision support systems (CDSS) to assist them in deciding on the most appropriate therapy. Again, the PMI has formed a company called GenXys to develop CDSS to assist the prescription practices of family doctors. The MYCO molecular you profiles are proving remarkably useful for early detection of disease and to guide lifestyle and diet changes to correct trends towards disease. GenXys, on the other hand, is commercializing a simple genetic test to guide drug prescription to avoid adverse drug reactions. This is achieved by construction of algorithms that incorporate genetic information together with standard clinical information to guide prescription of over 200 commonly prescribed drugs. 

Learning Objectives:

1. Integrated Omics (proteomic, genomic, microbiomic, metabolomic) profiling can be of use for empowering individuals to practice more effective preventive healthcare.
2. Molecular level information can be used by family physicians to assist in drug prescription on an individualized basis.

Pathology departments are under significant pressure to meet the demands of a precise medicine environment where general phenotypic attributes are no longer sufficient for accurately defining disease risk, clinical progression and therapeutic options.   The classical approach to solid tumor diagnostics combined with immunohistochemical analysis remains the foundation of anatomic pathology; however, recent developments in genomic medicine have altered the paradigm, specifically for lung cancer, colon cancer and melanoma, where DNA mutation detection with next gen sequencing is now part of the pathologist’s tool-box.   Although critical for therapeutic selection, there is considerable evidence that DNA analysis is only one part of the ‘precise equation’ as evidenced by the recent success of check-point inhibitors and the importance of in situ immune composition.  Furthermore, the field of systems or precise pathology which encompasses digital image analysis and quantitative protein detection integrated with deep learning processes is poised to have a tremendous impact on the practice of pathology in the future.   In addition to tissue based analytics the continued advances in the liquid biopsy space including circulating tumor cells, cell-tumor DNA and exosomes combined with serum proteomics will undoubtedly bring another level of complexity to the patient assessment process.     With the ever-changing and competitive healthcare atmosphere, novel technologies and data management – bioinformatics will continue to be at the forefront of clinical medicine.
 
Learning Objectives:

1. Define in your own words what is meant by:  Precise Medicine.
2. Provide a sentence on your understanding of systems –precise pathology and how this will change the practice of pathology.
3. What is meant by the terms ‘morphometry’ and how will it be used in precise pathology?
4. What is meant by the term ‘liquid biopsy’?  Please provide a few examples of how this approach will add information to tissue diagnostics and how it will be used clinically?

In this webinar the speaker discusses the approach taken by the Food and Drug administration in their pre-market review of in vitro diagnostic tests.  The legal bar passed by congress in the medical device amendment to the Federal Food and Cosmetic Act defined that the Agency needs to ascertain that there is a reasonable assurance that the device is safe and effective.  The talk explores how the FDA interprets that with respect to the analytical and clinical validity of a test and what that means in practical terms as the Agency weighs the risks and benefits of the device to make its determinations.  Two examples are put forth to show the difference between the review of a moderate risk device for which the clinical validity has been well established, and a new type of device that needs to demonstrate clinical validity.

Learning Objectives:

1.  To understand how the FDA evaluates in vitro diagnostic tests.
2.  To learn the relationship between the safety and effectiveness of an in vitro diagnostic test and the test clinical validity.

Oncologists and pathologists are increasingly utilizing information on genomic alterations in tumors to help guide patient care and treatment. Personalis, Inc., a genomic sequencing and interpretation company, has developed a tumor-profiling test that provides clinicians with accurate and comprehensive analysis and clinical reporting of 181 genes to guide treatment decisions.

Learning Objectives
 

1. Understand the current industry challenges with regard to NGS technology and tumor profiling for clinical care.
2. Appreciate how the use of Personalis’ accuracy and content enhanced (ACE) sequencing platform with DNA & RNA analysis improves precision and reporting in solid tumor testing.
3. Recognize, through case studies, some of the more common molecular changes identified that may assist in therapeutic management.

We have been developing methods to target drugs specifically to pathologic cells, thereby avoiding collateral toxicity to healthy cells. In the case of cancer, we have exploited up-regulation of the folate receptor on cancers of the ovary, lung, kidney, endometrium and breast to target imaging and therapeutic agents to these cancers. Clinical trials of six folate-linked drugs demonstrate that the ligand-targeting strategy holds promise for increasing drug potency while reducing unwanted toxicity. Data on treatment of tumor-bearing mice, dogs, and humans will be presented. We have also developed a targeting ligand that selectively delivers attached drugs to PSMA on prostate cancer cells. Imaging and therapeutic studies suggest that this targeting ligand can not only improve the diagnosis of prostate cancer, but also enhance treatment of the disease. Recent pre-clinical and clinical data on this targeting ligand confirm this anticipation. Additional cancer-specific ligands that target malignancies of the bladder, pancreas, stomach, brain, liver, colon, skin and esophagus are also under investigation. Moreover, use of these ligands to “light up” cancer tissues with tumor-targeted fluorescent dyes during surgeries are being developed and videos of recent surgeries of ovarian and lung cancers will be presented. Finally, ligand-targeted imaging and therapeutic agents for a number of autoimmune and inflammatory diseases (e.g. rheumatoid arthritis, Crohn’s disease, psoriasis, atherosclerosis, osteoarthritis, etc.) will also be described.

Cancer remains the second leading cause of death in the United States.  Most tumors arise from a myriad of genetic changes that dysregulate cell growth and prompt survival.  Identification of genetic alterations by next generation sequencing (NGS), using either targeted sequencing or whole exome sequencing (WES) has become the standard of care in genomic medicine.  WES applies NGS technology to identify genetic variants in the coding regions (exons) of genes, harboring the majority of disease causing-mutations.  Using WES, it is currently feasible to not only detect a rapidly growing set of known clinically relevant mutations, but also identify novel or unexpected important variations, including constitutional mutations in cancer predisposing genes.  Thus far, the use of WES in cancer has largely taken place in the setting of large research studies.  Integration of WES into precision cancer care has lagged behind primarily due to technical challenges such as small and poor quality (FFPE) tissues and low-tumor purity samples that have not been rigorously validated in the clinical setting.  Another challenge is the analytical and computational approaches used to detect the wide-spectrum of mutations and genes queried by WES, which requires a comprehensive validation procedure to demonstrate the ability of the test to identify actionable mutations with high accuracy and at an acceptable analytical sensitivity.  The third challenge is a clinical challenge to attain meaningful interpretations of the genomic data which then can be used for patient care.  While these challenges are well recognized and despite a wide range of assays and platforms available, WES application in cancer has not yet been validated for the clinical laboratory and has not been fully characterized in the literature with regard to the analytic and clinical validity of the testing and the various types of relevant mutations.  The few existing guidelines given by professional societies give only high-level directions for implementing NGS testing geared primarily towards the use of targeted panels rather than WES.  By all accounts, New York State-Department of Health (NYS-DOH) requirements are among the most rigorous guidelines yet published and are likely to serve as a paradigm for suggested future type of guidelines that might be required by the Food and Drug Administration (FDA).  These efforts are also in line with the new precision medicine initiative announced by U.S. President Obama with the intent to bring us closer to curing cancer and give all of us access to a more personalized and genomic-driven medicine.
   This presentation describes the development and analytical characteristics of NYS-DOH approved clinical exome cancer test suitable for simultaneous detection of somatic dingle nucleotide variants (SNVs), indels and copy number alterations (CNAs) using the Agilent HaloPlex capture platform and the Illumina HiSeq2500 system for sequencing.  Initial validation has focused on actionable mutations in five principal, clinically relevant genes and according to NYS-DOH guidelines.  The automated computational framework for data analysis, variant interpretation and reporting is also discussed. 

The objectives of this presentation are:

• To describe the development and analytical characteristics of a New York State-Department of Health (NYS-DOH) approved clinical Exome Cancer Test suitable for simultaneous detection of somatic single nucleotide variations (SNVs), indels and copy number alterations (CNAs). 
• To discuss the automated computational framework for data analysis, variant interpretation and reporting of whole exome sequencing (WES) data, using examples of clinical cases and reporting of WES results. 

This session will describe opportunities for laboratory-clinician collaboration. identify the laboratory’s role in improving patient outcomes, and provide insight into the reimbursement challenges to help create a successful laboratory-clinician partnership. Case studies will be provided with opportunities for Q and A.

Learning Objectives:

• Describe opportunities for laboratory-clinician collaboration
• Understand the laboratory’s role in improving patient outcomes
• Understand reimbursement challenges to a successful laboratory-clinician partnership

This session will provide an update on PAMA, related coding initiatives, and what we are seeing from the payor perspective so far this year.  Participants will have a deeper understanding of the current reimbursement and regulatory environment for clinical laboratories, as well as greatere insight into how to prepare for PAMA implementation.

Learning objectives:

• Participants will have a deeper understanding of the current reimbursement and regulatory environment for clinical laboratories
• Participants will hear how to better prepare for PAMA implementation.

Microbiome discovery efforts are underway in multiple disease areas.  Challenges exist in sample collection, processing, assay selection and bioinformatics.  Therefore heterogeneity exists in published findings for biomarkers.  Using the Amazon cloud and machine learning, sets of consistent biomarkers can be observed in biospecimens from diseased subjects that differentiate them from healthy controls.  The benefits of applying consistent assays with internal controls within each test will be discussed.  Since the same data collected for diagnostic discovery, also aids in therapeutic hypotheses generation, a platform that outputs both will be outlined.
 
Learning Objectives:
- Be able to list at least 2 disease areas where microbiome analyses are applied.
- Be able to list at least 2 sources of variation in biomarker discovery in microbiome analyses.
- Be able to identify the benefits of internal controls in evaluating assay value.
 

Success of the personalized medicine strategy depends on our ability to access the genetic variance landscape continuously before, during and after treatment.  Liquid biopsies provide us an easy and less intrusive way to monitor disease status.  The key challenge is the sensitivity and specificity of assays used to detect genetic variances in such small samples.  Recent advances in NGS have made it the ideal approach for the comprehensive analysis of the mutational landscape of samples. Specifically, the ability to enrich certain genomic targets known, or suspected, to harbor driver mutations prior to NGS is allowing researchers to achieve very deep levels of sequencing coverage, levels that cannot be achieved by either WGA or WES, thereby increasing the sensitivity of NGS assays. The ability to enrich genomic targets has also facilitated the use of liquid biopsies for the discovery of mutations that contribute to drug resistance. Several challenges remain though, mainly the specificity and uniformity of target enrichment approaches, the amount of required DNA, and the turnaround time needed to go from sample to insight. Attend this seminar to learn what solutions QIAGEN scientists have developed to overcome these challenges and how these solutions can be used to analyze mutations in a wide range of samples such as FFPE, cfDNA, and CTCs, thereby enabling researchers to use solid and liquid biopsies to continuously monitor the disease status. 
 

Recent advances in personalized medicine and associated companion diagnostic therapeutics have led to an increased utilization of genetic markers in oncology therapy selection.  The rapid acceleration of biomarker driven therapy has been widely accepted into clinical guidelines based upon proven clinical utility and unprecedented patient outcomes.  During this presentation, a discussion of processes used for tissue acquisition and processing, pre-analytics, biomarker testing, and result reporting will be presented.  A special emphasis will be given to the discussing the power and pitfalls of common biomarker testing techniques such as real-time PCR companion diagnostic testing, immunohistochemistry, FISH, and next-generation sequencing panels. The goal of this presentation is to help improve the oncology patient journey by increasing access to high quality biomarker testing.

Learing Objectives:

• To understand the fundamentals of personalized medicine and companion diagnostics
• To review current therapeutic products associated with companion and complementary diagnostics
• To gain an understanding of the future of personalized medicine in oncology

The advent of personalized medicine employing molecular targeted therapies has markedly changed the treatment of cancer in the past 10 years. Although tumor tissue biopsy-based genotyping is the current clinical practice for guiding clinical management, biopsy procedures can result in significant morbidity, limiting sampling to static snapshots which are further limited in scope by the inherent sampling bias of the analysis itself. To overcome these issues, technologies are needed for rapid, cost-effective, and noninvasive identification of biomarkers at various time points during the course of disease. Liquid biopsy is a rapidly emerging field to address this unmet clinical need as diagnostics based on cell-free circulating tumor DNA (ctDNA) can be a surrogate for the entire tumor genome. The use of ctDNA via liquid biopsy will facilitate analysis of tumor genomics that is urgently needed for molecular targeted therapy. Currently, most targeted approaches are based on PCR and/or next generation sequencing (NGS) for liquid biopsy applications with performance concordance in the 60-80% range with biopsy-based genotyping.

We have developed a liquid biopsy technology “Electric Field Induced Release and Measurement (EFIRM)- Liquid Biopsy (eLB)” provides the most accurate detection that can assist clinical treatment decisions for the most common subtype of lung cancer, non-small cell lung cancer (NSCLC), with tyrosine kinase inhibitors (TKI) that can extend the disease progress free survival period of these patients. eLB can detection ctDNA at single copy level whereas ddPCR detects ctDNA a minimum of 10 copy number. In addition eLB requires only 40 µl of sample volume, no sample processing, reaction time is 15min and can be performed at the point-of-care or high throughput reference lab using plasma or saliva. eLB detects actionable EGFR mutations in NSCLC patients with >90% concordance with biopsy-based genotyping. eLB is minimally/ non-invasive detecting the most common EGFR gene mutations that are treatable with TKI such as Gefitinib or Erlotinib to effectively extend the progression free survival of lung cancer patients.