Cambridge Healthtech Institute’s Fifth Annual
Clinical Application of Cell-Free DNA
Advancing Non-Invasive Diagnostics
August 22-23, 2018 | Grand Hyatt Washington | Washington, DC
The emergence of liquid biopsies is a game-changing tool that grew out of efforts to detect and profile circulating biomarkers with next-generation sequencing and genomic technologies. Applications are not limited to oncology but include cardiovascular disease, transplant medicine, CNS, fetal and maternal medicine. Oncology has been leading the way in the use of liquid biopsy for early detection, monitoring treatment response, determining therapeutic resistance, and measuring minimal residual disease. The review of prospective clinical trials and case studies to validate clinical utility with increasingly large patient cohorts will be presented. Cambridge Healthtech Institute’s Fifth Annual Clinical Application of Cell-Free DNA: Advancing Non-Invasive Diagnostics conference will highlight optimal clinical trial design, modifications and improvements in technical assays and recent regulatory challenges.
Final Agenda
Recommended Short Course*
SC1: Liquid Biopsy: Technology, Applications, Regulations and Reimbursement
Hatim Husain, MD, Physician, Medical Oncology, University of California, San Diego
John Simmons, PhD, Director, Translational Science & Diagnostics, Personal Genome Diagnostics
*Separate registration required
Scientific Advisory Board
Luis A. Diaz, MD, Head, Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center
Maximilian Diehn, MD, PhD, Associate Professor, Radiation Oncology, Stanford Cancer Institute, Institute for Stem Cell Biology & Regenerative Medicine, Stanford University
Scott Kopetz, MD, PhD, FACP, Associate Professor, Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center
Abhijit Patel, MD, PhD, Associate Professor, Yale University School of Medicine
WEDNESDAY, AUGUST 22
7:45 am Registration and Morning Coffee (Independence Foyer)
8:25 Chairperson’s Opening Remarks
Abhijit Patel, MD, PhD, Associate Professor, Yale University School of Medicine
8:30 Role of cfDNA in Immunotherapy
Shumei Kato, MD, Assistant Clinical Professor, Hematology & Oncology, Center for Personalized Cancer Therapy, UC San Diego Moores Cancer Center
Although immunotherapies can demonstrate salutary anti-cancer effect in a portion of patients, unfortunately not all patients benefit. Even in the presence of favorable response markers (e.g. positive PD-L1, MSI-high, high tumor mutation burden), the response rate is about 50-60%. Thus, further evaluation of immune biomarkers are required. We will present ctDNA (cell-free, circulating tumor DNA) as a potential tool to monitor the response from immunotherapy in cancer patients.
9:00 Tracking Immunotherapy Efficacy via ctDNA
Abhijit Patel, MD, PhD, Associate Professor, Therapeutic Radiology, Yale University School of Medicine
Immunotherapies are known to produce slow changes in radiographic tumor size. We hypothesized that real-time measurement of tumor cell death via ctDNA could enable earlier assessment of immunotherapy response in patients with lung cancer. This presentation will summarize our findings, showing that down-trending ctDNA levels correlate strongly with radiographic response and predict a longer duration of treatment benefit, as well as superior progression-free survival and overall survival.
9:30 The 4P’s of Liquid Biopsy: Predictive, Preventive, Personalized and Participatory
Nefize Sertac Kip, MD, PhD, Associate Professor, Molecular Oncology, Icahn School of Medicine, Mount Sinai
Multiple liquid biopsy assays are currently available for the detection of somatic mutations, with an analytical sensitivity of <0.1%, to assess minimal residual disease, detect resistance mutations, predict response to therapy, prognosticate disease, and determine not only late but also early stages of malignancy, with the ultimate goal of cancer prevention. Due to the ease of obtaining liquid biopsy specimens, patients are expected to participate more in such studies and thus help generate bigger data sets to better understand not only the individual’s tumor behavior with impact on precision medicine, but also improve population outcomes in cancer, with clinical and financial gains.
10:00 Building and Implementing Liquid Biopsy Assays with Industry’s Most Patient-Like Reference Materials
Omo Clement, PhD, Senior Product Manager, SeraCare Life Sciences
This presentation will describe the current challenges and needs for the development, validation and clinical implementation of liquid biopsy-based NGS assays, as well as solutions offered by Seraseq® ctDNA reference materials. These industry-leading reference standards incorporate clinical patient-like profiles in purified and encapsulated (plasma) formats, are highly multiplexed to detect all genomic variant types, with LOD as low as 0.1%.
10:30 Coffee Break in the Exhibit Hall with Poster Viewing (Independence Ballroom)
11:15 KEYNOTE PRESENTATION: Non-Invasive Early Detection of Cancer
Nickolas Papadopoulos, PhD, Professor, Oncology and Pathology; Director, Translational Genetics, Ludwig Center for Cancer Genetics & Therapeutics, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Institutions
Earlier detection of cancer is important to reducing cancer deaths. We developed CancerSEEK, a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. Furthermore, CancerSEEK localized the cancer to a small number of anatomic sites.
11:45 Circulating Tumor DNA Methylation Markers for Diagnosis and Prognosis of Hepatocellular Carcinoma
Kang Zhang, MD, PhD, Professor, Human Genetics and Nano-Engineering; Founding Director, Institute for Genomic Medicine, University of California, San Diego
We identified an HCC-specific methylation marker by comparing HCC tissue and normal blood leukocytes and showed that methylation profiles of HCC tumor DNA and matched plasma ctDNA are highly correlated. We constructed a diagnostic prediction model with high diagnostic specificity and sensitivity and was highly correlated with tumor burden, treatment response, and stage. Additionally, we constructed a prognostic prediction model that effectively predicted prognosis and survival.
12:15 pm Circulating Tumor DNA Analysis for Personalized Cancer Detection and Monitoring
Maximilian Diehn, MD, PhD, Associate Professor, Radiation Oncology, Stanford Cancer Institute, Institute for Stem Cell Biology & Regenerative Medicine, Stanford University
Circulating tumor DNA (ctDNA) represents a promising biomarker for sensitive, specific, and dynamic detection of disease burden in cancer patients. Mutations in tumor-derived DNA represent ideal potential biomarkers since they are highly specific to tumor cells and involved in disease pathogenesis. However, even in advanced cancer patients concentrations of ctDNA are often low and difficult to detect. We have developed a novel, ultra-sensitive and specific method for detection of circulatingtumor DNA called Cancer Personalized Profiling by Deep Sequencing (CAPP-Seq). This method was developed specifically for detection of ctDNA in non-small cell lung cancerpatients, although it is broadly applicable to other cancer types. In this presentation, I will describe our recent work on applications of ctDNA analysis in a variety of clinical settings.
12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:15 Session Break
1:45 Chairperson’s Remarks
Maximilian Diehn, MD, PhD, Associate Professor, Radiation Oncology, Stanford Cancer Institute, Institute for Stem Cell Biology & Regenerative Medicine, Stanford University
1:50 NEW: The Early Detection of Pancreatic Cancer: What Will It Take to Diagnose and Treat Curable Pancreatic Neoplasia?
Christopher Douville, PhD, Postdoctoral Researcher, Ludwig Center for Cancer Genetics & Therapeutics, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Institutions
2:20 Just Another Blood Test: The Path to Routine ctDNA Testing in Cancer
John Simmons, PhD, Director, Translational Science & Diagnostics, Personal Genome Diagnostics
2:50 Liquid Biopsy based on Flow Cytometry and Artificial Intelligence to Detect the Existence of a Solid Tumor
Amit Kumar, PhD, President and CEO, Anixa Diagnostics
We utilize flow cytometry of leukocytes with artificial intelligence to perform early detection of cancers. By monitoring the host immune system we are able to distinguish tumor-bearing individuals from healthy donors. Sensitivities and specificities are greater than 90% each. This is a simple, inexpensive, patented technology for liquid biopsy.
3:05 Implementation of Digital PCR in a Molecular Diagnostic Laboratory: Evaluation of Minimal Residual Disease
Benjamin Tournier, PhD, Laboratoire d'anatomie pathologique, CHU Dijon
In the Molecular Pathology department of the Dijon University Hospital, liquid biopsy analyses were set up since March 2016. Here we present the implementation of the 3-color Crystal Digital PCR system in our laboratory for the management of melanoma and lung cancer patients under targeted therapy.
3:20 Refreshment Break in the Exhibit Hall with Poster Viewing (Independence Ballroom)
3:55 Chairperson’s Remarks
Scott Kopetz, MD, PhD, FACP, Associate Professor, Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center
4:00 Circulating Tumor DNA as Prognostic and Predictive Marker in Colon, Lung and Pancreatic Cancer
Valerie Taly, PhD, CNRS Research Director (Dr2), Group Leader, Co-Director Ediag Platform, UFR Des Sciences Fondamentales Et Biomedicales, France
Recent technological and methodological developments such as droplet based digital PCR and optimized NGS have allowed the highly sensitive and quantitative detection of rare genetic and epigenetic events. We will present applications of these technologies to the highly sensitive and precise detection of circulating tumor DNA (ctDNA). In particular, we will illustrate the pertinence of ctDNA as a prognostic and predictive marker in colon, lung and pancreatic cancers.
4:30 Monitoring Cancer through the Blood
Cloud Paweletz, PhD, Head, Translational Research Laboratory, Belfer Center for Applied Cancer Science, Dana Farber Cancer Institute
Noninvasive assessment of tumor genotype using cell free DNA (cfDNA) represents an emerging technology that can overcome many of the current challenges in personalizing NSCLC care. There are a variety of assays available, some focused and rapid and others broad but more cumbersome (e.g. NGS). Indeed, some of these cfDNA genotyping technologies are being offered commercially for clinical use, however appropriate clinical application is uncertain and clinical validation efforts have been inconsistent. Here we present our institutional experiences implementing liquid biopsies into NSCLC care.
5:00 Treatment Response Monitoring and Minimal Residual Disease Detection on Adjuvant Study Design Considerations Utilizing Minimal Residual Disease
Scott Kopetz, MD, PhD, Associate Professor, Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center
Circulating tumor DNA (cfDNA) has the potential to identify patients with residual disease despite attempted curative resection with very high specificity. This opens possibilities for novel “adjuvant” study designs.
5:30 Networking Reception in the Exhibit Hall with Poster Viewing (Independence Ballroom)
6:30 Close of Day
THURSDAY, AUGUST 23
7:15 am Registration (Independence Foyer)
7:30 Problem Solving Breakout Sessions with Continental Breakfast (Independence F-I)
Clinical Implications of Clonal Hematopoiesis
Kelly Bolton, MD, Hematology-Oncology Fellow, Department of Medicine, Memorial Sloan Kettering
Complementarity of NGS and Optimized dPCR Approaches in Cancer Research
Valerie Taly, PhD, CNRS Research Director (Dr2), Group Leader, Co-Director Ediag Platform, UFR Des Sciences Fondamentales Et Biomedicales, France
- Pro and cons of both technics including recent optimizations
- Example of strategy using either approaches or combination of both
- How to choose the appropriate strategy for a given project?
8:25 Chairperson’s Remarks
Luis A. Diaz, MD, Head, Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, Conference Chairman
8:30 Clonal Hematopoiesis Is Common in Cancer Patients and Can Confound Clinical Genomic Profiling
Ahmet Zehir, PhD, Director, Clinical Bioinformatics, Assistant Attending, Pathology, Memorial Sloan Kettering Cancer Center
Clonal hematopoiesis (CH) is the somatic acquisition of genomic alterations in the hematopoietic stem cells/progenitors. CH is a common occurrence in advanced cancer patients that is strongly associated with aging, smoking and with radiation therapy. If unchecked, CH related genomic alterations can also confound genomic profiling of cancer patients in various settings. Here, I will describe our experience related to CH, in a prospective sequencing cohort at Memorial Sloan Kettering Cancer Center.
9:00 The Impact of Oncologic Therapy on the Risk of Clonal Hematopoiesis and Subsequent Hematologic Malignancy
Kelly Bolton, MD, Hematology-Oncology Fellow, Department of Medicine, Memorial Sloan Kettering
We used blood sequencing data from 17,000 solid tumor patients at MSKCC to identify clonal hematopoiesis. We show that exposure to radiation therapy and certain chemotherapy agents are associated with increased rates of CH which is, in turn, a major risk factor for therapy-related myeloid neoplasms. In 300 patients with CH with serial samples, we show that ongoing chemotherapy and radiation therapy influence clonal dynamics of CH.
9:30 SELECTED POSTER PRESENTATION: Single-Cell Small RNA-Seq by Microfluidic Chip Isotachophoresis with sRNA Library Preparation Using Chemically Modified Adapters
Dick Keys, PhD, Business Development Consultant, Trilink Biotechnologies
10:00 Coffee Break in the Exhibit Hall with Poster Viewing (Independence Ballroom)
11:15 am Chairperson’s Remarks
11:20 am - 12:00 pm TECHNOLOGY PANEL: Disruptive Technologies in Lab Medicine
Moderator: Gregory J. Tsongalis, PhD, HCLD, CC, Professor, Pathology; Director, Laboratory for Clinical Genomics and Advanced Technology (CGAT), Department of Pathology and Laboratory Medicine, Dartmouth Hitchcock Medical Center and The Audrey and Theodor Geisel School of Medicine at Dartmouth
- What is appropriate test utilization?
- How do you ensure both user and patient safety?
- How are tests implemented in the clinical setting?
- How do they get regulated?
- How do results get reported?
- How do you enforce quality control in implementation?
- How does it impact emerging applications such as liquid biopsies, infectious disease outbreaks, and POC diagnostics?
Panelists:
Rakesh Nagarajan, MD, PhD, Chief Biomedical Informatics Officer, PierianDx
Greg Richard, Chief Commercial Officer, Interpace Diagnostics
Crystal R. Icenhour, PhD, CEO, Aperiomics, Inc.
Additional Panelists to be Announced
12:00 - 12:45 pm Changing Approaches to Sustainable Funding in Diagnostics
Moderator: Bruce Quinn, MD, PhD, Principal, Bruce Quinn Associates
Today, many innovators in the diagnostics industry struggle for funding, and yet news of large scale acquisitions or large (over $30M) funding rounds pops up regularly. How can innovators better understand the changing dynamics of the funding environment to succeed? How can investors know if they are getting exposed to the potentially best investments? Whether government or private, what drives the final difficult decisions and how can companies raise their chances of success? This session features leaders from several different channels of funding for innovators, including the NIH, other federal programs, and corporate and traditional venture investors.
Panelists:
Alex DeWinter, PhD, Managing Director, GE Ventures
Tyler Merkeley, BARDA’s CARB-X Program Manager, Health Scientist, Division of CBRN Countermeasures, BARDA
Todd Haim, PhD, Program Director, National Cancer Institute SBIR Development Center
Wouter Meuleman, PhD, Director, Venture Investments, Illumina Ventures
12:45 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:15 Close of Clinical Application of Cell-Free DNA
6:30 - 9:00 pm Recommended Dinner Short Course*
SC11: Single-Cell RNA-Seq: Differential Expression Analysis and Quality Control
Michael Steinbaugh, PhD, Research Associate, Biostatistics, Harvard T.H. Chan School of Public Health
*Separate registration required