The use of circulating tumor DNA as a biomarker has grown in popularity given its ability to detect minimal residual disease and monitor treatment. Regardless of growing proof of its utility, much needs to be done to make liquid biopsy clinically useful.
With this in mind, Cambridge Healthtech Institute’s Third Annual Cell-Free DNA in Clinical Oncology will critically examine circulating biomarkers for use in guiding clinical diagnosis of cancer. This year’s event will place emphasis on
early detection, monitoring treatment response, and moving ctDNA into clinical practice. Logistical considerations for translation will also be addressed.
Final Agenda
TUESDAY, 11 APRIL
08:00 Registration and Morning Coffee
09:00 Chairperson’s Remarks
Helen Winter, Ph.D., Medical Oncologist and Clinical Research Fellow, Oncology, Green Templeton College, University of Oxford, United Kingdom
09:05 KEYNOTE PRESENTATION: Early Detection Using cfDNA: Promise and Challenges
Abhijit Patel, M.D., Ph.D., Assistant Professor, Therapeutic Radiology, Yale University, United
States
Because circulating tumor DNA can be identified on the basis of highly cancer-specific mutations, it holds great promise as a potential biomarker for the early detection of a variety of malignancies. However, there are several technical and biological
challenges that must be overcome to realize this goal. This presentation will review these challenges and the approaches being taken to address them.
09:35 Microfluidic Isolation of Cancer Cells from Body Fluids for Early and Non-Invasive Diagnosis of Cancer: Towards the Realization of Point-of-Care Liquid Biopsy
Lorena Diéguez, Ph.D., Staff Researcher, Life Sciences, International Iberian
Nanotechnology Laboratory, Portugal
Tumor cells escape the primary tumor and disseminate through the blood stream and lymphatic system, potentially invading other organs and causing metastasis. Cancer cells from primary tumors also shed into surrounding body fluids, thus the study of
tumor cells contained in body fluids offers unique opportunities for low invasive sampling in cancer patients, either for early diagnosis or for accurate prognosis. Our goal is to provide efficient inexpensive microfluidic tools to isolate and
molecularly characterize tumor cells from unprocessed samples, overall relevant for early cancer detection, better prognosis and personalized treatment.
10:05 Nu.Q Triage Colorectal Cancer Screening Test
Mark Eccleston, Business Development Director, Volition, Belgium
Individuals who screen +ve by faecal immunochemical test (FIT) are referred for colonoscopy. However, < 95% have colorectal cancer placing a severe burden on the patient and the healthcare system. Triaging FIT +ve patients using a blood-based Nu.Q
Triage Colorectal Cancer Screening Test can reduce colonoscopy referrals by 25%.
10:20 Multiplex Assays on Liquid Biopsy: A Practical Approach for CDx by πCode Technology
Stuart Palmer, Ph.D., COO, PlexBio Co., Ltd., Taiwan
PlexBio has developed a multiplex detection platform based on the Precision Image Code (πCode) Technology
which is applicable to high complexity mutation analysis. PlexBio’s IntelliPlex Mutation Kits are designed to be used in combination with the SelectAmp PCR technology to assess the status of mutations in a number of key genes (e.g. EGFR,
KRAS, BRAF, NRAS, PIK3CA, ALK and ROS1).
10:35 Coffee Break in the Exhibit Hall with Poster Viewing
11:15 Clinical Impact of a High-Sensitivity ctDNA Assay and Analytics for Low Frequency Mutations for Patient Monitoring and Stratification
Vincent Plagnol, Ph.D., Vice President, Computational Biology, Inivata, United Kingdom
Inivata has developed a highly sensitive assay for the detection and quantification of circulating cancer mutations in plasma. This incorporates improved molecular and analytical processes. We will show how very accurate ctDNA measurements can impact
the management of cancer patients, and can be used for longitudinal monitoring of resistance mutations and choice of treatment. We will also highlight the value of refined analytics for detection of these calls.
11:45 Monitoring and Sequencing Cell-Free DNA in Patients Receiving Selective Internal Radiation
Helen Winter, Ph.D., Medical Oncologist and Clinical Research Fellow, Oncology, Green Templeton
College, University of Oxford, United Kingdom
Analysis of cell-free (cf)DNA to monitor response to treatment is an emerging research priority. The objective of this study was to sequence serial cfDNA from patients with metastatic liver disease receiving SIRT, exploring the feasibility of
this method to detect the evolution of somatic mutations after high dose radiation. Results presented are from patients at 3 time points: baseline (before SIRT), 4 and 10 weeks after SIRT using Ion Torrent Amplicon sequencing.
12:15 Parsortix: Utilise Both cfDNA and CTCs from a Single Patient Sample
Michael O’Brien, MBA, Business Development Director, ANGLE plc, United Kingdom
Maximising the ‘liquid biopsy’ insight from each patient sample is important. The Parsortix system from ANGLE, allows collection of plasma for cfDNA analysis whilst isolating CTCs. It captures all subtypes of CTCs from blood, using
an epitope independent isolation approach, and hence outperforms more widely available antibody based technologies. Here we share a range of studies and outputs using Parsortix to illustrate the opportunities it opens up for research……getting
the most out of every sample.
12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
13:15 Session Break
14:15 Chairperson’s Remarks
Abhijit Patel, Ph.D., Assistant Professor, Therapeutic Radiology, Yale University, United States
14:20 Methylated Circulating DNA in Monitoring Cancer Treatment Response
Kristina Warton, Ph.D., Senior Research Officer, Garvan Institute of Medical
Research, Australia
The levels of tumour-derived circulating DNA in blood are related to tumour burden, and fluctuations can reflect the response to clinical interventions such as surgery and chemotherapy, helping to guide treatment choices. Compared to DNA mutations,
which are highly variable, DNA methylation is relatively consistent between individual tumours, and can also be measured by PCR. Measuring tumour-specific circulating DNA methylation offers a time-efficient, cost-efficient approach to
monitoring tumour dynamics.
14:50 Cell-Free DNA: A Novel Gateway to the Genome of Hodgkin/Reed-Sternberg Cells in Hodgkin’s Lymphoma?
Peter Vandenberghe, Ph.D., Head, Haematology, University Hospitals
Leuven, Belgium
The rapid normalisation of circulating cell-free DNA profiles on therapy initiation suggests a potential role for circulating cell-free DNA profiling in early response monitoring. This finding creates several new possibilities for exploring
the diversity of Hodgkin’s lymphoma, and has potential implications for the future clinical development of biomarkers and precision therapy for this malignancy.
15:20 Could Circulating Tumor Cells (CTCs) Monitoring and Characterization, Reflect the Response to Treatment in NSCLC?
Elisabetta Rossi, Ph.D., Researcher, Surgical Oncology and Gastroenterology, University of Padova, Italy
Circulating tumour cells (CTCs) serve as valuable biomarkers. Recent experiences demonstrated that CTC detection could help improve diagnosis and predict prognosis in patients with non–small cell lung cancer (NSCLC). However, EpCAM positive
CTCs are less frequently detected in NSCLC patients compared to other epithelial tumours. We questioned whether we could detect a higher number of CTCs by implementing the standard CellSearch® assay and if we could better monitor response
to therapy.
15:50 Refreshment Break in the Exhibit Hall with Poster Viewing
16:30 Role of dPCR in Supporting the Standardisation of Liquid Biopsy Measurements
Alison Devonshire, Ph.D., Science Leader, Molecular and Cellular
Biology, LGC Ltd., United Kingdom
Molecular measurements of tumour associated mutations in cfDNA offer an increasingly popular option for cancer management; however mechanisms to ensure reproducible clinical analysis are yet to be established. Digital PCR (dPCR) has the potential
to ensure greater confidence in measurement by acting as a reference method for reference material certification and clinical samples analysis. This talk will discuss dPCR performance when varying assays, reaction chemistries and platforms
when measuring single nucleotide variants. An inter-laboratory study involving >20 laboratories was also performed to evaluate reproducibility when analysing a mutation commonly measured in liquid biopsies.
17:00 Standardization of Liquid Biopsies for Precision Medicine in Oncology – A Task for Clinical Biobanks?
Jens K. Habermann, Ph.D., Professor and Head, Surgery, Translational Surgical
Oncology & Biobanking, University of Lübeck, Germany
Liquid biopsies harbor an enormous potential for precision medicine. However, clinical implementation requires standardization. This is in contrast to e.g., CTC assessment in colorectal cancer, which is still hampered by major inter-study
heterogeneity. This talk will address (i) current challenges for standardized assessment of CTCs, cfDNA, RNA, and exosomes, (ii) how standardization can be facilitated, and (iii) how clinical biobanks can support liquid biopsies’
use for research and precision medicine.
17:30 Standardization of ctdna Analysis for Use in the Clinical Setting Under the Umbrella of CANCER-ID
Thomas Schlange, Senior Biomarker Scientist, Global Biomarker Research, Bayer,
Germany
The IMI CANCER-ID consortium with 36 partners from academia, clinic and industry collaborate on the evaluation of liquid biopsy technologies and development of corresponding workflows for the use of these technologies in the clinical setting.
The focus in ctDNA analysis is directed at preanalytics, use of standards for NGS approaches on NSCLC and breast cancer plasma samples, detection limits, concordance between liquid and conventional biopsy and comparison of bioinformatics
methods.
18:00 Welcome Reception in the Exhibit Hall with Poster Viewing
19:00 Close of Day
WEDNESDAY, 12 APRIL
08:00 Registration and Morning Coffee
09:00 Chairperson’s Remarks
Kristina Warton, Ph.D., Senior Research Officer, Garvan Institute of Medical Research, Australia
09:05 Clinical Applications of Liquid Biopsy: Potential and Challenges
Klaus Pantel, M.D., Professor and Founding Director, Institute of Tumor Biology, University
Medical Center Hamburg-Eppendorf, Germany
Clinical applications of liquid biopsies in precision medicine include early detection of cancer, surveillance of minimal residual disease and stratification of patients for targeted therapies based on the molecular analysis of genes such
as EGFR or KRAS that encode therapeutic targets or confer resistance mechanisms. The potential and challenges of liquid biopsy analyses (cfDNA vs. CTCs) will be discussed in the context of specific therapies (e.g., drug-induced blockades
of EGFR or immune checkpoint inhibitors) and tumor types.
09:35 Monitoring Treatment Response and Identification of Actionable Targets from Plasma DNA
Ellen Heitzer, Ph.D., Associate Professor, Institute of Human Genetics, Medical
University Graz, Austria
Molecular stratification of patients to targeted therapies is currently based on a molecular characterization of tumors tissues. A liquid biopsy, i.e. the analysis of circulating tumour DNA (ctDNA), is a promising alternative to tissue biopsies
since it is minimal-invasive, it can be immediately analyzed, and most likely provides a more complete molecular profile of tumor heterogeneity than a single biopsy achieves. Moreover, a continuous monitoring of tumor-specific changes
during the entire course of the disease, can be achieved.
10:05 Improved Material for Developing, Validating and Monitoring Liquid Biopsy Assays
Dale Yuzuki, MA, Med, Director, Market Development - Oncology, SeraCare Life Sciences
Random ultrasonication-based fragmentation methods have inherent weaknesses. Current liquid biopsy reference material needs include standards that are more commutable to native samples, and behave in NGS library preparation close to native
DNA from plasma. SeraCare has highly multiplexed, human-like NIPT and ctDNA QC standards that are stabilized in plasma matrices.
10:20 Crystal
Digital PCR for Detection and Quantification of Circulating EGFR Mutations in Advanced Non-Small Cell Lung Cancer
Cécile Jovelet, Pharm.D., Ph.D., Postdoctoral Fellow, Translational Research
Lab, Gustave Roussy Institute, France
Targeted therapies increase the progression-free survival for non-small cell lung cancer patients harboring specific mutations. Molecular monitoring of tumor is required to detect the resistance mutation EGFR T790M which requires alternative
therapeutic approaches. This talk discusses the use of Crystal™ Digital™ PCR for monitoring the EGFR mutational status in ctDNA.
10:35 Coffee Break in the Exhibit Hall with Poster Viewing
11:05 Establishment and Characterization of a Cell Line from Human Circulating Colon Cancer Cells
Catherine Alix-Panabières, Ph.D., Maître
de Conférence, Praticien Hospitalier, Associate Professor, Director, Laboratory of Rare Human Circulating Cells, Institute of Research in Biotherapy, Saint-Eloi Hospital, University Medical Centre of Montpellier, France
The unique colon CTC-MCC-41 cell line displays a very specific transcription program. Interestingly, among the 1,624 transcripts exclusively upregulated in CTC-MCC-41 samples compared to other colon cancer cell lines obtained from primary
tumors or from metastatic sites, key genes related to energy metabolism, DNA repair and stemness genes were observed. Such data may supply insights for the discovery of new biomarkers to identify the most aggressive CTC sub-populations
and for the development of new drugs to inhibit metastasis-initiator CTCs in colon cancer.
11:35 Circulating Tumor DNA Clinical Application
Pierre Laurent-Puig, M.D., Ph.D., Professor, Paris Descartes University,
France
The clinical implication of circulating tumor DNA will be discussed in different tumor locations (pancreas, colon and lung cancer).
12:05 Close of Cell-Free DNA in Clinical Oncology