Clinical Application of Cell-Free DNA

In the era of personalised medicine, personalised diagnostics are essential to guide clinicians’ choice of therapies. Cell-free DNA (cfDNA) testing is proving to be a pioneering technology that meets the clinical need of non-invasiveness and ease of use. cfDNA technologies have been maturing rapidly and are continuing to be improved for better sensitivity and specificity. However, experts in the field are still working to establish how to implement these technologies in clinical settings. In this year’s conference, we will focus on emerging clinical applications of cell-free DNA tests, such as longitudinal monitoring of disease progression, assessment of treatment response, and prognosis following curative-intent therapy. We will also address standardization of pre-analytical and analytical methodologies, which is much needed for implementation of cell-free DNA in a clinical context.

Final Agenda

Recommended Short Course*

SC3: Liquid Biopsy for P4 Medicine: Predictive, Preventive, Personalized and Participatory [View Detailed Agenda]

Lorena Diéguez, PhD, Staff Researcher, Diagnostic Tools and Methods Research Group, Life Sciences, International Iberian Nanotechnology Laboratory, Portugal

Clotilde Costa Nogueira, PhD, Head, Liquid Biopsy Line, Roche-Chus Joint Unit, University Hospital of Santiago de Compostela, Spain

P4 Medicine is Predictive, Preventive, Personalized and Participatory. The P4 medicine concept is fully realised in the context of Liquid Biopsy, since the patient’s blood is used as a biomarker for the prognosis and diagnosis of the disease status. Therefore, Liquid Biopsy provides the ideal scheme to personalize the treatment in precision medicine. P4 medicine will permit to identify predictive and preventive biomarkers and genomic mapping, adapting treatments to each patient, and having the patients engaged for a successful outcome.

*Separate Registration required.



08:00 Registration and Morning Coffee

09:00 Chairperson’s Remarks

Jacqui Shaw, PhD, Professor, Translational Medicine, University of Leicester, United Kingdom


09:05 KEYNOTE PRESENTATION: Liquid Biopsies: Detection and Monitoring of Breast and Lung Cancer

Jacqui Shaw, PhD, Professor, Translational Medicine, University of Leicester, United Kingdom

We are living in an era of remarkable innovation and progress in cancer research such that we have transitioned over the last 20 years from 1 in 3 people surviving cancer to now 1 in 2, with the expectation that similar progress will allow 3 in 4 to survive by 2034. One of the most exciting innovations for patients with cancer is the recent development of the so-called “liquid biopsy”, which involves taking a small blood sample (1-2 table spoons of blood) and testing this in the laboratory for cancer specific markers allowing earlier diagnosis, detection of disease progression, monitoring patients on treatment and enabling better targeted treatments to be offered to the patient. My group has systematically reviewed ctDNA blood biomarkers for the early detection of cancer. In this talk I will focus on liquid biopsies ofr detection and monitoring of breast and lung cancers.

09:35 Impact of Circulating Tumor DNA Analysis on Prognosis and Therapy Monitoring in Metastatic Cancer Patients

Ellen_HeitzerEllen Heitzer, PhD, Associate Professor, Institute of Human Genetics, Medical University Graz, Austria

Tumor-specific sequence alterations in plasma were used to quantify tumor burden or for genome-wide analyses of tumor genomes, and it has been shown that ctDNA can be used to monitor tumor dynamics. Here, the use of untargeted ctDNA analysis, i.e plasma-Seq and mFAST-SeqS, for patient stratification and monitoring treatment response will be discussed.

10:05 Implementation of Digital PCR in a Molecular Diagnostic Laboratory: Evaluation of Minimal Residual Disease

Benjamin_TournierBenjamin Tournier, PhD, Laboratoire d’anatomie pathologique, CHU Dijon, France
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. 

10:35 Coffee Break in the Exhibit Hall with Poster Viewing

11:15 Tracking Circulating Tumor DNA for Cancer Patient Follow-Up

Valerie_TalyValerie Taly, PhD, CNRS Research Director (Dr2), Group Leader, Co-Director Ediag Platform, UFR Des Sciences Fondamentales Et Biomedicales, France

Droplet based digital PCR and newly developed optimized NGS technologies allow us to highlight rare genetic events with an unprecedented sensitivity and precision. The application of these strategies to solve important challenges in personalized medicine will be exemplified. Results of retrospective and prospective studies will be presented. In particular, we will highlight the pertinence of the quantitative analysis of circulating tumor DNA to: (i) perform advanced or locally advanced cancer patients follow up including specific application to treatment efficiency monitoring and (ii) detect early recurrence of cancer for localized cancer patients.

11:45 Circulating Cell-Free DNA for Metastatic Cervical Cancer Detection, Genotyping and Monitoring

Liang_CaoLiang Cao, PhD, Head, Molecular Targets Core Lab, National Cancer Institute (NCI), MD, United States

We developed novel cell-free DNA (ccfDNA) assays and showed that ccfDNA analysis is effective for genotyping of tumor HPV in patient selection for a targeted T-cell therapy. In addition, our data further demonstrate a potential for ccfDNA for assessing the response and monitoring remission in recurrent metastatic cervical cancer patients with complete responses to the HPV-specific T cell therapy.

12:15 Epigenetic Biomarkers for Early Detection and Monitoring of Cancer

Guro_LindGuro Elisabeth Lind, PhD, Professor and Group Leader, Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, Norway

Highly sensitive analyses of body fluids have emerged as a promising approach for identifying disease-specific molecular alterations. We will demonstrate how analyses of DNA methylation biomarkers in biomaterials such as urine and bile can be used for early detection of cancer and for monitoring of disease.

12:45 Nucleosomics® - Development and Clinical Applications of Cell Free Circulating Nucleosome Profiling Immunoassays

Mark_EcclestonMark Eccleston, Business Development Director, Volition, Belgium

Volition has developed a range of low cost, simple to use Immunoassays to quantify epigenetic features on nucleosomes. These Nu.Q™ assays can be used to profile circulating cell free nucleosomes in blood samples in a range of cancers to generate profiles with diagnostic and screening applications. Volition is finalising diagnostic and screening panels for colorectal cancer in large clinical studies. The Nu.Q™assay range is being developed for research use applications to explore additional application.

13:15 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

13:45 Session Break


14:15 Clinical Relevance of Circulating, Cell-Free and Exosomal microRNAs in Plasma and Serum of Breast and Ovarian Cancer Patients

Heidi_SchwarzenbachHeidi Schwarzenbach, PhD, Associate Professor, Group Leader, Tumor Biology, University Medical Center Hamburg-Eppendorf, Germany

Our studies show a network of deregulated cell-free and exosomal microRNAs involved in regulation of cancer-associated signaling pathways and associated with a particular biology of gynecological tumors. Moreover, the excessive secretion of exosomes in breast and ovarian cancer patients is reflected by a predominant microRNA presence in exosomes.


14:45 Chairperson’s Remarks

Daniel Wetterskog, PhD, Senior Scientific Officer, Treatment Resistance, Molecular Pathology, ICR, Royal Marsden NHS Foundation Trust, United Kingdom

14:50 Predicting Response to Radical (Chemo)Radiotherapy with Circulating HPV DNA Locally-Advanced Head and Neck Squamous Carcinoma

Shreerang_BhideShreerang Bhide, PhD, MBBS, MRCP, FRCR, Consultant Clinical Oncologist and Honorary Senior Lecturer, The Royal Marsden Hospital, The Institute of Cancer Research, United Kingdom

Following chemo-radiotherapy (CCRT) for human papilloma virus positive (HPV+) locally advanced head and neck cancer, patients frequently undergo unnecessary neck dissection (ND) and/or repeated biopsies for abnormal PET-CT, which causes significant morbidity. We assessed the role of circulating HPV DNA in identifying “true” residual disease. We demonstrate that HPV16-detect is a highly sensitive and specific test for identification of HPV DNA in plasma at diagnosis. HPV DNA post-treatment correlates with clinical response.

15:20 Clinical Implication and Real-World-Experience of PCR-Beaming in RAS Assessment in Metastatic Colorectal Cancer Patients

Jesus_Garcia-FoncillasJesus Garcıa-Foncillas, MD, PhD, Director, Cancer Institute, University Hospital “Fundacion Jimenez Diaz”, Autonomous University, Madrid, Spain

The importance of RAS mutation for advanced colorectal cancer treatment is well established. However, due to delays in turnaround time, low-quality tissue samples, and/or lack of standardization of testing methods, a significant proportion of patients are being treated without this information. The overall concordance between liquid biopsy and standard of care tissue testing is very high. This presentation reviews the clinical utility and potential applications of this minimally invasive method.

15:50 Clinical Application of Liquid Biopsies in the Management of Patients with Prostate Cancer

Daniel_WetterskogDaniel Wetterskog, PhD, Senior Scientific Officer, Treatment Resistance, Molecular Pathology, ICR, Royal Marsden NHS Foundation Trust, United Kingdom

Our group has been using liquid biopsies to interrogate resistance in castration-resistant prostate cancer (CRPC) and develop biomarkers for selecting treatment. Previously, we demonstrated the potential utility of analyzing circulating tumour DNA to identify prostate cancer patients likely to benefit from the targeted therapies abiraterone and enzalutamide. Our current projects are investigating RNA expression profiles and methylation status of ctDNA found in liquid biopsies as predictive and prognostic biomarkers. In addition, using a rapid autopsy program, we have gained understanding how ctDNA reflects the genomic and epigenomic landscape of different metastatic lesions.

16:20 Refreshment Break in the Exhibit Hall with Poster Viewing

17:00 Breakout Discussions

Role of Free Nucleic Acids in Acute Neural Injuries

Andrea Regner, MD, PhD, Cellular and Molecular Biology Applied to Health, Lutheran University of Brazil, Canoas, Brazil; Course of Medicine, Lutheran University of Brazil, Canoas, Brazil

  • Are free nucleic acids involved in neural injury progression in the traumatic penumbra?
  • Are free nucleic acids a promise for neurorestoration?
  • From bench-to-bedside: what is the prognostic value of free nucleic acids in critically ill patients?

Quantification of Exosomal MicroRNAs

Heidi Schwarzenbach, PhD, Associate Professor, Group Leader, Tumor Biology, University Medical Center Hamburg-Eppendorf, Germany

  • Extraction methods of exosomes and microRNAs
  • Predominant circulation of microRNAs in exosomes or as cell-free molecules
  • microRNA normalization with a reliable reference microRNA
  • Discrepancies in up- and downregulation of microRNAs

18:00 Welcome Reception in the Exhibit Hall with Poster Viewing

19:00 Close of Day



08:00 Registration and Morning Coffee

09:00 Chairperson’s Remarks

Daniel Wetterskog, PhD, Senior Scientific Officer, Treatment Resistance, Molecular Pathology, ICR, Royal Marsden NHS Foundation Trust, United Kingdom

09:05 Liqbiopsens: A Novel, Reliable and Affordable Platform for Colorectal Cancer Patients Screening.

M_Jose_SerranoM. Jose Serrano Fernández, PhD, Director, Liquid Biopsies Division, Liquid Biopsies & Metastasis Group Senior Research UGC Oncologia, Hospital Virgen de las Nieves, Spain

The overall aim of LIQBIOPSENS project is the further development and validation in real settings of a novel diagnostic platform for the early and fast detection of ctDNA and their KRAS and BRAF mutations associated to colorectal cancer through blood samples. The main features of LIQBIOPSENS are: reliability (detection rates vary from 95–100 %), low-cost (40-50 € per sample analysis), sensitivity (in the zM range), multiplexing capabilities (analysis of 27 KRAS and BRAF mutations simultaneously), short analysis time (30-60 min.), user-friendly interface and flexibility.


09:35 The Role of Cell-Free Nucleic Acids in Prognosis Prediction and Neurorestoration after Severe Traumatic Brain Injury

Andrea_RegnerAndrea Regner, MD, PhD, Professor, Cellular and Molecular Biology Applied to Health, Course of Medicine, Lutheran University of Brazil, Canoas, Brazil

Traumatic brain injury (TBI) is the leading cause of mortality in young individuals worldwide. In this context, the investigation of cell-free nucleic acids following acute neural injuries may indicate patients at higher risk for deterioration and guide novel therapeutic strategies. We will present (i) results of a prospective cohort including 400 severe TBI patients, and (ii) discuss the role of cell-free nucleic acids in prognosis prediction and neurorestoration after neurotrauma.

10:05 Identification of Tissue-Specific Cell Death Using Methylation Patterns of Circulating DNA

Yuval_DorYuval Dor, PhD, Professor, Developmental Biology and Cancer Research, The Hebrew University-Hadassah Medical School, Jerusalem, Israel

We have developed a method of detecting tissue-specific cell death, based on cfDNA methylation patterns. We identified tissue-specific DNA methylation signatures, and used bisulfite sequencing to detect these in cfDNA. I will present analysis of the tissue sources of cfDNA in healthy individuals and in diabetes, myocardial infarction, sepsis and cancer. The approach allows monitoring a broad spectrum of human pathologies, as well as better understanding of normal tissue dynamics.

 Biorad10:35 Cerebrospinal Fluid ctDNA: A Potential Tool for the Molecular Diagnostics of Gilomas using Droplet Digital PCR

Regina_Mayor-FerrerasRegina Mayor Ferreras, PhD, Vall d’Hebron Institute of Oncology

Diffuse gliomas are the most common primary tumors of the brain and include different subtypes with diverse prognosis. The genomic characterization of diffuse gliomas facilitates their molecular diagnosis. Taking advantage of the presence of circulating tumor DNA in the cerebrospinal fluid of glioma patients, we have developed a molecular platform, to simultaneously and rapidly genotype seven genes by targeted exome sequencing and droplet digital PCR, facilitating patient sub-classification to support their surgical and clinical management.

11:05 Coffee Break in the Exhibit Hall with Poster Viewing

plenary session

11:35 Plenary Introduction

John_CarranoJohn Carrano, CEO, Paratus Diagnostics, LLC, United States

11:45-12:15 The New EU IVD Regulation – What Will It Mean for Your Lab?

David_BartonDavid E. Barton, PhD, Chief Molecular Geneticist, National Centre for Medical Genetics, Our Lady’s Hospital for Sick Children, Ireland

In May 2017, Europe passed a new Regulation on in vitro Diagnostic Devices (IVDs). The regulation sets up a framework for controlling the market for diagnostic tests within the EU, setting out standards for the design and manufacture of in-vitro diagnostic devices (IVDs) and providing mechanisms for the oversight of these standards. This presentation will outline the content of the new regulations, with a particular focus on molecular diagnostics, and highlight the new requirements for clinical laboratories.

12:15-12:25 Introduction: Medicinal Product Regulators Point of View: Scientific-Regulatory Aspects of Companion Diagnostics and Challenges for Validation during Clinical Co-Development (Quality-Related Aspects)

Jorg_EngelbergsJörg Engelbergs, PhD, Scientific Expert and Assessor Biomedicines (Quality, Non-Clinic & Personalized Medicine), Section Mono- and Polyclonal Antibodies, Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, Germany

In Europe, the legislation for marketing of medicinal products (MP) and IVDs including predictive biomarker-based assays (Companion Diagnostics, CDx) are not directly linked which is challenging for co-development. The new IVDD involves MP regulators in the CDx review process for CE marking. This presentation will outline from the perspective of MP regulators the scientific-regulatory challenges for technical validation of CDx. Differences between exploratory assays and assays used for patient stratification, as well as aspects for complex assays will be addressed.

12:25-13:30 PANEL DISCUSSION: Changing Landscape for IVDs in the EU

Charlotte_RyckmanCharlotte Ryckman, Covington & Burling LLP, Belgium

David_BartonDavid E. Barton, PhD, Chief Molecular Geneticist, National Centre for Medical Genetics, Our Lady’s Hospital for Sick Children, Ireland

Jorg_EngelbergsJörg Engelbergs, PhD, Section Mono- and Polyclonal Antibodies, Scientific Expert Biomedicines, Quality, Non-Clinic & Personalized Medicine (Biomarker/CDx), Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, Germany

Maria_NevesMaria Judite Neves, Health Products Director, Health Products Directorate, INFARMED – National Authority of Medicines and Health Products, Portugal

Sue_SpencerSue Spencer, Global Service Director, Regulatory, UL, United Kingdom

Andreas_StangeAndreas F. Stange, PhD, Vice President, MHS Global IVD, TÜV SÜD, Germany

Doris-Ann_WilliamsDoris-Ann Williams, MBE, Chief Executive, British In Vitro Diagnostics Association (BIVDA), United Kingdom

  • Practical impact of the new IVD Regulation
  • Regulatory aspects of companion diagnostics
  • Challenges for validation
  • Role of IVDs in the market

13:30 Close of Clinical Application of Cell-Free DNA