Session: Liquid Profiling to Guide Cancer Therapies

Session Chair: Dr. Christof Winter, Prof. Dr. Stefan Holdenrieder, Prof. Dr. Stefan Holdenrieder, Dr. med. Christof Winter
Englisch

Liquid Biopsy in Oncology - From research to clinical practice

Frank Holtrup, Sysmex Inostics
Evidence supporting the utilization of liquid biopsies in clinical practice continues to increase. With the introduction of many new liquid diagnostic assays, it is now more complex than ever to select the right test for each clinical intended use. It is essential to understand how the performance characteristics of liquid biopsy testing strategies impact the results and the extent to which patient management can be informed. In this presentation, we will review Sysmex Inostics’ highly sensitive circulating tumor DNA (ctDNA) technologies including OncoBEAM™ enhanced digital PCR and SafeSEQ NGS, which were initially developed by experts at the Johns Hopkins University School of Medicine [1, 2, 3]. OncoBEAM and SafeSEQ assays can detect the presence of very few ctDNA mutant molecules amidst a population of predominantly wildtype molecules, making them suitable for a wide variety of tumor types and clinical intended uses. In addition to targeted therapy selection, these technologies have enabled pioneering work in treatment response monitoring and detection of emerging resistance, as well as measurable residual disease detection. Recent evidence will be described which demonstrates how incorporating OncoBEAM and SafeSEQ ctDNA assessments into patient management can influence patient care decisions and may improve clinical outcomes.
Englisch

Liquid Biopsy in Oncology - From research to clinical practice

Frank Holtrup, Sysmex Inostics
Evidence supporting the utilization of liquid biopsies in clinical practice continues to increase. With the introduction of many new liquid diagnostic assays, it is now more complex than ever to select the right test for each clinical intended use. It is essential to understand how the performance characteristics of liquid biopsy testing strategies impact the results and the extent to which patient management can be informed. In this presentation, we will review Sysmex Inostics’ highly sensitive circulating tumor DNA (ctDNA) technologies including OncoBEAM™ enhanced digital PCR and SafeSEQ NGS, which were initially developed by experts at the Johns Hopkins University School of Medicine [1, 2, 3]. OncoBEAM and SafeSEQ assays can detect the presence of very few ctDNA mutant molecules amidst a population of predominantly wildtype molecules, making them suitable for a wide variety of tumor types and clinical intended uses. In addition to targeted therapy selection, these technologies have enabled pioneering work in treatment response monitoring and detection of emerging resistance, as well as measurable residual disease detection. Recent evidence will be described which demonstrates how incorporating OncoBEAM and SafeSEQ ctDNA assessments into patient management can influence patient care decisions and may improve clinical outcomes.
Englisch

Liquid Biopsy in Oncology - From research to clinical practice

Frank Holtrup, Sysmex Inostics
Evidence supporting the utilization of liquid biopsies in clinical practice continues to increase. With the introduction of many new liquid diagnostic assays, it is now more complex than ever to select the right test for each clinical intended use. It is essential to understand how the performance characteristics of liquid biopsy testing strategies impact the results and the extent to which patient management can be informed. In this presentation, we will review Sysmex Inostics’ highly sensitive circulating tumor DNA (ctDNA) technologies including OncoBEAM™ enhanced digital PCR and SafeSEQ NGS, which were initially developed by experts at the Johns Hopkins University School of Medicine [1, 2, 3]. OncoBEAM and SafeSEQ assays can detect the presence of very few ctDNA mutant molecules amidst a population of predominantly wildtype molecules, making them suitable for a wide variety of tumor types and clinical intended uses. In addition to targeted therapy selection, these technologies have enabled pioneering work in treatment response monitoring and detection of emerging resistance, as well as measurable residual disease detection. Recent evidence will be described which demonstrates how incorporating OncoBEAM and SafeSEQ ctDNA assessments into patient management can influence patient care decisions and may improve clinical outcomes.
Englisch

Liquid profiling of head and neck cancer patients with plasma and saliva

Romina Rösch, Klinikum rechts der Isar der TU München
Tumor-derived DNA is present in body fluids of cancer patients. Hence, liquid profiling is a promising minimal-invasive tool with great diagnostic and monitoring potential. It can complement invasive biopsies that provide only a snapshot of an often heterogeneous tumor. In contrast, repeated liquid profiling can track changes over time and detect tumor resistance occurring during therapy. Here, we share our latest results on liquid profiling in blood and saliva of head and neck cancer patients.
Englisch

Liquid profiling of head and neck cancer patients with plasma and saliva

Romina Rösch, Klinikum rechts der Isar der TU München
Tumor-derived DNA is present in body fluids of cancer patients. Hence, liquid profiling is a promising minimal-invasive tool with great diagnostic and monitoring potential. It can complement invasive biopsies that provide only a snapshot of an often heterogeneous tumor. In contrast, repeated liquid profiling can track changes over time and detect tumor resistance occurring during therapy. Here, we share our latest results on liquid profiling in blood and saliva of head and neck cancer patients.
Englisch

Liquid profiling of head and neck cancer patients with plasma and saliva

Romina Rösch, Klinikum rechts der Isar der TU München
Tumor-derived DNA is present in body fluids of cancer patients. Hence, liquid profiling is a promising minimal-invasive tool with great diagnostic and monitoring potential. It can complement invasive biopsies that provide only a snapshot of an often heterogeneous tumor. In contrast, repeated liquid profiling can track changes over time and detect tumor resistance occurring during therapy. Here, we share our latest results on liquid profiling in blood and saliva of head and neck cancer patients.
Englisch

Liquid Biopsy – A Molecular Pathology Perspective

Claudia Vollbrecht, Charité - Universitätsmedizin Berlin
The approval of liquid biopsies (LB) for mutation detection of resistances in non-small cell lung cancer (NSCLC) was the start of a new and increasing field in the molecular pathology. The minimal-invasive analysis of circulating tumor DNA (ctDNA) from blood can be an alternative approach to identify patients carrying therapeutic relevant mutations. Beside the great potential of the LB approach, there are several drawbacks. The successful use of LB for the detection of druggable mutations is influenced by a number of variables that are still not fully understood (e.g. origin and release of cfDNA, conditions during sampling). Therefore, a deep understanding of the entire workflow and highly standardized protocols are essential to ensure reliable and reproducible results for the benefit of correct patient stratification.
Englisch

Liquid Biopsy – A Molecular Pathology Perspective

Claudia Vollbrecht, Charité - Universitätsmedizin Berlin
The approval of liquid biopsies (LB) for mutation detection of resistances in non-small cell lung cancer (NSCLC) was the start of a new and increasing field in the molecular pathology. The minimal-invasive analysis of circulating tumor DNA (ctDNA) from blood can be an alternative approach to identify patients carrying therapeutic relevant mutations. Beside the great potential of the LB approach, there are several drawbacks. The successful use of LB for the detection of druggable mutations is influenced by a number of variables that are still not fully understood (e.g. origin and release of cfDNA, conditions during sampling). Therefore, a deep understanding of the entire workflow and highly standardized protocols are essential to ensure reliable and reproducible results for the benefit of correct patient stratification.
Englisch

Liquid Biopsy – A Molecular Pathology Perspective

Claudia Vollbrecht, Charité - Universitätsmedizin Berlin
The approval of liquid biopsies (LB) for mutation detection of resistances in non-small cell lung cancer (NSCLC) was the start of a new and increasing field in the molecular pathology. The minimal-invasive analysis of circulating tumor DNA (ctDNA) from blood can be an alternative approach to identify patients carrying therapeutic relevant mutations. Beside the great potential of the LB approach, there are several drawbacks. The successful use of LB for the detection of druggable mutations is influenced by a number of variables that are still not fully understood (e.g. origin and release of cfDNA, conditions during sampling). Therefore, a deep understanding of the entire workflow and highly standardized protocols are essential to ensure reliable and reproducible results for the benefit of correct patient stratification.

Liquid biopsy - a molecular perspective

The approval of 3rd generation tyrosine kinase inhibitors for the treatment of non-small cell lung cancer based on mutation detection by liquid biopsy (LB) led to integration of LB analysis in molecular pathology diagnostics [1]. Due to poor accessibility and the often unfavorable general clinical condition of patients with advanced tumor stage the assessment of standard tissue biopsies is sometimes difficult [2]. LB enable mutation detection using cell-free, circulating tumor DNA (ctDNA), are minimally invasive and can be an alternative to conventional tissue biopsy. However, the results of LB analysis are influenced by many factors like tumor status, patient's condition, the blood collection, ctDNA extraction and analysis methods as well as data interpretation. In the past years, experience showed the need for standardized protocols to minimize the impact of various factors on the results and to ensure comparability across different sites. This also includes communication with physicians to coordinate the processes for blood sampling and regular participation of round robin tests [3]. Meanwhile, LB analysis found its way to colorectal therapy guidelines for RAS mutation testing and can be an option for PIK3CA testing in breast cancer patients [4,5]. Currently, LB are rarely exploited in everyday clinical practice but taking into account and harmonizing the criteria mentioned, the molecular analysis of ctDNA from the plasma of blood samples can be a very reliable and sensitive method in the context of molecular applications. To overcome the issues of missing standardizations and restricted reimbursement, prospective clinical trials are needed to provide evidence driving the implementation of LB into the management of patients and to support their implementation into clinical guidelines.
21.06.2022 12:30 - 12:52 Europe/Berlin (UTC+01:00)
21.06.2022 12:30 - 12:52 Europe/Berlin (UTC+01:00)

Multiple liquid biopsy analytes in metastatic breast cancer

Molecular characterization of a systemic heterogeneous oncological disease, as metastatic breast cancer, is enabled in real-time by liquid biopsy testing. In this regard, blood analysis before therapy initiation and in a longitudinal manner under therapy can provide information suitable for personalized treatment decisions and therapy surveillance. Multiple analytes that circulate in the blood are useful for liquid biopsy testing, mainly cell-free DNA (cfDNA), extracellular vesicles (EVs), circulating tumor cells (CTCs) [1]. While it has already been shown that single liquid biopsy analytes have prognostic value [2, 3], can predict relapse [4] and can lead to targeted therapy decisions [5], it is to question whether a specific analyte is more suitable than another one. On the meta-level, it is to ask whether the molecular characterization of multiple analytes has additive value. Recent findings and methodical details of a multimodal liquid biopsy study characterizing the transcriptional profiles of EVs and CTCs and the genomic profiles of cfDNA and CTCs from matched samples of metastatic breast cancer patients will be presented [6] and existing challenges, to be overcome before translation into clinical practice, will be discussed.
21.06.2022 13:38 - 14:00 Europe/Berlin (UTC+01:00)
21.06.2022 13:38 - 14:00 Europe/Berlin (UTC+01:00)

Liquid Profiling in Head and Neck Cancer

Introduction Tumor-derived DNA is present in body fluids of cancer patients. Hence, liquid profiling is a promising minimally invasive tool with great diagnostic, prognostic, and monitoring potential. It can complement invasive biopsies that provide only a snapshot of an often heterogeneous tumor. In contrast, repeated liquid profiling can track molecular tumor changes over time and detect therapy resistance occurring during treatment. Here, we share our latest results on liquid profiling in blood and saliva of head and neck cancer patients. As part of a prospective single-center study, we designed personalized, tumor-specific droplet digital PCR (ddPCR) assays and analyzed their suitability for early recurrence detection by measuring circulating tumor DNA (ctDNA) in blood and saliva. Material and Methods In 8 HNSCC pts. blood and saliva samples were prospectively collected. In 7 pts. we collected pre-operative plasma samples, in 7 pts. additional saliva samples in the postoperative course. Mutations in the primary tumor tissue were analyzed with panel sequencing (45 genes, 224 amplicons). Based on NGS-results, tumor-specific ddPCRmutation assays were designed and ctDNA was analyzed in plasma and saliva. Results On average, 6 blood and 2 saliva samples per patient were examined. Using tumorspecific ddPCR assays, ctDNA was detected in preoperative plasma samples in 71% of the pts. (5 of 7 pts.). During the follow-up period, we detected ctDNA in 50% (4 of 8 pts.) in plasma and 100% (7 of 7 pts.) in saliva samples. 5 of the pts. developed a tumor recurrence, 3 pts. are currently clinically tumor-free. An increase in ctDNA levels was associated with a clinical recurrence in 80% (plasma) and/or 100% (saliva) of the examined pts. Using minimally invasive liquid profiling a ctDNA increase was measured in a median of 6 months (1 to 20 mo.) in plasma and 7 months (1 to 15 mo.) in saliva before clinical recurrence diagnosis. Conclusion CtDNA detection with tumor-specific ddPCR-mutation assays is a promising minimally invasive tool for tumor monitoring. Saliva appears to be well-suited for the early recurrence detection of even small tumors of the oral cavity and oropharynx.
21.06.2022 13:15 - 13:37 Europe/Berlin (UTC+01:00)
21.06.2022 13:15 - 13:37 Europe/Berlin (UTC+01:00)

New perspectives on the importance of cfDNA biology in the development of liquid biopsy assays

Liquid biopsies, in particular the profiling of circulating tumor DNA (ctDNA), has become a principle centre of interest in precision oncology and promises to reshape cancer care in the near-future [1]. Despite spectacular progress in this field, however, remarkably little is known about several aspects of ctDNA molecules, including (i) the mechanisms underlying its generation and release into body fluids, (ii) various epigenetic features, and (iii) the plethora of physiological/biological factors that modulate both the genetic and epigenetic characteristics of ctDNA in vivo and in collected biospecimens [2]. Yet, it is becoming increasingly clear that a deeper understanding of these aspects is crucial for the successful development and wide-spread implementation of ctDNA assays into routine clinical diagnostics. On one hand, this knowledge is critical for understanding fluctuations in the baseline values of ctDNA molecules, which informs the development of assays with increased diagnostic sensitivity and specificity. On the other hand, systematic mapping of ctDNA biology will lead to the discovery of increasingly specific biomarkers in relation to various cancer indications [3].
21.06.2022 12:53 - 13:15 Europe/Berlin (UTC+01:00)
21.06.2022 12:53 - 13:15 Europe/Berlin (UTC+01:00)