Shared Perspectives #3 : CGI-Clinics, from NGS diagnostics to Patients bedside prescription.
Christophe MICHEL, PhD
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Shared Perspectives continues CGI-Clinics twin-headed interviews focusing European projects on Precision Oncology
For many reasons like bigger volumes triggered by global population ageing combined with the discovery and availability of complex immune therapy treatments in oncology until enhancing the efficacy of chemo- and conventional therapies, the importance of Personnalized Medicine
Some collaborative projects of importance, such as the €375 million European Partnership on Personalized Medicine[1] show greater interest from the institutions, public and private sectors. This requires a strong data storage and extended cloud analytics infrastructure to cope with both the volume of genomic data and the ever-increasing difficulty of NGS analysis, paving the way for Whole Exome/Genome Sequencing (WES/WGS)
Disclaimer?: the CGI-Clinics project is funded by the European Union. Views and opinions expressed are however those of the interviewees only and do not necessarily reflect those of the European Union or the European Health and Digital Executive Agency [3] (HADEA). Neither the European Union nor the granting authority can be held responsible for them.
Key takeaways:
Kostas Stamatopoulos and Pierre Saintigny, are representatives of CGI-Clinics oncologists and hematologists task force, they highlight that integration of big panels NGS and whole genome sequencing analysis in precision oncology facilities, are now integrated in the routine of translational medicine practice with a well described workflow involving sample collection, analysis, interpretation, and treatment decision based on mutations found. Funding for these tests varies by country (Greece and France examples are shown in that interview). In both cases, CGI-Clinics has helped to reduce costs and has demonstrated improved efficacy in variant interpretation. Patient engagement
Pierre Saintigny [PS-Left], is university professor at the Lyon Est School of medicine, France, medical oncologist and team leader at Cancer Research Center of Lyon. He has joined the Centre Léon Bérard (CLB) in Lyon since 2013. His work focuses on lung and head and neck cancer translational research and engaged in the implementation of new decision tools and approaches in the Molecular Tumour Board in the context of precision medicine in Oncology [6,7,8]. He is involved in the French Genomic Medicine Plan 2025 through his role in the AURAGEN platform, and member of the Worldwide Innovative Network Consortium in Precision Oncology Directorate.
Kostas Stamatopoulos [KS-Right], is haematologist, Research Director of the Institute of Applied Biosciences at CERTH in Thessaloniki, Greece and Visiting Professor at the Karolinska Institute in Stockholm, Sweden. Kostas’ work work focuses on precision medicine in cancer, immunobiology of lymphoid malignancies, and patient empowerment in care. A former coordinator of the Hellenic Precision Medicine Network in Oncology (2018-2021), he serves on various committees within the European Hematology Association and ERIC, the European Research Initiative on chronic lymphocytic leukemia (https://ericll.org/), where he oversees the activities of the IG Network [5].
KS and PS have been implicated in the CGI-Clinics project from the beginning as national translational research advisors in precision oncology.
Note: a new set of WGS preindications have been validated in February 2024 by the Haute Autorité de Santé working group and the operational committee of the PFMG 2025. Now approaching 2025, the question of the PFMG 2025's assessment begins.
Describe your main activity your facility (Translational oncology (PS, JB), expertises, precision diagnostic /oncology.
[KS] INAB|CERTH is a leading institution in precision oncology globally, thanks to its significant expertise and extensive experience in next-generation sequencing (NGS) studies and bioinformatics. Our Institute spearheaded the pilot phase of the Hellenic Precision Medicine Network in Oncology and is currently participating in several EU consortia and scientific organizations. We are proud to be a reference laboratory for immunogenetics and to provide NGS diagnostics (targeted panels, RNAseq or WES) to patients with cancer, particularly hematologic malignancies, from all over Greece. Our expertise is also sought by the ERIC, European Research Initiative on Chronic lymphocytic leukemia; and the Euroclonality-NGS Working Group.
[PS] At CLB in Lyon, we have developed a strong molecular screening program for 10 years that is used as a platform to recommend therapies during the Molecular Tumor Board. We often use it in the context of clinical trials. Depending on the study (PROFILER, PLANET, FMG2025...), we sequence tumor and/or liquid biopsies for a gene panel and RNAseq or WES/WGS and RNAseq. We have developed a strong expertise in data curation of NGS data through computational biology. We are deeply involved in identifying innovative approaches to improve data interpretation by molecular pathologists/biologists and clinicians to help improve treatment recommendations.
Can you describe the work flow between the referral of oncogenomics diagnosis and the onset of precision oncology treatment (or "classical" cancer therapy like surgery, chemotherapy or radiotherapy).
[KS] The journey to precision oncology therapy is a demanding process that relies heavily on cutting-edge genomic technologies coupled with comprehensive bioinformatics support. At the outset, it’s crucial to identify the appropriate candidates for testing, determine the optimal timing for these tests, and decide on the specific genomic inquiries to be made. This requires physicians to be not only up-to-date with the latest advancements but also adept at communicating complex information to their patients effectively.
During the pre-analytical phase, the focus is on the meticulous collection, annotation, delivery, and registration of the primary patient sample. Processing this sample to secure high-quality material is essential, as it lays the foundation for successful oncogenomics. The robustness of this phase is critical to ensure the reliability and precision of the results, which is why our Institute emphasizes this stage in accordance with the stringent ISO 15189 accreditation standards.
Moving into the analytical phase, NGS analysis is performed on a selection of clinically significant genes. These genes are chosen based on international guidelines that highlight their diagnostic importance and, more crucially, their predictive value, often referred to as “actionability.” The post-analytical phase involves a thorough examination of the NGS findings, utilizing dedicated software and databases to characterize the genomic alterations. The insights gained from this analysis form the basis of the laboratory report, which is subsequently reviewed in collaboration with the consulting physician. Together, they deliberate on the findings to deduce the most effective treatment strategy for the individual patient.
CGI-Clinics plays a transformative role in several facets of this intricate process. Its most notable contributions include the acceleration of the analysis timeline without sacrificing quality and providing confidence in the accuracy of the genomic interpretations. This, in turn, empowers physicians to make well-informed treatment decisions for their patients. [PS] The decision to perform an oncogenomics diagnosis is made on a case-by-case basis, either as part of the routine care of patients or within the context of clinical trials. The initial discussion between the patient and their treating physician is crucial in determining the most appropriate course of action. In addition to the tumour type, the disease stage and the overall condition of the patient, treatment is increasingly guided by the identification of ‘driver’ mutations. Once a tumor and/or blood sample has been collected in the clinic, it is processed through standard operating procedures and submitted to various types of next-generation sequencing. This is either done in our molecular pathology lab (commercial panels and routine care), or in our Genomic Medicine Core (molecular screening programs/clinical trials) or in the AURAGEN Core (France Médecine Génomique 2025), in which the CLB is heavily involved. The next step is data curation and interpretation, which is done using commercial software for routine care or in-house solutions put in place by our bioinformatics platform. A report signed by a certified molecular pathologist is discussed at an organ-specific (routine care) or at the Molecular Tumor Board in the case of oncogenomic tests done in molecular screening programs/clinical trials. The recommendation is finally explained and discussed by the treating physician during a follow-up consultation.
What kind of financial support do you have for the analysis of big NGS panels in your country. How can another bioinformatic tool help in costs reductions.
[KS] Currently, the majority of NGS diagnostic tests are not reimbursed in Greece. Financial support is primarily provided by grants from government agencies, the national healthcare system (to a limited extent), private foundations, or non-profit organizations. Additionally, academic institutions often allocate internal funding for sequencing projects, while collaborations with industry partners and pharmaceutical companies can also provide supplementary support.
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The CGI-Clinics tool presents a significant opportunity to reduce costs, extending beyond the mere automation of the analysis process and the reduction of manual curation by specialists. CGI-Clinics opens avenues for discovering novel biomarkers but also streamlines medical resource allocation by pinpointing the most pertinent clinical findings with precision, hence promoting innovation in healthcare for patients with cancer.
[PS] In the context of routine care, funding is fully supported by the French social security as any other cost associated with the care of cancer. In the context of molecular screening programs/clinical trials, financial support comes from either the Ministry of Health (DGOS, e.g. France Médecine Génomique 2025, RIHN) or from pharmaceutical companies sponsoring clinical trials or research grants. The development of CGI-Clinics, by decreasing the rate of variants of unknown significance, may eventually lead to reduced costs by facilitating data interpretation.
CGI-Clinics is better known as an analytic tool. How are medical oncologists interested in the identification of actionalble Variants? Can it help a medical oncologist in his routine patient care?
[KS] Variant annotation heavily relies on genomic databases and online resources that have compiled associations with specific histologies or diseases, as well as their prognostic and/or predictive value of response to specific therapies. Yet, information is multifaceted. For example, data contained within these knowledge bases may vary significantly in scope, encompassing pre-clinical biological and functional insights to clinical associations. Therefore, assessing every piece of information is imperative. Furthermore, aside from mutations with established clinical relevance, a substantial portion of the detected variants are of unknown clinical significance. Dealing with these variants poses a significant challenge. Interpretations often diverge or are entirely absent, correlations with specific phenotypes can be challenging or altogether impossible, while the evidence is frequently conflicting and scattered across different sources. In this context, CGI-Clinics can make a significant contribution to the field, by promoting knowledge but also confidence and trust, thereby assisting onco-hematologists in clinical decision making.
[PS] The variant annotation process relies heavily on genomic databases and online resources that have compiled associations with specific histologies or diseases, as well as their prognostic and/or predictive value of response to specific therapies. However, the information available is multifaceted. For instance, data within these knowledge bases may vary significantly in scope, encompassing pre-clinical biological and functional insights to clinical associations. Therefore, it is essential to assess every piece of information. Furthermore, aside from mutations with established clinical relevance, a substantial portion of the detected variants are of unknown clinical significance. Dealing with these variants poses a significant challenge. Interpretations often diverge or are entirely absent, correlations with specific phenotypes can be challenging or altogether impossible, while the evidence is frequently conflicting and scattered across different sources. In this context, CGI-Clinics can make a significant contribution to the field by promoting knowledge, confidence, and trust, thereby assisting onco-hematologists in clinical decision-making.
Is there a way that the engagement of patients themselves help in the design of a more effcient CDS tool??
[KS] Patient engagement is crucial for the development of an effective CDS tool. By involving patients in the design process, we gain invaluable insights that enable us to fine-tune clinical algorithms, making them more responsive to individual health needs. This collaborative approach not only builds a sense of ownership among patients but also fosters trust, significantly enhancing the tool’s adoption and usage by both patients and healthcare providers. Integrating patient input also facilitates clearer communication, simplifying the management of treatment plans and health data. Continuous engagement with patients is crucial for the iterative development of the tool, ensuring it stays relevant and aligned with evolving patient needs. By engaging a diverse patient population, we enhance the tool’s usability across different demographics, which helps reduce health disparities. Ultimately, integrating the principles of patient empowerment—information provision, self-management, and support—into the CDS tool's design will significantly improve its capability to offer clear, actionable, and personalized information and support. This approach will not only boost patient satisfaction and treatment adherence but also ensure that the tool remains intuitive and user-friendly, aligning with the objectives of precision medicine.
[PS] In my view, a CDS tool should provide two types of output: one for the treating physician and one for the patient. The latest version will help the patient engage in his or her treatment and increase the level of information required for the patient to consent to a treatment, whether it is proposed as part of routine care or in the context of a clinical trial. Patient engagement will in turn improve treatment observance and the patient's willingness to participate actively in innovative research programs, creating a virtuous circle.
In your final perspective, is CGI-Clinics a more profitable tool for the patient, the oncologist or the pathologist?
[KS] CGI-Clinics holds potential and value for all stakeholders in cancer, from patients to healthcare professionals (of different disciplines) and beyond (i.e. the pharma and biotech industry)
[PS] At the end, both patients, oncologists and molecular pathologists/biologists will benefit from CGI-Clinics.
Related publications and websites
1 The European Partnership for Personalized Medicine?: https://www.eppermed.eu/
3 HADEA: https://hadea.ec.europa.eu/index_en
4 CGI-Clinics: Data-driven cancer genome interpretation for personalised cancer treatment https://www.cgiclinics.eu/project/
5 Blood. 2021 Mar 11;137(10):1365-1376
6 Cancer Med. 2024 Apr;13(7):e7115
7 JCO Clin Cancer Inform. 2021 Mar;5:256-265
8 Nat Med. 2019 May;25(5):751-758
#NGS, #cds, #personalizedmedicine, #precisiononcology, #artificialintelligence, #OpenScience