Integrated Medicine for Sarcomas
A sarcoma is a malignant tumor that derives from connective tissue, muscle or bone. These tissues constitute two thirds of the volume of the human body and are involved in the functions of support, protection, nutrition, binding, tissue repair, movement, immune response, growth and storage. Sarcomas are rare cancers, about 1% of diagnoses, and affect all ages. Although recent advances in molecular biology and genetics have helped to clarify their classification, their diagnosis and treatments are still problematic. Current targeted chemotherapies and therapies do not provide long-term results.
IMS (Integrated Medecine for Sarcomas), which is based on the recognized expertise of the Bordeaux teams, is a multidisciplinary program that allows researchers in genetics, preclinical, psychology, sociology and epidemiology to work in synergy to improve care of these cancers.
IMS is an ambitious program to improve the results of sarcoma treatment with a multidimensional approach including:
- Clinical research in genomics and data integration to improve knowledge of tumor biology and evaluate the results of new therapies;
- Preclinical studies to identify new therapeutic targets;
- Research in psychology and sociology to assess the consequences of diagnosis at the patient and societal level;
- Epidemiological research to improve the assessment of environmental exposure for a better understanding of the environmental etiology of sarcomas.
Antoine Italiano, Carlo Luchesi, Francois Le Loarer and Simone Mathoulin-Pelissier co-coordinate all the research projects of the IMS project within BRIO, in constant connection with the manager program. They set up the main strategic axes of the clinical and preclinical research of the program, in accordance with the budgets, the competitive and medical environment. They co-lead the 2 annual program progress meetings as well as the preparatory meetings of the Scientific Advisatory Board (SAB).
As part of the IMS program, several clinical studies are being monitored:
* Filipo, (phase IV) impact treatment with anti-eGFR patients with liposarcoma (NCT03303885), evaluating the effect of anti-EGFR therapy in patients with liposarcomas
* Access* (prospective collection of patient samples with sarcoma)
* Etiosarc, phase IV, Environmental etiology of sarcomas (NCT03670927)
* Pembrosarc phase II, advanced sarcomas (NCT02406781)
* Pembrotaz to evaluate the effectiveness of the combination of several treatments
* Multisarc (phase II, NCT03784014 )
All studies are available at www.clinicaltrials.gouv.
Sarcoma Specialists: The Sarcoma Unit includes an interdisciplinary team of medical specialists, nurses and health professionals, all of whom have special interest and international experience in the management of this rare disease. This unit has special expertise in all aspects of symptom diagnosis, treatment and control to ensure effective, efficient and user-friendly service. The IB sarcoma unit manages a stream of clinical trials dedicated to sarcomas. These tests are of all types, from phase 0 to phase 3.
Staff of the Sarcomas Unit: Head of Unit Pr. Antoine Italiano, Consultant in Medical Oncology
Surgeons Dr. Eberhard Stoeckle, Consultant in Surgical Oncology; Dr. Audrey Michot, Consultant in Surgical Oncology
Pathologist Jean-Michel Coindre, Consultant in Histopathology; Dr. François le Loarer, histopathology consultant
Radiologist Dr. Michèle Kind, radiology consultant; Dr. Amandine Crombe, consultant radiologist
Medical oncology Pr Antoine Italiano, consultant on medical oncology; Dr. Sophie Cousin, consultant on medical oncology; Dr. Maud Toulmonde, consultant on medical oncology
Bioinformatics team: Carlo Lucchesi is the bioinformatics team leader of the Institut Bergonié, which is responsible for the analysis of all sequencing data.
Psychology: Marion Barrrault is a psychologist specializing in Oncology Support Care at the Institut Bergonié. His activity is notably based on mindfulness meditation to improve to improve the quality of life in patients with cancer.
BRIO referrals: Dr. François Le Loarer (Anatomo-Cyto-pathologist, Inserm U1218, Bergonié Institute) – Pr. Antoine Italiano (Director of the Early Testing Unit at the Bergonié Institute, Professor of Oncology, Institut Bergonié)
Expertise: Translational Research
The Inserm Unit U1218 ACTION relies on its integration into the Bergonié Institute to develop translational research through its fundamental researchers in connection with the clinical teams. Three themes are developed:
SARCOTARGET TEAM: Sensitivity and resistance to sarcomas,
MLO TEAM: Genetic diversity and treatment response: mammary and leukemic oncogenesis
VINTAGE TEAM: Validation and Identification of New Cancer and Aging Targets. Each of these groups has biological and clinical assets that will enable them to complete their projects. Located in a Cancer Control Center with privileged access to tumor samples and clinical data and well integrated in the university context, this unit has the resources needed to develop a competitive research at French and European level.
BRIO referee: Rodrigue Rossignol (Research Director, Cellomet CEO, Inserm U1211, University of Bordeaux)
This team has recognized international expertise in the study of energy metabolism in physiology and pathology. Rodrigue Rossignol is also CEO of Cellomet, a CRO technology platform dedicated to the study of metabolic remodeling triggered by tumor development, drug resistance and anticancer drug activity. At the preclinical stage, the team is developing precision bioenergetic medicine strategies for lung cancer that combine the inhibition of molecular oncology targets with the bioenergetic stratification of tumors. CELLOMET provides pharmaceutical companies with services to decipher the metabolic impact and toxicity of various anti-cancer compounds.
BRIO referee: Olivier Saut (Research Director of the ONCology modeling project “MONC”, CNRS UMR 5251 Mathematical Institute of Bordeaux), Dr Amandine Crombé (Radiologist, CNRS UMR 5251 Mathematical Institute of Bordeaux, Institut Bergonié)
Expertise: Computer modeling, artificial intelligence
The INRIA Monc project team develops new tools for clinical decision support using mathematical modeling and artificial intelligence approaches. The scientific fields mobilized are numerous: mechanistic modeling, scientific computing, data assimilation, image processing, statistical learning and neural networks. It aims to answer the important questions that biologists or doctors ask themselves about the knowledge of the disease, its treatments or its follow-up. The issues addressed are, for example, the study of the interactions of different mechanisms influencing the progression of the disease, the detection or diagnosis of lesions using imaging, or the early evaluation of the efficacy of a treatment.
Référent BRIO : Pr Simone Mathoulin-Pélissier (Professeur en Santé Publique et Épidémiologie, Directrice de l’équipe EPICENE, Inserm U1219, Institut de Santé Publique d’Épidémiologie et de Développement, Université de Bordeaux, Institut Bergonié), Dr Silviane Darquy (Chargée de recherche, Bordeaux Population Health, Inserm Centre 1219, équipe EPICENE, Université de Bordeaux), Pr Isabelle Baldi (Praticienne Hospitalière, Bordeaux Population Health, Inserm UMR1219, équipe EPICENE, Université de Bordeaux), Dr Aude Lacourt (Epidémiologiste, Bordeaux Population Health, UMR 1219, Équipe EPICENE, Institut de Santé Publique d’Épidémiologie et de Développement, Université de Bordeaux), Dr Brice Amadeao (Epidémiologiste, Bordeaux Population Health, UMR 1219, Équipe EPICENE, Institut de Santé Publique d’Épidémiologie et de Développement, Université de Bordeaux), Dr Carine Bellera (Biostatisticienne, Université de Bordeaux), Dr Alain Monnereau (Praticien spécialisé dans la surveillance épidémiologique, Institut Bergonié)
Expertise : Epidémiologie, biostatistiques et expositions environnementales
L’équipe EPICENE développe des recherches sur les relations entre les expositions à des nuisances environnementales et professionnelles avec la survenue de cancers et le pronostic de ces maladies. Par des méthodes épidémiologiques et statistiques innovantes elle étudie la survenue des cancers et le devenir des populations. Par des approches multidisciplinaires, elle développe des méthodes spécifiques pour la mesure des expositions. Les champs de recherche de cette équipe sont :
– Développer et valider des méthodes statistiques permettant d’évaluer le devenir des populations atteintes d’un cancer, notamment la survie.
– Proposer des méthodes pour estimer les expositions individuelles récentes ou sur l’ensemble de la vie à des nuisances environnementales et/ou professionnelles.
– Évaluer le rôle de certaines nuisances environnementales et/ou professionnelles dans la survenue de cancers rares (sarcomes, mésothéliomes, tumeurs du système nerveux central, hémopathies, …).*
BRIO referee: Pr Simone Mathoulin-Pélissier (Professor of Public Health and Epidemiology, Director of the EPICENE team, Inserm U1219, Institute of Public Health Epidemiology and Development, University of Bordeaux, Bergonié Institute), Dr Silviane Darquy (Chargée de research, Bordeaux Population Health, Inserm Center 1219, EPICENE team, University of Bordeaux), Pr Isabelle Baldi (Hospital Practitioner, Bordeaux Population Health, Inserm UMR1219, EPICENE team, University of Bordeaux), Dr Aude Lacourt (Epidemiologist, Bordeaux Population Health, UMR 1219 , EPICENE Team, Institute of Public Health Epidemiology and Development, University of Bordeaux), Dr Brice Amadeao (Epidemiologist, Bordeaux Population Health, UMR 1219, Team EPICENE, Institute of Public Health Epidemiology and Development, University of Bordeaux) , Dr Carine Bellera (Biostatistician, University of Bordeaux), Dr Alain Monnereau (Practitioner specialized in epidemiological surveillance, Institut Bergonié)
Expertise: Epidemiology, biostatistics and environmental exposures
The EPICENE team is developing research on the relationship between exposures to environmental and occupational nuisances with the occurrence of cancers and the prognosis of these diseases. Through innovative epidemiological and statistical methods it studies the occurrence of cancer and the future of populations. Through multidisciplinary approaches, she develops specific methods for measuring exposures. The research fields of this team are:
– Develop and validate statistical methods to assess the future of populations with cancer, including survival.
– Propose methods for estimating recent individual or lifetime exposures to environmental and / or occupational nuisances.
– To evaluate the role of certain environmental and / or professional nuisances in the occurrence of rare cancers (sarcomas, mesotheliomas, tumors of the central nervous system, blood disorders, …).
Référent BRIO : Hélène Budzinski (Chimiste de l’environnement, CNRS UMR5805 EPOC, équipe LPTC, Université de Bordeaux)
Expertise : Environnement
L’activité du LPTC concerne l’étude de la présence des transport et transfert inter-compartiments, des phénomènes de bioaccumulation et de biotransformation ainsi que de l’impact des contaminants organiques au niveau moléculaire dans les compartiments environnementaux (air – eau – sol). Les recherches effectuées s’articulent autour des trois axes suivants :
Sources et présence des micropolluants organiques,
Interactions et Transferts.
BRIO referee: Hélène Budzinski (Environmental Chemist, CNRS UMR5805 EPOC, LPTC team, University of Bordeaux)
The activity of the LPTC concerns the study of the presence of inter-compartmental transport and transfer, bioaccumulation and biotransformation phenomena as well as the impact of organic contaminants at the molecular level in environmental compartments (air – water – soil). The research carried out revolves around the following three axes:
Sources and presence of organic micropollutants,
Interactions and Transfers.
BRIO referrals: Pr Hervé Fridman (Physician-Immunologist, UMRS 1138, Cordeliers Research Center, Paris), Pr Catherine Sautes-Fridman (Director of the Cancer Immunology and Immunopathology Department, UMRS 1138, Cordeliers Research Center, Paris)
Expertise: Cancer, Immunology, Immunopathology
The relationship between basic research and clinical research is a strong point of the Cordeliers Research Center with innovations in the field of biomarkers, the production of proteins for therapeutic use or endocrine treatments. The team of Catherine Sautes-Fridman directs its work according to several axes:
– Information sciences at the service of personalized medicine,
– Cancer and anti-tumor immunity,
– Complement and diseases,
– Immunology and integrative oncology,
– Immunology and therapeutic immuno-intervention,
– Apoptosis, cancer, immunity,
– Cell death and resistance to treatment in hematological malignancies.
Referee BRIO: Audrey Vezian (Sociologist, CNRS UMR 5206, Ecole Normale Supérieure, Lyon)
Expertise: Sociology of Health
The Triangle laboratory is a multidisciplinary UMR (Mixed Research Unit) grouping a large number of actors with diverse skills (political science, political philosophy, history of political thought and economic thought). The laboratory is structured in 4 specialty areas:
– Public action,
– Politicization and participation,
– Political Thought and Social Sciences,
– Economy: history, institutions, society.
BRIO referee: Sylvain Besle (Sociologist, Inserm UMR 1252 Team Canbios SESSTIM), Emilien Schultz (Sociologist, SESSTIM / Gustave Roussy, University Aix-Marseille / Paris)
Expertise: Sociology of health, access to innovation, care pathway in oncology
The Sociology of Innovations in Cancerology (SINCRO) program developed at Gustave Roussy and in the SESSTIM CANBIOS team studies the influence of innovations on oncology care pathways. As such, several projects are underway on access to therapeutic innovations for adults as well as children and adolescents around the development of precision medicine. These projects, which link patient experience with scientific and technical developments in medicine, are implemented collaboratively with inter-center and inter-SIRIC partners in order to understand the transformations of cancer nationally.
Clinical research and translational studies
+ Pazopanib for treatment of advanced malignant and dedifferentiated solitary fibrous tumour: a multicentre,single-arm, phase 2 trial.
The Lancet oncology , Jan 2019
Martin-Broto J et al.
+ T2 -based MRI Delta-radiomics improve response prediction in soft-tissue sarcomas treated by neoadjuvant chemotherapy.
Journal of magnetic resonance imaging, Dec 2018
Crombé A, et al.
+ Is There Value in Molecular Profiling of Soft-Tissue Sarcoma?
Current treatment options in oncology, Dec 2018
+ MRI assessment of surrounding tissues in soft-tissue sarcoma during neoadjuvant chemotherapy can help predicting response and prognosis.
European journal of radiology, Dec 2018
Crombé A, et al.
+ Efficacy and safety of regorafenib in adult patients with metastatic osteosarcoma: a non-comparative, randomised, double-blind, placebo-controlled, phase 2 study.
Lancet oncology, Jan 2019
Duffaud F, et al.
+ Systemic Anti-Cancer Therapy in Synovial Sarcoma: A Systematic Review.
Cancers, Nov 2018
Riedel RF, et al.
+ Pharmacokinetic Effects and Safety of Olaparib Administered with Endocrine Therapy: A Phase I Study in Patients with Advanced Solid Tumours.
Advances in therapy, Nov 2018
Plummer R, et al.
+ Prognostic and predictive factors for angiosarcoma patients receiving paclitaxel once weekly plus or minus bevacizumab: an ancillary study derived from a randomized clinical trial.
BMC cancer, Oct 2018
Lebellec L, et al.
+ Phase I study of onapristone, a type I antiprogestin, in female patients with previously treated recurrent or metastatic progesterone receptor-expressing cancers.
PLoS One, Oct 2018
Cottu PH, et al.
+ Trends in Modern Phase 1 Oncology Trials.
The new England journal of medicine, Sep 2018
+ EPIGIST: An observational real-life study on patients with metastatic gastrointestinal stromal tumors receiving imatinib.
PLoS One, Sep 2018
Bouché O, et al.
+ High-grade soft-tissue sarcoma: optimizing injection improves MRI evaluation of tumor response.
European radiology, Feb 2019
Crombé A, et al.
+ Outcome of 449 adult patients with rhabdomyosarcoma: an observational ambispective nationwide study.
Cancer medicine, Aug 2018
Bompas E, et al.
+ Targeting ERBB2 mutations in solid tumors: biological and clinical implications.
Journal of hematology and oncology, Jun 2018
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+ Efficacy and safety of regorafenib compared to placebo and to post-cross-over regorafenib in advanced nonadipocytic soft tissue sarcoma.
European journal of cancer, Aug 2018
Brodowicz T, et al.
+ Future Prospects for PD-1 Targeting, Macrophage Infiltration, and IDO Pathway Activation in Patients With Sarcomas-Reply.
JAMA oncology, Aug 2018
+ A first-in-human study investigating biodistribution, safety and recommended dose of a new radiolabeled MAb targeting FZD10 in metastatic synovial sarcoma patients.
BMC cancer, Jun 2018
Giraudet AL, et al.
+ Encouraging Trends in Modern Phase 1 Oncology Trials.
The new England journal of medicine, Jun 2018
Chakiba C, et al.
+ Crizotinib in patients with advanced, inoperable inflammatory myofibroblastic tumours with and without anaplastic lymphoma kinase gene alterations (European Organisation for Research and Treatment of Cancer 90101 CREATE): a multicentre, single-drug, prospective, non-randomised phase 2 trial.
The Lancet Respiratory Medicine, Jun 2018
Schöffski P, et al.
+ Prospective assessment of the predictive value of the BRCA1 gene status in sarcoma patients treated with trabectedin: an updated analysis of the EORTC 62091 trial.
Cancer medicine, May 2018
Italiano A, et al.
+ Outcomes of Elderly Patients with Advanced Soft Tissue Sarcoma Treated with First-Line Chemotherapy: A Pooled Analysis of 12 EORTC Soft Tissue and Bone Sarcoma Group Trials.
The Oncologist, Oct 2018
Younger E, et al.
+ Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: a first-in-human, open-label, phase 1 study.
The Lancet Oncology , May 2018
Italiano A, et al.
+ Nilotinib in locally advanced pigmented villonodular synovitis: a multicentre, open-label, single-arm, phase 2 trial.
The Lancet oncology, May 2018
Gelderblom H, et al.
+ Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an openlabel, single-arm, phase 2 study.
The Lancet Oncology, May 2018
Garassino MC, et al.
+Programmed cell death 1 (PD-1) targeting in patients with advanced osteosarcomas: results from the PEMBROSARC study.
European journal of cancer, Sept 2019
Le Cesne A. Et al
+ Newer therapeutic strategies for soft-tissue sarcomas.
Pharmacology and therapeutics, Aug 2018
Bourcier K, Italiano A.
+ Management of metastatic retroperitoneal sarcoma: a consensus approach from the Trans-Atlantic Retroperitoneal Sarcoma Working Group (TARPSWG).
Annals of oncology , official of the European Society for Medical Oncology, Apr 2018
Trans-Atlantic Retroperitoneal Sarcoma Working Group (TARPSWG).
+ Prognostic factors for soft tissue sarcoma patients with lung metastases only who are receiving first-line chemotherapy: An exploratory, retrospective analysis of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG).
International journal of cancer, Jun 2018
Lindner LH, et al.
+ Clinicopathologic Features of CIC-NUTM1 Sarcomas, a New Molecular Variant of the Family of CIC-fused Sarcomas.
The American journal of surgical pathology, Feb 2019
Le Loarer F, et al.
+ PD-1 inhibition in sarcoma still needs investigation.
The Lancet Oncology, Jan 2018
Toulmonde M, et al.
+ A Retrospective Multicentric Study of Ewing Sarcoma Family of Tumors in Patients Older Than 50: Management and Outcome.
Scientic reports, Dec 2017
Rochefort P, et al.
+ Pre- and Postoperative Chemotherapy in Localized Extremity Soft Tissue Sarcoma: A European Organization for Research and Treatment of Cancer Expert Survey.
The oncologist, Apr 2018
Rothermundt C, et al.
+ Results of methotrexate-etoposide-ifosfamide based regimen (M-EI) in osteosarcoma patients included in the French OS2006/sarcome-09 study.
European journal of cancer, Jan 2018
Gaspar N, et al.
+ Molecular determinants of acquired resistance to BRAF inhibition in human lung cancer.
Lung cancer, Dec 2018
Lucchesi C, et al.
+ Targetable Alterations in Adult Patients With Soft-Tissue Sarcomas: Insights for Personalized Therapy.
JAMA oncology, Oct 2018
Lucchesi C, et al.
+ Increased infiltration of M2-macrophages, T-cells and PD-L1 expression in high grade leiomyosarcomas supports immunotherapeutic strategies.
Oncoimmunology, Oct 2017
Kostine M, et al.
+ Biology and Management of Undifferentiated Pleomorphic Sarcoma, Myxofibrosarcoma, and Malignant Peripheral Nerve Sheath Tumors: State of the Art and Perspectives.
Journal of Clinical Oncology: official journal of the American Society of Clinical Oncology, Jan 2018
Widemann BC, et al.
+ Surrogate endpoints in advanced sarcoma trials: a meta-analysis.
Oncotarget, Oct 2018
Savina M, et al.
+ Olaratumab failure in sarcomas: what are the lessons learned?
European journal of cancer, Jun 2019
+ Soft-Tissue Sarcomas: Assessment of MRI Features Correlating with Histologic Grade and Patient Outcome.
Radiology, Jun 2019
Crombé A, et al.
+ Imaging features of SMARCA4-deficient thoracic sarcomas: a multi-centric study of 21 patients.
European radiology, feb 2019
Crombé A, et al.
+ Alveolar soft-part sarcoma: can MRI help discriminating from other soft-tissue tumors? A study of the French sarcoma group.
European radiology, Jun 2019
Crombé A et al.
+ Clinicopathologic and Molecular Features of a Series of 41 Biphenotypic Sinonasal Sarcomas Expanding Their Molecular Spectrum.
The American journal of surgical pathology, Jun 2019
Le Loarer F,et al.
+ Pleomorphic Sarcomas: The State of the Art.
Surgical pathology clinic, mar 2019
Carvalho SD, et al.
+ SMARCA4-deficient Thoracic Sarcomas: Clinicopathologic Study of 30 Cases With an Emphasis on Their Nosology and Differential Diagnoses.
The American Journal of surgical pathology, Apr 2019
Perret R, et al.
+ Clinicopathologic Features of CIC-NUTM1 Sarcomas, a New Molecular Variant of the Family of CIC-Fused Sarcomas.
The American Journal of surgical pathology, feb 2019
Le Loarer F, et al.
+ Identifying and targeting cancer stem cells in leiomyosarcoma : prognostic impact and role to overcome secondary resistance to PI3K/mTOR inhibition.
Journal of hematology and oncology, jan 2019
Fourneaux B, et al.
+ Pazopanib or methotrexate-vinblastine combination chemotherapy in adult patients with progressive desmoid tumours (DESMOPAZ): a non-comparative, randomised, open-label, multicentre, phase 2 study.
The lancet oncology, Juil 2019
Toulmonde M, et al.
+ Abnormal vascularization of soft-tissue sarcomas on conventional MRI: Diagnostic and prognostic values.
European journal of radiology, Aug 2019
Ledoux P et al.
Humanities & Social Sciences / Epidemiology / Public Health
+ Outcome of Patients with Soft-Tissue Sarcomas: An Age-Specific Conditional Survival Analysis.
Oncologist , Apr 2019
Bourcier K, et al.