Lung cancer program


Board

Pr. Marco Alifano
Surgeon
Pr. Françoise                                   Le Pimpec-Barthes
Surgeon
Pr. Elizabeth Fabre
Physician


Steering Committee

Pr. Hélène Blons - Biologist
Pr. Francois Goldwasser - Physician
Pr. Karen Leroy - Biologist
Pr. Diane Damotte - Pathologist
Dr. Marie-Pierre Revel - Radiologist
Dr. Philippe Giraud - Physicist
Pr. Catherine Durdux - Physician
Pr. Guy Meyer - Physician
Pr. Nicolas Roche - Physician
Pr. Isabelle Cremer - Scientist
Dr. Ludovic Fournel - Surgeon
Pr. Valérie Quevreux - Health Manager
Dr. Constance Thibault - Physician
Dr. Olivier Huillard - Physician
Pr. Dominique Helley - Biologist
Pr. Jerome Galon - Immunologist

Two sites of Paris Cancer Institute: CARPEM have a strong activity in thoracic oncology and the lung cancer program involved 4 departments of APHP.Centre (Pulmonary, Imaging and Pathology, Biology and Oncology) working together. It is the most important surgical centre dedicated to thoracic oncology in the Great Paris area and at the national level. 31 physicians, surgeons and biologists are mainly dedicated to lung cancer patients care and altogether 65 beds are dedicated to thoracic oncology. This program took in charges 4440 new cases of lung cancer during the last 3 years. It involves 2 sites of the APHP.5 sites (EGP and Cochin) with similar organization. On both sites, there are both medical and surgery strengths and 2784 new cases of thoracic tumors have been surgically removed during the last 3 years, 1682 patients have been treated by chemotherapy and 1002 patients have received radiotherapy (for detail annex 1). 

All these activities are structured around 2 weekly cancer multidisciplinary team meetings (one on each site) including members of the lung programs (Monday and Wednesday). These meetings follow the INCA national guidelines, and ESMO guidelines.

A remarkable feature of these 2 sites is that they are able to provide not only all possible modalities of therapeutic care from surgery to stereotaxic radiotherapy but also all diagnostic activities. Since 2018, one the site of Cochin hospital, the lung cancer program has set up, in one site a pilot project for rapid and ambulatory diagnosis of lung cancer: office with dedicated email, technical platforms with dedicate schedules, coordinating nurse. The lung cancer program is also aiming to become a leader in screening of lung cancer in the Great Paris area with a large project dedicated to screening of smoking women.

Physicians surgeon and biologists of this program are strongly involved in clinical and translational research. 

Clinical research

Clinical research is performed with more than 20 open ongoing clinical trials (>15 phase III, >10 phase II) see annex 2. A strong interaction with in-site physicians highly renowned in the diagnosis and treatment of pulmonary embolism has been developed through several trials conducted during last years (Meyer G. et al. Eur Respir J. 2018). D. Damotte, H. Blons member of this program are involved at national level in national clinical research groups mainly in the IFCT (Intergroupe Français de Chirurgie Thoracique) and the GFPC (Groupe Français de Pneumo-cancerologie). In order to find prognostic and predictive markers of therapeutic responses in lung cancers, Lung Cancer Team had a rich academic program focused on the search for interrelationship between tumors and host (nutritional status, systemic inflammation, sarcopenia, fitness) and the risk factors of women lung cancers through a large epidemiological study (WELCA for Women Epidemiology Lung Cancer) including 800 cases matched to 800 cancer-free controls.

Translational research

Translational research involves 8 senior researchers and mainly 4 Inserm research Team located to the PARCC and the Cordeliers Research Center. These research teams are led by Isabelle Cremer, Pierre Laurent-Puig, Eric Tartour, and Jessica Zucman-Rossi. The main translational research fields are about the microenvironment and genomics of the lung tumors (including mesothelioma). Among the main recent results, we can mention the advances we made in the understanding of the heterogeneity of malignant pleural mesothelioma leading to a reconsideration of malignant pleural mesothelioma molecular classifications (Blum et al. Nature Comm 2019). A second approach concerns patients with multiple pulmonary nodules. Multiple nodules in the lung are being diagnosed with an increasing frequency thanks to high-quality computed tomography imaging. For clinical management, it is important to classify the disease as intrapulmonary metastasis or multiple primary lung carcinoma. We studied consecutive patients undergoing an operation with curative intent for lung adenocarcinoma (N = 120) and harboring two tumors (N = 240). Histological diagnosis according to the WHO 2015 classification and molecular profiling using next-generation sequencing targeting 22 hotspot genes allowed classification of samples as multiple primary lung adenocarcinomas or as intrapulmonary metastasis (Mansuet-Lupo A, J Thorac Oncol. 2019). Another example was to analyze microenvironment of lung adenocarcinomas according to routine genotyping results allowing us to demonstrate the interrelationship between genomic alterations, microenvironment pattern and response to immune therapy (Biton J, Clin Cancer Res 2018).

These research areas are developed in the program 1 and 2 of the SIRIC CARPEM.

The Lung Cancer Program integrates close to 10 interns each year and more than 5 fellows.

Medical and surgical teams are widely involved in the university teaching of thoracic pathologies in Paris Descartes University and in several national teaching degrees/master’s degrees in the field of oncology:

  • Françoise Le Pimpec Barthes and Marie Wislez are coordinators of national DIU in thoracic oncology coordinated
  • Marie Wislez participated in Master 2 of physiology of respiration and circulation / Biology of the cancer cell
  • Marie Wislez is responsible of the Oncology for Pulmonology diploma, of Thoracic Head&neck dermatology for specialization in oncology
  • François Goldwasser coordonated Targeted therapies for specialization in oncology)
  • Françoise Le Pimpec-Barthes is director and J Das Neves Pereira coordinator of the DU Extreme perioperative Fast Track.

Based on our skillness we would like to

  • improve inclusion in therapeutic trials with an inclusion rate of 10 to 20% of patients

  • develop translational research, particularly study of microenvironment and biomarkers of immunotherapies

  • implement lung cancer screening

  • implement a rehabilitation unit in oncology including thoracic oncology

     

Name Surname Title/Position Speciality Research Unit Resarch Team
Marco ALIFANO MD PhD/ Full Prof Surgeon UMRS 1138 Centre d eRecherche des Cordeliers Inflammation, Complement and Cancer
Jennifer ARRONDEAU Full time  physician Oncologist
Hélène BLONS Full Prof Biologist UMRS 1138 Centre d eRecherche des Cordeliers Perzonalized medecine therapeutic optimization
Antonio BOBBIO Full time  physician Surgeon
Emelyne CANNY-HAMELIN Full time  physician Surgeon UMRS 1138 Centre d eRecherche des Cordeliers Inflammation, Complement and Cancer
Pascaline BOUDOU-ROUQUETTE Full time  physician Oncologist
Jeanne CHAPRON Full time  physician Pneumologist
Jérome CLERC Full Prof Nuclearist
Isabelle CREMER Full Prof Scientist UMRS 1138 Centre d eRecherche des Cordeliers Inflammation, Complement and Cancer
Diane DAMOTTE Full time  physician Pathologist UMRS 1138 Centre d eRecherche des Cordeliers Inflammation, Complement and Cancer
Catherine DURDUX Full Prof Radiotherapist
Elizabeth FABRE Full time  physician Oncologist UMRS 970 Immunotherapy and anti-angiogenic treatment in cancerology
Ludovic FOURNEL Associate prof Surgeon INSERM UMR 1124 Cellular Homeostasis and Cancer Signaling
Benoit GAZEAU Full time  physician Oncologist
Fréderique GIRAUD Full time  physician Pneumologist
Philippe GIRAUD Full Prof Radiotherapist
François  GOLDWASSER Full Prof Oncologist EA4466 PRETRAM PRÉvention et Traitement de la Résistance à l’Anabolisme Musculaire – Laboratoire de Biologie de la Nutrition
Laure GIBAULT Full time  physician Pathologist
Clemence GRANIER DR Scientist UMRS 970 Immunotherapy and anti-angiogenic treatment in cancerology
Philippe ICARD Full prof Surgeon INSERM U1086 BioTICLA axis
Marie-claude JAURAND DRem Scientist UMRS 1138 Centre d eRecherche des Cordeliers Functional Genomics of Solid Tumors
Didier JEAN CRCN Scientist UMRS 1138 Centre d eRecherche des Cordeliers Functional Genomics of Solid Tumors
Pierre-Emmanuel JOUBERT DR Scientist UMRS 1138 Centre d eRecherche des Cordeliers Inflammation, Complement and Cancer
Françoise LE PIMPEC-BARTHES Full Prof Thoracic  surgeon UMRS 1138 Centre d eRecherche des Cordeliers Functional Genomics of Solid Tumors
Karen LEROY Full Prof Biologist UMRS 1138 Centre d eRecherche des Cordeliers Inflammation, Complement and Cancer
Audrey LUPO Associate Prof Pathologist UMRS 1138 Centre d eRecherche des Cordeliers Inflammation, Complement and Cancer
Marie-Pierre  REVEL Full Prof Radiologist
Sophie SIBERIL DR Scientist UMRS 1138 Centre d eRecherche des Cordeliers Inflammation, Complement and Cancer
Eric TARTOUR Full Prof Scientist UMRS 970 Immunotherapy and anti-angiogenic treatment in cancerology
Myriam WARTSKI Full time  physician Nuclearist
Marie WISLEZ Full Prof Pneumologist UMRS 1138 Centre d eRecherche des Cordeliers Inflammation, Complement and Cancer
Jessica ZUCMAN-ROSSI Full Prof Scientist UMRS 1138 Centre d eRecherche des Cordeliers Functional Genomics of Solid Tumors
Giuseppe MANGIAMELI Full time  physician Thoracic surgeon
Alain  BADIA Full time  physician Thoracic surgeon
Alex ARAME Full time  physician Thoracic surgeon
Joao DAS NEVES PEREIRA Partial time physician Thoracic surgeon

The selected following publications highlight the strength of clinical and translational research developed in the lung cancer program:

  1. Blum Y, Meiller C, Quetel L, Elarouci N, Ayadi M, Tashtanbaeva D, Armenoult L, Montagne F, Tranchant R, Renier A, de Koning L, Copin MC, Hofman P, Hofman V, Porte H, Le Pimpec-Barthes F, Zucman-Rossi J, Jaurand MC, de Reyniès A, Jean D. Dissecting heterogeneity in malignant pleural mesothelioma through histo-molecular gradients for clinical applications. Nat Commun. 2019 Mar 22;10(1):1333.
  2. Mansuet-Lupo A, Barritault M, Alifano M, Janet-Vendroux A, Zarmaev M, Biton J, Velut Y, Le Hay C, Cremer I, Régnard JF, Fournel L, Rance B, Wislez M, Laurent-Puig P, Herbst R, Damotte D, Blons H.Proposal for a Combined Histomolecular Algorithm to Distinguish Multiple Primary Adenocarcinomas from Intrapulmonary Metastasis in Patients with Multiple Lung Tumors. J Thorac Oncol. 2019 May;14(5):844-856.
  3. Biton J, Mansuet-Lupo A, Pécuchet N, Alifano M, Ouakrim H, Arrondeau J, Boudou-Rouquette P, Goldwasser F, Leroy K, Goc J, Wislez M, Germain C, Laurent-Puig P, Dieu-Nosjean MC, Cremer I, Herbst R, Blons H, Damotte D.TP53, STK11, and EGFR Mutations Predict Tumor Immune Profile and the Response to Anti-PD-1 in Lung Adenocarcinoma. Clin Cancer Res. 2018 Nov 15;24(22):5710-5723
  4. Biton J, Ouakrim H, Dechartres A, Alifano M, Mansuet-Lupo A, Si H, Halpin R, Creasy T, Bantsimba-Malanda C, Arrondeau J, Goldwasser F, Boudou-Rouquette P, Fournel L, Roche N, Burgel PR, Goc J, Devi-Marulkar P, Germain C, Dieu-Nosjean MC, Cremer I, Herbst R, Damotte D. Impaired Tumor-Infiltrating T Cells in Patients with Chronic Obstructive Pulmonary Disease Impact Lung Cancer Response to PD-1 Blockade. Am J Respir Crit Care Med. 2018 Oct 1;198(7):928-940.
  5. Legras A, Barritault M, Tallet A, Fabre E, Guyard A, Rance B, Digan W, Pecuchet N, Giroux-Leprieur E, Julie C, Jouveshomme S, Duchatelle V, Giraudet V, Gibault L, Cazier A, Pastre J, Le Pimpec-Barthes F, Laurent-Puig P, Blons H. Validity of Targeted Next-Generation Sequencing in Routine Care for Identifying Clinically Relevant Molecular Profiles in Non-Small-Cell Lung Cancer: Results of a 2-Year Experience on 1343 Samples. J Mol Diagn. 2018 Jul;20(4):550-564.
  6. Pécuchet N, Vieira T, Rabbe N, Antoine M, Blons H, Cadranel J, Laurent-Puig P, Wislez M. Molecular classification of pulmonary sarcomatoid carcinomas suggests new therapeutic opportunities. Ann Oncol. 2017 Jul 1;28(7):1597-1604.
  7. Nizard M, Roussel H, Diniz MO, Karaki S, Tran T, Voron T, Dransart E, Sandoval F, Riquet M, Rance B, Marcheteau E, Fabre E, Mandavit M, Terme M, Blanc C, Escudie JB, Gibault L, Barthes FLP, Granier C, Ferreira LCS, Badoual C, Johannes L, Tartour E. Induction of resident memory T cells enhances the efficacy of cancer vaccine. Nat Commun. 2017 May 24;8:15221.
  8. Tranchant R, Quetel L, Tallet A, Meiller C, Renier A, de Koning L, de Reynies A, Le Pimpec-Barthes F, Zucman-Rossi J, Jaurand MC, Jean D. Co-occurring Mutations of Tumor Suppressor Genes, LATS2 and NF2, in Malignant Pleural Mesothelioma. Clin Cancer Res. 2017 Jun 15;23(12):3191-3202.
  9. Mansuet-Lupo A, Alifano M, Pécuchet N, Biton J, Becht E, Goc J, Germain C, Ouakrim H, Régnard JF, Cremer I, Laurent-Puig P, Dieu-Nosjean MC, Blons H, Damotte D. Intratumoral Immune Cell Densities Are Associated with Lung Adenocarcinoma Gene Alterations. Am J Respir Crit Care Med. 2016 Dec 1;194(11):1403-1412.
  10. Pécuchet N, Zonta E, Didelot A, Combe P, Thibault C, Gibault L, Lours C, Rozenholc Y, Taly V, Laurent-Puig P, Blons H, Fabre E. Base-Position Error Rate Analysis of Next-Generation Sequencing Applied to Circulating Tumor DNA in Non-Small Cell Lung Cancer: A Prospective Study.PLoS Med. 2016 Dec 27;13(12):e1002199.

Annex 1:  Main indicators of clinical activities

Number of 2016 2017 2018
New Lung Cancer 1504 1420 1516
New Lung Cancer surgical resections 930 918 936
Patients with chemotherapies 552 550 590
Day-care treatments (chemo or ICI) 3192 3200 3323

Annex 2:  Ongoing Clinical Trials

Sponsor Title Phase NCT number Coordinator/investigator
Novartis Study of Efficacy and Safety of Canakinumab as Adjuvant Therapy in Adult Subjects With Stages AJCC/UICC v. 8 II-IIIA and IIIB (T>5cm N2) Completely Resected Non-small Cell Lung Cancer III NCT03447769 M Wislez / investigator
IFCT-1601 Immune Neoadjuvant Therapy Study of Durvalumab in Early Stage Non-small Cell Lung Cancer II NCT03030131 M Wislez / coordinator
MSD Efficacy and Safety Study of Stereotactic Body Radiotherapy (SBRT) With or Without Pembrolizumab (MK-3475) in Adults With Medically Inoperable Stage I or IIA Non-Small Cell Lung Cancer (NSCLC) (MK-3475-867/KEYNOTE-867) III NCT03924869 M Wislez / C Durdux / investigator           investigator
MSD Safety and Efficacy Study of Pemetrexed + Platinum Chemotherapy + Pembrolizumab (MK-3475) With or Without Lenvatinib (MK-7902/E7080) as First-line Intervention in Adults With Metastatic Nonsquamous Non-small Cell Lung Cancer (MK-7902-006/E7080-G000-315/LEAP-006) III NCT03829319 M Wislez / investigator
Novartis A randomized, open-label, phase II study of canakinumab or pembrolizumab as monotherapy or in combination as neoadjuvant therapy in subjects with resectable non-small cell lungcancer (CANOPY-N) II NCT03968419 M Wislez
BMS Randomized, Open Label Study to Compare Nivolumab plus Concurrent Chemoradiotherapy (CCRT) followed by Nivolumab plus Ipilimumab or Nivolumab plus CCRT Followed by Nivolumab vs CCRT followed by Durvalumab in Previously Untreated, Locally Advanced Non-small Cell Lung Cance CA20973L III Eudract : 2019-001222-98 M Wislez / C Durdux / investigator           investigator
MSD Pembrolizumab in Combination with Etoposide/Platinum Followed by Pembrolizumab with or without Maintenance Olaparib in the First-line Treatment of Participants with Extensive Stage Small Cell Lung Cancer Trial MK-7339 PN 005 III Ongoing M Wislez / investigator
IFCT GCO-001 Nivolumab +/- Ipilimumab in Patients With Advanced, Refractory Pulmonary or Gastroenteropancreatic Poorly Differentiated Neuroendocrine Tumors (NECs) (NIPINEC) II NCT03591731 M Wislez / investigator
IFCT-1802 SAVIMMUNE Etude de phase II évaluant la tolérance et l’efficacité du durvalumab chez les patients ayant un Performance Status ECOG 2-3, naïfs de traitement et présentant un Cancer Bronchique Non à petites Cellules (CBNPC) de stade IV exprimant fortement le PD-L1 II N° EUDRACT: 2018-004742-42 M Wislez / investigator
GFPC 08-2015 ENERGY Randomised phase III study testing nivolumab and ipilimumab versus a carboplatin based doublet in first line treatment of PS 2 or elderly (more than 70 years old) patients with advanced non-small cell lung cancer» III NCT03351361 M Wislez / investigator
IFCT-1902 ORAKLE Etude de phase II non-randomisée, mono-bras, en ouvert, multicentrique évaluant l’efficacité et la tolérance du lorlatinib en monothérapie après échec en 1ère ligne de traitement d’un inhibiteur d’ALK de 2ème génération chez des patients présentant un Cancer Bronchique Non à Petites Cellules (CBNPC) de stade avancé ALK positif II N° Eudract 2019-002230-37 M Wislez / investigator
IFCT-1805 ELDERLY Phase III randomized trial of atezolizumab in elderly patients with advanced Non-Small-Cell Lung Cancer and receiving monthly carboplatin with weekly paclitaxel chemotherapy III NCT03977194 M Wislez / investigator
Roche-A phase III multicenter study evaluating the efficacy and safety of multiple targeted therapies as treatments for patients with advanced or metastatic non small cell lung cancer (NSCLC) harboring actionable somatic mutations detected in blodd (B-Fast : blood-first assay screening trial) III N° Eudract 2017-000076-28 E. Fabre / investigator
IFCT1401- A phase III prospective double blind placebo controlled randomized study of adjuvant MEDI4736 in completely resected non-small cell lung cancer III N° Eudract 2014-004946-83 E. Fabre / investigator
IFCT-1601 A phase II prospective immune neoadjuvant therapy study of durvalumab (MEDI4736) in early stage non-small cell lung cancer A25 II N° EUDRACT : 2016-001849-15 F. Le Pimpec-Barthes
APHP- Long-term prophylaxis of venous thromboembolism with Low-molecular-weight heparin in patients with metastatic lung cancer and elevated D-dimer III N° EUDRACT : 2016-002546-23 E. Fabre / investigator
MSD- combination with lenvatinib (E7080/MK-7902) versus docetaxel in previously treated participants with metastatic nonsmall cell lung cancer (NSCLC) and progressive disease (PD) after platinum doublet chemotherapy and immunotherapy (anti-PD-1/PD-L1 inhibitor) III EudraCT : 2018-003791-12 E. Fabre / investigator
Lilly: A Phase 1/2 Study of Oral LOXO-292 in Patients with advanced solid tumors, including RET fusion-positive solid tumors, medullary thyroid cancer and other tumors with RET activation (LIBRETTO-001) I/II EudraCT : 2017-000800-59 J. Medioni / investigator
Astra-Zeneca: A Phase III, Randomized, Placebo-controlled, Double-blind, Multi-center, International Study of Durvalumab Following Stereotactic Body RadiationTherapy (SBRT) for the Treatment of Patients with unresected Stage I/II,lymph-node negative Non-small Cell Lung Cancer III EudraCT : 2018-002572-41 E. Fabre / investigator
If you are interested by this program and want to candidate to a PhD, post doctoral position, contact the leader
Pr Marie Wislez

Contact us

Centre Universitaire des Saints-Pères Etage 4 – Pièce 446B 45 rue des Saints-Pères -75006 Paris

Carina Binet : Secrétaire Général du CARPEM
Tél. : 01 76 53 43 85 – carina.binet@carpem.fr

Aurore Hattabi, PhD : Coordinatrice Scientifique du CARPEM
Tél : 01 76 53 43 85 – aurore.hattabi@carpem.fr

contact@carpem.fr