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

   

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

Annex 2:  Ongoing Clinical Trials

If you are interested by this program and want to candidate to a PhD, post doctoral position, contact the leader

Pr Marie Wislez