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1. Random survival forest to predict transplant-eligible newly diagnosed multiple myeloma outcome including FDG-PET radiomics: a combined analysis of two independent prospective European trials

Author: Diana Mateus, Cristina Nanni, Ludivine Morvan, Thomas Carlier, Caroline Bodet-Milin, Clément Bailly, Stephane Chauvie, Elena Zamagni, Bastien Jamet, Françoise Kraeber-Bodéré, Cyrille Touzeau, Anne-Victoire Michaud, Philippe Moreau, Département de Médecine Nucléaire [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire des Sciences du Numérique de Nantes (LS2N), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Policlinico S. Orsola-malpighi, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO)-Servizio sanitario regionale Emilia-Romagna, Santa Croce e Carle Hospital [Cuneo, Italy], Service d'Hématologie [Nantes], University of Bologna/Università di Bologna, Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Bernardo, Elizabeth, Jamet B., Morvan L., Nanni C., Michaud A.-V., Bailly C., Chauvie S., Moreau P., Touzeau C., Zamagni E., Bodet-Milin C., Kraeber-Bodere F., Mateus D., Carlier T., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), University of Bologna, Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA)
Subjects: medicine.medical_specialty, Poor prognosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Newly diagnosed, Tumor heterogeneity, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Risk groups, Radiomics, [SDV.CAN] Life Sciences [q-bio]/Cancer, Fluorodeoxyglucose F18, Multiple myeloma, Positron Emission Tomography Computed Tomography, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, business.industry, Hazard ratio, Random survival forest, General Medicine, Prognosis, medicine.disease, FDG-PET/CT, 3. Good health, 030220 oncology & carcinogenesis, Radiology, Radiopharmaceuticals, Radiomic, business, Prognostic value, Treatment Arm
Abstract: International audience; Purpose: Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is included in the International Myeloma Working Group (IMWG) imaging guidelines for the work-up at diagnosis and the follow-up of multiple myeloma (MM) notably because it is a reliable tool as a predictor of prognosis. Nevertheless, none of the published studies focusing on the prognostic value of PET-derived features at baseline consider tumor heterogeneity, which could be of high importance in MM. The aim of this study was to evaluate the prognostic value of baseline PET-derived features in transplant-eligible newly diagnosed (TEND) MM patients enrolled in two prospective independent European randomized phase III trials using an innovative statistical random survival forest (RSF) approach.Methods: Imaging ancillary studies of IFM/DFCI2009 and EMN02/HO95 trials formed part of the present analysis (IMAJEM and EMN02/HO95, respectively). Among all patients initially enrolled in these studies, those with a positive baseline FDG-PET/CT imaging and focal bone lesions (FLs) and/or extramedullary disease (EMD) were included in the present analysis. A total of 17 image features (visual and quantitative, reflecting whole imaging characteristics) and 5 clinical/histopathological parameters were collected. The statistical analysis was conducted using two RSF approaches (train/validation + test and additional nested cross-validation) to predict progression-free survival (PFS).Results: One hundred thirty-nine patients were considered for this study. The final model based on the first RSF (train/validation + test) approach selected 3 features (treatment arm, hemoglobin, and SUVmaxBone Marrow (BM)) among the 22 involved initially, and two risk groups of patients (good and poor prognosis) could be defined with a mean hazard ratio of 4.3 ± 1.5 and a mean log-rank p value of 0.01 ± 0.01. The additional RSF (nested cross-validation) analysis highlighted the robustness of the proposed model across different splits of the dataset. Indeed, the first features selected using the train/validation + test approach remained the first ones over the folds with the nested approach.Conclusion: We proposed a new prognosis model for TEND MM patients at diagnosis based on two RSF approaches.Trial registration: IMAJEM: NCT01309334 and EMN02/HO95: NCT01134484.
Published: 2021

2. The EPICURE study: a pilot prospective cohort study of heterogeneous and massive data integration in metastatic breast cancer patients

Author: Valérie Seegers, Mathilde Colombié, Pascal Jézéquel, Frédéric Bigot, Jean-Sébastien Frenel, Mathieu Rubeaux, Mario Campone, Malbec, Odile, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Keosys, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: Oncology, Quality of life, Cancer Research, medicine.medical_specialty, Return to work, Collection, [SDV]Life Sciences [q-bio], Integration, Molecular imaging, Breast Neoplasms, Pilot Projects, Disease, lcsh:RC254-282, Cohort Studies, 03 medical and health sciences, Study Protocol, 0302 clinical medicine, Breast cancer, Internal medicine, Epidemiology, Genetics, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Heterogeneous, Neoplasm Metastasis, Prospective cohort study, Multi-omics data, business.industry, Cohort, Cancer, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Metastatic breast cancer, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Drug resistance, Female, Trial registration: ClinicalTrials.gov identifier (NCT number): NCT03958136. Registration 21st of May, retrospectively registered Metastatic breast cancer, business, Prediction
Abstract: Background Breast cancer is the most common cancer in women and the first cancer concerning mortality. Metastatic breast cancer remains a disease with a poor prognosis and about 30% of women diagnosed with an early stage will have a secondary progression. Metastatic breast cancer is an incurable disease despite significant therapeutic advances in both supportive cares and targeted specific therapies. In the management of a metastatic patient, each clinician follows a highly complex and strictly personal decision making process. It is based on a number of objective and subjective parameters which guides therapeutic choice in the most individualized or adapted manner. Methods/design The main objective is to integrate massive and heterogeneous data concerning the patient’s environment, personal and familial history, clinical and biological data, imaging, histological results (with multi-omics data), and microbiota analysis. These characteristics are multiple and in dynamic interaction overtime. With the help of mathematical units with biological competences and scientific collaborations, our project is to improve the comprehension of treatment response, based on health clinical and molecular heterogeneous big data investigation. Discussion Our project is to prove feasibility of creation of a clinico-biological database prospectively by collecting epidemiological, socio-economic, clinical, biological, pathological, multi-omic data and to identify characteristics related to the overall survival status before treatment and within 15 years after treatment start from a cohort of 300 patients with a metastatic breast cancer treated in the institution. Trial registration ClinicalTrials.gov identifier (NCT number): NCT03958136. Registration 21st of May, 2019; retrospectively registered.
Published: 2021

3. Targeting Stereotactic Body Radiotherapy on Metabolic PET- and Immuno-PET-Positive Vertebral Metastases

Author: Ludovic Ferrer, Françoise Kraeber-Bodéré, Gregory Delpon, B. Pichon, Stéphane Supiot, Matthieu Le Turnier, David M. Goldenberg, Caroline Rousseau, Vincent Libois, Cédric Lenoble, Caroline Bodet-Milin, Audrey Blanc-Lapierre, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA), Clinique Pasteur [Toulouse], Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), Service de Médecine Nucléaire [Nantes], Hôpital Laennec, Center for Molecular Medicine and Immunology [Mendham, NJ, USA] (C2MI), Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
Subjects: GTV, PET-CT, vertebral metastases, Medicine (miscellaneous), [SDV.CAN]Life Sciences [q-bio]/Cancer, General Biochemistry, Genetics and Molecular Biology, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, CEA, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Positron emission, stereotactic ablative body radiotherapy (SABR), lcsh:QH301-705.5, targeting, medicine.diagnostic_test, business.industry, Communication, Medullary thyroid cancer, Magnetic resonance imaging, radiation oncology, stereotactic body radiation therapy (SBRT), medicine.disease, Spinal cord, Metastatic breast cancer, 3. Good health, bispecific antibody, medicine.anatomical_structure, lcsh:Biology (General), Positron emission tomography, 030220 oncology & carcinogenesis, immuno-PET, CTV, Tomography, Nuclear medicine, business
Abstract: (1) Background: Stereotactic body radiotherapy (SBRT) for vertebral metastases (VM) allows the delivery of high radiation doses to tumors while sparing the spinal cord. We report a new approach to clinical target volume (CTV) delineation based on anti-carcinoembryonic antigen (CEA) positron emission tomography (pretargeted immuno-PET; “iPET”) in patients with metastatic breast cancer (BC) or medullary thyroid cancer (MTC). (2) Methods: All patients underwent iPET, spine magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT) using 18F-deoxyglucose (FDG) for BC or 18F-dihydroxy-phenylalanine (F-DOPA) for MTC. Vertebrae locations and vertebral segments of lesions were recorded and the impact on CTV delineation was evaluated. (3) Results: Forty-six VM eligible for SBRT following iPET were evaluated in eight patients (five BC, three MTC). Eighty-one vertebral segments were detected using MRI, 26 with FDG or F-DOPA PET/CT, and 70 using iPET. iPET was able to detect more lesions than MRI for vertebral bodies (44 vs. 34). iPET-based delineation modified MRI-based CTV in 70% (32/46) of cases. (4) Conclusion: iPET allows a precise mapping of affected VM segments, and adds complementary information to MRI in the definition of candidate volumes for VM SBRT. iPET may facilitate determining target volumes for treatment with stereotactic body radiotherapy in metastatic vertebral disease.
Published: 2020

4. Prognostic impact of phenotype heterogeneity of grade 1-2 metastatic gastroenteropancreatic neuroendocrine tumors documented by 18FDG PET-CT and 68Ga-DOTANOC PET-CT

Author: Barbaud, M., Touchefeu, Y., Le Bras, M., Fleury, V., Carlier, T., Bailly, C., Frampas, E., Rauscher, A., Kraeber-Bodere, F., Ansquer, C., Département de Médecine Nucléaire [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Clinique d'Endocrinologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut du Thorax, Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA), Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Département de Radiologie [CHU Nantes], Unité de Pharmacie [ICO, Saint Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, European-Association-of-Nuclear-Medicine (EANM), Bernardo, Elizabeth, Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020

5. Incidental findings suggestive of COVID-19 in asymptomatic cancer patients undergoing 18F-FDG PET/CT in a low prevalence region

Author: Amandine Pallardy, Françoise Kraeber-Bodéré, Catherine Labbe, Vincent Fleury, Renan Liberge, Caroline Bodet-Milin, Caroline Rousseau, Service de Médecine Nucléaire [Nantes], Hôpital Laennec, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA), Service de Radiologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Bernardo, Elizabeth, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and UNICANCER-UNICANCER
Subjects: Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), PET/CT, Short Communication, [SDV.CAN]Life Sciences [q-bio]/Cancer, Asymptomatic, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Fluorodeoxyglucose F18, Neoplasms, Positron Emission Tomography Computed Tomography, medicine, Prevalence, Humans, Radiology, Nuclear Medicine and imaging, Lung, Asymptomatic Infections, Aged, PET-CT, Incidental Findings, Geographic area, business.industry, COVID-19, General Medicine, Middle Aged, Lung involvement, 3. Good health, 18F-FDG, medicine.anatomical_structure, Radiology Nuclear Medicine and imaging, 030220 oncology & carcinogenesis, Orthopedic surgery, Fdg pet ct, Female, Radiology, medicine.symptom, Radiopharmaceuticals, business, Infection
Abstract: Purpose To assess the rate and pattern of incidental interstitial lung abnormalities suggestive of COVID-19 on 18F-FDG PET/CT in asymptomatic cancer patients during the period of active COVID-19 circulation between March and April 2020 in a geographic area of low prevalence of the virus. Methods 1396 18F-FDG PET/CT performed between January 1, 2020, and February 21, 2020, and between March 16, 2020, and April 17, 2020 for routine oncological indication were retrospectively analyzed. No patients had symptoms suggestive of COVID-19 at the time of the 18F-FDG PET/CT. Incidental interstitial pneumonias suggestive of COVID-19 were identified, and the 18F-FDG PET/CT patterns were described. We compared the incidence of these lesions in the pre-COVID and pandemic phases. Results We observed a 1.6% increase in interstitial lung abnormalities during the period of COVID-19 circulation. All had
Published: 2020
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6. ImmunoPET in Multiple Myeloma—What? So What? Now What?

Author: Bailly, Clément, Chalopin, Benjamin, Gouard, Sébastien, Carlier, Thomas, Remaud-Le Saec, Patricia, Marionneau-Lambot, Séverine, Moreau, Philippe, Touzeau, Cyrille, Kraeber-Bodéré, Françoise, Bodet-Milin, Caroline, Chérel, Michel, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service de Médecine Nucléaire [Nantes], Hôpital Laennec, Département d'Hématologie Clinique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA), Bernardo, Elizabeth, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and UNICANCER-UNICANCER
Subjects: theranostic, [SDV.CAN]Life Sciences [q-bio]/Cancer, companion imaging agents, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, daratumumab, lcsh:RC254-282, PD-1/PD-L1, multiple myeloma, [SDV.CAN] Life Sciences [q-bio]/Cancer, precision imaging, Perspective, immunotherapy, pharmacokinetic, heterogeneity, immunoPET
Abstract: International audience; Despite constant progress over the past three decades, multiple myeloma (MM) is still an incurable disease, and the identification of new biomarkers to better select patients and adapt therapy is more relevant than ever. Recently, the introduction of therapeutic monoclonal antibodies (mAbs) (including direct-targeting mAbs and immune checkpoint inhibitors) appears to have changed the paradigm of MM management, emphasizing the opportunity to cure MM patients through an immunotherapeutic approach. In this context, immuno-positron emission tomography (immunoPET), combining the high sensitivity and resolution of a PET camera with the specificity of a radiolabelled mAb, holds the capability to cement this new treatment paradigm for MM patients. It has the potential to non-invasively monitor the distribution of therapeutic antibodies or directly monitor biomarkers on MM cells, and to allow direct observation of potential changes over time and in response to various therapeutic interventions. Tumor response could, in the future, be anticipated more effectively to provide individualized treatment plans tailored to patients according to their unique imaging signatures. This work explores the important role played by immunotherapeutics in the management of MM, and focuses on some of the challenges for this drug class and the significant interest of companion imaging agents such as immunoPET.
Published: 2020

7. Adapting palliative radiation therapy for bone metastases during the Covid-19 pandemic : GEMO position paper

Author: Jean-Jacques Body, Frédéric Lecouvet, Marie-Hélène Vieillard, F. Paycha, Francesco Giammarile, Martine Duterque-Coquillaud, Jean Christophe Faivre, Sébastien Thureau, Cyrille B. Confavreux, Laetitia Morardet, Françoise Debiais, Dominique Heymann, Emmanuel Biver, Richard Assaker, Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Normandie Université (NU), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Geneva University Hospital (HUG), University of Geneva [Switzerland], Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain = Catholic University of Louvain (UCL), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire Brugmann [Bruxelles] (CHU), Equipe Quantification en Imagerie Fonctionnelle [QuantIF-LITIS], Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes [LITIS], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] [UNICANCER/ICL], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Service de rhumatologie[Lille], Institut de biologie de Lille - IBL [IBLI], Centre de Recherche en Cancérologie et Immunologie Nantes-Angers [CRCINA], Institut de Cancérologie de l'Ouest [Angers/Nantes] [UNICANCER/ICO], Institut de Recherche Expérimentale et Clinique [IREC], Université Catholique de Louvain = Catholic University of Louvain [UCL], Centre Hospitalier Universitaire Brugmann [Bruxelles] [CHU], Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hospices Civils de Lyon (HCL), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain (UCL), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Noel, Anne-Laure, Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Université de Genève = University of Geneva (UNIGE), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Subjects: 0301 basic medicine, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine.medical_specialty, Respiratory complications, lcsh:Diseases of the musculoskeletal system, Palliative Radiation Therapy, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], lcsh:RC254-282, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Biopsychologie et psychopathologie, Pandemic, Health care, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Medicine, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, ddc:616, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, Neurosciences cognitives, Cancer, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, Radiation therapy, 030104 developmental biology, Oncology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 030220 oncology & carcinogenesis, Position paper, lcsh:RC925-935, business
Abstract: The current health crisis caused by COVID-19 is a challenge for oncology treatment, especially when it comes to radiotherapy. Cancer patients are already known to be very fragile and COVID-19 brings about the risk of severe respiratory complications. In order to treat patients safely while protecting medical teams, the entire health care system must optimize the way it approaches prevention and treatment at a time when social distancing is key to stemming this pandemic. All indications and treatment modalities must be re-discussed. This is particularly the case for radiotherapy of bone metastases for which it is possible to reduce the number of sessions, the frequency of transport and the complexity of treatments. These changes will have to be discussed according to the organization of each radiotherapy department and the health situation, while medical teams must remain vigilant about the risks of complications of bone metastases, particularly spinal metastases. In this short piece, the members of the GEMO (the European Study Group of Bone Metastases) offer a number of recommendations to achieve the above objectives, both in general and in relation to five of the most common situations on radiation therapy for bone metastases., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2020

8. Haute Couture or Ready-To-Wear? Tailored Pelvic Radiotherapy for Prostate Cancer Based on Individualized Sentinel Lymph Node Detection

Author: Valentine Guimas, Stéphane Supiot, Maelle Le Thiec, Anne-Victoire Michaud, Mathilde Colombié, Caroline Rousseau, Claire Dupuy, Emmanuel Rio, Vincent Fleury, Ludovic Ferrer, M. Doré, T. Rousseau, Benoit Samain, Gregory Delpon, Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA), Service de la Radio-Oncologie [Saint-Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Unité de physique médicale [ICO, Saint Herblain], Clinique Urologique Nantes Atlantis [Saint Herblain], Endothelium Radiobiology and Targeting (CRCINA-ÉQUIPE 14), Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
Subjects: Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Sentinel lymph node, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, sentinel lymph node, [SDV.CAN] Life Sciences [q-bio]/Cancer, SPECT/CT pelvic irradiation, medicine, Lymph node, radiotherapy, personalized therapy, Contouring, business.industry, Aortic bifurcation, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, prostate cancer, 3. Good health, Radiation therapy, body regions, medicine.anatomical_structure, Lymphatic system, Oncology, 030220 oncology & carcinogenesis, Radiology, business, Pelvic radiotherapy
Abstract: International audience; Prostate cancer (PCa) pelvic radiotherapy fields are defined by guidelines that do not consider individual variations in lymphatic drainage. We examined the feasibility of personalized sentinel lymph node (SLN)-based pelvic irradiation in PCa. Among a SLN study of 202 patients, we retrospectively selected 57 patients with a high risk of lymph node involvement. Each single SLN clinical target volume (CTV) was individually segmented and pelvic CTVs were contoured according to Radiation Therapy Oncology Group (RTOG) guidelines. We simulated a radiotherapy plan delivering 46 Gy and calculated the dose received by each SLN. Among a total of 332 abdominal SLNs, 305 pelvic SLNs (beyond the aortic bifurcation) were contoured (mean 5.4/patient). Based on standard guidelines, CTV missed 67 SLNs (22%), mostly at the common iliac level (40 SLNs). The mean distance between iliac vessels and the SLN was 11mm, and despite a 15mm margin around the iliac vessels, 9% of SLNs were not encompassed by the CTV. Moreover, 42 SLNs (63%) did not receive 95% of the prescribed dose. Despite a consensus on contouring guidelines, a significant proportion of SLNs were not included in the pelvic CTV and did not receive the prescribed dose. A tailored approach based on individual SLN detection would avoid underdosing pelvic lymph nodes that potentially contain tumor cells.
Published: 2020

9. Long-term Trace of Radiation Pneumonitis With 18F-Fluoroestradiol

Author: Sophie Chiavassa, Caroline Rousseau, Bruno Maucherat, Françoise Kraeber-Bodéré, Agnes Morel, Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA), Département de Physique [Saint Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Bernardo, Elizabeth, Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: medicine.medical_specialty, Fluorine Radioisotopes, medicine.medical_treatment, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, FES PET, Asymptomatic, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, Radiology, Nuclear Medicine and imaging, Stage (cooking), Radiation Pneumonitis, radiation pneumonia, Estradiol, business.industry, General Medicine, Pet imaging, medicine.disease, 3. Good health, Radiation therapy, 030220 oncology & carcinogenesis, Positron-Emission Tomography, Asymptomatic Diseases, Female, Radiology, medicine.symptom, Complication, business
Abstract: International audience; Radiation pneumonitis (RP) can be an adverse complication of radiotherapy and usually occurs as an acute reaction from 6 to 12 weeks after radiotherapy. FDG PET is described as an early and adequate barometer for RP diagnosis. Only 1 case of fluoroestradiol uptake contemporary of metabolic FDG changes attributed to RP is reported. We report a case of a breast cancer patient with asymptomatic RP, who at 1 year later, at sequelar stage on CT, showed long-term memory of RP by 18 F-fluoroestradiol PET imaging with nonmetabolic FDG PET. (Clin Nucl Med 2020;45: e403-e405) REFERENCES 1. Demirev AK, Kostadinova ID, Gabrovski IR. 18 F-FDG PET/CT in patients with parenchymal changes attributed to radiation pneumonitis. Mol Imaging Radionucl Ther. 2018;27:107-112. 2. Liao GJ, Clark AS, Schubert EK, et al. 18 F-fluoroestradiol PET: current status and potential future clinical applications.
Published: 2020

10. Prognostic value of F-18-FDG-PET in patients with mantle cell lymphoma: results from the LyMa-PET Project Reply

Author: Bailly, Clément, Carlier, Thomas, Kraeber-Bodéré, Françoise, Le Gouill, Steven, Bodet-Milin, Caroline, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Département de Médecine Nucléaire [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Service d'Hématologie [Nantes], Bernardo, Elizabeth, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and UNICANCER-UNICANCER
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; No abstract available
Published: 2020

11. ARRONAX Cyclotron: Setting up of In-HouseHospital Radiopharmacy

Author: Ferid Haddad, C. Bourdeau, Aurélien Vidal, Tracy Garcia, Mathieu Frindel, Mickaël Bourgeois, Alain Faivre-Chauvet, Bernardo, Elizabeth, Cyclotron ARRONAX [Saint-Herblain], ARRONAX - (GIP) Groupement d'Intérêt Public [Saint-Herblain] (Institut de Recherche Public), Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine Nucléaire [Nantes], Hôpital Laennec, Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: 0301 basic medicine, medicine.medical_specialty, Article Subject, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Humans, Medical physics, General Immunology and Microbiology, business.industry, General Medicine, 3. Good health, Clinical trial, 030104 developmental biology, Facility Design and Construction, 030220 oncology & carcinogenesis, Medicine, Nuclear Medicine, Radiopharmaceuticals, Pharmacy Service, Hospital, business, Research Article
Abstract: International audience; Whilst radiopharmaceuticals have an important role to play in both imaging and treatment of patients, most notably cancer patients, nuclear medicine and radiopharmacy are currently facing challenges to create innovative new drugs. Traditional radiopharmaceutical manufacture can be considered as either a routine hospital production or a large-scale industrial production. The gap between these two practices has meant that there is an inability to supply innovative radiopharmaceuticals for use at the local level for mono-or multicentric clinical trials with satisfactory quality and safety specifications. This article highlights the regulatory requirements in aseptic pharmaceutical processing and in nuclear medicine to be able to locally produce radiopharmaceuticals. We validate the proof-of-concept for an "in-house" hospital-based radiopharmacy including an on-site cyclotron, that can fulfill the conflicting requirements between radiation safety and aseptic processing. The ARRONAX in-house radiopharmacy is currently able to provide sterile and pyrogenic-free injectable radiopharmaceutical compounds for both industrial and institutional clinical trials.
Published: 2020

12. A comparison of two modalities of stereotactic body radiation therapy for peripheral early-stage non-small cell lung cancer: results of a prospective French study

Author: P. Boisselier, Pierre Yves Bondiau, Sophie Dussart, Karine Peignaux-Casasnovas, Line Claude, Marc-André Mahé, Magali Morelle, Emmanuel Touboul, David Pasquier, Véronique Beckendorf, Isabelle Martel-Lafay, Lionel Perrier, Frederic Gassa, Centre Léon Bérard [Lyon], Groupe d'Analyse et de Théorie Economique Lyon - Saint-Etienne (GATE Lyon Saint-Étienne), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Département de Radiothérapie, Centre René Gauducheau-Centre de Lutte Contre le Cancer Nantes Atlantique 'René Gauducheau' (CLCC)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Méthodes et Outils pour la Conception Intégrée de Systèmes (MOCIS), Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Groupe d'analyse et de théorie économique (GATE Lyon Saint-Étienne), Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Centre de Lutte Contre le Cancer Nantes Atlantique 'René Gauducheau' (CLCC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université Côte d'Azur (UCA)-UNICANCER
Subjects: Male, medicine.medical_specialty, Lung Neoplasms, medicine.medical_treatment, Radiosurgery, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Carcinoma, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Stage (cooking), Lung cancer, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Aged, Neoplasm Staging, Aged, 80 and over, Modalities, Full Paper, business.industry, General Medicine, Middle Aged, medicine.disease, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, 3. Good health, Peripheral, Treatment Outcome, 030220 oncology & carcinogenesis, Observational study, Female, Radiology, France, business
Abstract: Objectives: This prospective, observational, non-randomized multicentric study was conducted to compare efficiency and toxicity using different modalities of stereotactic body radiation therapy (SBRT) in early-stage peripheral non-small cell lung cancer (NSCLC). Methods: From 9 April to 11 December, 106 patients were treated according to the local equipment availability for peripheral NSCLC with SBRT: 68 by linear accelerator equipped for SBRT and 38 by Cyberknife®. Multivariate analysis and propensity score analysis using Inverse Probability Treatment Weighting (IPTW) were undertaken in an effort to adjust for potential bias due to non-randomization. Results: 2-year local control rates were 97.0% (95% CI: [90.6%; 99.4%]) with SBRT by Linac vs 100% (95% CI: ([100%; 100%]) with Cyberknife® (p = 0.2839). 2-year PFS and 2-year OS rates were 52.7% (95% CI [39.9%;64.0%]) versus 54.1% (95% CI [36.8; 68.6%]) (p = 0.8582) and 65.1% (95% CI: [51.9%; 75.5%] versus 83.9% (95% CI: [67.5%; 92.4%] (p = 0.0831) using Linac and Cyberknife® respectively. Multivariate regression analysis indicates no significant effect of SBRT treatment type on PFS or OS. Local relapse could not be modeled due to the small number of events (n = 2). Acute and late toxicity rates were not significantly different. After IPTW adjustment, results were unchanged. Conclusions: No difference in efficiency or toxicity was shown after SBRT of peripheral NSCLC treatment using Linac or Cyberknife®. Advances in knowledge: This is the first large prospective non-randomized study focusing on peripheral localized NSCLC comparing SBRT using an appropriately equipped linac with Cyberknife®. No significant difference in efficiency or toxicity was shown in this situation.
Published: 2020

13. Risk factors for acquisition of OXA-48-producing Klebsiella pneumonia among contact patients: a multicentre study

Author: Caroline Neulier, Alexandra Lomont, J. Merrer, B. Grandbastien, J.C. Lucet, Jean-Ralph Zahar, Delphine Hilliquin, V. Thepot Seegers, Didier Lepelletier, R. Le Guern, Anne-Marie Rogues, C. Legeay, V. Marie, CHU Lille, Université de Lille, Centre Hospitalier Universitaire d'Angers [CHU Angers], Recherche translationnelle : relations hôte-pathogènes - EA 7366, Recherche translationelle relations hôte-pathogènes, Institut de Cancérologie de l'Ouest [Angers/Nantes] [UNICANCER/ICO], AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU de Bordeaux Pellegrin [Bordeaux], Centre hospitalier universitaire de Nantes [CHU Nantes], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), and Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: 0301 basic medicine, Multivariate analysis, [SDV]Life Sciences [q-bio], Mesh:Adult, 0302 clinical medicine, Mesh:Risk Factors, Mesh:Case-Control Studies, 030212 general & internal medicine, Mesh:Aged, Mesh:Klebsiella pneumoniae/enzymology, OXA-48, Aged, 80 and over, Mesh:Klebsiella Infections/microbiology, Univariate analysis, Screening, Contact patients, Carbapenemases, Carbapenemase-producing, Risk factors, Enterobacteriaceae, General Medicine, Middle Aged, 3. Good health, Klebsiella pneumoniae, Infectious Diseases, Mesh:Klebsiella Infections/epidemiology, Adult, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Mesh:Young Adult, beta-Lactamases, Young Adult, 03 medical and health sciences, Mesh:Retrospective Studies, Mesh:Klebsiella pneumoniae/isolation & purification, Mesh:Middle Aged, Internal medicine, Mesh:80 and over, medicine, Humans, Aged, Retrospective Studies, business.industry, Case-control study, Retrospective cohort study, Odds ratio, medicine.disease, Confidence interval, Klebsiella Infections, Mesh:beta-Lactamases/analysis, Surgery, Mesh:Humans, Case-Control Studies, Concomitant, Klebsiella pneumonia, business
Abstract: International audience; BACKGROUND: Cohorting carbapenemase-producing Enterobacteriaceae (CPE) carriers during hospitalization limits in-hospital spreading.OBJECTIVE: To identify risk factors for CPE acquisition among contacts of an index patient in non-cohorted populations.METHODS: A multicentre retrospective matched case-control study was conducted in five hospitals. Each contact patient (case) who acquired Klebsiella pneumoniae (KP)-OXA-48 from an index patient was compared to three contact (controls) with the same index patients matched with hospitalization in the same unit and similar exposure times.RESULTS: Fifty-one secondary cases and 131 controls were included. By univariate analysis, exposure time (odds ratio: 1.06; 95% confidence interval: 1.02-1.1; P = 0.006), concomitant infection at admission (3.23; 1.42-7.35; P = 0.005), antimicrobial therapy within the last month before hospitalization (2.88; 1.34-6.2; P = 0.007), antimicrobial therapy during the exposure time (5.36; 2.28-12.6; P
Published: 2018

14. Bifunctional aryliodonium salts for highly efficient radioiodination and astatination of antibodies

Author: Aurélia Roumesy, Cyrille Alliot, Yong-Sok Lee, Michel Chérel, François Guérard, Jean-François Gestin, Laurent Navarro, Martin W. Brechbiel, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Center for Molecular Modeling - Office of Intramural Research [Bethesda, MA, USA], National Institutes of Health [Bethesda] (NIH), Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique] (GIP ARRONAX), Université de Nantes (UN)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Radioimmune & Inorganic Chemistry Section - Radiation Oncology Branch [Bethesda, MA, USA], National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), The Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and Center for Information Technology., ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), ANR-11-EQPX-0004,ARRONAXPLUS,Nucléaire pour la Santé(2011), Bernardo, Elizabeth, Radiopharmaceutiques Innovants en Oncologie et Neurologie - - IRON2011 - ANR-11-LABX-0018 - LABX - VALID, Nucléaire pour la Santé - - ARRONAXPLUS2011 - ANR-11-EQPX-0004 - EQPX - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université de Nantes (UN)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and UNICANCER-UNICANCER
Subjects: Clinical Biochemistry, Pharmaceutical Science, [SDV.CAN]Life Sciences [q-bio]/Cancer, Conjugated system, 010402 general chemistry, 01 natural sciences, Biochemistry, Article, radiolabeled antibodies, Iodine Radioisotopes, radioiodination, chemistry.chemical_compound, [SDV.CAN] Life Sciences [q-bio]/Cancer, Drug Discovery, Molecule, Organic chemistry, Moiety, Hydrocarbons, Iodinated, Bifunctional, Molecular Biology, Bioconjugation, Molecular Structure, 010405 organic chemistry, Aryl, Organic Chemistry, Temperature, Antibodies, Monoclonal, astatination, Regioselectivity, 0104 chemical sciences, chemistry, Yield (chemistry), Iodonium salts, Molecular Medicine, Salts, Astatine
Abstract: International audience; In this report we describe the development of an alternative approach to arylstannane chemistry for radiolabeling antibodies with radioiodine or astatine based on aryliodonium salts precursors. Bifunctional aryliodonium salts were designed and tested for the synthesis of 125 I and 211 At labeled prosthetic groups for bioconjugation. The nature of the electron rich aryl group was varied and its impact on the regioselectivity of radiohalogenation was evaluated. Unexpectedly, whereas the 2-thienyl group provided the best regioselectivity towards the radioiodination of the aryl moiety of interest (98:2), it was less selective for astatination (87:13); the anisyl group providing the best regioselectivity in this case (94:6). Under optimized conditions, both radioiodination and astatination could be performed very efficiently in mild conditions (radiochemical yields > 85%). The ionic nature of the precursors was exploited to develop an efficient purification approach: the HPLC step that is usually necessary in conventionnal approaches to optimize removal of organotin toxic precursors and side products was replaced by a filtration through a silica cartridge with a significantly reduced loss of radiolabeled product. The purified radioiodinated and astatinated prosthetic groups were then conjugated efficiently to an anti-CD138 monoclonal antibody (75-80% conjugation yield). By using this novel and simple radiohalogenation procedure, higher overall radiochemical yields of astatination were obtained in comparison with the use of an arylstannane precursor and procedures of the litterature for labeling the same antibody. Overall, due to their simplicity of use and high robustness, these new precursors should simplify the labeling of proteins of interest with iodine and astatine radioisotopes for imaging and therapeutic applications.
Published: 2017

15. Carboxylate anion generation in aqueous solution from carbonate radiolysis, a potential route for abiotic organic acid synthesis on Earth and beyond

Author: G. Blain, Véronique Baty, Massoud Fattahi, A. Costagliola, Johan Vandenborre, Laurent Truche, Emeline Craff, Ferid Haddad, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique] (GIP ARRONAX), Université de Nantes (UN)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Université de Nantes (UN)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and UNICANCER-UNICANCER
Subjects: Molar concentration, Aqueous solution, 010504 meteorology & atmospheric sciences, Inorganic chemistry, 010502 geochemistry & geophysics, 01 natural sciences, 6. Clean water, Oxalate, chemistry.chemical_compound, Geophysics, chemistry, 13. Climate action, Space and Planetary Science, Geochemistry and Petrology, Radiolysis, Carbon dioxide, Earth and Planetary Sciences (miscellaneous), Carbonate, Formate, Carboxylate, [CHIM.RADIO]Chemical Sciences/Radiochemistry, Geology, 0105 earth and related environmental sciences
Abstract: Highlights • Carbonate radiolysis leads to successive formation of formate, acetate and oxalate. • H2 radiolytic production is significantly enhanced in the presence of carbonate. • Oxalate may reach the millimolar concentration level in deep ancient fracture fluids. • Carboxylates radiolytic production does not need catalyst or hydrothermal conditions. • These radiolytic by-products represent a source of energy for the deep biosphere. Low molecular weight carboxylate anions such as formate (HCOO−), acetate (CH3COO−) and oxalate (C2O ) have been shown to play an important role in supporting deep subsurface microbial ecosystems. Their origin whether biological or abiotic is currently highly debated, but surprisingly radiolytic production has rarely been considered, as it is the case for H2. Here, we address this question through dedicated irradiation experiments. Aqueous solutions containing carbonate, formate, acetate or oxalate have been irradiated using both the 60.7 MeV α-beam of the ARRONAX cyclotron (Nantes, France) and 661.7 keV γ-Ray in order to reveal the mechanism and chemical yield of radiation-induced dissolved carbonate degradation. The yields (G-values) of carboxylate anions production/degradation in low-concentration carbonate solution (0.01 to 1 mmol L−1) are measured. Carbonate degradation occurs through three consecutive steps (Carbonate Formate Acetate Oxalate) involving formate radical (CO2−•), dihydrogen (H2), and carbon dioxide (CO2) generation. Dissolved carbonate radiolysis provides a consistent pathway for both enhancing two-fold the radiolytic H2 production compared to pure water and generating carboxylic species, chiefly oxalate, readily available for microbes. Radiation-induced carbonate degradation may produce substantial amount (millimolar concentration) of carboxylate anions in ancient groundwaters from deep crystalline bedrocks. Subsurface lithoautotrophic microbial ecosystems may not only be supported by radiolytic H2 but also by carboxylate species from carbonate radiolysis. Carbonate radiolysis can be also an endogenous source of carboxylate species on Mars and other planetary bodies.
Published: 2021

16. Initial FDG-PET/CT predicts survival in adults Ewing sarcoma family of tumors

Author: Ludovic Ferrer, Bastien Jamet, Loïc Campion, Sylvie Girault, Thomas Carlier, Emmanuelle Bompas, Yann Venel, Caroline Rousseau, Fanny Borrely, Maxime Rousseau, Françoise Kraeber-Bodéré, Département de Médecine Nucléaire [Saint Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Département de Médecine Nucléaire (NANTES - Médecine Nucléaire), Centre hospitalier universitaire de Nantes (CHU Nantes), Département d'Oncologie [Saint Herblain], Département de Médecine Nucléaire [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Département de Médecine Nucléaire [Tours], Hôpital Bretonneau [Tours], UNICANCER, Département de Physique [Saint Herblain], Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
Subjects: Oncology, medicine.medical_specialty, Multivariate analysis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Ewing sarcoma family of tumors, 030218 nuclear medicine & medical imaging, survival analysis, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Progression-free survival, Stage (cooking), Survival analysis, business.industry, Cancer, Retrospective cohort study, computer.file_format, medicine.disease, FDG-PET/CT, 3. Good health, 030220 oncology & carcinogenesis, oncology, ICO, Sarcoma, prognosis, Nuclear medicine, business, computer, Research Paper
Abstract: // Bastien Jamet 1 , Thomas Carlier 2, 3 , Loic Campion 2, 4 , Emmanuelle Bompas 4 , Sylvie Girault 5 , Fanny Borrely 6 , Ludovic Ferrer 7 , Maxime Rousseau 1 , Yann Venel 6 , Francoise Kraeber-Bodere 1, 2, 3 and Caroline Rousseau 1, 2 1 Nuclear Medicine Unit, ICO Cancer Center Gauducheau, Saint Herblain, France 2 Nantes-Angers Cancer Research Center, INSERM U892, CNRS UMR 6299, University of Nantes, Nantes, France 3 Nuclear Medicine Unit, University Hospital, Nantes, France 4 Oncology Unit, ICO Cancer Center Gauducheau, Saint Herblain, France 5 Nuclear Medicine Unit, ICO Cancer Center Papin, Angers, France 6 Nuclear Medicine Unit, University Hospital Bretonneau, Tours, France 7 Physics Unit, ICO Cancer Center Gauducheau, Saint Herblain, France Correspondence to: Bastien Jamet, email: bastien.jamet@chu-nantes.fr Keywords: FDG-PET/CT, oncology, Ewing sarcoma family of tumors, survival analysis, prognosis Received: May 11, 2017 Accepted: June 27, 2017 Published: August 18, 2017 ABSTRACT Purpose: The aim of this retrospective study was to determine, at baseline, the prognostic value of different FDG-PET/CT quantitative parameters in a homogenous Ewing Sarcoma Family of Tumors (ESFT) adult population, compared with clinically relevant prognostic factors. Methods: Adult patients from 3 oncological centers, all with proved ESFT, were retrospectively included. Quantitative FDG-PET/CT parameters (SUV (maximum, peak and mean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary lesion of each patient were recorded before treatment, as well as usual clinical prognostic factors (stage of disease, location, tumor size, gender and age). Then, their relation with progression free survival (PFS) and overall survival (OS) was evaluated. Results: 32 patients were included. Median age was 21 years (range, 15 to 61). Nineteen patients (59%) were initially metastatic. On multivariate analysis, high SUV max remained independent predictor of worst OS (p=0.02) and PFS (p=0.019), metastatic disease of worst PFS (p=0.01) and high SUVpeak of worst OS (p=0.01). Optimal prognostic cut-off of SUV peak was found at 12.5 in multivariate analyses for PFS and OS ( p =0.0001). Conclusions: FDG-PET/CT, recommended at ESFT diagnosis for initial staging, can be a useful tool for predicting long-term adult patients outcome through semi-quantitative parameters.
Published: 2017

17. Exploring Tumor Heterogeneity Using PET Imaging: The Big Picture

Author: Clément Bailly, Caroline Bodet-Milin, Mickaël Bourgeois, Sébastien Gouard, Catherine Ansquer, Matthieu Barbaud, Jean-Charles Sébille, Michel Chérel, Françoise Kraeber-Bodéré, Thomas Carlier, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Département de Médecine Nucléaire [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), ARRONAX - (GIP) Groupement d'Intérêt Public [Saint-Herblain] (Institut de Recherche Public), Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA), ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), ANR-11-EQPX-0004,ARRONAXPLUS,Nucléaire pour la Santé(2011), ANR-16-IDEX-0007,NExT (I-SITE),NExT (I-SITE)(2016), Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Bernardo, Elizabeth, Radiopharmaceutiques Innovants en Oncologie et Neurologie - - IRON2011 - ANR-11-LABX-0018 - LABX - VALID, Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID, Nucléaire pour la Santé - - ARRONAXPLUS2011 - ANR-11-EQPX-0004 - EQPX - VALID, NExT (I-SITE) - - NExT (I-SITE)2016 - ANR-16-IDEX-0007 - IDEX - VALID, and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: PET, [SDV.CAN] Life Sciences [q-bio]/Cancer, radiomics, [SDV.CAN]Life Sciences [q-bio]/Cancer, Review, nuclear medicine, heterogeneity, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, radiopharmaceuticals, SUV
Abstract: International audience; Personalized medicine represents a major goal in oncology. It has its underpinning in the identification of biomarkers with diagnostic, prognostic, or predictive values. Nowadays, the concept of biomarker no longer necessarily corresponds to biological characteristics measured ex vivo but includes complex physiological characteristics acquired by different technologies. Positron-emission-tomography (PET) imaging is an integral part of this approach by enabling the fine characterization of tumor heterogeneity in vivo in a non-invasive way. It can effectively be assessed by exploring the heterogeneous distribution and uptake of a tracer such as 18F-fluoro-deoxyglucose (FDG) or by using multiple radiopharmaceuticals, each providing different information. These two approaches represent two avenues of development for the research of new biomarkers in oncology. In this article, we review the existing evidence that the measurement of tumor heterogeneity with PET imaging provide essential information in clinical practice for treatment decision-making strategy, to better select patients with poor prognosis for more intensive therapy or those eligible for targeted therapy.
Published: 2019

18. FLASHMOD : vers une plateforme d’irradiation préclinique en protonthérapie FLASH à ARRONAX

Author: Métivier, Vincent, Chiavassa, S., DELPON, G., Guertin, Arnaud, Haddad, Ferid, Koumeir, Charbel, Poirier, Freddy, Ralite, F., Servagent, Noël, Varmenot, N., Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique] (GIP ARRONAX), Université de Nantes (UN)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], and ANR-11-EQPX-0004,ARRONAXPLUS,Nucléaire pour la Santé(2011)
Subjects: [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2019

19. FLT3 ligand plasma levels have no impact on outcomes after allotransplant in acute leukemia

Author: Marion Eveillard, Olivier Theisen, Cyrille Touzeau, Michel Chérel, Nicolas Blin, Joëlle Gaschet, Yannick Le Bris, Anne Lok, Alice Garnier, Antoine Bonnet, Thomas Gastinne, Nelly Robillard, Patrice Chevallier, Marie-C. Béné, Camille Debord, Soraya Wuilleme, Viviane Dubruille, Thierry Guillaume, Steven Le Gouill, Amandine Le Bourgeois, Pierre Peterlin, Beatrice Mahe, Catherine Godon, Philippe Moreau, Bernardo, Elizabeth, Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Centre hospitalier universitaire de Nantes (CHU Nantes), Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Département d'hématologie et de biologie [CHU Nantes], Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), This study was supported by a grant from the DHU Oncogreffe of Nantes. https://www.dhu-oncogreffe.com/en, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA)
Subjects: 0301 basic medicine, Oncology, Acute Myeloid Leukemia, Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hematopoietic stem cell transplantation, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, FMS-like tyrosine kinase 3 ligand, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, hemic and lymphatic diseases, medicine, Immunology and Allergy, Humans, Transplantation, Homologous, In patient, Molecular Biology, Aged, Acute leukemia, business.industry, Myeloid leukemia, Membrane Proteins, Hematology, Plasma levels, Middle Aged, Acute Lymphoblastic Leukemia, 3. Good health, Allogeneic stem cell transplantation, Haematopoiesis, Leukemia, Myeloid, Acute, 030104 developmental biology, surgical procedures, operative, Treatment Outcome, Solubility, 030220 oncology & carcinogenesis, Flt3 ligand, Female, business, Fms-like tyrosine kinase 3 ligand
Abstract: International audience; Objective: This study was designed to assess the impact on outcomes of early soluble Fms-like tyrosine kinase 3 ligand concentrations (sFLc) in patients receiving an allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Methods: This was a prospective monocentric study including all allo-HSCT patients included in the previous FLAM/FLAL study (Peterlin et al., 2019). Blood samples collected before the start of conditioning then post-transplant were frozen, stored and tested by ELISA. The parameters considered were hematopoietic recoveries, Leukemia Free Survival and Overall Survival, acute and chronic GVHD, grade 3 or 4 acute and/or extensive chronic GVHD-free and relapse-free survival (GRFS). Results: Forty-one patients were included, a total of 179 samples were assayed for sFLc. There was no impact of sFLc levels (< =median vs > median) on acute and chronic GVHD incidences, LFS, OS nor GRFS. Conclusion: At variance with induction results for AML (Peterlin et al., 2019) endogenous sFLc do not appear to be a prognostic marker at the time of or after allo-HSCT. Even though the results are negatives, this is, to the best of our knowledge, the only prospective series specifically addressing the question of sFLc impact after allo-HSCT in acute leukemias.
Published: 2019

20. 68Ga-PSMA-11 PET-CT study in prostate cancer patients with biochemical recurrence and non-contributive 18F-Choline PET-CT : impact on therapeutic decision-making and biomarker changes

Author: Rousseau, Caroline, Michaud, A., Barbaud, M., Morvant, C., Maucherat, B., Le Thiec, M., Rusu, D., Morel, A., Fleury, V., Colombie, M., Rauscher, A., Frindel, Mathieu, Baumgartner, P., Fleury, N., Campion, Loïc, Kraeber-Bodéré, Françoise, Bernardo, Elizabeth, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Unité de Pharmacie [ICO, Saint Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Délégation à la recherche clinique [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Unité de Biométrie [ICO, Saint Herblain], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA)
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, urologic and male genital diseases
Abstract: International audience; Aim/Introduction: The aim of this retrospective study was to investigate the impact of 68Ga-PSMA-11 PET/CT on current management of recurrence prostate cancer patients with negative PET/CT F-Choline. Materials and Methods: Eightynine patients with previously negative 18F-Choline (FCH) were enrolled (PSA from 0.28 to 24.6 ng/mL). PET images were recorded 1 hour after injection of 150 MBq of 68Ga-PSMA. Referring patient physician was asked about the care before and after PSMA PET imaging to determine the influence of PSMA results on therapeutic strategy. Six months after the end of treatment, a PSA assay was requested to evaluate therapeutic efficacy. Results: Sixty-nine among the 89 patients (77,5%) had a positive PSMA PET/CT. Detection rates were 85.6% and 89.4% for serum PSA levels lower than 2 ng/ml, and > 2 ng/ml, respectively. Three hundred and one lesions were detected: 235/301 in lymph nodes (78.1%), 38/301 as metastatic sites (bone, mostly on axial skeleton, or lung) (12.6%) and 28/301 in the prostate bed (9.3%). The majority of lesions were detected in lymph nodes: in particular with 71.5% pelvic nodes, on the other hand with 17.9% of para-aortic nodes and 10.6% with sus diaphragmatic location. For the para-aortic and subdiaphragmatic node locations, initial surgical management associated with pelvic salvage radiotherapy were the most common initial management which could explain the frequently supra-pelvic node recurrence. The median number of lesions per patient was 2 [ranging from 0 to 67]. No particularity of the PSA serum level, doubling time or PSA velocity at the time of PSMA PET-CT could explain why 68Ga-PSMA PET-CT was unable to detect any suspicious tumor lesions in 20 patients. Thanks to PSMA PET/CT, therapeutic management changed in 59/69 patients (84.9%). With a follow-up of 5.7 ± 1.8 months, 62/89 (69.6%) PSA assays after treatment guided by PSMA PET-CT were collected. For 43.5% (27/62) of patients, the serum PSA level was lower than 0.2 ng/mL and a total PSA decrease of over 50% in 35 (56.5%) patients was obtained. Conclusion: Performing a PSMA PET-CT when FCH PET-CT was negative allows the recurrence localization in more 80% of patients and this had a major clinical impact, as it resulted in treatment change in more than 80% of patients as well as a significant decrease in PSA levels in more than 55% of them. References: None.
Published: 2019

21. FDG PET in Multiple Myeloma

Author: Françoise Kraeber-Bodéré, Philippe Moreau, Bastien Jamet, Anne-Victoire Michaud, Caroline Bodet-Milin, Clément Bailly, Cyrille Touzeau, Thomas Carlier, Département de Médecine Nucléaire [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Regulation of Bcl2 and p53 Networks in Multiple Myeloma and Mantle Cell Lymphoma (CRCINA-ÉQUIPE 10), Service d'Hématologie [Nantes], Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, This work has been supported in part by grants from the French National Agency for Research called 'Investissements d’Avenir' IRON Labex n° ANR-11-LABX-0018-01 and ArronaxPlus Equipex n° ANR-11-EQPX-0004, and by a grant INCa-DGOS-Inserm_12558 (SIRIC ILIAD)., ANR-11-EQPX-0004,ARRONAXPLUS,Nucléaire pour la Santé(2011), ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Bernardo, Elizabeth, Nucléaire pour la Santé - - ARRONAXPLUS2011 - ANR-11-EQPX-0004 - EQPX - VALID, and Radiopharmaceutiques Innovants en Oncologie et Neurologie - - IRON2011 - ANR-11-LABX-0018 - LABX - VALID
Subjects: Prognostic factor, medicine.diagnostic_test, business.industry, Negativity effect, [SDV.CAN]Life Sciences [q-bio]/Cancer, Therapeutic evaluation, medicine.disease, 3. Good health, carbohydrates (lipids), 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, Imaging Tool, [SDV.CAN] Life Sciences [q-bio]/Cancer, Positron emission tomography, Bone lesion, 030220 oncology & carcinogenesis, medicine, business, Nuclear medicine, Multiple myeloma, ComputingMilieux_MISCELLANEOUS, 030215 immunology
Abstract: The potential of 18Fluoro-deoxyglucose (FDG) positron emission tomography (PET) for the treatment of multiple myeloma has recently been evaluated. FDG-PET is a powerful imaging tool for the detection of bone lesions at initial diagnosis with high sensitivity and specificity values. The presence of extra-medullary lesions affects the prognosis. During therapeutic evaluation, FDG-PET is the reference imaging technique, because it can be performed much earlier than an MRI which lacks specificity. The negativity of FDG-PET before and after autologous stem cell transplantation is an independent favorable prognostic factor, especially for patients with a complete biological response.
Published: 2019

22. Prognostic Impact of Pretherapeutic FDG-PET in Localized Anal Cancer

Author: Sylvie Girault, Aude Testard, Ludovic Ferrer, Sandrine Hiret, Olivier Morel, Maelle Le Thiec, Françoise Kraeber-Bodéré, Bruno Maucherat, Loïc Campion, D. Rusu, Camille Guillerminet, Emmanuel Rio, Hadji Hamidou, Véronique Guérin Meyer, Marie Lacombe, Caroline Rousseau, Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA), Département de Médecine Nucléaire [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Département de Physique Médicale [Saint-Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Département de Physique Médicale [Angers], Service de la Radio-Oncologie [Angers], Service Oncologie Médicale [Angers], Service de la Radio-Oncologie [Saint-Herblain], Département d'oncologie médicale [Saint Herblain] (Centre René Gauducheau - ICO), Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Bernardo, Elizabeth
Subjects: Cancer Research, medicine.medical_specialty, Multivariate statistics, anal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, Standardized uptake value, lcsh:RC254-282, Article, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, parasitic diseases, medicine, Clinical endpoint, Anal cancer, FDG-PET, metabolic tumour volume, 10. No inequality, Lymph node, Fluorodeoxyglucose, medicine.diagnostic_test, business.industry, Anal Squamous Cell Carcinoma, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 3. Good health, medicine.anatomical_structure, Oncology, Positron emission tomography, 030220 oncology & carcinogenesis, prognosis, Radiology, business, medicine.drug
Abstract: International audience; Due to the heterogeneity of tumour mass segmentation methods and lack of consensus, our study evaluated the prognostic value of pretherapeutic positron emission tomography with fluorodeoxyglucose (FDG-PET) metabolic parameters using different segmentation methods in patients with localized anal squamous cell carcinoma (SCC). Eighty-one patients with FDG-PET before radiochemotherapy were retrospectively analyzed. Semiquantitative data were measured with three fixed thresholds (35%, 41% and 50% of Maximum Standardized Uptake Value (SUVmax)) and four segmentation methods based on iterative approaches (Black, Adaptive, Nestle and Fitting). Metabolic volumes of primary anal tumour (P-MTV) and total tumour load (T-MTV: P-MTV+ lymph node MTV) were calculated. The primary endpoint was event-free survival (EFS). Seven multivariate models were created to compare FDG-PET tumour volumes prognostic impact. For all segmentation thresholds, PET metabolic volume parameters were independent prognostic factor and T-MTV variable was consistently better associated with EFS than P-MTV. Patient's sex was an independent variable and significantly correlated with EFS. With fixed threshold segmentation methods, 35% of SUVmax threshold seemed better correlated with EFS and the best cutoff for discrimination between a low and high risk of event occurrence was 40 cm 3. Determination of T-MTV by FDG-PET using fixed threshold segmentation is useful for predicting EFS for primary anal SCC. If these data are confirmed in larger studies, FDG-PET could contribute to individualized patient therapies.
Published: 2020

23. Outcome of 449 adult patients with rhabdomyosarcoma: an observational ambispective nationwide study

Author: Bompas, Emmanuelle, Campion, Loïc, Italiano, Antoine, Le Cesne, Axel, Chevreau, Christine, Isambert, Nicolas, Toulmonde, Maud, Mir, Olivier, Ray-Coquard, Isabelle, Piperno-Neumann, Sophie, Saada-Bouzid, Esma, Rios, Maria, Kurtz, Jean-Emmanuel, Delcambre, Corinne, Dubray-Longeras, Pascale, Duffaud, Florence, Karanian, Marie, Le Loarer, Francois, Soulié, Patrick, Penel, Nicolas, Blay, Jean-Yves, CRLCC René Gauducheau, Institut Bergonié [Bordeaux], UNICANCER, Sarcome, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Centre Léon Bérard [Lyon], Institut Curie [Paris], Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Les Hôpitaux Universitaires de Strasbourg (HUS), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Assistance Publique - Hôpitaux de Marseille (APHM), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Service d'Oncologie Médicale, université de Bourgogne, LNC, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Lille-UNICANCER, CHU Lille, Université de Lille, METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694, Centre René Gauducheau, Institut Gustave Roussy [IGR], Département d'oncologie médicale [Centre Georges-François Leclerc], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] [UNICANCER/ICL], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] [UNICANCER/CRLC], Centre Jean Perrin [Clermont-Ferrand] [UNICANCER/CJP], CHU Marseille, Institut de Cancérologie de l'Ouest [Angers/Nantes] [UNICANCER/ICO], Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS], and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, Adolescent, genetic structures, [SDV]Life Sciences [q-bio], Review, Young Adult, pediatric, Adult cancer, rhabdomyosarcoma, Humans, Public Health Surveillance, Rhabdomyosarcoma, Embryonal, Aged, Retrospective Studies, Aged, 80 and over, musculoskeletal, neural, and ocular physiology, Middle Aged, Prognosis, musculoskeletal system, Combined Modality Therapy, Survival Analysis, eye diseases, Patient Outcome Assessment, [SDV] Life Sciences [q-bio], Treatment Outcome, Female, France, Cancer Prevention, human activities
Abstract: IF 3.202; International audience; Five-year overall survival (OS) of localized RMS exceeds 70% in children (
Published: 2018

24. PET Pronostic Biomarkers Exploratory Analyses About Initial FDG-PET In Patients With Anal Carcinoma

Author: Testard, A., Le Thiec, M., Ferrer, Ludovic, Guillerminet, C., Morel, O., Kraeber-Bodéré, Françoise, Rousseau, Caroline, Bernardo, Elizabeth, Département de Médecine Nucléaire [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Département de Physique [Angers], Université d'Angers (UA), Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: International audience; Introduction: In anal squamous cell carcinoma (SCC), pre-treatment prognostic factors able to identify more accurately patients with high risk of recurrence who may benefit from optimized treatment are lacking. There are increasing evidences that FDG PET examinations are useful in anal SCC management. Our objective was to explore, by two different analyses, the value of pre-treatment quantitative imaging to predict progression-free survival (PFS) in anal SCC patients. Subjects & Methods: We conducted a retrospective study on FDG PET examinations for 81 consecutive anal SCC patients at initial staging. Along with clinical variables (age, sex, T-stage, N-stage, HIV and human papilloma virus infections) collection, tumor and lymph nodes (LN) FDG metrics (SUVmax, TLG, MTV) were measured using 7 3D-thresholding methods on PET images: 3 with fixed SUVmax threshold (T35%, T41% and T50%) and 4 adaptative methods [M11, M22, M33, M44]. Each semi-quantitative PET variable is associated with 26 events free survival as a residual disease, local recurrence, distant metastasis or deaths at 0.10 threshold in univariate analysis. A multivariate analysis was conducted with an AIC criterion based Cox model. Evidence ratio (ER) was calculated for each model when PET variable remained significant after adjustment. Due to a small sized cohort with few events compared to the information to be processed, 2 analyses were conducted according to 4 quartiles and median FDG quantitative parameters respectively. Results: Six (7.5%), 18 (22.2%), 39 (48.1%) and 18 (22.2%) patients had respectively disease of stage I to IV. Median follow up was 3.3y (2.5-5y). As clinical data, male sex was the uniquely prognostic biomarker (HR: 3.32; CI: 1.38-8.02; p=0.007) of progression free survival (PFS) on univariate analysis. Out of the 57 tumor image intensity features, only 27 were predictive of PFS (0.0032
Published: 2018

25. Comparison of Immuno-PET of CD138 and PET imaging with 64CuCl2 and 18F-FDG in a preclinical syngeneic model of multiple myeloma

Author: Bailly, Clément, Gouard, Sébastien, Lacombe, Marie, Saëc, Patricia Remaud-Le, Chalopin, Benjamin, Bourgeois, Mickael, Chouin, Nicolas, Tripier, Raphaël, Halime, Zakaria, Haddad, Ferid, Faivre-Chauvet, Alain, Kraeber-Bodéré, Françoise, Chérel, Michel, Bodet-Milin, Caroline, Département de Médecine Nucléaire (NANTES - Médecine Nucléaire), Centre hospitalier universitaire de Nantes (CHU Nantes), Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Animaux modèles pour la recherche en oncologie comparée (AMaROC), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Chimie, Electrochimie Moléculaires et Chimie Analytique (CEMCA), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), ARRONAX - (GIP) Groupement d'Intérêt Public [Saint-Herblain] (Institut de Recherche Public), RENARD, NICOLAS, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Université de Brest (UBO)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique] (GIP ARRONAX), Université de Nantes (UN)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), and Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)
Subjects: multiple myeloma, syngeneic model, TE2A-C-functiollaized, Copper-64, [SDV.CAN] Life Sciences [q-bio]/Cancer, immuno-PET, murine CD138, [SDV.CAN]Life Sciences [q-bio]/Cancer, Research Paper
Abstract: International audience; Purpose:Although recent data from the literature suggest that PET imaging with [18]-Fluorodeoxyglucose (18F-FDG) is a promising technique in multiple myeloma (MM), the development of other radiopharmaceuticals seems relevant. CD138 is currently used as a standard marker in many laboratories for the identification and purification of myeloma cells, and could be used in phenotype tumor imaging. In this study, we evaluated a 64Cu-labeled anti-CD138 murine antibody (64Cu-TE2A-9E7.4) and a metabolic tracer (64CuCl2) for PET imaging in a MM syngeneic mouse model.Experimental Design and Results:64Cu-TE2A-9E7.4 antibody and 64CuCl2 were evaluated via PET imaging and biodistribution studies in C57BL / KaLwRij mice bearing either 5T33-MM subcutaneous tumors or bone lesions. These results were compared to 18F-FDG-PET imaging. Autoradiography and histology of representative tumors were secondly conducted. In biodistribution and PET studies, 64Cu-TE2A-9E7.4 displayed good tumor uptake of subcutaneous and intra-medullary lesions, greater than that demonstrated with 18F-FDG-PET. In control experiments, only low-level, non-specific uptake of 64Cu-labeled isotype IgG was observed in tumors. Similarly, low activity concentrations of 64CuCl2 were accumulated in MM lesions. Histopathologic analysis of the immuno-PET-positive lesions revealed the presence of plasma cell infiltrates within the bone marrow.Conclusions:64Cu-labeled anti-CD138 antibody can detect subcutaneous MM tumors and bone marrow lesions with high sensitivity, outperforming 18F-FDG-PET and 64CuCl2 in this preclinical model. These data support 64Cu-anti-CD138 antibody as a specific and promising new imaging radiopharmaceutical agent in MM.
Published: 2018

26. Preliminary results of 68Ga-PSMA PET/CT prospective study in prostate cancer occult recurrence patients : diagnostic performance and impact on therapeutic decision-making

Author: Rousseau, C., Le Thiec, M., Ferrer, L., Rusu, D., Rauscher, A., Maucherat, B., Frindel, M., Baumgartner, P., Fleury, V., Denis, A., Varmenot, N., Debeaupuis, E., Campion, L., Kraeber-Bodere, F., Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Physique médicale [CRG-ICO, Saint-Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Unité de Pharmacie [ICO, Saint Herblain], Délégation à la recherche clinique et à l'innovation [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Integrative Oncogenomics of Multiple Myeloma Pathogenesis and Progression (CRCINA-ÉQUIPE 11), Unité de Biométrie [ICO, Saint Herblain], Bernardo, Elizabeth, and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, urologic and male genital diseases
Abstract: International audience; Introduction: The aim of this prospective study was to investigate the impact of 68Ga-PSMA-11 PET/CT on current management of prostate cancer patients with occult biochemical recurrence (BCR). Subjects & Methods: 130 hormone-naïve occult BCR (PSA from 0.05 to 1.6 ng/mL) patients were enrolled in a prospective study (NCT03443609). All patients received a radical treatment (prostatectomy +/- radiotherapy) which allowed to an undetectable PSA level. Before PSMA PET/CT, patients were screened by conventional imaging as mpMRI and bone scan (+ trunk SPECT/ CT) and enrolled only if conventional imaging was doubtful or normal. PET images were recorded 1 and 2 hours after injection of 150 MBq of tracer and images interpreted by 2 nuclear physicians. Referring patient physician completed 2 questionnaires to assess PSMA PET imaging influence on therapeutic strategy: one prior and one after PSMA PET/CT indicating treatment plan without and with PSMA PET/CT information respectively. Six months after the end of treatment, a PSA assay was requested to evaluate therapeutic efficacy. Results: Currently, we have complete data analysis of the first 52 patients. After pre-screening, 7 patients were excluded due to positive MRI (5 pts) or bone scan (2 pts). The median time from radical prostatectomy or radiotherapy to BCR was 4.92y (0.6-15.46). Thirty-eight among the 52 patients (73%) had a positive PSMA PET/CT. Ninety-four lesions were detected, 53/94 in lymph nodes (56.4%) predominantly dispatched on pelvic area (75.5%), 25/94 in bone (26.6%) (mostly on axial skeleton) and 12/94 into prostate bed (12.7%). Detection rates were 56 %, 87 % and 74% for patients with PSA value ranging from 0.05 to 0.3, 0.3 to 0.6 and 0.6 to 1.6 ng/ml respectively. Thanks to PSMA PET/CT, therapeutic management changed in 35/52 patients (67.3%). PSMA-positive patients had undetectable PSA level after stereotaxic radiotherapy or focal surgery based on PSMA results in 30.7% (16/52). In this particular hormone naïve patient population, Rauscher’s nomogram (1) was not validate, may be due a too small population. Conclusion: Preliminary results of this prospective study showed, in more than half of patients, a major impact of PSMA PET/CT on treatment management allowing them to benefit very early from focal therapy with the great result for 30% of them of PSA complete response. Reference: (1) Rauscher I., et al: doi:10.1016/j.eururo.2018.01.006
Published: 2018

27. Why should we take care about occupational dosimetric impact when routine use of gallium-68 in nuclear medicine ? A preliminary study

Author: Varmenot, N., Ferrer, L., Frindel, M., Rauscher, A., Baumgartner, P., Delaunay, F., Mathey, A., Pitel, C., Zulian, H., Kraeber-Bodere, F., Denis, A., Rousseau, C., Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Unité de physique médicale [ICO, Saint Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Unité de Pharmacie [ICO, Saint Herblain], Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Bernardo, Elizabeth, and Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: International audience; Introduction: Medical research in PET/CT diagnosis involving new gallium-68 radiolabelled pharmaceuticals is steadily rising in the last years thanks to the combined improvement of both radionuclide production and radiolabelling. Publications demonstrate benefits for the patient but few studies evaluate the occupational dosimetric impact when use the gallium-68 in routine, in terms of effective and equivalent dose. Subjects & Methods: In this study, extremities, crystallin and whole body exposure are evaluated for three technologists when use of the gallium-68 radiolabelling with DOTATOC peptide (10 runs) requiring handmade steps and PSMA-11 peptide (5 runs) that is an automated process. Electronic dosimeter ED3 (APVL) is used to access to instantaneous dose-rate that can be afterward related to steps of handling. OSL pellets (LANDAUER) are used to measure the cumulative dose. Dosimeters are placed on fingers, protection eyeglass and chest. During the production runs, we separate radiolabelling phase from injection handmade phase to the patient (150 MBq/patient). The annual equivalent and effective doses are extrapolated on a mean of 2.5 patients per day during 52 weeks of 5 days with 68Ga-PSMA-11 or 68Ga-DOTATOC lonely. Results: The measurements show high exposures heterogeneity, confirmed with ED3 measurements that present high punctual peaks during the production runs. For 68Ga-PSMA-11, the median equivalent dose to extremities, per production run and per syringe, is 228 μSv [208; 493] and, at the injection time, the median equivalent dose to extremities per syringe is 212 μSv [188; 278]. For 68Ga-DOTATOC, the median equivalent dose to extremities, per production run and per syringe, is 315 μSv [28; 875] and, at the injection time, the median equivalent dose to extremities per syringe is 493 μSv [111; 1225]. The extrapolated annual equivalent dose to extremities lead to 288 mSv [257; 501] and 525 mSv [90; 1365], respectively for 68Ga-PSMA-11 and 68Ga-DOTATOC. The extrapolated annual equivalent dose to crystallin lead to 6,5 mSv [4,9; 11,7] and 1,3 mSv [background; 113,1], respectively for 68Ga-PSMA-11 and 68Ga-DOTATOC. The extrapolated annual effective dose lead to 1,3 mSv [background; 16,9] and 1,3 mSv [background; 53,3], respectively for 68Ga-PSMA-11 and 68Ga-DOTATOC. Conclusion: This study highlights that the use in routine of radiolabelled gallium-68 could lead to significant equivalent doses for technologist, especially since the protocol is not automated. This advocates strongly for a specific attention when routine use of a new radiopharmaceuticals, particularly on radiation optimisation of radiolabelling protocol and injection phase, also on high practical training of technologist.
Published: 2018

28. Immuno-PET for Clinical Theranostic Approaches

Author: Bailly, Clément, Cléry, Pierre-François, Faivre-Chauvet, Alain, Bourgeois, Mickael, Guérard, François, Haddad, Ferid, Barbet, Jacques, Chérel, Michel, Kraeber-Bodéré, Françoise, Carlier, Thomas, Bodet-Milin, Caroline, Service de Médecine Nucléaire [Nantes], Hôpital Laennec, Département de Médecine Nucléaire (NANTES - Médecine Nucléaire), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique] (GIP ARRONAX), Université de Nantes (UN)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), ARRONAX - (GIP) Groupement d'Intérêt Public [Saint-Herblain] (Institut de Recherche Public), Université de Nantes (UN)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Département de Médecine Nucléaire [Saint Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), ANR-11-LABX-0018,IRON,Radiopharmaceutiques Innovants en Oncologie et Neurologie(2011), ANR-11-EQPX-0004,ARRONAXPLUS,Nucléaire pour la Santé(2011), Bernardo, Elizabeth, Radiopharmaceutiques Innovants en Oncologie et Neurologie - - IRON2011 - ANR-11-LABX-0018 - LABX - VALID, and Nucléaire pour la Santé - - ARRONAXPLUS2011 - ANR-11-EQPX-0004 - EQPX - VALID
Subjects: Antibodies, Monoclonal, [SDV.CAN]Life Sciences [q-bio]/Cancer, Review, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], molecular imaging, lcsh:Chemistry, lcsh:Biology (General), lcsh:QD1-999, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neoplasms, Positron-Emission Tomography, antibody, immuno-PET, Animals, Humans, Radiopharmaceuticals, lcsh:QH301-705.5, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; Recent advances in molecular characterization of tumors have allowed identification of new molecular targets on tumor cells or biomarkers. In medical practice, the identification of these biomarkers slowly but surely becomes a prerequisite before any treatment decision, leading to the concept of personalized medicine. Immuno-positron emission tomography (PET) fits perfectly with this approach. Indeed, monoclonal antibodies (mAbs) labelled with radionuclides represent promising probes for theranostic approaches, offering a non-invasive solution to assess in vivo target expression and distribution. Immuno-PET can potentially provide useful information for patient risk stratification, diagnosis, selection of targeted therapies, evaluation of response to therapy, prediction of adverse effects or for titrating doses for radioimmunotherapy. This paper reviews some aspects and recent developments in labelling methods, biological targets, and clinical data of some novel PET radiopharmaceuticals.
Published: 2017

29. Risque de radionécrose après radiothérapie hypofractionnée en conditions stéréotaxiques du lit opératoire de métastases cérébrales

Author: S. Chibbaro, Georges Noël, Gregory Delpon, F. Lefebvre, C. Bourrier, Alexander Keller, M. Doré, F. Thillays, F. Proust, Delphine Antoni, I. Darié, D. Jarnet, Jean-Baptiste Clavier, I. Menoux, Lissalde, Claire, UNICANCER, Département de Radiations Oncologie [Centre Paul Strauss, Strasbourg], Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Laboratoire de Biostatistique [HUS, Strasbourg] (Faculté de Médecine), Les Hôpitaux Universitaires de Strasbourg (HUS), Fluides Complexes et Instabilités Hydrodynamiques (IJLRDA-FCIH), Institut Jean le Rond d'Alembert (DALEMBERT), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Hôpital de Hautepierre [Strasbourg], Centre Hospitalier Régional d'Orléans (CHRO), Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA)
Subjects: business.industry, Lit opératoire, [SDV.CAN]Life Sciences [q-bio]/Cancer, 3. Good health, Stereotactic radiotherapy, 03 medical and health sciences, Radiation necrosis, Radionécrose, 0302 clinical medicine, Oncology, [SDV.CAN] Life Sciences [q-bio]/Cancer, 030220 oncology & carcinogenesis, Stéréotaxie, Medicine, Radiology, Nuclear Medicine and imaging, Resection Cavity, Nuclear medicine, business, Métastase cérébrale, 030217 neurology & neurosurgery
Abstract: Resume Objectif Identifier les facteurs predictifs de radionecrose apres l’irradiation en conditions stereotaxiques de la cavite d’exerese de metastases cerebrales operees. Materiels et methodes Une analyse retrospective a ete realisee dans deux centres francais utilisant un protocole d’irradiation trifractionnee (trois seances de 7,7 Gy, prescrites sur l’isodose 70 %), comme traitement adjuvant des lits operatoires de metastases cerebrales. Les patients initialement irradies dans l’encephale en totalite ont ete exclus de l’etude. Le diagnostic de radionecrose cerebrale a ete pose apres avis d’experts d’apres un faisceau d’arguments clinicoradiologiques, ou apres confirmation histologique. Des analyses uni- et multifactorielles ont ete realisees afin de determiner les facteurs predictifs de radionecrose, en testant plusieurs variables cliniques et dosimetriques, notamment le volume de tissu sain recevant une dose specifique (V8 Gy a V22 Gy). Resultats Cent quatre-vingt-un patients (189 cavites) ont ete pris en charge entre mars 2008 et fevrier 2015. Trente-cinq patients (18,5 %) ont vu se developper des signes de radionecrose en mediane 15 mois (extremes : 3–38 mois) apres l’irradiation. Un tiers des radionecroses etaient symptomatiques. En analyse multifactorielle, la localisation sous-tentorielle de la metastase operee etait predictive de radionecrose (hazard ratio [HR] : 2,97 ; intervalle de confiance a 95 % [IC 95 %] : 1,47–6,01 ; p = 0,0025). Aucun des Vx analyses n’etait associe au delai d’apparition de radionecrose, le V14 Gy approchait la signification (p = 0,059). Conclusion L’analyse des differents facteurs cliniques et dosimetriques a montre que la localisation sous-tentorielle d’une metastase cerebrale etait predictive de radionecrose apres irradiation en conditions stereotaxiques du lit operatoire.
Published: 2017

30. Contribution of endocrine therapy in oestrogen receptor-positive pT1a-b breast cancer: Results of a retrospective study

Author: Gilles Houvenaeghel, Alexandre de Nonneville, Monique Cohen, Jean-Marc Classe, Fabien Reyal, Chafika Mazouni, Christelle Faure, Alejandra Martinez, Marie-Pierre Chauvet, Emile Daraï, Charles Coutant, Pierre-Emmanuel Colombo, Pierre Gimbergues, Anne-Sophie Azuar, Roman Rouzier, Christine Tunon de Lara, Patrice Crochet, Sandrine Rua, Anthony Gonçalves, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Chirurgie Oncologique [Institut Paoli-Calmettes, Marseille], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Département de chirurgie, Institut Curie [Paris], CRLCC Jean Godinot, Residual Tumor & Response to Treatment Laboratory [Paris] (RT2Lab), Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Institut du Cancer de Montpellier (ICM), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Hopital de Grasse, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'oncologie chirurgicale, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Department of Obstetrics and Gynecology, Assistance Publique H^opitaux de Marseille, La Conception Hospital, 13005 Marseille, Aix Marseille University, France, and Aix Marseille Université (AMU)
Subjects: Cancer Research, Receptors, Estrogen, Oncology, Chemotherapy, Adjuvant, Receptor, ErbB-2, [SDV]Life Sciences [q-bio], Humans, Female, Breast Neoplasms, Disease-Free Survival, Retrospective Studies
Abstract: Introduction: Few data have been reported regarding endocrine therapy (ET) in patients with small pT1a-b ER-postive breast cancer (BC). Thus, we conducted a study to detect possible survival improvements due to ET in such patients. Methods: Our retrospective observational study included 5545 patients with pT1a-b ERpositive BC treated in 15 French centres, excluding patients with HER2-positive status, neoadjuvant chemotherapy, ER-negative status, unknown pN status or in situ BC. We estimated disease-free survival (DFS), recurrence-free survival (RFS) and overall survival (OS) via univariate analysis and multivariate Cox regression. Results: Most patients (80.3%: 4453) received ET and-when compared to those without ET -experienced increases of 2.5% and 3.3% in DFS and 1.9% and 4.3% in RFS after 5 and 7 years of follow-up, respectively, with little difference in OS. In Cox regression analysis, no ET was significantly associated with decreased DFS (hazard ratio, HR = 1.275, p = 0.047, 95% CI[1.003-1.620]) but not OS or RFS in all patients, while in 2363 patients with pT1ab ER-positive grade 2-3 BC, no ET was significantly associated with decreased DFS (HR = 1.502, p = 0.049, 95% CI[1.001-2.252]), but not OS (HR = 1.361, p = 0.272). ET omission was not significantly associated with decreased survival in 3047 patients with pT1a-b ER-positive grade 1 BC. Conclusion: Our results indicate that while ET provided a beneficial impact on survival to patients with pT1a-bN0 ER-positive BC-and especially in those with grade 2-3 tumours-no such impact was observed in grade 1 tumours. Consequently, ET should be discussed with these patients, particularly in those with pT1a grade 1 tumours. 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Published: 2022

31. Interactions of radiation therapy with common and innovative systemic treatments: Antidiabetic treatments, antihypertensives, lipid-lowering medications, immunosuppressive medications and other radiosensitizing methods

Author: Y, Zhou, A, Larnaudie, Y, Ghannam, L, Ollivier, Y, Gounane, A, Laville, A, Coutte, A, Huertas, P, Maroun, C, Chargari, S, Bockel, Institut de Chimie et des Matériaux Paris-Est (ICMPE), Institut de Chimie du CNRS (INC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Département de Radio-Oncologie [Baclesse, Caen], Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Université d'Angers (UA), Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Groupe Avril, Institut Gustave Roussy (IGR), Curiethérapie, Département de radiothérapie [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), and Department of Radiotherapy
Subjects: Antidiabétiques, Lung Neoplasms, Antihypertenseurs, Statin, Antidiabetic treatments, Lipids, Médicaments hypolipémiants, Metformin, Oncology, Lipid-lowering medications, Immunosuppresseurs, Immunosuppressive medications, Humans, Hypoglycemic Agents, Nanoparticles, Radiology, Nuclear Medicine and imaging, Immunotherapy, Antihypertensive Agents, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Antihypertensives
Abstract: International audience; The invention and approval of innovative anticancer therapies in the last decade have revolutionized oncology treatment. Radiotherapy is one of the three traditional pillars in oncology treatment with surgery and systemic therapies. Some standard-of-care combinations of chemoradiotherapy widened the therapeutic window of radiation, while some other chemotherapies such as gemcitabine caused unacceptable toxicities when combined with radiation in lung cancers. Fast-paced progress are specially focused on immunotherapies, targeted-therapies, anti-angiogenic treatment, DNA repair inhibitors, hormonotherapy and cell cycle inhibitors. New anticancer therapeutic arsenals provided new possibilities of combined oncological treatments. The interactions of the radiotherapy with other systemic treatments, such as non-anticancer immunomodulatory/immunosuppressive medications are sometimes overlooked even though they could offer a real therapeutic benefit. In this review, we summarize the new opportunities and the risks of historical and novel combined therapies with radiation: non-anticancer immunomodulatory/immunosuppressive drugs, systemic reoxygenation, new therapies such as nanoparticles and SMAC mimetics. Key biological mechanisms, pre-clinical and available clinical data will be provided to demonstrate the promising opportunities in the years to come.
Published: 2022

32. Minors at risk of von Hippel-Lindau disease: 10 years’ experience of predictive genetic testing and follow-up adherence

Author: Roseline Vibert, Khadija Lahlou-Laforêt, Maryam Samadi, Valérie Krivosic, Thomas Blanc, Laurence Amar, Nelly Burnichon, Caroline Abadie, Stéphane Richard, Anne-Paule Gimenez-Roqueplo, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Références Cancers Rares (PREDIR), INCA, Institut national du cancer [Boulogne] (INCA), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Intégrité du génome et cancers (IGC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université Paris Cité (UPCité), and Favier, Judith
Subjects: [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, von Hippel-Lindau Disease, Adolescent, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Kidney Neoplasms, Von Hippel-Lindau Tumor Suppressor Protein, Child, Preschool, Genetics, Humans, Genetic Testing, Child, Genetics (clinical), Follow-Up Studies, Retrospective Studies
Abstract: International audience; Von Hippel-Lindau (VHL) disease is one of the most common cancer predisposition syndromes. Penetrance is high with around 20% of children presenting detectable and curable manifestations of the disease at 15 years old. VHL predictive genetic testing (PGT) is recommended during childhood from age 5 years in France. Insufficient compliance to surveillance of VHL pathogenic variant (PV) carriers is associated with severe outcome. PGT experienced by children and their parents is probably critical in influencing future acceptance of the result and adherence to surveillance. We conducted a retrospective study on minors tested (aged 5 to 16 years old) from 2010 to 2020, in a multidisciplinary oncogenetics consultation which follows a 3-step protocol based on psychological familial support. The objectives were to assess the adherence to follow-up within the National Expert Center for inherited predispositions to renal tumors (PREDIR) network of VHL PV carriers and its benefit through tumor detection and medical interventions. A VHL PGT was carried out in 34 children. Among the 16 children diagnosed as VHL PV carriers addressed to the PREDIR network, none had discontinued surveillance after a median of 41 months. Follow-up examinations detected 11 tumors in 6 children, 4 have been surgically treated. All had a favorable outcome. Our data suggest that a specific and adapted procedure for PGT in at-risk VHL children as well as a follow-up, organized within a specialized expert network, fosters a complete adherence to the surveillance protocol and thus lead to a favorable clinical outcome.
Published: 2022

33. Cost-effectiveness of hypofractionated versus conventional radiotherapy in patients with intermediate-risk prostate cancer: An ancillary study of the PROstate fractionated irradiation trial – PROFIT

Author: Zhou, K., Renouf, M., Perrocheau, G., Magné, N., Latorzeff, I., Pommier, P., Créhange, G., Paumier, A., Bera, G., Martin, J., Catton, C., Bellanger, Martine, Supiot, S., Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Institut de Cancérologie Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Léon Bérard [Lyon], Institut Curie [Paris], CRLCC Paul Papin, Groupe Hospitalier Bretagne Sud (GHBS), University of Newcastle [Callaghan, Australia] (UoN), University of Toronto, École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre de Recherches sur l'Action Politique en Europe (ARENES), Université de Rennes (UR)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), and This study received a grant from French ministry of health (Ministère des Solidarités et de la Santé, DGOS, Grant No: DGOS_2574). The funder had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.
Subjects: Male, Prostate cancer, Cost-effectiveness analysis, Cost-Benefit Analysis, Prostate, Prostatic Neoplasms, Hematology, Image Guided Radiation Therapy, Intensity Modulated Radiation Therapy, Treatment Outcome, Oncology, Quality of Life, Hypofractionation, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Radiology, Nuclear Medicine and imaging, France, Prospective Studies
Abstract: International audience; Purpose: To evaluate the cost-effectiveness of moderate Hypofractionated Radiotherapy (H-RT) compared to Conventional Radiotherapy (C-RT) for intermediate-risk prostate caner (PCa).Methods: A prospective randomized clinical trial including 222 patients from six French cancer centers was conducted as an ancillary study of the international PROstate Fractionated Irradiation Trial (PROFIT). We carried-out a cost-effectiveness analysis (CEA) from the payer's perspective, with a time horizon of 48 months. Patients assigned to the H-RT arm received 6000 cGy in 20 fractions over 4 weeks, or 7800 cGy in 39 fractions over 7 to 8 weeks in the C-RT arm. Patients completed quality of life (QoL) questionnaire: Expanded Prostate Cancer Index Composite (EPIC) at baseline, 24 and 48 months, which were mapped to obtain a EuroQol five-dimensional questionnaire (EQ-5D) equivalent to generate Quality Adjusted Life Years (QALY). We assessed differences in QALYs and costs between the two arms with Generalized Linear Models (GLMs). Costs, estimated in euro (€) 2020, were combined with QALYs to estimate the Incremental Cost-effectiveness ratio (ICER) with non-parametric bootstrap.Results: Total costs per patien were lower in the H-RT arm compared to the C-RT arm €3,062 (95 % CI: 2,368 to 3,754) versus €4,285 (95 % CI: 3,355 to 5,215), (p < 0.05). QALY were marginally higher in the H-RT arm, however this difference was not significant: 0.044 (95 % CI: - 0.016 to 0.099).Conclusions: Treating localized prostate cancer with moderate H-RT could reduce national health insurance spending. Adopting such a treatment with an updated reimbursement tariff would result in improving resource allocation in RT management.
Published: 2022

34. Hydrogen Peroxide (H2O2) production in response to multiple beam irradiation of protons at UHDR

Author: Evin, Manon, Fiegel, Vincent, Delpon, Grégory, Mouchard, Quentin, Emeline, Craff, Haddad, Ferid, Koumeir, Charbel, Maigne, Lydia, Métivier, Vincent, Potiron, Vincent, Servagent, Noël, Supiot, Stéphane, Vandenborre, Johan, Blain, Guillaume, Chiavassa, Sophie, Laboratoire de physique subatomique et des technologies associées (SUBATECH), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, GIP ARRONAX [Nantes], Université de Nantes (UN), Laboratoire de Physique de Clermont (LPC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Unité en Sciences Biologiques et Biotechnologies de Nantes (US2B), Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, and FLASHMOD
Subjects: FLASHMOD project, Radiochemistry, FLASH effect mecanisms, [SDV.CAN]Life Sciences [q-bio]/Cancer, External beam therapy, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], [CHIM.RADIO]Chemical Sciences/Radiochemistry
Abstract: International audience
Published: 2023

35. Résonance Paramagnétique Electronique utilisée en radiochimie: De la radiolyse de l’eau vers de nombreuses applications en radiochimie

Author: Blain, G., Laurane, Léost, Vandenborre, Johan, Haddad, Ferid, Fattahi, M., Laboratoire SUBATECH Nantes (SUBATECH), Mines Nantes (Mines Nantes)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique] (GIP ARRONAX), Université de Nantes (UN)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Université de Nantes (UN)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]
Subjects: [CHIM.RADIO]Chemical Sciences/Radiochemistry
Published: 2016

36. De la Radiolyse à la Radiochimie : La Spéciation du Technétium et de l’Uranium sous Rayonnement

Author: Vandenborre, Johan, Blain, G., Haddad, Ferid, Fattahi, M., Laboratoire SUBATECH Nantes (SUBATECH), Mines Nantes (Mines Nantes)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique] (GIP ARRONAX), Université de Nantes (UN)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Université de Nantes (UN)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and UNICANCER-UNICANCER
Subjects: [CHIM.RADIO]Chemical Sciences/Radiochemistry
Published: 2016

37. La Radiolyse α Pulsée en radiochimie: De la radiolyse de l’eau vers de nombreuses applications en radiochimie

Author: Blain, G., Vandenborre, Johan, Haddad, Ferid, Fattahi, M., Laboratoire SUBATECH Nantes (SUBATECH), Mines Nantes (Mines Nantes)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique] (GIP ARRONAX), Université de Nantes (UN)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Université de Nantes (UN)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and UNICANCER-UNICANCER
Subjects: [CHIM.RADIO]Chemical Sciences/Radiochemistry, ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 2016

38. COMPORTEMENT DE LA CALCITE (CaCO3) IRRADIEE PAR UN FAISCEAU D’HELIONS (60,7 MeV)

Author: Costagliola, A., Vandenborre, Johan, Blain, G., Haddad, Ferid, Fattahi, M., Laboratoire SUBATECH Nantes (SUBATECH), Mines Nantes (Mines Nantes)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique] (GIP ARRONAX), Université de Nantes (UN)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Université de Nantes (UN)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and UNICANCER-UNICANCER
Subjects: [CHIM.RADIO]Chemical Sciences/Radiochemistry, ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 2016

39. Effet des rayonnements ionisants sur des phases élémentaires (magnétite – sidérite – calcite – pyrite) mises en jeu lors du conditionnement de déchets HA et MAVL

Author: Costagliola, A., Vandenborre, Johan, Blain, G., Haddad, Ferid, Fattahi, M., Laboratoire SUBATECH Nantes (SUBATECH), Mines Nantes (Mines Nantes)-Université de Nantes (UN)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique] (GIP ARRONAX), Université de Nantes (UN)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Université de Nantes (UN)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]
Subjects: [CHIM.RADIO]Chemical Sciences/Radiochemistry, ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 2016

40. Immuno-PET Using Anticarcinoembryonic Antigen Bispecific Antibody and 68Ga-Labeled Peptide in Metastatic Medullary Thyroid Carcinoma: Clinical Optimization of the Pretargeting Parameters in a First-in-Human Trial

Author: Thomas Carlier, Alain Faivre-Chauvet, Vincent Rohmer, Delphine Drui, Olivier Couturier, Aurore Rauscher, Jacques Barbet, David M. Goldenberg, Robert M. Sharkey, Evelyne Cerato, Caroline Bodet-Milin, Françoise Kraeber-Bodéré, Mickaël Bourgeois, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine Nucléaire [Nantes], Hôpital Laennec, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Nucléaire (Med Nuc - ANGERS), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d'Endocrinologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Immunomedics, Inc., IBC Pharmaceuticals, Accélérateur pour la Recherche en Radiochimie et Oncologie [Nantes Atlantique] (GIP ARRONAX), Université de Nantes (UN)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Bernardo, Elizabeth, Université de Nantes (UN)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]
Subjects: Male, Saint- Herblain, France Key Words: medullary thyroid carcinoma, pretargeting, 030218 nuclear medicine & medical imaging, Immunoscintigraphy, 0302 clinical medicine, Antibodies, Bispecific, Medicine, Neoplasm Metastasis, Pretargeting, biology, New Jersey, and 9 GIP Arronax, Thyroid, Middle Aged, 68 Ga, 3. Good health, Inc, bispecific antibody, medicine.anatomical_structure, Isotope Labeling, 030220 oncology & carcinogenesis, immuno-PET, Female, Antibody, Oligopeptides, Hapten, pharmacokinetics, Adult, Gallium Radioisotopes, Morris Plains, [SDV.CAN]Life Sciences [q-bio]/Cancer, Heterocyclic Compounds, 1-Ring, 03 medical and health sciences, Pharmacokinetics, Antigen, [SDV.CAN] Life Sciences [q-bio]/Cancer, Humans, Radiology, Nuclear Medicine and imaging, Thyroid Neoplasms, Aged, business.industry, 7 IBC Pharmaceuticals, Carcinoembryonic Antigen, Carcinoma, Neuroendocrine, Radioimmunodetection, Calcitonin, Positron-Emission Tomography, 8 Immunomedics, biology.protein, business, Nuclear medicine
Abstract: International audience; Earlier clinical studies reported a high sensitivity of pretargeted immunoscintigraphy using murine or chimeric anticarcinoembryonic antigen (CEA) bispecific antibody (BsMAb) and peptides labeled with 111 In or 131 I in medullary thyroid carcinoma (MTC). Preclinical studies showed that new-generation humanized recombinant anti-CEA · antihistamine-succinyl-glycine (HSG) trivalent BsMAb TF2 and radiolabeled HSG peptide (IMP288) present good features for PET. This study aimed at optimizing molar doses and pretargeting interval of TF2 and 68 Ga-labeled IMP288 for immuno-PET in relapsed MTC patients with calcitonin serum levels greater than 150 pg/mL. Methods: Five cohorts (C1–C5) of 3 patients received variable molar doses of TF2 and approximately 150 MBq of 68 Ga-IMP288 after different pretargeting time intervals (C1: 120 nmol TF2, 6 nmol IMP288, 24 h; C2: 120 nmol TF2, 6 nmol IMP288, 30 h; C3: 120 nmol TF2, 6 nmol IMP288, 42 h; C4: 120 nmol TF2, 3 nmol IMP288, 30 h; and C5: 60 nmol TF2, 3 nmol IMP288, 30 h). TF2 and 68 Ga-IMP288 phar-macokinetics were monitored. Whole-body PET was recorded 60 and 120 min after 68 Ga-IMP288 injection. Tumor maximal SUV (T-SUV max) and T-SUV max –to–mediastinum blood-pool (MBP) SUV mean ratios (T/ MBP) were determined. Results: In C1, T-SUV max and T/MBP ranged from 4.09 to 8.93 and 1.39 to 3.72 at 60 min and 5.14 to 11.25 and 2.73 to 5.38 at 120 min, respectively. Because of the high MBP, the delay was increased to 30 h in C2, increasing T-SUV max and T/MBP. Further increasing the delay to 42 h in C3 decreased T-SUV max and T/ MBP, showing that 30 h was the most favorable delay. In C4, the TF2-to-peptide mole ratio was increased to 40 (delay 30 h), resulting in high T-SUV max but with higher MBP than in C2. In C5, the molar dose of TF2 was reduced, resulting in lower imaging performance. Pharmaco-kinetics demonstrated a fast TF2 clearance and a clear relationship between blood activity clearance and the ratio between the molar amount of injected peptide to the molar amount of circulating TF2 at the time of peptide injection. Conclusion: High tumor uptake and contrast can be obtained with pretargeted anti-CEA immuno-PET in relapsed MTC patients, especially using optimized pretargeting parameters: a BsMAb-to-peptide mole ratio of 20 and 30 h pretar-geting delay. Medul lary thyroid carcinoma (MTC) is relatively infrequent, accounting for less than 10% of all thyroid cancers (1). After initial surgery, serum calcitonin is still detectable in nearly 20% of patients , suggesting residual disease, and imaging including neck ultrasonography, neck and chest CT, liver contrast-enhanced CT or MRI, and spine and pelvic bone MRI is recommended when serum calcitonin is higher than 150 pg/mL (1,2). With the ability to characterize and quantify cancer molecular processes, 18 F-DOPA or 18 F-FDG PET/CT also show high performance in relapsed MTC patients and great potential as surrogate biomarkers, useful for early response evaluation and prediction of clinical outcome (3–6). MTC is characterized by an intense expression of CEA, and previous clinical trials showed the high sensitivity of pretargeted immunoscintigraphy using murine or chimeric anti-CEA bispecific antibody (BsMAb) and pretargeted haptens-peptides labeled with 111 In or 131 I (5,7,8). These results and the high potential of immuno-PET reported in other solid tumors using different radioimmuno-conjugates suggested that pretargeted haptens labeled with PET emitters would allow high-sensitivity and-specificity imaging under good conditions of radiation protection and dosimetry (9,10). Today, new pretargeting reagents have been designed (11–15). TF2 is an engineered trivalent BsMAb composed of a humanized anti–histamine-succinyl-glycine Fab fragment derived from the murine 679 antibody and 2 humanized anti-CEA Fab fragments derived from the hMN-14 antibody, formed into a 157-kD protein by the dock-and-lock procedure (11). IMP288 is a bivalent histamine-succinyl-glycine hapten that can be labeled with a variety of radionuclides for therapy
Published: 2016

41. Radio- immunothérapie alpha : Principes et intérêts en immunité antitumorale

Author: Nolwenn Fichou, Jérémie Ménager, François Davodeau, Jean-Baptiste Gorin, Françoise Kraeber-Bodéré, Michel Chérel, Joëlle Gaschet, Frank Bruchertseifer, Alfred Morgenstern, Yannick Guilloux, Sébastien Gouard, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), JRC Institute for Transuranium Elements [Karlsruhe] (ITU ), European Commission - Joint Research Centre [Karlsruhe] (JRC), European Commission's Joint Research Centre, Service de Médecine Nucléaire [Nantes], Hôpital Laennec, Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA), Centre René Gauducheau-Institut Régional du Cancer Nantes-Atlantique (IRCNA)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, and Bernardo, Elizabeth
Subjects: 0301 basic medicine, business.industry, medicine.drug_class, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, Immunotherapy, Monoclonal antibody, General Biochemistry, Genetics and Molecular Biology, Tumor antigen, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Immunity, 030220 oncology & carcinogenesis, Radioimmunotherapy, Cancer research, Cytotoxic T cell, Medicine, business
Abstract: International audience; > La radioimmunothérapie alpha (RITα) est une thérapie anticancéreuse vectorisée utilisant généralement un anticorps monoclonal spécifique d'un antigène tumoral couplé à un émetteur de particules α. Les émetteurs α représentent un outil idéal pour éradiquer les tumeurs disséminées ou les métastases. De récentes données démontrent que les rayonnements ionisants, en plus de leur cytotoxicité directe, peuvent aussi induire une immunité antitumorale efficace. Les effets biologiques de l'irradiation pourraient donc être utilisés pour potentialiser la réponse à différents types d'immunothérapie, et ainsi ouvrir la voie au développement de nouvelles thérapies combinant RITα et immunothérapies. < radionucléide. Le choix du radionu-cléide repose sur des considérations pratiques (le coût, la disponibilité, le type de techniques de radiomar-quage et la facilité d'utilisation), le type d'émission du radioélément, le transfert d'énergie linéique (TEL : quantité d'énergie transférée au milieu par la particule incidente, par unité de longueur de la trajectoire en keV 1 /µm) et la demi-vie physique du radioisotope (durée nécessaire pour que la moitié des noyaux radioactifs d'une source se soient désintégrés) [2]. Cette dernière doit être, autant que possible, en adéquation avec la pharmacocinétique du vecteur utilisé, afin de délivrer la plus grande dose possible de radioactivité à la tumeur après l'injection. Une demi-vie trop courte entraînera un nombre élevé de désintégrations avant d'atteindre la cible. À l'inverse, une demi-vie trop longue engendrera un grand nombre de désintégrations du radionucléide pendant la phase d'éli-mination du vecteur, rendant le radioimmunoconjugué plus toxique. La demi-vie doit également être compatible avec les applications cliniques et la prise en charge du patient. Ainsi, le temps nécessaire au transfert du radionucléide du site de production jusqu'à l'hôpital, 1 1 keV (kiloélectronvolts) = 10 3 eV ; 1 MeV (megaélectonvolts) = 10 6 eV.
Published: 2016

42. Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial

Author: Stéphane Supiot, Pierre Richaud, Bernard Dubray, Celine Ferlay, M. Bosset, Tan Dat Nguyen, Alain Ruffion, Christian Carrie, Nicolas Barbier, François Lesaunier, Jean-Léon Lagrange, Ali Hasbini, Véronique Beckendorf, Philippe Fourneret, Guy de Laroche, Muriel Habibian, Jean-Philippe Suchaud, Igor Latorzeff, Jean-Philippe Wagner, Gilles Créhange, Stéphane Guerif, Sophie Dussart, Centre Léon Bérard [Lyon], GCS-ETOILE, Biologie végétale et microbiologie environnementale - UMR7265 (BVME), Institut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB) (BIAM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Département de Radiothérapie, Centre René Gauducheau-Centre de Lutte Contre le Cancer Nantes Atlantique 'René Gauducheau' (CLCC)-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Centre Alexis Vautrin (CAV), Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Laboratoire Electronique, Informatique et Image [UMR6306] (Le2i), Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Centre Catalan d'Oncologie, Institut des Sciences cognitives Marc Jeannerod - Laboratoire sur le langage, le cerveau et la cognition (L2C2), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Biologie végétale et microbiologie environnementale - UMR7265 ( BVME ), Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Aix Marseille Université ( AMU ), Centre René Gauducheau-Institut de Cancérologie de l'Ouest (ICO)-Centre de Lutte Contre le Cancer Nantes Atlantique 'René Gauducheau' (CLCC), Centre Alexis Vautrin ( CAV ), Equipe Quantification en Imagerie Fonctionnelle ( QuantIF-LITIS ), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes ( LITIS ), Université Le Havre Normandie ( ULH ), Normandie Université ( NU ) -Normandie Université ( NU ) -Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Institut national des sciences appliquées Rouen Normandie ( INSA Rouen Normandie ), Normandie Université ( NU ) -Université Le Havre Normandie ( ULH ), Normandie Université ( NU ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Laboratoire Electronique, Informatique et Image ( Le2i ), Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Botanique et Modélisation de l'Architecture des Plantes et des Végétations ( UMR AMAP ), Centre de Coopération Internationale en Recherche Agronomique pour le Développement ( CIRAD ) -Institut national de la recherche agronomique [Montpellier] ( INRA Montpellier ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD [France-Sud] ), Institut des Sciences cognitives Marc Jeannerod - Laboratoire sur le langage, le cerveau et la cognition ( L2C2 ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Centre de Lutte Contre le Cancer Nantes Atlantique 'René Gauducheau' (CLCC), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Arts et Métiers (ENSAM), HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon
Subjects: Male, Survival, medicine.medical_treatment, 030232 urology & nephrology, Salvage therapy, Androgen suppression, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Androgen deprivation therapy, 0302 clinical medicine, Prospective Studies, Aged, 80 and over, education.field_of_study, Prostatectomy, Goserelin, Prostate, Middle Aged, Prognosis, Combined Modality Therapy, 3. Good health, Survival Rate, Prostate-specific antigen, Oncology, 030220 oncology & carcinogenesis, France, medicine.drug, medicine.medical_specialty, Patients, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma, methods, Time, 03 medical and health sciences, medicine, Biomarkers, Tumor, Humans, education, Survival rate, radiotherapy, Aged, Neoplasm Staging, Salvage Therapy, therapy, business.industry, Prostatic Neoplasms, Androgen Antagonists, Prostate-Specific Antigen, Surgery, Radiation Oncology, Neoplasm Recurrence, Local, Radiotherapy, Conformal, business, Follow-Up Studies
Abstract: International audience; BACKGROUND: How best to treat rising prostate-specific antigen (PSA) concentration after radical prostatectomy is an urgent clinical question. Salvage radiotherapy delays the need for more aggressive treatment such as long-term androgen suppression, but fewer than half of patients benefit from it. We aimed to establish the effect of adding short-term androgen suppression at the time of salvage radiotherapy on biochemical outcome and overall survival in men with rising PSA following radical prostatectomy. METHODS: This open-label, multicentre, phase 3, randomised controlled trial, was done in 43 French study centres. We enrolled men (aged \textgreater/=18 years) who had received previous treatment for a histologically confirmed adenocarcinoma of the prostate (but no previous androgen deprivation therapy or pelvic radiotherapy), and who had stage pT2, pT3, or pT4a (bladder neck involvement only) in patients who had rising PSA of 0.2 to less than 2.0 mug/L following radical prostatectomy, without evidence of clinical disease. Patients were randomly assigned (1:1) centrally via an interactive web response system to standard salvage radiotherapy (three-dimensional [3D] conformal radiotherapy or intensity modulated radiotherapy, of 66 Gy in 33 fractions 5 days a week for 7 weeks) or radiotherapy plus short-term androgen suppression using 10.8 mg goserelin by subcutaneous injection on the first day of irradiation and 3 months later. Randomisation was stratified using a permuted block method according to investigational site, radiotherapy modality, and prognosis. The primary endpoint was progression-free survival, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00423475. FINDINGS: Between Oct 19, 2006, and March 30, 2010, 743 patients were randomly assigned, 374 to radiotherapy alone and 369 to radiotherapy plus goserelin. Patients assigned to radiotherapy plus goserelin were significantly more likely than patients in the radiotherapy alone group to be free of biochemical progression or clinical progression at 5 years (80% [95% CI 75-84] vs 62% [57-67]; hazard ratio [HR] 0.50, 95% CI 0.38-0.66; p\textless0.0001). No additional late adverse events occurred in patients receiving short-term androgen suppression compared with those who received radiotherapy alone. The most frequently occuring acute adverse events related to goserelin were hot flushes, sweating, or both (30 [8%] of 366 patients had a grade 2 or worse event; 30 patients [8%] had hot flushes and five patients [1%] had sweating in the radiotherapy plus goserelin group vs none of 372 patients in the radiotherapy alone group). Three (8%) of 366 patients had grade 3 or worse hot flushes and one patient had grade 3 or worse sweating in the radiotherapy plus goserelin group versus none of 372 patients in the radiotherapy alone group. The most common late adverse events of grade 3 or worse were genitourinary events (29 [8%] in the radiotherapy alone group vs 26 [7%] in the radiotherapy plus goserelin group) and sexual disorders (20 [5%] vs 30 [8%]). No treatment-related deaths occurred. INTERPRETATION: Adding short-term androgen suppression to salvage radiotherapy benefits men who have had radical prostatectomy and whose PSA rises after a postsurgical period when it is undetectable. Radiotherapy combined with short-term androgen suppression could be considered as a reasonable option in this population. FUNDING: French Ministry of Health, AstraZeneca, and La Ligue Contre le Cancer
Published: 2015

43. Cytotoxic Effect of Hyperthermia and Chemotherapy with Platinum Salt on Ovarian Cancer Cells: Results of an in vitro Study

Author: Michel Chérel, P.-F. Dupré, M. Collet, Sébastien Gouard, M. Muller, Jean-Marc Classe, Service de Gynécologie-Obstétrique (BREST - Gynéco-Obs), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de médecine nucléaire [Saint-Herblain], Centre René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Institut Régional du Cancer Nantes-Atlantique (IRCNA), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), and UNICANCER
Subjects: Oncology, Hyperthermia, MESH: Combined Modality Therapy, medicine.medical_specialty, MESH: Cell Line, Tumor, endocrine system diseases, Cell Survival, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Antineoplastic Agents, Carboplatin, MESH: Dose-Response Relationship, Drug, 03 medical and health sciences, 0302 clinical medicine, MESH: Carboplatin, Cell Line, Tumor, Internal medicine, medicine, Humans, Cytotoxic T cell, In vitro study, MESH: Hyperthermia, Induced, 030304 developmental biology, Ovarian Neoplasms, 0303 health sciences, Chemotherapy, MESH: Humans, Dose-Response Relationship, Drug, business.industry, Hyperthermia, Induced, medicine.disease, Combined Modality Therapy, MESH: Drug Resistance, Neoplasm, 3. Good health, MESH: Ovarian Neoplasms, MESH: Cell Survival, MESH: Cisplatin, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Ovarian cancer cells, MESH: Antineoplastic Agents, Female, Surgery, Hyperthermic intraperitoneal chemotherapy, Cisplatin, business, Ovarian cancer, MESH: Female
Abstract: Purpose: Hyperthermic intraperitoneal chemotherapy is continuously under evaluation in ovarian cancer. The purpose of the present study was to evaluate the effect of chemotherapy, drug concentration and temperature. Materials and Methods: A human ovarian carcinoma cell line was used. The effect of hyperthermia combined with chemotherapy was analyzed. Results: When hyperthermia was combined with chemotherapy, the 50% lethal dose (LD50) decreased with the duration of exposure. The effect of temperature was similar between 39 and 43°C for a 30-min exposure. For a 60- to 90-min exposure, the LD50 was equivalent between 38 and 43°C. Beyond 40°C, an increase in platinum salt concentration was necessary to obtain similar results according to the duration of exposure. Conclusions: The cytotoxic effect of the combination seemed to be potentiated and limited at 40°C.
Published: 2011

44. First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743

Author: Peters, S., Scherpereel, A., Cornelissen, R., Oulkhouir, Y., Greillier, L., Kaplan, M.A., Talbot, T., Monnet, I., Hiret, S., Baas, P., Nowak, A.K., Fujimoto, N., Tsao, A.S., Mansfield, A.S., Popat, S., Zhang, X., Hu, N., Balli, D., Spires, T., Zalcman, G., CHUV, Lausanne (Departement d'Oncologie), Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Service de pneumologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Nord [CHU - APHM], Dicle University, Royal Cornwall Hospital, Service de Pneumologie [CHI Créteil], CHI Créteil, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, CRLCC René Gauducheau, Département d'oncologie médicale [Saint Herblain], UNICANCER-UNICANCER, Leiden University Medical Center (LUMC), Universiteit Leiden, Royal Marsden Hospital, Department of Energy and Process Engineering, Norwegian University of Science and Technology (NTNU), Bristol-Myers Squibb [Princeton], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Pulmonary Medicine
Subjects: Adult, PD-L1, [SDV]Life Sciences [q-bio], overall survival, Mesothelioma, Malignant, Hematology, Ipilimumab, Progression-Free Survival, immune checkpoint inhibitors, Nivolumab, Oncology, dual immunotherapy, Antineoplastic Combined Chemotherapy Protocols, Humans, CTLA-4, first-line
Abstract: International audience; Background: In the phase III CheckMate 743 study (NCT02899299), first-line nivolumab plus ipilimumab significantly improved overall survival (OS) versus chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM). We report updated data with 3-year minimum follow-up. Patients and methods: Adults with previously untreated, histologically confirmed, unresectable MPM and Eastern Cooperative Oncology Group performance status of = 3 years after discontinuation. Conclusions: With 3 years' minimum follow-up, nivolumab plus ipilimumab continued to provide long-term survival benefit over chemotherapy and a manageable safety profile, supporting the regimen as standard-of-care treatment for unresectable MPM, regardless of histology.
Published: 2022

45. Impact of breast cancer care pathways and related symptoms on the return-to-work process: results from a population-based French cohort study (CONSTANCES)

Author: Anne-Lise Rolland, Bertrand Porro, Sofiane Kab, Céline Ribet, Yves Roquelaure, Mélanie Bertin, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre de Recherches sur l'Action Politique en Europe (ARENES), Université de Rennes (UR)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), This manuscript was prepared in context of the SIRIC ILIAD program supported by a grant from the French National Cancer Institute (INCa), the French Ministry of Health, and the Institute of Health and Medical Research (Inserm), contract INCa-DGOS-Inserm_12558. The Constances cohort is supported and funded by the Caisse nationale d’assurance maladie (CNAM). The Constances Cohort Study is an 'Infrastructure nationale en Biologie et Santé' and benefits from a grant from ANR (ANR-11-INBS-0002) and from the Ministry of Research. Constances is also partly funded by MSD and L’Oréal., ANR-11-INBS-0002,CONSTANCES,La cohorte CONSTANCES - Infrastructure épidémiologique ouverte pour la recherche et la surveillance(2011), and EHESP-Irset (EHESP-Irset)
Subjects: Breast cancer, Return to work, Care pathways, Sequence analysis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Patterns
Abstract: Background Breast cancer (BC) treatments and related symptoms may affect return to work (RTW). The objective of this study was to investigate the impact of BC care pathways (timing and sequence of treatments) and related symptoms on RTW. Methods The study population included working-age women with BC who were enrolled in the French CONSTANCES cohort from 2012 to 2018. BC treatments, antidepressant/anxiolytic and antalgic drug deliveries (used as proxies of depression and pain, respectively) and statutory sick pay (used to estimate RTW and time to RTW) were assessed monthly using data from the French national healthcare system database. BC care pathways were identified with the sequence analysis method. Cox models with time-dependent covariates were used to investigate the impact of BC care pathways and related symptoms on RTW and time to RTW, after adjusting for age and socioeconomic characteristics. Results 73.2% (231/303) of women returned to work within 2 years after BC diagnosis. Five BC care pathway patterns were identified: (i) BC surgery only, (ii) BC surgery and radiotherapy, (iii) BC surgery and chemotherapy, (iv) BC surgery and chemotherapy and radiotherapy, and (v) BC surgery and long-term alternative chemotherapy/radiotherapy. The hazards ratios of non-RTW were significantly higher for women who received BC surgery and long-term alternative chemotherapy/radiotherapy and for > 55-year-old women. Time to RTW was significantly longer in women who received chemotherapy (patterns iii to v) and in women with antidepressant/anxiolytic and antalgic drug deliveries. Conclusion This study highlights the value of considering the dynamic, cumulative and temporal features of BC care pathways and related symptoms to facilitate the RTW of women with BC.
Published: 2023

46. Incidence and Characteristics of Pseudoprogression in IDH-mutant High-Grade Gliomas: A POLA Network Study

Author: Antoine Seyve, Caroline Dehais, Olivier Chinot, Apolline Djelad, Elisabeth Cohen-Moyal, Charlotte Bronnimann, Carole Gourmelon, Evelyne Emery, Philippe Colin, Mathieu Boone, Elodie Vauléon, Olivier Langlois, Anna-Luisa di Stefano, Romuald Seizeur, François Ghiringhelli, Anne D’Hombres, Loic Feuvret, Jacques Guyotat, Laurent Capelle, Catherine Carpentier, Louis Garnier, Jérôme Honnorat, David Meyronet, Karima Mokhtari, Dominique Figarella-Branger, François Ducray, Hospices Civils de Lyon, Departement de Neurologie (HCL), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Bordeaux [Bordeaux], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Service de Neurochirurgie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Culture et Environnements, Préhistoire, Antiquité, Moyen-Age (CEPAM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Service de neurochirurgie [Brest], Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Hospices Civils de Lyon (HCL), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Référence Maladie Rare 'Syndromes neurologiques Paranéoplasiques', Hospices Civils de Lyon (HCL)-Hopital Neurologique, and Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL]
Subjects: Cancer Research, High-grade glioma, Oncology, pseudoprogression, Neurology (clinical), IDH-mutant, chemotherapy, radiotherapy, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Incidence and characteristics of pseudoprogression in isocitrate dehydrogenase-mutant high-grade gliomas (IDHmt HGG) remain to be specifically described. Methods We analyzed pseudoprogression characteristics and explored the possibility of pseudoprogression misdiagnosis in IDHmt HGG patients, treated with radiotherapy (RT) (with or without chemotherapy [CT]), included in the French POLA network. Pseudoprogression was analyzed in patients with MRI available for review (reference cohort, n = 200). Pseudoprogression misdiagnosis was estimated in this cohort and in an independent cohort (control cohort, n = 543) based on progression-free survival before and after first progression. Results In the reference cohort, 38 patients (19%) presented a pseudoprogression after a median time of 10.5 months after RT. Pseudoprogression characteristics were similar across IDHmt HGG subtypes. In most patients, it consisted of the appearance of one or several infracentimetric, asymptomatic, contrast-enhanced lesions occurring within 2 years after RT. The only factor associated with pseudoprogression occurrence was adjuvant PCV CT. Among patients considered as having a first true progression, 7 out of 41 (17%) in the reference cohort and 35 out of 203 (17%) in the control cohort were retrospectively suspected to have a misdiagnosed pseudoprogression. Patients with a misdiagnosed pseudoprogression were characterized by a time to event and an outcome similar to that of patients with a pseudoprogression but presented with larger and more symptomatic lesions. Conclusion In patients with an IDHmt HGG, pseudoprogression occurs later than in IDH-wildtype glioblastomas and seems not only frequent but also frequently misdiagnosed. Within the first 2 years after RT, the possibility of a pseudoprogression should be carefully considered.
Published: 2023

47. Gene-expression molecular subtyping of triple-negative breast cancer tumours: importance of immune response

Author: Wilfried Gouraud, Delphine Loussouarn, Catherine Guérin-Charbonnel, Pascal Jézéquel, Mario Campone, Loïc Campion, Véronique Verriele, Catherine Guette, Isabelle Valo, Hamza Lasla, Antoine Vanier, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Unité Mixte de Génomique du Cancer [ICO, Saint Herblain] (Site René Gauducheau), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]-Hôpital Laennec, Unité de bioinfomique [ICO, Saint Herblain], UNICANCER-UNICANCER, Département de Biopathologie [ICO, Saint Herblain], Service d'Anatomie Pathologique B [Saint Herblain], Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain], Unité de Biostatistiques [ICO, Saint Herblain], Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UNICANCER, Laboratoire d’Anatomie Pathologique [ICO, Angers] (Site Paul Papin), Service d'Oncologie Médicale [ICO, Saint Herblain], CRLCC René Gauducheau-Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Tissues used in this work were provided by: Institut Régional du Cancer Nantes-Atlantique tumour bank, funded by the Institut National du Cancer (INCa) and the Cancéropôle Grand Ouest, and Anjou Maine ICO Paul Papin tumour bank funded by the INCa., and Bernardo, Elizabeth
Subjects: Adult, Oncology, medicine.medical_specialty, Triple Negative Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Kaplan-Meier Estimate, Biology, Breast cancer, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Biomarkers, Tumor, medicine, Cluster Analysis, Humans, Triple-negative breast cancer, Survival analysis, Aged, Neoplasm Staging, Retrospective Studies, Medicine(all), Gene Expression Profiling, Computational Biology, Reproducibility of Results, Molecular Sequence Annotation, Retrospective cohort study, Middle Aged, Prognosis, medicine.disease, Immunohistochemistry, Immunity, Innate, Tumor Burden, 3. Good health, Gene Expression Regulation, Neoplastic, Androgen receptor, Immunology, biology.protein, Nottingham Prognostic Index, Female, Antibody, Transcriptome, Research Article
Abstract: Introduction Triple-negative breast cancers need to be refined in order to identify therapeutic subgroups of patients. Methods We conducted an unsupervised analysis of microarray gene-expression profiles of 107 triple-negative breast cancer patients and undertook robust functional annotation of the molecular entities found by means of numerous approaches including immunohistochemistry and gene-expression signatures. A triple-negative external cohort (n = 87) was used for validation. Results Fuzzy clustering separated triple-negative tumours into three clusters: C1 (22.4%), C2 (44.9%) and C3 (32.7%). C1 patients were older (mean = 64.6 years) than C2 (mean = 56.8 years; P = 0.03) and C3 patients (mean = 51.9 years; P = 0.0004). Histological grade and Nottingham prognostic index were higher in C2 and C3 than in C1 (P
Published: 2015

48. Change in the value of work after breast cancer: evidence from a prospective cohort

Author: Elsa Caumette, Antonio Di Meglio, Inès Vaz-Luis, Cécile Charles, Julie Havas, Garazi Ruiz de Azua, Elise Martin, Laurence Vanlemmens, Suzette Delaloge, Sibille Everhard, Anne-Laure Martin, Asma Dhaini Merimeche, Olivier Rigal, Charles Coutant, Marion Fournier, Christelle Jouannaud, Patrick Soulie, Paul-Henri Cottu, Olivier Tredan, Gwenn Menvielle, Agnès Dumas, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université de Montpellier (UM), Institut Gustave Roussy (IGR), Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Département de médecine oncologique [Gustave Roussy], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, UNICANCER, Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Institut Curie [Paris], Centre Léon Bérard [Lyon], Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité)
Subjects: Oncology, Oncology (nursing), [SDV]Life Sciences [q-bio]
Abstract: Return to work (RTW) after cancer can be modulated by psychosocial factors, including a reordering of one's life values, with more emphasis on private life than work-life. This change in patients' outlook on work-life is however poorly understood.We used data from a French cohort (CANTO, NCT01993498) of women diagnosed with stage I-III primary breast cancer (BC) prospectively assessing life priorities between work and private life at diagnosis and 2 years after diagnosis. We identified women who reported a shift in life values toward private life, and we investigated the clinical, demographic, work-related, and psychosocial determinants of this change using logistic regressions.Overall, 46% (N = 1097) of the women had reordered their life priorities toward private life 2 years after diagnosis. The factors positively associated with this shift included being diagnosed with stage III BC, perceiving one's job as not very interesting, being an employee/clerk (vs. executive occupation), perceiving no support from the supervisor at baseline, perceiving negative interferences of cancer in daily life, and perceiving a positive impact from experiencing cancer. Depressive symptoms were negatively associated with this shift.After BC, there seems to be an important reordering of life values, with more emphasis on private life. This change is influenced by clinical determinants, but also by work-related and psychosocial factors.Stakeholders should consider this change in a patient's outlook on work-life as much as the classical physical late effects when designing post-BC programs to support RTW.
Published: 2022

49. La phase socle en oncologie : retour d’expérience sur les trois premières années d’application de la réforme du troisième cycle

Author: Pierre-Yves Cren, Julie Chartier, Nicolas Penel, Florence Huguet, Jean-Philippe Spano, Luc Ollivier, Matthieu Delaye, Anthony Turpin, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Institut Universitaire de Cancérologie [Sorbonne Université] (IUC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, and Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: Cancer Research, Oncology, [SDV]Life Sciences [q-bio], Radiology, Nuclear Medicine and imaging, Hematology, General Medicine
Published: 2022

50. Treatment strategies for thymic carcinoma in a real-life setting. Insights from the RYTHMIC network

Author: Arthur Petat, Eric Dansin, Fabien Calcagno, Laurent Greillier, Eric Pichon, Mallorie Kerjouan, Christelle Clement-Duchene, Bertrand Mennecier, Virginie Westeel, François Thillays, Xavier Quantin, Youssef Oulkhouir, Luc Thiberville, Charles Ricordel, Vincent Thomas De Montpreville, Lara Chalabreysse, Véronique Hofman, Thierry Molina, Pierre Fournel, Laurence Bigay Game, Benjamin Besse, Nicolas Girard, Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Pontchaillou [Rennes], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, CHU Strasbourg, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Rouen, Normandie Université (NU), Centre Chirurgical Marie Lannelongue (CCML), Hôpital Pasteur [Nice] (CHU), Département de Pathologie [CHU Necker], Université Sorbonne Paris Cité (USPC)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), and Institut Curie [Paris]
Subjects: Cancer Research, Thymoma, Radiotherapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Thymus Neoplasms, Guidelines, Cohort Studies, Thymic carcinoma, Oncology, Humans, Chemotherapy, Surgery, Neoplasms, Glandular and Epithelial, Prospective Studies, Neoplasm Staging, Retrospective Studies
Abstract: Thymic carcinomas are aggressive and difficult to treat a subset of thymic epithelial tumours that represent a heterogeneous group of rare intrathoracic malignancies. The treatment strategy of thymic carcinomas is based on whether surgical resection may be achieved, which represents the most significant favourable prognostic factor on survival. For this study, we took advantage of the unique prospective Réseau tumeurs THYMiques et Cancer (RYTHMIC) database to describe baseline characteristics, analyse treatment strategies in light of existing guidelines and provide landmark patient outcomes data with regards to response and survival of patients in a real-life clinical practice setting.Inclusion criteria for this analysis were the following: (1) histologically-confirmed thymic carcinomas - excluding neuroendocrine tumours-after pathological review by the RYTHMIC pathology panel, (2) discussion of the case at the RYTHMIC multidisciplinary tumour board, (3) at least one active treatment modality.A total of 213 patients were analysed. Overall, 60 (28%) patients were considered as surgical candidates upfront, 91 (43%) patients received primary chemotherapy, and 62 (29%) patients received exclusive chemotherapy. Median overall survival (OS) was 49.2 months (IC95%: 34.8-63.6); OS was significantly longer in patients with a lower stage at diagnosis (p 0.001), who were operated on upfront, as opposed to patients who received primary or exclusive chemotherapy (p 0.001). Surgery, conducted upfront or after primary chemotherapy, was significantly associated with more prolonged OS (p 0.001); complete resection and postoperative radiotherapy were also predictors of better outcome (p = 0.018 and p = 0.051, respectively).Our cohort is the first to analyse in-depth outcomes and treatment strategies in a prospective cohort of consecutive patients with thymic carcinoma. While we confirm the major prognostic impact of surgery, our data highlight the need for optimised multidisciplinary management and innovative therapies as the survival of patients remains limited.
Published: 2022

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