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1. Interest and Limits of [18F]ML-10 PET Imaging for Early Detection of Response to Conventional Chemotherapy.

Author

Jouberton, Elodie, Schmitt, Sébastien, Maisonial-Besset, Aurélie, Chautard, Emmanuel, Penault-Llorca, Frédérique, and Cachin, Florent

Subjects
POSITRON emission tomography, IMAGE analysis, CANCER chemotherapy, CELL death, RADIOACTIVE tracers
Abstract

One of the current challenges in oncology is to develop imaging tools to early detect the response to conventional chemotherapy and adjust treatment strategies when necessary. Several studies evaluating PET imaging with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) as a predictive tool of therapeutic response highlighted its insufficient specificity and sensitivity. The [18F]FDG uptake reflects only tumor metabolic activity and not treatment-induced cell death, which seems to be relevant for therapeutic evaluation. Therefore, to evaluate this parameter in vivo , several cell death radiotracers have been developed in the last years. However, few of them have reached the clinical trials. This systematic review focuses on the use of [18F]ML-10 (2-(5-[18F]fluoropentyl)-2-methylmalonic acid) as radiotracer of apoptosis and especially as a measure of tumor response to treatment. A comprehensive literature review concerning the preclinical and clinical investigations conducted with [18F]ML-10 was performed. The abilities and applications of this radiotracer as well as its clinical relevance and limitations were discussed. Most studies highlighted a good ability of the radiotracer to target apoptotic cells. However, the increase in apoptosis during treatment did not correlate with the radiotracer tumoral uptake, even using more advanced image analysis (voxel-based analysis). [18F]ML-10 PET imaging does not meet current clinical expectations for early detection of the therapeutic response to conventional chemotherapy. This review has pointed out the challenges of applying various apoptosis imaging strategies in clinical trials, the current methodologies available for image analysis and the future of molecular imaging to assess this therapeutic response. [ABSTRACT FROM AUTHOR]

Published
2021
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2. Stimulated thyroglobulin and thyroglobulin reduction index predict excellent response in differentiated thyroid cancers

Author

Gay-Bellile, Mathilde, DESSENNE, Pascal, LAQUET, Claire, Boussion, Véronique, Béguinot, Marie, PETIT, Marie-Françoise, Gremeau, Anne-Sophie, Verlet, Céline, Chaptal, Charlotte, Broult, Marilyn, Jouvency, Sylvie, Duclos, Martine, Bignon, Yves-Jean, Petit, Marie, Barres, Bertrand, KELLY, ANTONY, Kwiatkowski, Fabrice, Batisse-Lignier, Marie, Fouilhoux, Geneviève, Aubert, Bernadette, Dutheil, Frederic, Tauveron, Igor, Cachin, Florent, Maqdasy, Salwan, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Service d'endocrinologie, diabétologie et maladies métaboliques [Clermont-Ferrand], CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Service Santé Travail Environnement [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, WittyFit, Australian Catholic University (ACU), Faculté de Médecine - Clermont-Auvergne (FM - UCA), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Jean Perrin, CRLCC Jean Perrin, Caisse Primaire Assurance Maladie (CAPM), Mollecular Oncology Laboratory, Laboratoire BDR CECOS - FIV AMP, CHU Estaing [Clermont-Ferrand], Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne, Unité de Nutrition Humaine (UNH), Clermont Université-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Recherche Agronomique (INRA), Université de Poitiers, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Faculté des Sciences du SportFaculté des Sciences du Sport, UFR STAPS, Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Université Clermont Auvergne (UCA), Génétique, Reproduction et Développement - Clermont Auvergne (GReD ), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Ferrand (UFR STAPS - UBP), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])

Subjects
Oncology, Male, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, Biochemistry, Iodine Radioisotopes, 0302 clinical medicine, Endocrinology, Medicine, Lymph node, Thyroid cancer, Cancer, HBOC, Thyroid, Remission Induction, Middle Aged, Combined Modality Therapy, 3. Good health, medicine.anatomical_structure, Treatment Outcome, 030220 oncology & carcinogenesis, Predictive value of tests, Thyroidectomy, Female, Coping, Adult, Group sharing, medicine.medical_specialty, Thyroid Hormones, education, 030209 endocrinology & metabolism, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, Oncogenetics, Psychodrama, Thyroglobulin, 03 medical and health sciences, Hope, Predictive Value of Tests, Internal medicine, Humans, Thyroid Neoplasms, differentiated thyroid cancer (DTC), Retrospective Studies, Radiofrequency Ablation, business.industry, Biochemistry (medical), Antineoplastic Protocols, Retrospective cohort study, medicine.disease, Young women, business
Abstract

Context Despite its good prognosis, differentiated thyroid cancer (DTC) is characterized by high rates of disease persistence and recurrence. Estimation of long-term remission (excellent response) thanks to specific parameters could help to individualize the active surveillance schedule. Objective Evaluation of the ability of stimulated thyroglobulin (Tg) and Tg reduction index (TRI) to predict long-term remission in patients with DTC managed by thyroidectomy and radioactive iodine (RAI) remnant ablation. Patients and Interventions Observational retrospective study of 1093 patients treated for DTC between 1995 and 2010. Preablation stimulated thyroglobulin (presTg) was measured under thyroid hormone withdrawal just before RAI. Recombinant human TSH–stimulated thyroglobulin (sTg) was measured at first evaluation of the initial management 6 to 12 months after RAI. TRI was calculated based on pre-Tg and sTg. Results After univariate and multivariate analyses, lymph node invasion (N1, OR = 2.08; 95% CI, 1.19 to 3.64), presTg (OR = 4.04; 95% CI, 2.56 to 6.38), sTg (OR = 2.62; 95% CI, 2.05 to 3.34), and TRI (OR = 0.43; 95% CI, 0.21 to 0.88) were identified as independent prognostic factors influencing the rate of disease persistence or recurrence after the initial management. Receiver operating characteristic analysis identified presTg cutoff (60% for the entire cohort and 62.5% for locally advanced disease (T3/T4, N1) was sensitive predictor for excellent response. Conclusion This study identifies presTg, sTg, and TRI as highly sensitive predictors of excellent response in patients with DTC and subsequently disease-free status. The cutoff of such parameters is also adapted for patients with higher tumor stages (T3/T4, N1).

Published
2019
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3. Age, thyroglobulin levels and ATA risk stratification predict 10-year survival rate of differentiated thyroid cancer patients

Author

Kelly, Antony, Barres, Bertrand, Kwiatkowski, Fabrice, Batisse-Lignier, Marie, Aubert, Bernadette, Valla, Clémence, Somda, Frédéric, Cachin, Florent, Tauveron, Igor, Maqdasy, Salwan, Bodescot, Myriam, Service de médecine nucléaire [Clermont-Ferrand], Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER-UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Département de recherche clinique [Clermont-Ferrand], Service d'endocrinologie, diabétologie et maladies métaboliques [Clermont-Ferrand], CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Faculté de Médecine - Clermont-Auvergne (FM - UCA), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Cancer Treatment, Thyroid Gland, Biochemistry, Lung and Intrathoracic Tumors, Iodine Radioisotopes, Thymic Tumors, Medicine and Health Sciences, Postoperative Period, Endocrine Tumors, Thyroid, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Age Factors, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Prognosis, Survival Rate, Treatment Outcome, Oncology, Preoperative Period, Thyroidectomy, Medicine, Female, Anatomy, Research Article, Adult, Endocrine System Procedures, Science, Endocrine System, Surgical and Invasive Medical Procedures, [SDV.CAN]Life Sciences [q-bio]/Cancer, Thyroglobulin, Carcinomas, Risk Assessment, Lymphatic System, [SDV.CAN] Life Sciences [q-bio]/Cancer, Diagnostic Medicine, Humans, Thyroid Neoplasms, Retrospective Studies, Biology and Life Sciences, Proteins, Cancers and Neoplasms, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Radiotherapy, Adjuvant, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Thyroid Carcinomas, Lymph Nodes, Follow-Up Studies
Abstract

IntroductionDifferentiated thyroid cancer (DTC) is the most common of endocrine cancers. Many studies have focused on recurrence-free survival of DTC patients, however, few studies have addressed overall survival rates. Given its very good prognosis, estimating overall or long-term survival in patients with DTC seems rational. So far, neither the impact of pre- and post-ablation thyroglobulin, nor that of initial American Thyroid Association (ATA) risk stratification on long-term disease-specific survival, have been sufficiently studied.ObjectiveThe aim of this study was to determine the factors that influence long-term disease-specific survival and thyroglobulin levels in patients with DTC who have been previously treated with thyroidectomy and radioactive iodine (RAI) remnant ablation.Patients and methodsThis observational retrospective study included 1093 patients who were treated for DTC between 1995 and 2010 and are still monitored in our tertiary center. Only patients who needed RAI ablation after thyroidectomy were included in this study. Patients who were treated with RAI following rhTSH stimulation, patients who presented positive anti-thyroglobulin antibodies, and patients who had micro-cancers were excluded. Pre-ablation stimulated thyroglobulin (Pre-ablation sTg) was measured after thyroid hormone withdrawal (THW), just before RAI.ResultsAccording to ATA standards, 29 patients (2.7%) were classified as high-risk patients. Initial ATA high-recurrence risk rating (HR 21.9; 95% CI: 8.5-56.3), age>55 years (HR 23.8; 95%-CI: 7.5-75.3) and pre-ablation sTg≥30 μg/l (HR 8.4; 95% CI: 4.6-15.3) significantly impacted ten-year survival. Moreover, age over 45 years, ATA moderate-risk and follicular DTC were also significant. Ten-year survival was lower in ATA high-risk patients (51% vs 95% and 93% for the low and intermediate risk; pConclusionInitial ATA high-risk classification, age over 55 years old and pre-ablation sTg ≥30 μg/l are the main negative factors that influence the ten-year survival in DTC. We suggest three categories of overall survival rates. Patients older than 55 years with pre-ablation sTg ≥30 μg/l have the worst survival rate.

Published
2019
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4. Radium 223 dichloride for prostate cancer treatment

Author

Mathieu Roumiguié, Philippe Beuzeboc, Constance Thibault, François Rozet, Diana Kassab-Chahmi, Florent Cachin, Damien Huglo, Nadine Houédé, Emmanuel Deshayes, Christophe Hennequin, Xavier Rebillard, Urologie, andrologie et transplantation rénale, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Department of Medical Oncology, Institut Curie [Paris], Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Therapies Interventionnelles Assistees Par l'Image et la Simulation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Service d'Oncologie Médicale [Montsouris], Institut Mutualiste de Montsouris (IMM), Service d'urologie, Clinique Beausoleil, Institut Bergonié [Bordeaux], 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), Institut du Cancer de Montpellier (ICM), Département d'Urologie-Andrologie et Transplantation Rénale [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Therapies Interventionnelles Assistees Par l'Image et la Simulation - U 703 (Thiais), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Clinique Beau Soleil [Montpellier], Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), and CACHIN, Florent

Subjects
Male, 0301 basic medicine, Oncology, Drug, medicine.medical_specialty, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Pharmaceutical Science, mechanism, Antineoplastic Agents, Bone Neoplasms, Review, Malignant disease, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Prostate, Internal medicine, Drug Discovery, Tumor Microenvironment, medicine, Tumor cell death, Animals, Humans, DNA Breaks, Double-Stranded, Radium-223 Dichloride, development, media_common, bone metastasis, Radioisotopes, Pharmacology, Drug Design, Development and Therapy, business.industry, Bone metastasis, drug, mCRPC, medicine.disease, 3. Good health, agents, Clinical trial, [SDV] Life Sciences [q-bio], Prostatic Neoplasms, Castration-Resistant, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, business, Radium
Abstract

Emmanuel Deshayes,1,2 Mathieu Roumiguie,3 Constance Thibault,4 Philippe Beuzeboc,5 Florent Cachin,6 Christophe Hennequin,7 Damien Huglo,8 François Rozet,9 Diana Kassab-Chahmi,10 Xavier Rebillard,11 Nadine Houédé1,12 1Radiobiology Unit, INSERM U1194, Institut du Cancer de Montpellier (ICM), 2Department of Nuclear Medicine, Institut du Cancer de Montpellier (ICM), Montpellier, 3Urology Department, Andrology and Renal Transplantation, CHU Rangueil, Toulouse, 4Medical Oncology Department, Hôpital Européen Georges Pompidou, 5Oncology Department, Institut Curie, 6Department of Nuclear Medicine, CHU, Clermont-Ferrand, 7Radiotherapy Department, Hôpital Saint Louis, Paris, 8Department of Nuclear Medicine, CHRU, Lille, 9Urology Department, Institut Mutualiste Montsouris, 10Intergroupe coopérateur francophone de recherche en onco-urologie, Paris, 11Urology Department, Clinique BeauSoleil, Montpellier, 12Medical Oncology Department, Institut de Cancérologie du Gard – CHU Caremeau, Nîmes, France Abstract: Prostate cancer is the most common malignant disease in men. Several therapeutic agents have been approved during the last 10 years. Among them, radium-223 dichloride (Xofigo®) is a radioactive isotope that induces irreversible DNA double-strand breaks and consequently tumor cell death. Radium-223 dichloride is acalcium-mimetic agent that specifically targets bone lesions. Radium-223 dichloride has been approved for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases, without known visceral metastases. In this review, first we summarize the interplay between prostate tumor cells and bone microenvironment; then, we discuss radium-223 dichloride mechanism of action and present the results of the available clinical trials and future developments for this new drug. Keywords: bone metastasis, mCRPC, mechanism, drug, agents, development&nbsp

Published
2017
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