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3 results on '"MESH : Bone Neoplasms"'

1. Phase II study of the mammalian target of rapamycin inhibitor ridaforolimus in patients with advanced bone and soft tissue sarcomas

Author

John W. Loewy, George D. Demetri, Lori Berk, Laurence H. Baker, Victor M. Rivera, Arthur P. Staddon, Gina Z. D'Amato, Tim Clackson, Monica M. Mita, Kamalesh Kumar Sankhala, Frank G. Haluska, Scott M. Schuetze, Jean-Yves Blay, Anthony W. Tolcher, Sant P. Chawla, International Institute of Clinical Studies, Pennsylvania Oncology Hematology Associates, 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-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Léon Bérard [Lyon], Department of Cancer Biology, Dana-Farber Cancer Institute [Boston], Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), and 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 )

Subjects
Male, Vascular Endothelial Growth Factor A, Oncology, Cancer Research, Pathology, MESH : Aged, Phases of clinical research, Kaplan-Meier Estimate, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, chemistry.chemical_compound, 0302 clinical medicine, MESH : Tumor Markers, Biological, Clinical endpoint, Medicine, MESH : Female, Infusions, Intravenous, MESH: Treatment Outcome, MESH: Aged, 0303 health sciences, education.field_of_study, MESH: Middle Aged, TOR Serine-Threonine Kinases, Soft tissue, Sarcoma, MESH : Infusions, Intravenous, Middle Aged, MESH : Adult, MESH: Bone Neoplasms, 3. Good health, MESH : Antineoplastic Agents, Treatment Outcome, 030220 oncology & carcinogenesis, MESH : Vascular Endothelial Growth Factor A, MESH : TOR Serine-Threonine Kinases, MESH : Disease-Free Survival, Female, Adult, medicine.medical_specialty, MESH : Male, MESH : Sex Factors, Population, MESH : Drug Administration Schedule, Antineoplastic Agents, Bone Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Treatment Outcome, Bone Sarcoma, MESH: Drug Administration Schedule, MESH : Sarcoma, Disease-Free Survival, Drug Administration Schedule, Ridaforolimus, MESH : Kaplan-Meier Estimate, 03 medical and health sciences, Sex Factors, MESH: Sex Factors, Internal medicine, Biomarkers, Tumor, Humans, MESH : Middle Aged, education, MESH: Infusions, Intravenous, MESH: TOR Serine-Threonine Kinases, MESH: Kaplan-Meier Estimate, Aged, 030304 developmental biology, MESH : Bone Neoplasms, Sirolimus, MESH: Humans, Errata, Akt/PKB signaling pathway, business.industry, MESH : Sirolimus, MESH: Vascular Endothelial Growth Factor A, MESH : Humans, MESH: Adult, MESH: Male, Clinical trial, chemistry, MESH: Sarcoma, MESH: Tumor Markers, Biological, MESH: Disease-Free Survival, MESH: Antineoplastic Agents, MESH: Sirolimus, business, MESH: Female
Abstract

Purpose Ridaforolimus is an inhibitor of mammalian target of rapamycin, an integral component of the phosphatidyl 3-kinase/AKT signaling pathway, with early evidence of activity in sarcomas. This multicenter, open-label, single-arm, phase II trial was conducted to assess the antitumor activity of ridaforolimus in patients with distinct subtypes of advanced sarcomas. Patients and Methods Patients with metastatic or unresectable soft tissue or bone sarcomas received ridaforolimus 12.5 mg administered as a 30-minute intravenous infusion once daily for 5 days every 2 weeks. The primary end point was clinical benefit response (CBR) rate (complete response or partial response [PR] or stable disease ≥ 16 weeks). Safety, progression-free survival (PFS), overall survival (OS), time to progression, and duration of response were also evaluated. Results A total of 212 patients were treated in four separate histologic cohorts. In this heavily pretreated population, 61 patients (28.8%) achieved CBR. Median PFS was 15.3 weeks; median OS was 40 weeks. Response Evaluation Criteria in Solid Tumors (RECIST) confirmed response rate was 1.9%, with four patients achieving confirmed PR (two with osteosarcoma, one with spindle cell sarcoma, and one with malignant fibrous histiocytoma). Archival tumor protein markers analyzed were not correlated with CBR. Related adverse events were generally mild or moderate and consisted primarily of stomatitis, mucosal inflammation, mouth ulceration, rash, and fatigue. Conclusion Single-agent ridaforolimus in patients with advanced and pretreated sarcomas led to PFS results that compare favorably with historical metrics. A phase III trial based on these data will further define ridaforolimus activity in sarcomas.

Published
2012
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2. Incidence of sarcoma histotypes and molecular subtypes in a prospective epidemiological study with central pathology review and molecular testing

Author

Pierre-Paul Bringuier, Christophe Bergeron, Luc Istier, Laurent Alberti, Philippe Chalabreysse, A. Lurkin, Dominic Cellier, Michel Peoc'h, Françoise Ducimetière, Jean-Yves Blay, Isabelle Ray-Coquard, Anne-Valérie Decouvelaere, Anne-Marie Schott, Dominique Ranchère-Vince, Christine B. Müller, Jean-Yves Scoazec, Département d'Oncologie Médicale, Centre Léon Bérard [Lyon]-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Santé-Individu-Société 'SIS', Centre Léon Bérard [Lyon], Département d'anatomopathologie, biopathologie, Biologie, Ingénierie et Imagerie de la Greffe de Cornée ( EA 2521, JE2521, IFR143 ), Université Jean Monnet [Saint-Étienne] ( UJM ), Institute of Functional Interfaces, Karlsruhe Institute of Technology ( KIT ), Equipe 11, Centre de Recherche en Cancérologie de Lyon ( 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 ) -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 ), Equipe 4, equipe 4, Laboratoire Central d'Anatomie et de Cytologie Pathologiques [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Centre de Recherche en Cancérologie de Lyon ( CRCL ), Département d'information médicale, Hospices Civils de Lyon ( HCL ) -Université de Lyon, Service d'Oncologie, Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] ( IHOPe ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Merck Serono, Parcours santé systémique (P2S), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Biologie, Ingénierie et Imagerie pour l'Ophtalmologie (BIIO), Université Jean Monnet - Saint-Étienne (UJM), Karlsruhe Institute of Technology (KIT), Oncogénèse et progression tumorale, 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 de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL)-Université de Lyon, Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Merck & Co. Inc, Santé Individu Société (SIS), Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie, Ingénierie et Imagerie de la Greffe de Cornée (EA 2521, JE2521, IFR143), Université Jean Monnet [Saint-Étienne] (UJM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Santé Individu Société - SIS (SIS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Moulin - Lyon 3 (UJML), and Université de Lyon-Université Lumière - Lyon 2 (UL2)

Subjects
Male, Pathology, Epidemiology, MESH : Prospective Studies, MESH : Aged, Soft Tissue Neoplasms, MESH : Sarcoma, Kaposi, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, MESH : Female, Prospective Studies, MESH: Incidence, Prospective cohort study, MESH: Aged, 0303 health sciences, education.field_of_study, MESH: Middle Aged, MESH: Epidemiologic Studies, Multidisciplinary, Incidence, Incidence (epidemiology), Sarcoma, Middle Aged, MESH : Adult, MESH: Bone Neoplasms, MESH : Incidence, 3. Good health, Oncology, MESH: Young Adult, 030220 oncology & carcinogenesis, Medicine, Female, Cancer Epidemiology, Research Article, MESH: Soft Tissue Neoplasms, Adult, Leiomyosarcoma, medicine.medical_specialty, Adolescent, MESH : Male, Science, Population, MESH : Young Adult, Bone Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Liposarcoma, Bone Sarcoma, MESH : Sarcoma, MESH : Epidemiologic Studies, Young Adult, 03 medical and health sciences, Internal medicine, MESH : Adolescent, medicine, Humans, MESH : Middle Aged, education, Sarcoma, Kaposi, Aged, 030304 developmental biology, MESH : Bone Neoplasms, MESH: Adolescent, MESH: Humans, business.industry, MESH : Humans, MESH: Adult, medicine.disease, MESH: Male, MESH: Prospective Studies, Epidemiologic Studies, MESH: Sarcoma, MESH: Sarcoma, Kaposi, business, MESH: Female, MESH : Soft Tissue Neoplasms
Abstract

International audience; BACKGROUND: The exact overall incidence of sarcoma and sarcoma subtypes is not known. The objective of the present population-based study was to determine this incidence in a European region (Rhone-Alpes) of six million inhabitants, based on a central pathological review of the cases. METHODOLOGY/PRINCIPAL FINDINGS: From March 2005 to February 2007, pathology reports and tumor blocks were prospectively collected from the 158 pathologists of the Rhone-Alpes region. All diagnosed or suspected cases of sarcoma were collected, reviewed centrally, examined for molecular alterations and classified according to the 2002 World Health Organization classification. Of the 1287 patients screened during the study period, 748 met the criteria for inclusion in the study. The overall crude and world age-standardized incidence rates were respectively 6.2 and 4.8 per 100,000/year. Incidence rates for soft tissue, visceral and bone sarcomas were respectively 3.6, 2.0 and 0.6 per 100,000. The most frequent histological subtypes were gastrointestinal stromal tumor (18%; 1.1/100,000), unclassified sarcoma (16%; 1/100,000), liposarcoma (15%; 0.9/100,000) and leiomyosarcoma (11%; 0.7/100,000). CONCLUSIONS/SIGNIFICANCE: The observed incidence of sarcomas was higher than expected. This study is the first detailed investigation of the crude incidence of histological and molecular subtypes of sarcomas.

Published
2011
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3. Risk of a second malignant neoplasm after cancer in childhood treated with radiotherapy: correlation with the integral dose restricted to the irradiated fields

Author

Sylvie Guerin, Ibrahima Diallo, Dimitri Lefkopoulos, Michael M. Hawkins, Florent de Vathaire, Odile Oberlin, Carole Rubino, Akthar Samand, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Epidémiologie des cancers : Radiocarcinogénèse et effets iatrogènes des traitements, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of Public Health and Epidemiology, University of Birmingham [Birmingham], Scottish Universities Physics Alliance ( SUPA ), University of Edinburgh, Département de Pédiatrie, Institut Gustave Roussy ( IGR ), Département de radiothérapie [Gustave Roussy], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Scottish Universities Physics Alliance (SUPA), and Institut Gustave Roussy (IGR)

Subjects
Oncology, Male, MESH: Neoplasms, Radiation-Induced, Neoplasms, Radiation-Induced, medicine.medical_treatment, MESH: Regression Analysis, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Correlation, 0302 clinical medicine, MESH : Child, MESH: Child, MESH : Regression Analysis, MESH : Hodgkin Disease, Medicine, MESH: Incidence, MESH : Neoplasms, Second Primary, Child, Radiation, MESH: Risk, Incidence, MESH : Infant, MESH: Bone Neoplasms, MESH: Infant, MESH : Incidence, 3. Good health, MESH : Antineoplastic Agents, Integral dose, England, 030220 oncology & carcinogenesis, Child, Preschool, Cohort, Regression Analysis, MESH : Dose-Response Relationship, Radiation, Cohort study, medicine.medical_specialty, MESH : Cohort Studies, Antineoplastic Agents, Bone Neoplasms, 03 medical and health sciences, MESH : Adolescent, Humans, MESH : Bone Neoplasms, MESH: Adolescent, MESH: Humans, MESH: Child, Preschool, MESH : Humans, Infant, Dose-Response Relationship, Radiation, medicine.disease, MESH : Neoplasms, Radiation therapy, Relative risk, MESH: Antineoplastic Agents, MESH: Female, Cancer Research, MESH : Risk, MESH : Child, Preschool, 030218 nuclear medicine & medical imaging, Cohort Studies, MESH: England, Neoplasms, MESH: Neoplasms, MESH : Female, Survivors, MESH: Radiotherapy Dosage, MESH: Cohort Studies, MESH : Neoplasms, Radiation-Induced, MESH: Survivors, MESH : England, MESH : Radiotherapy Dosage, MESH: Infant, Newborn, Neoplasms, Second Primary, Radiotherapy Dosage, Hodgkin Disease, MESH: Hodgkin Disease, MESH: Sarcoma, Ewing's, MESH : Sarcoma, Ewing's, Female, France, Risk, MESH: Neoplasms, Second Primary, Adolescent, MESH : Survivors, MESH : Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, Sarcoma, Ewing, MESH : Infant, Newborn, Internal medicine, MESH: Dose-Response Relationship, Radiation, Radiology, Nuclear Medicine and imaging, MESH : France, Chemotherapy, business.industry, Infant, Newborn, Cancer, MESH: Male, MESH: France, business, Nuclear medicine
Abstract

International audience; PURPOSE: After successful treatment of cancers in childhood, the occurrence of second malignant neoplasm (SMN) came to the fore. Few studies have considered the relationship between the radiation dose received and the risk of developing an SMN. To take into account the heterogeneity of the dose distribution so as to evaluate the overall risk of an SMN after a childhood cancer, we therefore focused on the integral dose restricted to the irradiated fields. METHODS AND MATERIALS: The study was performed in a cohort of 4,401 patients who were 3-year survivors of all types of childhood cancer treated between 1947 and 1986 in France and Great Britain. For each patient, the integral dose was estimated for the volume inside the beam edges. RESULTS: We found a significant dose-response relationship between the overall risk of an SMN and the estimated integral dose. The excess relative risk for each incremental unit of the integral dose was only 0.008 in a linear model and 0.017 when a negative exponential term was considered, when adjusted for chemotherapy. The risk of SMN occurrence was 2.6 times higher in the case of irradiation. However among patients who had received radiotherapy, only those who had received the highest integral dose actually had a higher risk. CONCLUSIONS: The integral dose in our study cannot be considered as a good predictor of later risks. However other studies with the same study design are obviously needed to evaluate the use of the integral dose as a tool for decision making concerning different radiotherapy techniques.

Published
2008
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