28 results on '"Stefanie Hecker-Nolting"'
Search Results
2. Ultra-Late Osteosarcoma Recurrences: An Analysis of 17 Cooperative Osteosarcoma Study Group Patients with a First Recurrence Detected More Than 10 Years After Primary Tumor Diagnosis
- Author
-
Stefanie Hecker-Nolting, Leo Kager, Thomas Kühne, Daniel Baumhoer, Claudia Blattmann, Godehard Friedel, Thekla von Kalle, Mathias Kevric, Regine Mayer-Steinacker, Rudolf Schwarz, Benjamin Sorg, Thomas Wirth, and Stefan S. Bielack
- Subjects
Oncology ,Pediatrics, Perinatology and Child Health - Published
- 2023
3. Das kraniofaziale Osteosarkom: eine interdisziplinäre Herausforderung
- Author
-
Stefanie Hecker-Nolting, Claudia Blattmann, Stefan S. Bielack, Leo Kager, and Thorsten Langer
- Subjects
Gynecology ,medicine.medical_specialty ,Oncology ,business.industry ,medicine ,Head and neck surgery ,business - Abstract
Das Osteosarkom (OS) ist der haufigste maligne primare Knochentumor. Er tritt v. a. an den Extremitaten junger Menschen auf, kann jedoch auch kraniofazial entstehen, mit entscheidenden epidemiologischen, therapeutischen und prognostischen Besonderheiten. Die Therapie des kraniofazialen Osteosarkoms (CFOS) wird masgeblich von der Operation gepragt, die im Gesunden erfolgen muss, um eine realistische Heilungschance zu gewahren. Andere lokaltherapeutische Verfahren wie innovative Strahlentherapien sind zwar beim CFOS haufig erforderlich, aber deutlich nachrangig. Adjuvante chemotherapeutische Verfahren konnen auch beim CFOS zum Einsatz kommen und werden von europaischen Leitlinien empfohlen. Nach der Therapie bedurfen Betroffene einer lebenslangen, risikoadaptierten Nachsorge.
- Published
- 2021
4. Osteosarcomas in older adults: A report from the Cooperative Osteosarcoma Study Group
- Author
-
Stefan S. Bielack, Lars H. Lindner, Gerlinde Egerer, Katrin Benzler, Claudia Blattmann, Matthias Grube, Dennis Hahn, Leo Kager, Thomas Kühne, Vanessa Mettmann, Peter Reichardt, and Stefanie Hecker-Nolting
- Subjects
Oncology ,Geriatrics and Gerontology - Published
- 2023
5. Osteosarcoma pre-diagnosed as another tumor: a report from the Cooperative Osteosarcoma Study Group (COSS)
- Author
-
Stefanie Hecker-Nolting, Daniel Baumhoer, Claudia Blattmann, Leo Kager, Thomas Kühne, Matthias Kevric, Susanna Lang, Vanessa Mettmann, Benjamin Sorg, Matthias Werner, and Stefan S. Bielack
- Subjects
Cancer Research ,Oncology ,General Medicine - Abstract
Purpose: The course of osteosarcoma patients primarily treated as such has been well described. Little, however, is known about patients who were primarily treated assuming a different tumor diagnosis.Methods: The database of the Cooperative Osteosarcoma Study Group COSS was searched (4.445 primary high-grade central osteosarcomas registered prior to 01/01/21). A different tumor entity had to have been assumed for at least one month after the initial diagnostic procedure before the correct diagnosis of osteosarcoma was finally made. Identified patients were analyzed for demographic, tumor-, and treatment-related factors as well as for survival outcomes.Results: 37 patients were identified. They were a median of 19.7 (2.7 - 60.4) years old at first presentation and were more likely to be females than males (23:14). Bone cysts (n=8), giant cell tumor of bone (n=6), and osteoblastoma (n=6) were the most frequent of 29/37 (78%) benign, chondrosarcoma and its variants (n= 6) the most frequent of 8/37 (22%) malignant original diagnoses. Tumors affected the extremities in 23 (62%), the trunk in 11 (30%), and the craniofacial bones in 3 (8%). Only one patient received systemic treatment while assuming the different diagnosis (1/37, 3%). The median time until the correct diagnosis of osteosarcoma was made was 8 months (range: 1 month – 14.1 years). At that time, 6/37 (16%) presented with metastatic disease. All patients went on to receive chemotherapy, 17/37 (46%) neoadjuvantly. Histologic response was only evaluated in 13/17 (76%) patients and was good (Conclusion: Osteosarcoma may initially be misdiagnosed and hence subjected to inappropriate treatment including misguided surgery. Once diagnosed correctly, some of the affected patients may still be cured if finally treated according to modern osteosarcoma standards.
- Published
- 2022
6. Establishment, Maintenance, and Performance of the Cooperative Osteosarcoma Study Group (COSS)
- Author
-
Stefan S. Bielack, Leo Kager, Thomas Kühne, Thorsten Langer, Peter Reichardt, Claudia Blattmann, Matthias Kevric, Vanessa Mettmann, Benjamin Sorg, and Stefanie Hecker-Nolting
- Subjects
Cancer Research ,Oncology - Abstract
Introduction: Osteosarcoma treatment has benefitted greatly from collaborative research. This paper describes the history and accomplishments of the Cooperative Osteosarcoma Study Group (COSS), mainly dedicated to clinical questions, as well as remaining challenges. Materials and Methods: Narrative review of over four decades of uninterrupted collaboration within the multi-national German–Austrian–Swiss COSS group. Results: Since its very first prospective osteosarcoma trial starting in 1977, COSS has continuously been able to provide high-level evidence on various tumor- and treatment-related questions. This includes both the cohort of patients enrolled into prospective trials as well as those patients excluded from them for various reasons, followed in a prospective registry. Well over one hundred disease-related publications attest to the group’s impact on the field. Despite these accomplishments, challenging problems remain. Discussion: Collaborative research within a multi-national study group resulted in better definitions of important aspects of the most common bone tumor, osteosarcoma, and its treatments. Important challenges continue to persist.
- Published
- 2023
7. Proton Therapy for Primary Bone Malignancy of the Pelvic and Lumbar Region – Data From the Prospective Registries ProReg and KiProReg
- Author
-
Rasin Worawongsakul, Theresa Steinmeier, Yi-Lan Lin, Sebastian Bauer, Jendrik Hardes, Stefanie Hecker-Nolting, Uta Dirksen, and Beate Timmermann
- Subjects
Cancer Research ,sarcoma ,Oncology ,Medizin ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,pelvic ,bone malignancy ,bone tumor ,Proton therapy ,lumbar ,RC254-282 - Abstract
Purpose/Objective(s)Multimodality treatments together with local proton therapy (PT) are commonly used in unresectable primary bone malignancies in order to provide better tumor control rate while maintaining good feasibility. The aim of this study is to provide data on outcome of PT for the challenging cohort of pelvic and lumbar bone tumors.Methods and MaterialsThis retrospective study includes all patients with primary bone malignancy of the pelvis and lumbar spine receiving PT in our institution between May 2013 and December 2019 enrolled in the prospective registries KiProReg and ProReg collecting information on demographics, treatment, tumor characteristics, toxicities, and outcome.ResultsEighty-one patients were enrolled with a median age of 19.7 years (1.3–85.8). The median follow-up time was 27.5 months (1.2–83.2). The majority of patients was male (64.2%), ECOG status of 0–1 (75.2%), underwent only biopsy (50.6%), received chemotherapy (69.1%) and was assigned for definite PT (70.4%). The predominant tumor characteristics were as follows: Ewing’s sarcoma histology (58%), negative nodal involvement (97.5%) and no metastasis at diagnosis (81.5%). Median maximal diameter of tumor was 8 cm (1.4–20). LC, EFS and OS rate were 76.5, 60, and 88.1% at two years and 72.9, 45.7, and 68.9% at three years, respectively. Age over 20 years was a significant negative factor for LC, EFS, and OS. Metastatic disease at initial diagnosis affected OS and ECOG status of 2–4 affected EFS only. Regarding 17 relapsed cases (21%), isolated distant relapse was the most common failure (46.9%) followed by local failure (40.6%). Eleven out of 14 evaluable patients relapsed within high-dose region of radiotherapy. Acute grade 3–4 toxicity was found in 41 patients (50.6%) and all toxicities were manageable. Late grade 3 toxicity was reported in 7 patients (10.4%) without any of grade 4. Most common higher grade acute and late side effects concerned hematologic and musculoskeletal toxicity.ConclusionProton therapy resulted in good oncological outcomes when being part of the multimodality treatment for pelvic and lumbar primary bone malignancies. However, distant metastases and local failures within the high-dose region of radiotherapy are still a common issue. Acute and late toxicities of combined therapy were acceptable.
- Published
- 2022
8. Pathological Fracture and Prognosis of High-Grade Osteosarcoma of the Extremities: An Analysis of 2,847 Consecutive Cooperative Osteosarcoma Study Group (COSS) Patients
- Author
-
Daniel Baumhoer, Michaela Nathrath, Thekla von Kalle, Thomas Wirth, Matthias Kevric, Hans Rechl, Per-Ulf Tunn, Lisa Marie Kelley, Bernhard Haller, Miriam Schlegel, Katja Specht, Stefan S. Bielack, Thomas Kühne, Leo Kager, Stefanie Hecker-Nolting, Reinhard Windhager, Georg Gosheger, Irene von Lüttichau, Stefan Burdach, Mathias Werner, Claudia Rossig, and Peter Reichardt
- Subjects
Adult ,Male ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Adolescent ,MEDLINE ,Bone Neoplasms ,Cohort Studies ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,Internal medicine ,medicine ,Humans ,Child ,Pathological ,Aged ,Retrospective Studies ,Osteosarcoma ,business.industry ,Extremities ,Middle Aged ,Prognosis ,medicine.disease ,Neoadjuvant Therapy ,Europe ,Fractures, Spontaneous ,030104 developmental biology ,Child, Preschool ,030220 oncology & carcinogenesis ,Female ,Neoplasm Grading ,business - Abstract
PURPOSE The objective of this study was to investigate potential correlations between pathologic fractures (PFs) and prognosis of patients with primary central high-grade osteosarcoma of the extremities. METHODS We retrospectively analyzed 2,847 patients registered in the Consecutive Cooperative Osteosarcoma Study Group database with primary central high-grade osteosarcoma of the extremities, treated between 1980 and 2010. Intended treatment included pre- and postoperative chemotherapy and surgery. Univariable and multivariable survival analyses were performed for all patients and then differentiated for adult and pediatric (≤ 18 years at time of diagnosis) patients. RESULTS A total of 2,193 patients were ≤ 18 years of age; 11.3% of all patients had PFs. In the overall cohort, presence of PF correlated significantly with tumor site, histologic subtype, relative tumor size, and primary metastases, but not with body mass index or local surgical remission. In univariable analysis, 5-year overall survival (OAS) of patients with and without PF was 63% versus 71%, respectively ( P = .007), and 5-year event-free survival (EFS) was 51% versus 58% ( P = .026). In pediatric patients, OAS and EFS did not differ significantly between patients with and without PF. In adults, 5-year OAS in patients with and without PF was 46% versus 69% ( P < .001), and 5-year EFS was 36% versus 56% ( P < .001). In multivariable analysis, PF was not a statistically significant factor for OAS or EFS in the total cohort or in pediatric patients. In adult patients, PF remained an independent prognostic factor for OAS ( P = .013; hazard ratio [HR], 1.893). It was not a significant prognostic factor for EFS ( P = .263; HR, 1.312). CONCLUSION In this largest study to date with extremity osteosarcomas, we observed the occurrence of PF to correlate with inferior OAS expectancies in adult but not in pediatric patients.
- Published
- 2020
9. Current Insights into the Management of Late Chemotherapy Toxicities in Pediatric Osteosarcoma Patients
- Author
-
Thorsten Langer, Leo Kager, Stefanie Hecker-Nolting, Stefan S. Bielack, and Claudia Blattmann
- Subjects
Oncology ,Chemotherapy ,medicine.medical_specialty ,child ,business.industry ,medicine.medical_treatment ,Review ,chemotherapy ,Internal medicine ,osteosarcoma ,adolescent ,medicine ,late effects ,business ,Pediatric Osteosarcoma - Abstract
With ever increasing long-term, disease free survival rates, long-term toxicities of otherwise successful therapy have gained increasing importance. They can be grouped into potentially life-threatening, especially secondary malignancies and anthracycline cardiomyopathies, potentially disabling, particularly severe hearing loss and renal insufficiency, other, and rare events. Pathophysiology, frequency, and medical treatment approaches are discussed. Finally, fertility issues and quality of life issues are discussed, together with an outlook into the future. The challenge to cure as many patients as possible from osteosarcoma while enabling a life free of late effects will remain.
- Published
- 2021
10. Bone sarcoma: success through interdisciplinary collaboration
- Author
-
Stefanie Hecker-Nolting, Stefan S. Bielack, and Ana Maia Ferreira
- Subjects
Oncology ,medicine.medical_specialty ,Chemotherapy ,interdisciplinary collaboration ,business.industry ,medicine.medical_treatment ,Bone Sarcoma ,chemotherapy ,medicine.disease ,Bone tumours ,osteosarcoma ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,Osteosarcoma ,Orthopedics and Sports Medicine ,Sarcoma ,Current Concepts Review ,business ,Ewing sarcoma - Abstract
Purpose Osteosarcoma and Ewing sarcoma are the most frequent malignant bone tumours of childhood and adolescence. This review summarizes the oncologist's view of these diseases and their treatment. Methods A non-systematic literature review was performed, the personal impressions and experience of the authors is described. Results Local therapy and chemotherapy, each on their own, will not cure patients with malignant bone sarcomas. Together, they present a highly efficacious combination. While the most effective drugs were defined decades ago, progress since then has been limited. It is hoped that substances shown to be active in relapsed disease will be forwarded into even more efficacious frontline treatments. Good palliative therapy is necessary when cure is no longer an option. Conclusion Close interdisciplinary collaboration is the key to successful treatment of bone sarcomas in paediatric patients.
- Published
- 2021
11. PanCareLIFE
- Author
-
Julianne Byrne, Desiree Grabow, Helen Campbell, Kylie O'Brien, Stefan Bielack, Antoinette am Zehnhoff-Dinnesen, Gabriele Calaminus, Leontien Kremer, Thorsten Langer, Marry M. van den Heuvel-Eibrink, Eline van Dulmen-den Broeder, Katja Baust, Andrea Bautz, Jörn D. Beck, Claire Berger, Harald Binder, Anja Borgmann-Staudt, Linda Broer, Holger Cario, Leonie Casagranda, Eva Clemens, Dirk Deuster, Andrica de Vries, Uta Dirksen, Jeanette Falck Winther, Sophie Fosså, Anna Font-Gonzalez, Victoria Grandage, Riccardo Haupt, Stefanie Hecker-Nolting, Lars Hjorth, Melanie Kaiser, Line Kenborg, Tomas Kepak, Kateřina Kepáková, Lisbeth E. Knudsen, Maryna Krawczuk-Rybak, Jarmila Kruseova, Claudia E. Kuehni, Marina Kunstreich, Rahel Kuonen, Herwig Lackner, Alison Leiper, Erik A.H. Loeffen, Ales Luks, Dalit Modan-Moses, Renee Mulder, Ross Parfitt, Norbert W. Paul, Andreas Ranft, Ellen Ruud, Ralph Schilling, Claudia Spix, Joanna Stefanowicz, Gabriele Strauβ, Andre G. Uitterlinden, Marleen van den Berg, Anne-Lotte van der Kooi, Marloes van Dijk, Flora van Leeuwen, Oliver Zolk, Daniela Zöller, Peter Kaatsch, P. Kaatsch, D. Grabow, J. Byrne, H. Campbell, C. Clissmann, K. O'Brien, L.C.M. Kremer, T. Langer, E. van Dulmen-den Broeder, Dr. MH. van den Berg, M.M. van den Heuvel-Eibrink, A. Borgmann-Staudt, A. am Zehnhoff-Dinnesen, C.E. Kuehni, R. Haupt, T. Kepak, C. Berger, J.F. Winther, J. Kruseova, G. Calaminus, K. Baust, U. Dirksen, F. van Leeuwen, R. Schilling, G. Strauss, A. Ranft, M.-L. Garré, S. Fosså, A. Leiper, H. Lackner, A. Panasiuk, Dr. M. Krawczuk-Rybak, M. Kunstreich, H. Cario, O. Zolk, S. Bielack, J. Stefanowicz, V. Grandage, D. Modan, AR&D - Amsterdam Reproduction & Development, Paediatric Oncology, CCA - Cancer Treatment and Quality of Life, Pediatrics, Internal Medicine, Erasmus MC other, Obstetrics & Gynecology, Amsterdam Reproduction & Development (AR&D), CCA - Cancer Treatment and quality of life, Pediatric surgery, and APH - Quality of Care
- Subjects
Male ,Gerontology ,Cancer Research ,Longitudinal study ,Medizin ,Pilot Projects ,Childhood cancer survivors ,0302 clinical medicine ,Neoplasms ,LYMPHOMA ,Medicine ,Fertility preservation ,Child ,610 Medicine & health ,EARLY MENOPAUSE ,OVARIAN-FUNCTION ,media_common ,SURVIVORS ,OUTCOMES ,030219 obstetrics & reproductive medicine ,Fertility Preservation ,GENETIC-VARIATION ,CHEMOTHERAPY ,Europe ,Oncology ,Child, Preschool ,030220 oncology & carcinogenesis ,Cohort ,Female ,medicine.symptom ,360 Social problems & social services ,Adult ,Quality of life ,Adolescent ,Hearing loss ,media_common.quotation_subject ,Fertility ,Guidelines ,Young Adult ,03 medical and health sciences ,Quality of life (healthcare) ,SDG 3 - Good Health and Well-being ,Humans ,CHILDHOOD-CANCER ,business.industry ,Clinical study design ,Late effects ,HEARING-LOSS ,Infant, Newborn ,Infant ,Ototoxicity ,Long-Term Care ,Gonadal impairment ,Long-term care ,Feasibility Studies ,business ,FOLLOW-UP - Abstract
Aims: Survival after cancer diagnosed during childhood or adolescence continues to improve with new treatments and supportive therapies. Optimal long-term care requires that risks to vulnerable organs are clearly defined and translated into guidelines that are implemented into practice. PanCareLIFE is a pan-European consortium that addresses survivorship issues comprising fertility, hearing impairment and quality of life. This article describes the scientific basis of PanCareLIFE's studies.Methods: PanCareLIFE involves 17 partner institutions from eight European countries, with additional 11 data providers from five other countries. Study designs and methods include molecular genetic, cohort and case-control studies, a longitudinal study and an intervention study. Ethics and data protection issues have been taken into account from the beginning.Results: PanCareLIFE will investigate the way that treatment impairs female fertility, by evaluating anti-Mullerian hormone levels and the underlying genetic susceptibility to loss of fertility. For our fertility studies, more than 6000 survivors have completed questionnaires, more than 1500 provided serum samples and more than 400 case-control triads have been identified. Fertility preservation guidelines for boys and girls will be developed. More than 2000 survivors have contributed audiograms for the ototoxicity study. Almost 1000 samples were sent for genetic analysis related to ototoxicity and gonadal reserve. The SF-36 questionnaire will measure quality of life in more than 10,000 survivors.Conclusions: The large number of subjects enrolled in PanCareLIFE and the detailed information accumulated will allow in-depth evaluation of important outcomes. Fertility preservation guidelines will help patients and their families make informed decisions and contribute to their long-term well-being. (C) 2018 Elsevier Ltd. All rights reserved.
- Published
- 2018
12. The Pediatric Precision Oncology INFORM Registry: Clinical Outcome and Benefit for Patients with Very High-Evidence Targets
- Author
-
Steffen Hirsch, Caroline Hutter, Bianca Goemans, Kristian W. Pajtler, David Reuss, Gabriele Calaminus, Gnana Prakash Balasubramanian, Nicola Dikow, C. Michel Zwaan, Arndt Borkhardt, David T.W. Jones, Birgit Burkhardt, Matthias Schwab, Ingrid Øra, Ines B. Brecht, Uta Dirksen, Christian Sutter, Kathrin Schramm, Roman Tremmel, Bernarda Kazanowska, Peter Lichter, M. Scheer, Gudrun Fleischhack, André O. von Bueren, Mirjam Blattner-Johnson, David Capper, Felix Sahm, Simone Fulda, Natalie Jäger, Nicolas U. Gerber, Olaf Witt, Jan-Henning Klusmann, Irene Schmid, Petra Fiesel, Matthias Fischer, Roland Meisel, Stefan M. Pfister, Michaela Nathrath, Cornelis M. van Tilburg, Angelika Eggert, Sebastian Stark, Christof M. Kramm, Elke Pfaff, Kerstin Grund, Arend von Stackelberg, Andrej Lissat, Peter Vorwerk, Petra Ketteler, Angelika Freitag, Olli Lohi, Michael T. Meister, Ruth Witt, Norbert Graf, Annette Kopp-Schneider, Pascal D. Johann, Dominik T. Schneider, Karin P.S. Langenberg, Simone Hettmer, Dirk Reinhardt, Antonis Kattamis, Andreas E. Kulozik, Andreas von Deimling, Jan J. Molenaar, Wilhelm Wößmann, Maria Filippidou, Stephan Tippelt, Frank Westermann, Stephan Wolf, Michael C. Frühwald, Barbara C. Jones, Ewa Koscielniak, Till Milde, Stefanie Hecker-Nolting, Dietrich von Schweinitz, Pediatrics, Tampere University, Department of Paediatrics, and BioMediTech
- Subjects
Prioritization ,medicine.medical_specialty ,Treatment response ,3122 Cancers ,Medizin ,MEDLINE ,03 medical and health sciences ,0302 clinical medicine ,SDG 3 - Good Health and Well-being ,3123 Gynaecology and paediatrics ,Internal medicine ,Neoplasms ,medicine ,Humans ,Prospective Studies ,Registries ,Medical diagnosis ,Precision Medicine ,Child ,030304 developmental biology ,0303 health sciences ,ddc:618 ,business.industry ,Cancer ,medicine.disease ,Confidence interval ,Progression-Free Survival ,ddc ,3. Good health ,Oncology ,Precision oncology ,030220 oncology & carcinogenesis ,Molecular targets ,3111 Biomedicine ,business - Abstract
INFORM is a prospective, multinational registry gathering clinical and molecular data of relapsed, progressive, or high-risk pediatric patients with cancer. This report describes long-term follow-up of 519 patients in whom molecular alterations were evaluated according to a predefined seven-scale target prioritization algorithm. Mean turnaround time from sample receipt to report was 25.4 days. The highest target priority level was observed in 42 patients (8.1%). Of these, 20 patients received matched targeted treatment with a median progression-free survival of 204 days [95% confidence interval (CI), 99–not applicable], compared with 117 days (95% CI, 106–143; P = 0.011) in all other patients. The respective molecular targets were shown to be predictive for matched treatment response and not prognostic surrogates for improved outcome. Hereditary cancer predisposition syndromes were identified in 7.5% of patients, half of which were newly identified through the study. Integrated molecular analyses resulted in a change or refinement of diagnoses in 8.2% of cases. Significance: The pediatric precision oncology INFORM registry prospectively tested a target prioritization algorithm in a real-world, multinational setting and identified subgroups of patients benefiting from matched targeted treatment with improved progression-free survival, refinement of diagnosis, and identification of hereditary cancer predisposition syndromes. See related commentary by Eggermont et al., p. 2677 . This article is highlighted in the In This Issue feature, p. 2659
- Published
- 2021
13. Lenvatinib with etoposide plus ifosfamide in patients with refractory or relapsed osteosarcoma (ITCC-050) : a multicentre, open-label, multicohort, phase 1/2 study
- Author
-
Rajkumar Venkatramani, Quentin Campbell-Hewson, Nathalie Gaspar, Francisco Bautista, Soledad Gallego Melcon, Alessandra Longhi, Estelle Thebaud, Franco Locatelli, Isabelle Aerts, Michela Casanova, Bruce Morland, Cixin He, Claudia Rossig, Lea Dutta, Adela Cañete Nieto, Chinyere E. Okpara, Stefanie Hecker-Nolting, Perrine Marec-Berard, Sandra J. Strauss, Marion Gambart, Cyril Lervat, and Natacha Entz-Werle
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Drug-Related Side Effects and Adverse Reactions ,II TRIALS ,Phases of clinical research ,Bone Neoplasms ,Neutropenia ,THERAPY ,Cohort Studies ,chemistry.chemical_compound ,Young Adult ,PEDIATRIC-ONCOLOGY-GROUP ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Progression-free survival ,Ifosfamide ,Child ,COMBINATION ,Protein Kinase Inhibitors ,Etoposide ,Response Evaluation Criteria in Solid Tumors ,Osteosarcoma ,business.industry ,Phenylurea Compounds ,medicine.disease ,Progression-Free Survival ,Oncology ,chemistry ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,Drug Resistance, Neoplasm ,Child, Preschool ,Cohort ,Quinolines ,RECURRENCES ,Female ,PEDIATRIC ONCOLOGY ,Neoplasm Recurrence, Local ,Lenvatinib ,business ,medicine.drug ,Cohort study - Abstract
Background Tyrosine kinase inhibitors have shown activity in osteosarcoma and might enhance the efficacy of chemotherapy. We aimed to determine the recommended phase 2 dose and antitumour activity of lenvatinib with etoposide plus ifosfamide in patients with refractory or relapsed osteosarcoma. Methods This multicentre, open-label, multicohort, phase 1/2 trial was done at 17 hospitals in six countries. Eligible patients were aged 2-25 years, had relapsed or refractory osteosarcoma, measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors version 1.1, Lansky play-performance score or Karnofsky performance score of 50% or higher, up to one previous VEGF or VEGF receptor-targeted therapy, and a life expectancy of at least 3 months. This study includes a combination dose-finding phase 1 part (cohort 3A) and a phase 2 combination expansion in patients with osteosarcoma (cohort 3B). Lenvatinib was administered orally at a starting dose of 11 mg/m(2) per day, capped at 24 mg per day, and etoposide (100 mg/m(2) per day) plus ifosfamide (3000 mg/m(2) per day) were administered intravenously on days 1-3 of each 21-day cycle for a maximum of five cycles. Lenvatinib monotherapy continued after these five cycles until disease progression, toxic effects, or patient choice to discontinue. The phase 1 primary endpoint was to determine the recommended phase 2 dose by evaluating dose-limiting toxicity and the phase 2 primary endpoint was progression-free survival at 4 months. Progression-free survival was measured in the full analysis set, which included all patients enrolled for efficacy outcomes; safety was assessed in all patients who received any study drug. This study is registered with ClinicalTrials.gov, NCT02432274. Findings 30 patients were screened for enrolment into cohort 3A between May 9, 2016, and June 3, 2019, and 22 patients for enrolment into cohort 3B between Sept 13, 2018, and July 18, 2019. Eight patients from cohort 3A and two from cohort 3B were ineligible for enrolment in the study. In phase 1, dose-limiting toxicities were observed in three patients (one in the lenvatinib 11 mg/m(2) combination group and two in the 14 mg/m2 combination group) and the recommended phase 2 dose was determined as lenvatinib 14 mg/m(2) per day (with daily dose cap of 24 mg) and etoposide 100 mg/m(2) per day plus ifosfamide 3000 mg/m2 per day administered intravenously on days 1-3 of each 21-day cycle for a maximum of five cycles. 35 patients from phase 1 (cohort 3A; n=15) and phase 2 (cohort 3B; n=20) were treated at the recommended phase 2 dose and their results were pooled. Progression-free survival at 4 months was 51% (95% CI 34-69) in 18 of 35 patients per the binomial estimate. The most common grade 3-4 treatment-emergent adverse events were neutropenia (27 [77%] of 35), thrombocytopenia (25 [71%]), anaemia (19 [54%]), and decreased white blood cell count (19 [54%]). 26 [74%] of 35 patients had serious treatment-emergent adverse events and no treatment-related deaths occurred. Interpretation Lenvatinib with etoposide plus ifosfamide shows promising antitumour activity with no new safety signals in patients with refractory and relapsed osteosarcoma. These findings warrant further investigation in an ongoing randomised phase 2 study (NCT04154189). Copyright (C) 2021 Elsevier Ltd. All rights reserved.
- Published
- 2021
14. Outcome in dedifferentiated chondrosarcoma for patients treated with multimodal therapy: Results from the EUROpean Bone Over 40 Sarcoma Study
- Author
-
Elisabetta Setola, Virginia Ferraresi, Peter Reichardt, Sigbjørn Smeland, Torsten Kessler, Rudolf Schwarz, Pierro Picci, Pietro Ruggieri, Ivar Hompland, Marco Gambarotti, Stefan S. Bielack, Eric L. Staals, Stefano Ferrari, Anne Flörcken, Lina Hansson, Otte Brosjö, Bodil Bjerkehagen, Thomas Kühne, Daniel Baumhoer, Emanuela Palmerini, Roberto Biagini, Alessandro Comandone, Matthias Kevric, Kirsten Sundby Hall, Gaetano Apice, Stefanie Hecker-Nolting, Rossella Bertulli, Paolo G. Casali, Gerda Hofmann-Wackersreuther, Mikael Eriksson, Claudia Blattmann, Davide Maria Donati, Fatime Krasniqi, Leo Kager, Björn N. Heydrich, Hompland I., Ferrari S., Bielack S., Palmerini E., Hall K.S., Picci P., Hecker-Nolting S., Donati D.M., Blattmann C., Bjerkehagen B., Staals E., Kager L., Gambarotti M., Kuhne T., Eriksson M., Ferraresi V., Kevric M., Biagini R., Baumhoer D., Brosjo O., Comandone A., Schwarz R., Bertulli R., Kessler T., Hansson L., Apice G., Heydrich B.-N., Setola E., Florcken A., Ruggieri P., Krasniqi F., Hofmann-Wackersreuther G., Casali P., Reichardt P., and Smeland S.
- Subjects
0301 basic medicine ,Oncology ,Male ,Cancer Research ,Time Factors ,Survival ,medicine.medical_treatment ,Systemic treatment ,0302 clinical medicine ,Bone sarcoma ,Antineoplastic Combined Chemotherapy Protocols ,Chemotherapy ,Complete surgical remission ,Dedifferentiated chondrosarcoma ,EURO-B.O.S.S ,Sarcoma ,Medicine ,Prospective Studies ,Ifosfamide ,Multimodal therapy ,Middle Aged ,Chemotherapy regimen ,Neoadjuvant Therapy ,Europe ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Chondrosarcoma ,Bone Neoplasms ,Disease-Free Survival ,03 medical and health sciences ,Internal medicine ,Humans ,Doxorubicin ,Aged ,business.industry ,Cancer ,Cell Dedifferentiation ,medicine.disease ,030104 developmental biology ,Feasibility Studies ,Methotrexate ,business - Abstract
Introduction The role of chemotherapy for patients with dedifferentiated chondrosarcoma (DDCS) is still under discussion. Here, we present the outcome in patients with DDCS treated with intensive chemotherapy from the EUROpean Bone Over 40 Sarcoma Study. Materials and methods The chemotherapy regimen included doxorubicin, ifosfamide and cisplatin. Postoperative methotrexate was added in case of poor histological response. Toxicity was graded based on the National Cancer Institute expanded common toxicity criteria, version 2.0, and survival was analysed using Kaplan-Meier curves, log-rank tests and univariate Cox regression models. Results Fifty-seven patients with DDCS (localised, 34 [60%]; metastatic, 23 [40%]) aged 42–65 years were included. Surgical complete remission (SCR) was achieved in 36 (63%) patients. The median overall survival (OS) was 24 months (95% confidence interval, 22–25), and the 5-year OS was 39%. Patients with extremity localisation had a 5-year OS of 49% compared with 29% in patients with a central tumour (P = 0.08). Patients with localised disease had a 5-year OS of 46%, whereas patients with metastatic disease had a 5-year OS of 29% (P = 0.12). Patients in SCR had a 5-year OS of 49%, whereas patients not in SCR had a 5-year OS of 23% (P = 0.004). Chemotherapy toxicity was considerable but manageable. There was no treatment-related death, and 39 (70%) patients received ≥6 cycles of the planned nine chemotherapy cycles. Conclusions Adding intensive chemotherapy to surgery for treatment of DDCS is feasible and shows favourable survival data compared with previous reports. With the limitations of data from a non-controlled trial, we conclude that chemotherapy could be considered in the management of patients aged >40 years.
- Published
- 2021
15. Osteosarcoma-Approach to Therapy
- Author
-
Matthew G. Cable, Neyssa Marina, Stefan Bielack, R. Lor Randall, Richard Gorlick, Leo Kager, Stefanie Hecker-Nolting, and Jeremy Whelan
- Subjects
Oncology ,medicine.medical_specialty ,Chemotherapy ,Bone cancer ,business.industry ,Incidence (epidemiology) ,medicine.medical_treatment ,Cancer ,medicine.disease ,Internal medicine ,medicine ,Osteosarcoma ,Young adult ,business - Abstract
Osteosarcoma is the most common type of bone cancer in children and young adults with a peak incidence in adolescents. It has a propensity for lung metastases and is a prime example of a cancer where cure will only be achieved if many specialities closely cooperate within a dedicated multidisciplinary environment. Neither surgery nor chemotherapy alone will cure many patients, but their combination can lead to long-term, disease-free survival in 60–70%.
- Published
- 2020
16. Usefulness of current candidate genetic markers to identify childhood cancer patients at risk for platinum-induced ototoxicity: Results of the European PanCareLIFE cohort study
- Author
-
Thorsten Langer, Eva Clemens, Linda Broer, Lara Maier, Andre G. Uitterlinden, Andrica C. H. de Vries, Martine van Grotel, Saskia F.M. Pluijm, Harald Binder, Benjamin Mayer, Annika von dem Knesebeck, Julianne Byrne, Eline van Dulmen-den Broeder, Marco Crocco, Desiree Grabow, Peter Kaatsch, Melanie Kaiser, Claudia Spix, Line Kenborg, Jeanette Falck Winther, Catherine Rechnitzer, Henrik Hasle, Tomas Kepak, Anne-Lotte F. van der Kooi, Leontien C. Kremer, Jarmila Kruseova, Stefan Bielack, Benjamin Sorg, Stefanie Hecker-Nolting, Claudia E. Kuehni, Marc Ansari, Martin Kompis, Heleen van der Pal, Ross Parfitt, Dirk Deuster, Peter Matulat, Amelie Tillmanns, Wim J. E. Tissing, Jörn D. Beck, Susanne Elsner, Antoinette am Zehnhoff-Dinnesen, Marry M. van den Heuvel-Eibrink, Oliver Zolk, PanCareLIFE Consortium Group, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Paediatric Oncology, ARD - Amsterdam Reproduction and Development, Pediatrics, Internal Medicine, Obstetrics & Gynecology, Pediatric surgery, CCA - Cancer biology and immunology, and Amsterdam Reproduction & Development (AR&D)
- Subjects
0301 basic medicine ,Oncology ,Male ,Cancer Research ,Candidate gene ,Pharmacogenomic Variants ,Cancer survivors ,CHILDREN ,Anti-neoplastic drugs ,VARIANTS ,OCT2 ,Carboplatin ,0302 clinical medicine ,Hearing ,Risk Factors ,Neoplasms ,TPMT ,Hearing / drug effects ,Prospective Studies ,Age of Onset ,Child ,610 Medicine & health ,PREDICTORS ,media_common ,Hearing Loss, Sensorineural / physiopathology ,education.field_of_study ,ddc:618 ,Thiopurine methyltransferase ,biology ,carboplatin [Cisplatin] ,Neoplasms / drug therapy ,Organic Cation Transporter 2 ,Europe ,Cisplatin: carboplatin ,Cisplatin / adverse effects ,030220 oncology & carcinogenesis ,Child, Preschool ,Organic Cation Transporter 2 / genetics ,Female ,SENSITIVITY ,Childhood cancer ,360 Social problems & social services ,Cohort study ,Drug-induced ototoxicity ,medicine.medical_specialty ,INDUCED HEARING-LOSS ,Adolescent ,Multicenter cohort study ,Hearing Loss, Sensorineural ,Population ,Adverse drug reaction ,Antineoplastic Agents ,Polymorphism, Single Nucleotide ,Risk Assessment ,Hearing Loss, Sensorineural / chemically induced ,Carboplatin / adverse effects ,03 medical and health sciences ,ACYP2 ,Ototoxicity ,SDG 3 - Good Health and Well-being ,Internal medicine ,medicine ,Genetic predisposition ,media_common.cataloged_instance ,Humans ,Genetic Predisposition to Disease ,CISPLATIN-INDUCED OTOTOXICITY ,European union ,education ,Genetic Association Studies ,Genetic association ,Retrospective Studies ,business.industry ,Antineoplastic Agents / adverse effects ,Infant, Newborn ,Infant ,Odds ratio ,Guideline ,medicine.disease ,COMT ,Pharmacogenomic Testing ,030104 developmental biology ,Cross-Sectional Studies ,Pharmacogenetics ,biology.protein ,Genetic markers ,Hearing Loss, Sensorineural / genetics ,Cisplatin ,business - Abstract
Background Irreversible sensorineural hearing loss is a common side effect of platinum treatment with the potential to significantly impair the neurocognitive, social and educational development of childhood cancer survivors. Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in the FDA drug label and a pharmacogenetic guideline. The aim of this cross-sectional cohort study was to confirm the genetic associations in a large pan-European population and to evaluate the diagnostic accuracy of the genetic markers. Methods: Eligibility criteria required patients to be aged less than 19 years at the start of chemotherapy, which had to include cisplatin and/or carboplatin. Patients were assigned to three phenotype categories: no, minor, and clinically relevant hearing loss. Fourteen variants in eleven candidate genes (ABCC3, OTOS, TPMT, SLC22A2, NFE2L2, SLC16A5, LRP2, GSTP1, SOD2, WFS1, andACYP2) were investigated. Multinomial logistic regression was performed to model the relationship between genetic predictors and platinum ototoxicity, adjusting for clinical risk factors. Additionally, measures of the diagnostic accuracy of the genetic markers were determined. Findings: 900 patients were included in this study. In the multinomial logistic regression, significant unique contributions were found from SLC22A2 rs316019, the age at start of platinum treatment, cranial radiation, and the interaction term [platinum compound]*[cumulative dose of cisplatin]. Meta-analysis confirmed an allelic association of SLC22A2 rs316019 with cisplatin ototoxicity (odds ratio 1.46, 95% CI 1.10–1.95, p=0.009). Predictive performance of the genetic markers was poor, compared with the clinical risk factors. Interpretation: PanCareLIFE is the largest study of cisplatin-induced ototoxicity to date and confirmed a role for the polyspecific organic cation transporter SLC22A2. However, our study cannot recommend the use of any of the investigated genetic markers to guide the management and prevention of cisplatin-induced hearing loss. The study results will require a revision of the pharmacogenetic guideline and the FDA drug label. Funding Statement: This work was supported by the PanCareLIFE project that has received funding from the European Union’s Seventh Framework Programme for research, technological development, and demonstration under grant agreement no. 602030. CEK was funded by the Swiss Cancer Research Foundation (grant no. 4157-02-2017), the Swiss Cancer League (grant no. 3412-02-2014), the Bernese Cancer League, and the Lung League Bern. JFW received supplementary funding from the Danish Childhood Cancer Foundation and Soroptimist International Helsingor, Denmark. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The PanCareLIFE study has been approved by the local ethics committees: Kantonale Ethikkommission Bern, 362/2015; Comitate Etico Regionale, 507REG2014; Ethical Committee University Hospital Brno, June 11, 2016; Ethics Committee Fakultni Nemocnice v Motole, Prague; De Videnskabsetiske Komiteer Region Hovedstaden, H-1- 2014-125; Ethikkommission Medizinische Universitat Graz, 27-015 ex 14/15; Ethikkommission der Universitat Ulm, 160/17; Ethikkommission der Universitat zu Lubeck, 14/181; Ethik-Kommission der Arztekammer Westfalen-Lippe und der Westfalischen Wilhelms-Universitat Munster, 2014-619; Medische Ethische Toetsings Commissie Erasmus MC; Medisch Ethische Toetsingscommissie, 2015_202. The informed consent of the patient (if adult) or his/her legal representative has been obtained.
- Published
- 2020
17. Association of candidate pharmacogenetic markers with platinum-induced ototoxicity
- Author
-
Heleen J H van der Pal, Peter Matulat, Claudia Spix, Jeanette Falck Winther, Leontien C. M. Kremer, Peter Kaatsch, Jörn D. Beck, Line Kenborg, Anne-Lotte L F van der Kooi, Lara Maier, Melanie Kaiser, Saskia F.M. Pluijm, Harald Binder, Wim J. E. Tissing, Susanne Elsner, Linda Broer, André G. Uitterlinden, Oliver Zolk, Desiree Grabow, Claudia E. Kuehni, Antoinette am Zehnhoff-Dinnesen, Annika von dem Knesebeck, Marry M. van den Heuvel-Eibrink, Marco Crocco, Martin Kompis, Jarmila Kruseova, Marc Ansari, Martine van Grotel, Amelie Tillmanns, Benjamin Mayer, Julianne Byrne, Stefanie Hecker-Nolting, Dirk Deuster, Eline van Dulmen-den Broeder, Benjamin Sorg, Stefan S. Bielack, Eva Clemens, Henrik Hasle, Thorsten Langer, Tomáš Kepák, Ross Parfitt, Andrica C H de Vries, Catherine Rechnitzer, Amsterdam Reproduction & Development (AR&D), Pediatric surgery, CCA - Cancer biology and immunology, Pediatrics, Internal Medicine, Obstetrics & Gynecology, and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
Oncology ,Drug-induced ototoxicity ,medicine.medical_specialty ,Candidate gene ,Hearing loss ,Multicenter cohort study ,Cancer survivors ,Population ,Adverse drug reaction ,610 Medicine & health ,lcsh:Computer applications to medicine. Medical informatics ,03 medical and health sciences ,0302 clinical medicine ,360 Social problems & social services ,Internal medicine ,medicine ,Genetic predisposition ,education ,lcsh:Science (General) ,030304 developmental biology ,Genetic association ,0303 health sciences ,education.field_of_study ,Multidisciplinary ,Thiopurine methyltransferase ,biology ,carboplatin [Cisplatin] ,business.industry ,Medicine and Dentistry ,Pediatric cancer ,Cisplatin: carboplatin ,Pharmacogenetics ,biology.protein ,lcsh:R858-859.7 ,Genetic markers ,medicine.symptom ,business ,Childhood cancer ,030217 neurology & neurosurgery ,lcsh:Q1-390 - Abstract
Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The PanCareLIFE cross-sectional cohort study evaluated the genetic associations in a large pan-European population and assessed the diagnostic accuracy of the genetic markers. 1,112 pediatric cancer survivors who had provided biomaterial for genotyping were screened for participation in the pharmacogenetic association study. 900 participants qualified for inclusion. Based on the assessment of original audiograms, patients were assigned to three phenotype categories: no, minor, and clinically relevant hearing loss. Fourteen variants in eleven candidate genes (ABCC3, OTOS, TPMT, SLC22A2, NFE2L2, SLC16A5, LRP2, GSTP1, SOD2, WFSI, and ACYP2) were genotyped. The genotype and phenotype data represent a resource for conducting metaanalyses to derive a more precise pooled estimate of the effects of genes on the risk of hearing loss due to platinum treatment. (C) 2020 The Authors. Published by Elsevier Inc.
- Published
- 2020
18. Phase I/II study of single-agent lenvatinib in children and adolescents with refractory or relapsed solid malignancies and young adults with osteosarcoma (ITCC-050)☆
- Author
-
S. Gallego Melcon, Francisco Bautista, Isabelle Aerts, Rajkumar Venkatramani, Alessandra Longhi, Cyril Lervat, Michela Casanova, Claudia Rossig, Cixin He, Marion Gambart, Nathalie Gaspar, Estelle Thebaud, Natacha Entz-Werle, Quentin Campbell-Hewson, Lea Dutta, Chinyere E. Okpara, Sandra J. Strauss, Franco Locatelli, A. Canete Nieto, Bruce Morland, Stefanie Hecker-Nolting, Perrine Marec-Berard, Institut Català de la Salut, [Gaspar N] Department of Childhood and Adolescent Oncology, Gustave Roussy Cancer Campus, Villejuif, France. [Campbell-Hewson Q] The Great North Children's Hospital, Royal Victoria Infirmary, Newcastle Upon Tyne, UK. [Gallego Melcon S] Servei d'Oncologia i Hematologia Pediàtrica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Locatelli F] Department of Pediatric Hematology and Oncology, Ospedale Pediatrico Bambino Gesù, University of Rome, Rome, Italy. [Venkatramani R] Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, USA. [Hecker-Nolting S] Department of Pediatric Oncology, Hematology, Immunology, Klinikum Stuttgart - Olgahospital, Stuttgart, Germany, Vall d'Hebron Barcelona Hospital Campus, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Laboratoire de Bioimagerie et Pathologies (LBP), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Oncology ,Cancer Research ,medicine.medical_treatment ,lenvatinib ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,law.invention ,Iodine Radioisotopes ,chemistry.chemical_compound ,Randomized controlled trial ,law ,tyrosine kinase inhibitors ,Neoplasms::Neoplasms by Site::Bone Neoplasms [DISEASES] ,Clinical endpoint ,Child ,Original Research ,Osteosarcoma ,terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,neoplasias::neoplasias por localización::neoplasias óseas [ENFERMEDADES] ,solid tumors ,lenvatinib, osteosarcoma, pediatric, solid tumors, tyrosine kinase inhibitors ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,lenvatinib osteosarcoma pediatric solid tumors tyrosine kinase inhibitors ,Quinolines ,Lenvatinib ,medicine.drug ,medicine.medical_specialty ,Ossos - Càncer - Tractament ,Adolescent ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Antineoplastic Agents ,Bone Neoplasms ,Quimioteràpia combinada ,Young Adult ,Refractory ,Ossos - Malalties, en els infants ,Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Internal medicine ,medicine ,Humans ,Survival rate ,Chemotherapy ,Everolimus ,business.industry ,Phenylurea Compounds ,medicine.disease ,pediatric ,chemistry ,Neoplasm Recurrence, Local ,business - Abstract
Background We report results from the phase I dose-finding and phase II expansion part of a multicenter, open-label study of single-agent lenvatinib in pediatric and young adult patients with relapsed/refractory solid tumors, including osteosarcoma and radioiodine-refractory differentiated thyroid cancer (RR-DTC) (NCT02432274). Patients and methods The primary endpoint of phase I was to determine the recommended phase II dose (RP2D) of lenvatinib in children with relapsed/refractory solid malignant tumors. Phase II primary endpoints were progression-free survival rate at 4 months (PFS-4) for patients with relapsed/refractory osteosarcoma; and objective response rate/best overall response for patients with RR-DTC at the RP2D. Results In phase I, 23 patients (median age, 12 years) were enrolled. With lenvatinib 14 mg/m2, three dose-limiting toxicities (hypertension, n = 2; increased alanine aminotransferase, n = 1) were reported, establishing 14 mg/m2 as the RP2D. In phase II, 31 patients with osteosarcoma (median age, 15 years) and 1 patient with RR-DTC (age 17 years) were enrolled. For the osteosarcoma cohort, PFS-4 (binomial estimate) was 29.0% [95% confidence interval (CI) 14.2% to 48.0%; full analysis set: n = 31], PFS-4 by Kaplan–Meier estimate was 37.8% (95% CI 20.0% to 55.4%; full analysis set) and median PFS was 3.0 months (95% CI 1.8-5.4 months). The objective response rate was 6.7% (95% CI 0.8% to 22.1%). The patient with RR-DTC had a best overall response of partial response. Some 60.8% of patients in phase I and 22.6% of patients in phase II (with osteosarcoma) had treatment-related treatment-emergent adverse events of grade ≥3. Conclusions The lenvatinib RP2D was 14 mg/m2. Single-agent lenvatinib showed activity in osteosarcoma; however, the null hypothesis could not be rejected. The safety profile was consistent with previous tyrosine kinase inhibitor studies. Lenvatinib is currently being investigated in osteosarcoma in combination with chemotherapy as part of a randomized, controlled trial (NCT04154189), in pediatric solid tumors in combination with everolimus (NCT03245151), and as a single agent in a basket study with enrollment ongoing (NCT04447755)., Highlights • The recommended phase II dose of lenvatinib in children with relapsed/refractory solid malignant tumors is 14 mg/m2. • This dose is equivalent to the recommended dose of 24 mg/day for single-agent lenvatinib in adults with DTC. • Single-agent lenvatinib showed activity of interest in children and young adults with osteosarcoma. • Based on this initial report, lenvatinib is currently being investigated in combination with chemotherapy in osteosarcoma.
- Published
- 2021
19. Extraskeletal osteosarcoma
- Author
-
Andreas Leithner, R. Capanna, R. J. Grimer, Silvia Ferrari, M. De Lisa, Gianni Bisogno, Guido Scoccianti, Paul C Jutte, Giovanni Grignani, Andreas H. Krieg, Lia D'Ambrosio, Alessandra Longhi, Madeleine Willegger, Reinhard Windhager, Davide Maria Donati, Craig Gerrand, José Casanova, David Biau, Alessandro Gronchi, Jeremy Whelan, Frank M. Klenke, Stefan S. Bielack, Stefanie Hecker-Nolting, Longhi, A., Bielack, S.S., Grimer, R., Whelan, J., Windhager, R., Leithner, A., Gronchi, A., Biau, D., Jutte, P., Krieg, A.H., Klenke, F.M., Grignani, G., Donati, D.M., Capanna, R., Casanova, J., Gerrand, C., Bisogno, G., Hecker-Nolting, S., De Lisa, M., D'Ambrosio, L., Willegger, M., Scoccianti, G., Ferrari, S., Man, Biomaterials and Microbes (MBM), Public Health Research (PHR), and Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE)
- Subjects
0301 basic medicine ,Oncology ,EMSOS ,Extraskeletal osteosarcoma ,Localised osteosarcoma ,Adolescent ,Adult ,Aged ,Aged, 80 and over ,Antineoplastic Combined Chemotherapy Protocols ,Chemoradiotherapy ,Child ,Disease-Free Survival ,Europe ,Female ,Humans ,Male ,Middle Aged ,Neoadjuvant Therapy ,Neoplasm Metastasis ,Neoplasm Recurrence, Local ,Osteosarcoma ,Retrospective Studies ,Risk Factors ,Soft Tissue Neoplasms ,Tumor Burden ,Young Adult ,Cancer Research ,medicine.medical_treatment ,CLINICOPATHOLOGICAL ANALYSIS ,0302 clinical medicine ,Retrospective Studie ,80 and over ,610 Medicine & health ,Neoadjuvant therapy ,Univariate analysis ,Ifosfamide ,TUMORS ,Neoplasm Metastasi ,Local ,030220 oncology & carcinogenesis ,Europa ,medicine.drug ,Human ,medicine.medical_specialty ,Extraskeletal Osteosarcoma ,SOFT-TISSUES ,BREAST ,Quimiorradioterapia ,03 medical and health sciences ,Internal medicine ,medicine ,Soft Tissue Neoplasm ,Neoplasias dos Tecidos Moles ,Chemotherapy ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,Risk Factor ,Retrospective cohort study ,Radiation therapy ,Regimen ,030104 developmental biology ,Neoplasm Recurrence ,business ,OSTEOGENIC-SARCOMA - Abstract
Purpose: Prognosis of extraskeletal osteosarcoma (ESOS) is reported to be poorer than that of skeletal osteosarcoma. This multicenter retrospective study aimed to evaluate factors influencing ESOS prognosis.Patients and methods: Members of the European Musculoskeletal Oncology Society (EMSOS) submitted institutional data on patients with ESOS.Results: Data from 274 patients treated from 1981 to 2014 were collected from 16 EMSOS centres; 266 patients were eligible. Fifty (18.7%) had metastases at diagnosis. Of 216 patients with localised disease, 211 (98%) underwent surgery (RO = 70.6%, R1 = 27%). Five-year overall survival (OS) for all 266 patients was 47% (95% CI 40-54%). Five-year OS for metastatic patients was 27% (95% CI 13-41%). In the analysis restricted to the 211 localised patients who achieved complete remission after surgery 5-year OS was 51.4% (95% CI 44-59%) and 5-year disease-free survival (DFS) was 43% (95% CI 35-51%). One hundred twenty-one patients (57.3%) received adjuvant or neoadjuvant chemotherapy and 80 patients (37.9%) received radiotherapy. A favourable trend was seen for osteosarcoma-type chemotherapy versus soft tissue sarcoma-type (doxorubicin +/- ifosfamide) regimens. For the 211 patients in complete remission after surgery, patient age, tumour size, margins and chemotherapy were positive prognostic factors for DFS and OS by univariate analysis.At multivariate analysis, patient age (40 years) (P = 0.05), tumour size (P = 0.0001) and receipt of chemotherapy (P = 0.006) were statistically significant prognostic factors for survival.Conclusion: Patient age and tumour size are factors influencing ESOS prognosis. Higher survival was observed in patients who received perioperative chemotherapy with a trend in favour of multiagent osteosarcoma-type regimen which included doxorubicin, ifosfamide and cisplatin. (C) 2017 Elsevier Ltd. All rights reserved.
- Published
- 2017
20. Bone sarcomas: ESMO-PaedCan-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up
- Author
-
Laurence Brugières, K. Sundby Hall, Bruce Morland, Ioannis Boukovinas, Rolf D. Issels, Sebastian Bauer, D.A. Krakorova, Angela Buonadonna, E. de Álava, Nathalie Gaspar, P. Picci, Palma Dileo, Hans Gelderblom, Bernadette Brennan, Javier Martin Broto, Maria Abbondanza Pantaleo, Paul C Jutte, Ian Judson, Suzanne E. J. Kaal, B. Hassan, Ruth Ladenstein, Alexander Fedenko, Patrick Schöffski, Jean-Yves Blay, A. Le Cesne, Peter Hohenberger, Virginia Ferraresi, Sandra J. Strauss, Michael Montemurro, Robin L. Jones, Peter Reichardt, Stefan S. Bielack, Mikael Eriksson, Stefan Sleijfer, Akmal Safwat, Heikki Joensuu, Rick L. Haas, Bernd Kasper, Hannu T. Aro, Judith V.M.G. Bovée, Jeremy Whelan, A.M. Frezza, Antonio López Pousa, Stefanie Hecker-Nolting, Thomas Brodowicz, R. Biagini, Silvia Stacchiotti, S. Ferrari, Sylvie Bonvalot, S. Piperno-Neumann, Leo Kager, F. van Coevorden, Olga Zaikova, R. Piana, Catharina Dhooge, Piotr Rutkowski, M.H. Robinson, Ofer Merimsky, Katerina Kopeckova, X.G. del Muro, W.T.A. van der Graaf, Paolo G. Casali, N. Abecassis, Eva Wardelmann, Silvia Gasperoni, Giovanni Grignani, A. P. Dei Tos, Andrea Ferrari, Franca Fagioli, Alessandro Gronchi, Thierry Gil, Iwona Lugowska, M. Unk, Man, Biomaterials and Microbes (MBM), Public Health Research (PHR), Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Medical Oncology, Casali, P.G., Bielack, S., Abecassis, N., Aro, H.T., Bauer, S., Biagini, R., Bonvalot, S., Boukovinas, I., Bovee, J.V.M.G., Brennan, B., Brodowicz, T., Broto, J.M., Brugières, L., Buonadonna, A., De Álava, E., Dei Tos, A.P., Del Muro, X.G., Dileo, P., Dhooge, C., Eriksson, M., Fagioli, F., Fedenko, A., Ferraresi, V., Ferrari, A., Ferrari, S., Frezza, A.M., Gaspar, N., Gasperoni, S., Gelderblom, H., Gil, T., Grignani, G., Gronchi, A., Haas, R.L., Hassan, B., Hecker-Nolting, S., Hohenberger, P., Issels, R., Joensuu, H., Jones, R.L., Judson, I., Jutte, P., Kaal, S., Kager, L., Kasper, B., Kopeckova, K., Krákorová, D.A., Ladenstein, R., Le Cesne, A., Lugowska, I., Merimsky, O., Montemurro, M., Morland, B., Pantaleo, M.A., Piana, R., Picci, P., Piperno-Neumann, S., Pousa, A.L., Reichardt, P., Robinson, M.H., Rutkowski, P., Safwat, A.A., Schöffski, P., Sleijfer, S., Stacchiotti, S., Strauss, S.J., Sundby Hall, K., Unk, M., Van Coevorden, F., Van Der Graaf, W.T.A., Whelan, J., Wardelmann, E., Zaikova, O., and Blay, J.Y.
- Subjects
0301 basic medicine ,Oncology ,Biopsy ,Medizin ,Aftercare ,CHILDRENS-ONCOLOGY-GROUP ,Survivorship ,Medical Oncology ,0302 clinical medicine ,HIGH-DOSE CHEMOTHERAPY ,Positron Emission Tomography Computed Tomography ,Antineoplastic Combined Chemotherapy Protocols ,GIANT-CELL TUMOR ,Orthopedic Procedures ,PRIMITIVE NEUROECTODERMAL TUMOR ,Child ,Societies, Medical ,Osteosarcoma ,SOFT-TISSUE TUMORS ,Incidence (epidemiology) ,Incidence ,Age Factors ,Hematology ,RANDOMIZED CONTROLLED-TRIAL ,Magnetic Resonance Imaging ,Neoadjuvant Therapy ,Europe ,Self-Help Groups ,Treatment Outcome ,030220 oncology & carcinogenesis ,Sarcoma ,HIGH-GRADE OSTEOSARCOMA ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] ,Adult ,medicine.medical_specialty ,education ,Bone Neoplasms ,Bone Sarcoma ,Bone and Bones ,03 medical and health sciences ,POSITRON-EMISSION-TOMOGRAPHY ,Internal medicine ,medicine ,Humans ,Radionuclide Imaging ,STUDY-GROUP PROTOCOLS ,Neoplasm Staging ,ta3126 ,NONMETASTATIC EWINGS-SARCOMA ,business.industry ,Cancer ,medicine.disease ,Long-Term Care ,Cancer registry ,030104 developmental biology ,Primitive neuroectodermal tumor ,Radiotherapy, Adjuvant ,Chondrosarcoma ,Patient Participation ,business - Abstract
Primary bone tumours are rare, accounting for < 0.2% of malignant neoplasms registered in the EUROCARE (European Cancer Registry based study on survival and care of cancer patients) database. Different bone tumour subtypes have distinct patterns of incidence, and each has no more than 0.3 incident cases per 100 000 per year. Osteosarcoma (OS) and Ewing sarcoma (ES) have a relatively high incidence in the second decade of life, whereas chondrosarcoma (CS) is more common in older age.
- Published
- 2018
21. High-Grade Osteosarcoma of the Foot: Presentation, Treatment, Prognostic Factors, and Outcome of 23 Cooperative Osteosarcoma Study Group COSS Patients
- Author
-
Stefan S. Bielack, Daniel Baumhoer, Susanna Lang, Thekla von Kalle, Peter Reichardt, Matthias Kevric, Sylvie Lorenzen, Regine Mayer-Steinacker, Stefanie Hecker-Nolting, Mathias Werner, Monika Csóka, Reinhard Windhager, Thomas Wirth, Leo Kager, and Anne J. Schuster
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Article Subject ,medicine.medical_treatment ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,Retrospective analysis ,Overall survival ,medicine ,Preoperative chemotherapy ,Radiology, Nuclear Medicine and imaging ,Chemotherapy ,business.industry ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Surgery ,Rare tumor ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Osteosarcoma ,Presentation (obstetrics) ,business ,Foot (unit) ,Research Article - Abstract
Osteosarcoma of the foot is a very rare presentation of a rare tumor entity. In a retrospective analysis, we investigated tumor- and treatment-related variables and outcome of patients registered in the Cooperative Osteosarcoma Study Group (COSS) database between January 1980 and April 2016 who suffered from primary high-grade osteosarcoma of the foot. Among the 23 eligible patients, median age was 32 years (range: 6–58 years), 10 were female, and 13 were male. The tarsus was the most commonly affected site (n=16). Three patients had primary metastases. All patients were operated: 5 underwent primary surgery and 18 received surgery following preoperative chemotherapy. In 21 of the 23 patients, complete surgical remission was achieved. In 4 of 17 patients, a poor response to neoadjuvant chemotherapy was observed in the resected primary tumors. Median follow-up was 4.2 years (range: 0.4–18.5). At the last follow-up, 15 of the 23 patients were alive and 8 had died. Five-year overall and event-free survival estimates were 64% (standard error (SE) 12%) and 54% (SE 13%), which is similar to that observed for osteosarcoma in general. Event-free and overall survival correlated with primary metastatic status and completeness of surgery. Our findings show that high-grade osteosarcoma in the foot has a similar outcome as osteosarcoma of other sites.
- Published
- 2018
- Full Text
- View/download PDF
22. EURO-B.O.S.S.: A European study on chemotherapy in bone-sarcoma patients aged over 40: Outcome in primary high-grade osteosarcoma
- Author
-
Virginia Ferraresi, Stefan S. Bielack, Anna Paioli, Nina L. Jebsen, Kirsten Sundby Hall, Peter Reichardt, Fatime Krasniqi, Bodil Bjerkehagen, Alessandra Longhi, Otte Brosjö, Thekla von Kalle, Emanuela Palmerini, Marco Gambarotti, Stefano Ferrari, Matthias Kevric, Rossella Bertulli, Per Ulf Tunn, Benjamin Sorg, Wolfgang E. Berdel, Piero Picci, Davide Maria Donati, Mikael Eriksson, Mathias Werner, Rudolf Schwarz, Odd R. Monge, Sylvie Lorenzen, Anne Katrin Kasparek, Marilena Cesari, Sigbjørn Smeland, Alessandro Comandone, Giovanni Grignani, Stefanie Hecker-Nolting, Gerlinde Egerer, DIPARTIMENTO DI MEDICINA SPECIALISTICA, DIAGNOSTICA E SPERIMENTALE, DIPARTIMENTO DI SCIENZE BIOMEDICHE E NEUROMOTORIE, Facolta' di MEDICINA e CHIRURGIA, Ferrari, Stefano, Bielack, Stefan S, Smeland, Sigbjørn, Longhi, Alessandra, Egerer, Gerlinde, Sundby Hall, Kirsten, Donati, Davide, Kevric, Matthia, Brosjö, Otte, Comandone, Alessandro, Werner, Mathia, Monge, Odd, Palmerini, Emanuela, Berdel, Wolfgang E, Bjerkehagen, Bodil, Paioli, Anna, Lorenzen, Sylvie, Eriksson, Mikael, Gambarotti, Marco, Tunn, Per-Ulf, Jebsen, Nina L, Cesari, Marilena, von Kalle, Thekla, Ferraresi, Virginia, Schwarz, Rudolf, Bertulli, Rossella, Kasparek, Anne-Katrin, Grignani, Giovanni, Krasniqi, Fatime, Sorg, Benjamin, Hecker-Nolting, Stefanie, Picci, Piero, and Reichardt, Peter
- Subjects
0301 basic medicine ,Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,International Cooperation ,Treatment outcome ,Bone Neoplasms ,Bone Sarcoma ,chemotherapy ,elderly ,Chemotherapy related toxicity ,03 medical and health sciences ,0302 clinical medicine ,osteosarcoma, elderly, chemotherapy, bone tumors ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Ifosfamide ,Prospective Studies ,Prospective cohort study ,health care economics and organizations ,Survival analysis ,Aged ,Febrile Neutropenia ,bone tumors ,Chemotherapy ,Osteosarcoma ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Survival Analysis ,Europe ,030104 developmental biology ,Methotrexate ,Treatment Outcome ,Doxorubicin ,030220 oncology & carcinogenesis ,Female ,Sarcoma ,Cisplatin ,business - Abstract
Introduction: The EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) was the first prospective international study for patients 41-65 years old with high-grade bone sarcoma treated with an intensive chemotherapy regimen derived from protocols for younger patients with high-grade skeletal osteosarcoma. Methods: Chemotherapy based on doxorubicin, cisplatin, ifosfamide, and methotrexate was suggested, but patients treated with other regimens at the investigators’ choice were also eligible for the study. Results: The present report focuses on the subgroup of 218 patients with primary high-grade osteosarcoma. With a median follow-up of 47 months, the 5-year probability of overall survival (OS) was 66% in patients with localized disease and 22% in case of synchronous metastases. The 5-year OS in patients with localized disease was 29% in pelvic tumors, and 70% and 73% for extremity or craniofacial locations, respectively. In primary chemotherapy, tumor necrosis ≥90% was reported in 21% of the patients. There were no toxic deaths; however, hematological toxicity was considerable with 32% of patients experiencing 1 or more episodes of neutropenic fever. The incidence of nephrotoxicity and neurotoxicity (mainly peripheral) was 28% and 24%, respectively. After methotrexate, 23% of patients experienced delayed excretion, in 4 cases with nephrotoxicity. Conclusions: In patients over 40 years of age with primary high-grade osteosarcoma, an aggressive approach with chemotherapy and surgery can offer the probability of survival similar to that achieved in younger patients. Chemotherapy-related toxicity is significant and generally higher than that reported in younger cohorts of osteosarcoma patients treated with more intensive regimens.
- Published
- 2017
23. TThe ENCCA-WP7/EuroSarc/EEC/PROVABES/EURAMOS 3rd European Bone Sarcoma Networking Meeting/Joint Workshop of EU Bone Sarcoma Translational Research Networks; Vienna, Austria, September 24–25, 2015. Workshop Report
- Author
-
Ornella Gonzato, Marie-cecile Ledeley, Emmy D.G. Fleuren, Hans Gelderblom, Marta Fiocco, Winette T. A. van der Graaf, Joachim Gerß, David Thomas, Jenny Potratz, Stefanie Hecker-Nolting, Craig Gerrand, Heinrich Kovar, Franck Tirode, Anne-Marie Cleton-Jansen, Piero Picci, Bernadette Brennan, Ola Myklebost, Javier Martin Broto, Judith V.M.G. Bovée, Michaela Nathrath, Piotr Rutkowski, Oscar M. Tirado, Aurélie Dutour, Nathalie Gaspar, Katia Scotlandi, Jeremy Whelan, Laurence Brugières, B. Hassan, Lindsey Bennister, Leo Kager, Gilles Vassal, Martin G. McCabe, Gunther Richter, Stefan S. Bielack, Carlo Lancia, Christopher Copland, Ruth Ladenstein, Stephanie Klco-Brosius, Jakob K. Anninga, Françoise Rédini, David Herrero-Martin, Markus Metzler, Franca Fagioli, Denise Reinke, Uta Dirksen, Stefano Ferrari, Sandra J. Strauss, Department of Paediatrics [Vienna, Austria], Saint Anna Children's Hospital [Vienna, Austria]-Medizinische Universität Wien = Medical University of Vienna, Children’s Cancer Research Institute [Vienna, Austria], University College London Hospitals (UCLH), Universitätsklinikum Münster [Munster, Germany], University of Oxford [Oxford], Leids Universitair Medisch Centrum [Leiden, The Netherlands], Sarcoma Patients Euronet [London, UK], Sarcoma UK, Central Manchester University Hospitals [Manchester, U.K.], Hospital Universitario Virgen del Rocío [Sevilla], Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), CELT [York, UK], University of York [York, UK], 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), Regina Margherita University Children's Hospital [Turin, Italy], Istituto Ortopedico Rizzoli [Bologna, Italy], Radboud University Medical Centre [Nijmegen, The Netherlands], Newcastle upon Tyne Hospitals [Newcastle, UK], Institute of Cancer Research - ICR [London, U.K.], Klinikum Stuttgart-Olgahospital [Stuttgart, Germany], Molecular Oncology Laboratory [Barcelona, Spain] (Sarcoma Research Group), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL)-L’Hospitalet de Llobregat [Barcelona, Spain], Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), University of Manchester [Manchester], Universitätsklinikum Erlangen [Erlangen, Germany], Oslo University Hospital [Oslo], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Klinikum Kassel [Kassel, Germany], Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Sarcoma Alliance through Research and Collaboration [Ann Arbor, USA], Maria Sklodowska-Curie Memorial Institute and Cancer Centre [Warsaw, Poland], Garvan Institute of Medical Research [Darlinghurst, Australia], Centre de recherche de l'Institut Curie [Paris], Institut Curie [Paris], The research leading to these results and the information described in this article have received funding from ENCCA-WP7: The European Union’s Seventh Framework Programme (FP7/2007-2013) under the project ENCCA, Grant agreement HEALTH-F2-2011-261474. EuroSarc: EU project FP7-HEALTH-2011-two-stage, Project ID 278742 EUROSARC. EEC: European Union’s Seventh Framework Programme for research, technological development and demonstration under Grant agreement no. 602856PROVABES: ERA-Net-TRANSCAN (01KT1310). PanCareLife: (602030-2) EU-FP7German Cancer Aid: DKH 108128. EURAMOS: The EURAMOS-group has received support from multiple funders (see Bielack et al., J Clin Oncol 33(20):2279-87, 2015)., European Project: 261474,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,ENCCA(2011), European Project: 278742,EC:FP7:HEALTH,FP7-HEALTH-2011-two-stage,EUROSARC(2011), European Project: 602856,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,EEC(2013), European Project: 602030,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,PANCARELIFE(2013), Medizinische Universität Wien = Medical University of Vienna-Saint Anna Children's Hospital [Vienne] = St Anna Kinderspital (St. Anna Children's Hospital), University of Oxford, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Radboud University Medical Center [Nijmegen], Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Garvan Institute of medical research, maurice, sandrine, EUROPEAN NETWORK for CANCER research in CHILDREN and ADOLESCENTS - ENCCA - - EC:FP7:HEALTH2011-01-01 - 2015-12-31 - 261474 - VALID, European Clinical trials in Rare Sarcomas within an integrated translational trial network - EUROSARC - - EC:FP7:HEALTH2011-12-01 - 2016-11-30 - 278742 - VALID, EURO EWING Consortium – International Clinical Trials to Improve Survival from Ewing Sarcoma - EEC - - EC:FP7:HEALTH2013-10-01 - 2018-09-30 - 602856 - VALID, and PanCare Studies in Fertility and Ototoxicity to Improve Quality of Life after Cancer during Childhood, Adolescence and Young Adulthood - PANCARELIFE - - EC:FP7:HEALTH2013-11-01 - 2018-10-31 - 602030 - VALID
- Subjects
Pathology ,medicine.medical_specialty ,Translational research ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Meeting Report ,Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] ,Bone Sarcoma ,03 medical and health sciences ,0302 clinical medicine ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Medisinske Fag: 700 [VDP] ,Medizinische Fakultät ,Next generation sequencing ,Bone sarcoma ,Journal Article ,medicine ,In patient ,Medical physics ,ddc:610 ,030212 general & internal medicine ,Ewing sarcoma ,Immunotherapy ,Osteosarcoma ,Pharmacogenomics ,Tumors ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Manchester Cancer Research Centre ,business.industry ,ResearchInstitutes_Networks_Beacons/mcrc ,Joint bone ,medicine.disease ,3. Good health ,Clinical trial ,Oncology ,030220 oncology & carcinogenesis ,Sarcoma ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] - Abstract
Contains fulltext : 167540.pdf (Publisher’s version ) (Open Access) This report summarizes the results of the 3rd Joint ENCCA-WP7, EuroSarc, EEC, PROVABES, and EURAMOS European Bone Sarcoma Network Meeting, which was held at the Children's Cancer Research Institute in Vienna, Austria on September 24-25, 2015. The joint bone sarcoma network meetings bring together European bone sarcoma researchers to present and discuss current knowledge on bone sarcoma biology, genetics, immunology, as well as results from preclinical investigations and clinical trials, to generate novel hypotheses for collaborative biological and clinical investigations. The ultimate goal is to further improve therapy and outcome in patients with bone sarcomas.
- Published
- 2016
24. Pathological fracture and prognosis of high-grade osteosarcoma of the extremities. An analysis of 2,847 consecutive cooperative osteosarcoma study group (COSS) patients
- Author
-
I. Von Luettichau, T. von Kalle, Claudia Rossig, Georg Gosheger, Stefanie Hecker-Nolting, Peter Reichardt, Thomas Kühne, S. Burdach, Matthias Kevric, L. Kelley, Katja Specht, Reinhard Windhager, Stefan S. Bielack, Miriam Schlegel, Daniel Baumhoer, Per-Ulf Tunn, Michaela Nathrath, Leo Kager, and Mathias Werner
- Subjects
Cancer Research ,medicine.medical_specialty ,Oncology ,business.industry ,medicine ,Osteosarcoma ,business ,medicine.disease ,Pathological ,Surgery - Published
- 2017
25. More on osteosarcoma and phylloides tumor
- Author
-
Matthias Kevric, Stefan S. Bielack, Heribert Juergens, and Stefanie Hecker-Nolting
- Subjects
Osteosarcoma ,Myeloid ,business.industry ,MEDLINE ,Bone Neoplasms ,Neoplasms, Second Primary ,Hematology ,medicine.disease ,Leukemia ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Oncology ,Phyllodes Tumor ,Pediatrics, Perinatology and Child Health ,Cancer research ,Medicine ,Humans ,Female ,business - Published
- 2014
26. 3414 High-grade osteosarcomas of the pectoral girdle
- Author
-
Rudolf Schwarz, Leo Kager, M. Kuhlen, Stefanie Hecker-Nolting, Stefan S. Bielack, P.G. Schlegel, and Gernot Jundt
- Subjects
Cancer Research ,Oncology ,Pectoral girdle ,Anatomy ,Biology - Published
- 2015
27. Prognostic factors analysis of extraskeletal osteosarcoma: Updated results of an EMSOS study
- Author
-
Gianni Bisogno, David Biau, Stefanie Hecker-Nolting, Craig Gerrand, Frank M. Klenke, Andreas H. Krieg, Alessandra Longhi, Alberto Righi, Cristina Ferrari, Andreas Leithner, José Casanova, Stefano Ferrari, and Stefan S. Bielack
- Subjects
Cancer Research ,Pathology ,medicine.medical_specialty ,Extraskeletal Osteosarcoma ,Oncology ,business.industry ,Medicine ,Osteosarcoma ,Soft tissue ,Radiology ,business ,medicine.disease - Abstract
10526 Background: Extra Skeletal Osteosarcoma (ESO) account 1% among soft tissue sarcomas. There is no agreement on the best strategy of treatment. Methods: An EMSOS collaborative study was perform...
- Published
- 2015
28. Mesenchymal chondrosarcoma
- Author
-
Nicolas Haffner, Domenico Andrea Campanacci, Philipp T. Funovics, Stephen Bielack, Marilena Cesari, David Biau, Claire Esler, Craig Gerrand, Anna Maria Frezza, Andreas Leithner, Stefano Ferrari, Reinhard Windhager, Sylvia Höller, José Casanova, Stefanie Hecker-Nolting, Mikel San-Julian, Jeremy Whelan, Paul C Jutte, Robert J. Grimer, Lee Jeys, Joachim Thorkildsen, Bruno Vincenzi, Alessandro Gronchi, Daniel Baumhoer, Man, Biomaterials and Microbes (MBM), Public Health Research (PHR), and Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE)
- Subjects
Adult ,Male ,Mesenchymal chondrosarcoma ,Cancer Research ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Bone Neoplasms ,Young Adult ,Internal medicine ,medicine ,Humans ,Chemotherapy ,Young adult ,Child ,Societies, Medical ,Aged ,Outcome ,Aged, 80 and over ,business.industry ,Hazard ratio ,Neoplasias dos Ossos ,Condrossarcoma Mesenquimal ,Combination chemotherapy ,Middle Aged ,medicine.disease ,Prognosis ,Confidence interval ,Surgery ,Europe ,Oncology ,OSTEOSARCOMA ,Chondrosarcoma, Mesenchymal ,Female ,Sarcoma ,Chondrosarcoma ,business ,BONE - Abstract
Background: Mesenchymal chondrosarcoma (MCS) is a distinct, very rare sarcoma with little evidence supporting treatment recommendations.Patients and methods: Specialist centres collaborated to report prognostic factors and outcome for 113 patients.Results: Median age was 30 years (range: 11-80), male/female ratio 1.1. Primary sites were extremities (40%), trunk (47%) and head and neck (13%), 41 arising primarily in soft tissue. Seventeen patients had metastases at diagnosis. Mean follow-up was 14.9 years (range: 1-34), median overall survival (OS) 17 years (95% confidence interval (CI): 10.3-28.6). Ninety-five of 96 patients with localised disease underwent surgery, 54 additionally received combination chemotherapy. Sixty-five of 95 patients are alive and 45 progression-free (5 local recurrence, 34 distant metastases, 11 combined). Median progression-free survival (PFS) and OS were 7 (95% CI: 3.03-10.96) and 20 (95% CI: 12.63-27.36) years respectively. Chemotherapy administration in patients with localised disease was associated with reduced risk of recurrence (P = 0.046; hazard ratio (HR) = 0.482 95% CI: 0.213-0.996) and death (P = 0.004; HR = 0.445 95% CI: 0.256-0.774). Clear resection margins predicted less frequent local recurrence (2% versus 27%; P = 0.002). Primary site and origin did not influence survival. The absence of metastases at diagnosis was associated with a significantly better outcome (P Conclusions: Prognosis in MCS varies considerably. Metastatic disease at diagnosis has the strongest impact on survival. Complete resection and adjuvant chemotherapy should be considered as standard of care for localised disease. (C) 2014 Elsevier Ltd. All rights reserved.
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.