Stefano Ferrari1, Stefan S Bielack2, Sigbjørn Smeland3, Alessandra Longhi1, Gerlinde Egerer4, Kirsten Sundby Hall3, Davide Donati1, Matthias Kevric2, Otte Brosjö5, Alessandro Comandone6, Mathias Werner7, Odd Monge8, Emanuela Palmerini1, Wolfgang E Berdel9, Bodil Bjerkehagen3, Anna Paioli1, Sylvie Lorenzen10, Mikael Eriksson11, Marco Gambarotti1, Per-Ulf Tunn12, Nina L Jebsen13, Marilena Cesari1, Thekla von Kalle2, Virginia Ferraresi14, Rudolf Schwarz15, Rossella Bertulli16, Anne-Katrin Kasparek17, Giovanni Grignani18, Fatime Krasniqi19, Benjamin Sorg2, Stefanie Hecker-Nolting2, Piero Picci1, Peter Reichardt7. 1. 1 Oncology Department, Istituto Ortopedico Rizzoli, Bologna - Italy. 2. 2 Stuttgart Cancer Center, Pediatrics 5 (Oncology, Hematology, Immunology), Klinikum Stuttgart Olgahospital, Stuttgart - Germany. 3. 3 Division of Cancer Medicine, Oslo University Hospital and Institute of Clinical Medicine, Oslo - Norway. 4. 4 Department of Hematology, Oncology, and Rheumatology, Heidelberg University Hospital, Heidelberg - Germany. 5. 5 Department of Orthopedics, Karolinska University Hospital, Stockholm - Sweden. 6. 6 Oncology Department, Ospedale Humanitas-Gradenigo, Turin - Italy. 7. 7 Department of Orthopedic Pathology, HELIOS Klinikum Emil von Behring GmbH, Berlin - Germany. 8. 8 Department of Oncology and Radiotherapy, Haukeland University Hospital, Bergen - Norway. 9. 9 Department of Medicine A, University Hospital of Muenster, Muenster - Germany. 10. 10 Department of Hematology and Oncology, Klinikum rechts der Isar der TU Muenchen, Muenchen - Germany. 11. 11 Department of Oncology, Skane University Hospital and Lund University, Lund - Sweden. 12. 12 Department of Tumor Orthopedics, HELIOS Klinikum Berlin-Buch, Berlin - Germany. 13. 13 Department of Clinical Science, Haukeland University Hospital and Center for Cancer Biomarkers CCBIO, University of Bergen, Bergen - Norway. 14. 14 Oncology Department, Istituto Regina Elena, Rome - Italy. 15. 15 Department of Radiation Oncology, Medical Center Hamburg-Eppendorf, Hamburg - Germany. 16. 16 Oncology Department, Istituto Nazionale Tumori, Milan - Italy. 17. 17 Department of Internal Medicine, Division of Oncology, Medical University of Graz, Graz - Austria. 18. 18 Oncology Department, Istituto di Candiolo IRCCS, Turin - Italy. 19. 19 Oncology Deparment, University Hospital of Basel, Basel - Switzerland.
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.
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 osteosarcomapatients treated with more intensive regimens.
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