Survival after recurrent osteosarcoma: Data from 3 European Osteosarcoma Intergroup (EOI) randomized controlled trials

• Published in: European journal of cancer (1990) 2011-04, Vol.47 (6), p.895-902
• Main Authors: Gelderblom, Hans, Jinks, Rachel C, Sydes, Matthew, Bramwell, Vivien H.C, van Glabbeke, Martine, Grimer, Robert J, Hogendoorn, Pancras C.W, McTiernan, Anne, Lewis, Ian J, Nooij, Marianne A, Taminiau, Antonie H.M, Whelan, Jeremy
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Amputation; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Bone Neoplasms - drug therapy; Bone Neoplasms - mortality; Chemotherapy; Child; Child, Preschool; Cisplatin; Clinical trials; Data processing; Disease-Free Survival; Doxorubicin; Extremity; Female; Granulocyte colony-stimulating factor; Hematology, Oncology and Palliative Medicine; Humans; Infant; Kaplan-Meier Estimate; Lung; Male; Medical sciences; Metastases; Methotrexate; Middle Aged; Neoplasm Recurrence, Local - mortality; Osteosarcoma; Osteosarcoma - drug therapy; Osteosarcoma - mortality; Pharmacology. Drug treatments; Prognosis; Randomized Controlled Trials as Topic; Recurrence; Relapse; Survival; Treatment Outcome; Tumors; Young Adult
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2010.11.036

Abstract Background Recurrence after osteosarcoma usually leads to death; thus prognostic factors for survival are of great importance. Methods Between 1983 and 2002, the European Osteosarcoma Intergroup accrued 1067 patients to 3 randomized controlled trials of pre- and post-operative chemotherapy for patients with resectable non-metastatic high-grade osteosarcoma of the extremity. Control treatment in all trials was doxorubicin 75 mg/m2 and cisplatin 100 mg/m2 . The comparators were additional high-dose methotrexate (BO02), T10-based multi-drug regimen (BO03) and G-CSF intensified-DC (BO06). Post-recurrence survival (PRS) was investigated on combined data with standard survival analysis methods. Results Median recurrence-free survival was 31 months; 8 recurrences were reported more than 5 years after the diagnosis. In 564 patients with a recurrence (median 13 months post-randomisation), there was no difference in post-relapse survival between treatment arms. Patients whose disease recurred within 2 years after randomization had a worse prognosis than those recurring after 2 years. Patients with good initial histological response to pre-operative chemotherapy had a better overall survival after recurrence than poor responders. Local relapse was more often reported after limb-saving procedures (2 versus 8%; amputation versus limb-saving), independent of the primary tumour site. Site of first recurrence (local 20%, lung 62%, “other” 19%) affected survival, as patients recurring with non-lung distant metastases only or any combination of local relapse, lung metastases and non-lung metastases (=group “other”) had significantly worse overall survival (local 39%, lung 19%, “other” 9% at 5 years). Conclusions These data describing a large series of patients with recurrent extremity osteosarcoma confirm the relationship between early recurrence and poor survival. There was better PRS in patients after good histological response to pre-operative chemotherapy, or with local-only recurrence.