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Long-term follow-up and post-relapse survival in patients with non-metastatic osteosarcoma of the extremity treated with neoadjuvant chemotherapy
Authors:S Ferrari  G Bacci  P Picci  M Mercuri  A Briccoli  D Pinto  A Gasbarrini  A Tienghi and A Brach del Prever
Institution:(1) Bone Tumor Department, Istituto Ortopedico Rizzoli, Bologna, Italy;(2) Medical Oncology Division + Paediatric Department, Ravenna, Italy;(3) University of Torino, Torino, Italy
Abstract:Background: Most of the studies of the treatment of non-metastaticosteosarcoma of the extremity have reported results in terms of probabilityof survival up to five years with a minimum follow-up of less than two tothree years. Definition of reliable indicators of prognosis and predictivefactors for survival require mature data derived from a long-term survivalanalysis.Patients and methods: A review of 127 patients with non-metastaticosteosarcoma of the extremity, treated between March 1983 and June 1986, wasperformed. The treatment protocol consisted of primary chemotherapy with MTX(randomization to high vs. moderate dosages) and CDP followed by surgery.Postoperatively, patients with <60% tumor necrosis received ADMand BCD; those with tumor necrosis ge60% < 90% (FairResponders FR) were given MTX, CDP and ADM. Up to January 1984, patientswith tumor necrosis >90% received MTX and CDP only, and after thenthey were given the same treatment as for FR. A multivariate analysis totest predictive factors for survival was performed.Results: With a median follow-up of 134 months (range 114–153), the12-year DFS was 46%. A good histologic response, an LDH baselinevalue within the normal range, and the use of high-dose MTX were positivepredictive factors for DFS. With a median time of observation for survivorsof 130 months, the 12-year overall survival was 53%. None of thepatients who relapsed with local or distant recurrences other than lungmetastasis are now alive. Patients with a relapse-free interval longer than24 months had a significantly better post-relapse survival than those with ashorter relapse-free interval (40% vs. 7%; P = 0.0159). All ofthe patients who were not surgically treated had disease progression anddied within 40 months after the first recurrence. The surgically-treatedpatients had a 30% post-relapse survival probability.Conclusions: In non-metastatic osteosarcoma of the extremity,chemotherapy-induced tumor necrosis, the baseline LDH serum value and the useof HDMTX are significant predictive factors for DFS. The relapse-free intervaland the possibility of metastasectomy are significant factors conditioning thepost-relapse survival.
Keywords:high-dose methotrexate  lactic dehydrogenase  metastasectomy  neoadjuvant chemotherapy  non-metastatic osteosarcoma of the extremity  tumor necrosis
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