High dose chemotherapy and autologous stem cell transplantation improves survival of patients with osteosarcoma which respond poorly to neoadjuvant chemotherapy
High dose chemotherapy and autologous stem cell transplantation improves survival of patients with osteosarcoma which respond poorly to neoadjuvant chemotherapy
Abstract
Background: Despite the great advancement in outcome for osteosarcoma, patients who respond poorly to neo-adjuvant chemotherapy show poor outcome with 5-year event free survival (EFS) of 35-45%. This retrospective analysis evaluated the role of high dose chemotherapy and autologous stem cell transplantation (HDCT & ASCT) in osteosarcoma patients with poor response to neoadjuvant chemotherapy as a sole risk factor. Methods: A retrospective medical chart review was done on all the patients who were diagnosed with osteosarcoma between June 1997 and May 2015 at Seoul National University Children’s Hospital and the patients with tumor necrosis below 90% after neoadjuvant chemotherapy as a sole risk factor were identified. The outcome of the patients treated with conventional chemotherapy only (Group 1) and that of those treated with HDCT & ASCT (Group 2) were compared. Conditioning regimen for HDCT & ASCT consisted of melphalan 140 mg/m2 on day -7 and 70 mg/m2 on day -6, etoposide 200 mg/m2 and carboplatin 400 mg/m2 from day -8 to day -5. Results: This review included 21 patients (17 male, 4 female) who were diagnosed at a median age of 11.7 years old and all of them had a single primary mass in the extremities and none of them had metastatic lesions. All of them underwent neoadjuvant chemotherapy and subsequent wide excision and limb salvage operation. The EFS of the patients in Group 1 (n=11) was 63.6% at median 7.8 (range, 0.8-16.2) years from diagnosis whereas that of those in Group 2 (n=10) was 100% at median 5.6 (range, 1.7-8.9) years from diagnosis and at 5.1 (range, 0.7-8.0) years from ASCT (p=0.042). Of the patients in Group 1, 2 patients had lung metastases at median 0.8 years from diagnosis, and 2 patients had primary site relapses at median 1.4 years from off-therapy. The overall survival of the patients in Group 1 was 72.7% at median 8.3 (range, 2.2-16.2) years from diagnosis whereas that of those in Group 2 was 100% at median 5.6 (1.7-8.9) years from diagnosis and at 5.1 (0.7-8.0) years from ASCT (p=0.113). Three patients in Group 1 died of disease. During ASCT, 1 patient experienced moderate-grade veno-occlusive disease which resolved with supportive care. Conclusion: HDCT & ASCT with melphalan, etoposide and carboplatin improves the EFS of the osteosarcoma patients with poor response to neoadjuvant chemotherapy as a sole risk factor.