title: Comparative outcome of Thai pediatric osteosarcoma treated with two protocols: the role of high-dose methotrexate (HDMTX) in a single institute experience.
abstract: BACKGROUND
  High-dose methotrexate (HD-MTX) is recognized as an efficient component of therapy against pediatric osteosarcoma in combination with other drugs such as cisplatin (CDP), carboplatin (CBDCA), doxorubicin (ADM), etoposide (VP-16) and ifosfamide (IFO).
  
  
  OBJECTIVE
  To demonstrate the feasibility and effectiveness of the HD-MTX/CDP/DOX/VP-16/IFO [MTX(+)] protocol comparable to CDP/ADM/CBDCA/IFO [MTX(-)] for treating childhood osteosarcoma at Ramathibodi Hospital (1999-2014).
  
  
  METHODS
  A retrospective analysis was conducted of osteosarcoma patients aged less than 18 years treated with two chemotherapeutic regimens between 1999 and 2014. A total of 45 patients received the MTX(-) and 21 the MTX(+) protocol.
  
  
  RESULTS
  Overall limb-salvage and amputation rate were 12.9% and 77.7%, respectively. Kaplan- Meier analysis results for 3-year disease free survival (DFS) and overall survival (OS) regardless of treatment regimens were 43.4±6.0% and 53.2±6.1% respectively. The 3-year DFS and OS were improved significantly with the MTX(+) protocol compared to MTX(-) protocol (p=0.010 and p=0.009, log rank test) [69.8±10.5%, 79.8±9.1% for MTX(+) and 31.1±6.9%, 42.2±7.4% for MTX(-) protocol, respectively]. Patients with metastatic osteosarcoma treated with the MTX(+) protocol had statistically significant higher 3-year DFS and OS than those treated with the MTX(-) protocol (66.7±13.6% and 15.0±8.0% for 3-year DFS, p=0.010, 73.3±13.2% and 20±8.9% for 3-year OS, p=0.006, respectively). The independent risk factors for having inferior 3-year DFS and OS were poor histological response (tumor necrosis <90%) and treatment with the MTX(-) protocol. The multivariate analysis identified only the treatment with the MTX(-) protocol as an independent predictor of inferior OS with a hazard ratio (HR) of 3.53 (95% confidence interval of 1.2-10.41, p=0.022).
  
  
  CONCLUSIONS
  Our study demonstrated the tolerability, feasibility and efficacy of the HDMTX-based regimen improving the survival rate in pediatric osteosarcoma cases, in line with reports from developed countries.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Thailand E-mail : suradej.hon@mahidol.ac.th.
authors.forename: Worawut
authors.initials: W
authors.lastname: Choeyprasert
authors.forename: Samart
authors.initials: S
authors.lastname: Pakakasama
authors.forename: Nongnuch
authors.initials: N
authors.lastname: Sirachainan
authors.forename: Duantida
authors.initials: D
authors.lastname: Songdej
authors.forename: Ampaiwan
authors.initials: A
authors.lastname: Chuansumrit
authors.forename: Usanarat
authors.initials: U
authors.lastname: Anurathapan
authors.forename: Suradej
authors.initials: S
authors.lastname: Hongeng
authors.forename: Adisak
authors.initials: A
authors.lastname: Nartthanarung
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage; D005121:Extremities; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D020714:Maximum Tolerated Dose; D008727:Methotrexate / Q000008:administration & dosage; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D012516:Osteosarcoma / Q000188:drug therapy* / Q000401:mortality* / Q000556:secondary; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D005047:Etoposide; D016190:Carboplatin; D002945:Cisplatin; D007069:Ifosfamide; D008727:Methotrexate