title: Perioperative chemotherapy in the treatment of osteosarcoma: a 26-year single institution review.
abstract: BACKGROUND
  Chemotherapy in the multimodality treatment of osteosarcoma has improved survival. Reported outcomes on adult patients are limited. Poor necrosis rates post neoadjuvant chemotherapy (NAC) is considered an adverse prognostic factor and attempts have been made to improve survival in this group.
  
  
  METHODS
  Adult and young adult patients diagnosed with osteosarcoma between January 1986 and August 2012 were retrospectively reviewed. Patients identified were stratified according to stage (localised or metastatic) and age (≤40 and >40 years). Event free survival (EFS) and overall survival (OS) outcomes were determined. In patients with localised disease ≤40 years, survival was assessed according to necrosis rates post NAC (<90 and ≥90%). NAC consisted of two cycles of methotrexate alternating with doxorubicin/cisplatin (MAP) followed by definitive surgery. Those with ≥90% tumour necrosis continued on MAP. Patients with <90% necrosis received ifosfamide and etoposide (IE) post operatively.
  
  
  RESULTS
  A total of 108 patients were reviewed and 97 were included. Median age was 23 years (range 16-75) and 70% of patients were male. Five year EFS and OS across all groups was 57% and 63% respectively. Of the patients with localised disease (N = 81), 5-year overall survival (OS), with a median follow up of 7 years (2-26) was 70% (p < 0.0001). Patients aged 16-40 (N = 68) with localised osteosarcoma had a significantly improved 5-year OS (74%) compared to those >40 years (N = 13) (42%) (p = 0.004). Of the 68 patients with localised osteosarcoma ≤40 years, 62 were evaluated according to necrosis rates post MAP. In 33 patients who achieved ≥90% necrosis and continued MAP, 5-year OS was 82%. In 29 patients who had <90% tumour necrosis and received adjuvant IE, 5-year OS was 68% (p = 0.15). Multivariate analysis confirmed age and stage as prognostic factors but not poor necrosis rates in our treated population.
  
  
  CONCLUSIONS
  Long-term survival outcomes in a predominantly adult Irish population are similar to large reported trials. Age and stage at diagnosis are prognostic. Postoperative ifosfamide/etoposide alone in patients with poor necrosis rates is a feasible regimen, but its role in the adjuvant setting remains uncertain.
authors.affiliation: Department of Medical Oncology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland.
authors.forename: G M
authors.initials: GM
authors.lastname: O'Kane
authors.affiliation: Gynaecologic Medical Oncology Service, Memorial Sloan-Kettering Cancer Centre, 300 East 66th Street, New York, NY 10065 USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Cadoo
authors.affiliation: Department of Medical Oncology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland.
authors.forename: E M
authors.initials: EM
authors.lastname: Walsh
authors.affiliation: Department of Medical Oncology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland.
authors.forename: R
authors.initials: R
authors.lastname: Emerson
authors.affiliation: Department of Histopathology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland.
authors.forename: P
authors.initials: P
authors.lastname: Dervan
authors.affiliation: Department of Histopathology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland.
authors.forename: C
authors.initials: C
authors.lastname: O'Keane
authors.affiliation: Department of Orthopaedic Surgery, Cappagh National Orthopaedic Hospital, Finglas, Dublin 11, Ireland.
authors.forename: B
authors.initials: B
authors.lastname: Hurson
authors.affiliation: Department of Orthopaedic Surgery, Cappagh National Orthopaedic Hospital, Finglas, Dublin 11, Ireland.
authors.forename: G
authors.initials: G
authors.lastname: O'Toole
authors.affiliation: Department of Orthopaedic Surgery, Cappagh National Orthopaedic Hospital, Finglas, Dublin 11, Ireland.
authors.forename: S
authors.initials: S
authors.lastname: Dudeney
authors.affiliation: Department of Radiology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland.
authors.forename: E
authors.initials: E
authors.lastname: Kavanagh
authors.affiliation: Department of Radiology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland.
authors.forename: S
authors.initials: S
authors.lastname: Eustace
authors.affiliation: Department of Medical Oncology, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland.
authors.forename: D N
authors.initials: DN
authors.lastname: Carney
keywords: Adult osteosarcoma; Ifosfamide/etoposide; MAP; Neoadjuvant chemotherapy; Poor necrosis rates