Perioperative chemotherapy in the treatment of osteosarcoma: a 26-year single institution review.

G M O’Kane,K A Cadoo,S Eustace,D N Carney,B Hurson,P Dervan,S Dudeney,E Kavanagh,E M Walsh,C O’Keane,R Emerson,G O’Toole

doi:10.1186/s13569-015-0032-0

Abstract

BackgroundChemotherapy 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.Patients and methodsAdult 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.ResultsA 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.ConclusionsLong-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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13569-015-0032-0) contains supplementary material, which is available to authorized users.

Highlights

Chemotherapy in the multimodality treatment of osteosarcoma has improved survival
In this article we review the outcomes of a predominantly adult population over a 26-year period and assess the impact of switching chemotherapy to ifosfamide and etoposide (IE) in patients with
Patient population A retrospective review was undertaken of patients with a diagnosis of osteosarcoma seen by the oncology department at the Mater Misericordiae University Hospital from January 1986 to August 2012

Summary

Introduction

Chemotherapy in the multimodality treatment of osteosarcoma has improved survival. Since the incorporation of chemotherapy, multimodality treatment has improved survival to approximately 70% at 5 years with little improvement in the last two decades [4, 6, 7]. Trials demonstrating this survival have largely included paediatric patients and outcomes in adult patients alone are limited. NAC versus immediate surgery and adjuvant chemotherapy has not been shown to improve OS [6], it does allow for optimal surgical planning [9] and avoids the need for amputation in most patients. The most appropriate combination of these drugs continues to be debated [8]

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Discussion

Conclusion