Anti-Tumour Treatment
Osteosarcoma treatment – Where do we stand? A state of the art review

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Abstract

Long-term outcome for patients with high-grade osteosarcoma has improved with the addition of systemic chemotherapy, but subsequent progress has been less marked. Modern, multiagent, dose-intensive chemotherapy in conjunction with surgery achieves a 5-year event-free survival of 60–70% in extremity localized, non-metastatic disease. A major, as yet unsolved, problem is the poor prognosis for metastatic relapse or recurrence, and for patients with axial disease. This article reviews the current state of the art of systemic osteosarcoma therapy by focusing on the experiences of cooperative osteosarcoma groups. Also, we shed light on questions and challenges posed by the aggressiveness of the tumor, and we consider potential future directions that may be critical to progress in the prognosis of high-grade osteosarcoma.

Introduction

Following the implementation of chemotherapy in the 1970s, the treatment of high-grade malignant osteosarcoma (OS) has made important progress. However, survival rates continue to be unsatisfactory in the metastatic and relapse setting. Understanding OS biology still remains a complex challenge. An unknown etiology, high genetic instability of OS cells, a wide histological heterogeneity, lack of biomarkers, high local aggressiveness, and a rapid metastasizing potential create pivotal questions to be answered. The purpose of this paper is to outline recent developments in the field of osteosarcoma therapies.

Section snippets

Search strategy and selection criteria

We searched PubMed for the past 12 years (January 2001–October 2013) with the terms “osteosarcoma” and “treatment”. The abstracts were screened to identify those research studies and review articles we judged relevant to our objectives. This procedure identified 166 potentially eligible publications which were studied in detail. A particular relevance was given to reports on systemic therapy. References from these articles were also obtained, and review articles are cited to provide readers with

Background

Osteosarcoma (OS) defines neoplasms that share the histological finding of osteoid production in association with malignant mesenchymal cells. These tumors are generally locally aggressive and tend to produce early systemic metastases [1]. A distinction is generally drawn between different histologic types of OS (conventional, teleangiectatic, parosteal, periosteal, low-grade central, small cell, not otherwise specified). The conventional type is the most common, and has been subdivided based

Pediatric Oncology Group (POG) and Children’s Oncology Group (COG)

The advantages of presurgical chemotherapy include early administration of systemic chemotherapy, shrinkage of primary tumor, and pathologic identification of risk groups. The theoretic disadvantage is that it exposes a large tumor burden to marginally effective chemotherapy [50]. A randomized study of the Pediatric Oncology Group (POG 8651) compared immediate surgery with delayed surgery after induction of chemotherapy. Outcome was not significantly different between both arms, which means

European and American Osteosarcoma Study Group (EURAMOS)

EURAMOS was founded in 2001. Four trial groups (COSS, COG, EOI, and SSG) joined together to undertake the first clinical trial of EURAMOS, EURAMOS-1, which opened in 2005. The study design includes a standard preoperative therapy using MAP. Following surgery, patients were stratified according to histological response. Patients classified as good responders (⩾90% necrosis) were randomized to continue MAP or to receive MAP followed by maintenance pegylated interferon alpha (IFN-α), while poor

Conflict of interest

None declared.

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    Recipient of a non-restricted grant by Takeda GmbH.

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