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Chemotherapy and radiation therapy in the management of osteosarcoma

Authors
Katherine A Janeway, MD
Robert Maki, MD, PhD
Section Editors
Alberto S Pappo, MD
Thomas F DeLaney, MD
Deputy Editor
Diane MF Savarese, MD

INTRODUCTION

Osteosarcomas are primary malignant tumors of bone that are characterized by the production of osteoid or immature bone by the malignant cells. Osteosarcomas are uncommon; approximately 750 to 900 cases are diagnosed each year in the United States, of which 400 are in children and adolescents under the age of 20 [1,2]. (See "Osteosarcoma: Epidemiology, pathogenesis, clinical presentation, diagnosis, and histology".)

This topic review will cover the use of adjuvant and neoadjuvant chemotherapy and radiation therapy (RT) in the management of osteosarcoma. The same principles apply to other primary bone tumors, such as fibrosarcoma and undifferentiated high-grade pleomorphic sarcoma (previously referred to as malignant fibrous histiocytoma of bone), and they are treated similarly [3,4]. On the other hand, primary bone angiosarcomas do not behave clinically like other primary bone tumors, and these patients are treated according to the principles of soft tissue sarcoma rather than osteosarcoma. (See "Local treatment for primary soft tissue sarcoma of the extremities and chest wall" and "Adjuvant and neoadjuvant chemotherapy for soft tissue sarcoma of the extremities".)

The surgical management of patients with primary bone tumors, the clinical features, epidemiology, diagnosis, pathology, and pathogenesis of osteosarcoma, the management of osteosarcomas arising in the head and neck, the management of chondrosarcomas in general and of chordomas and chondrosarcomas arising in the skull base, and the treatment of Ewing sarcoma are addressed separately. (See "Bone sarcomas: Preoperative evaluation, histologic classification, and principles of surgical management" and "Osteosarcoma: Epidemiology, pathogenesis, clinical presentation, diagnosis, and histology" and "Head and neck sarcomas", section on 'Osteosarcoma' and "Chondrosarcoma" and "Chordoma and chondrosarcoma of the skull base" and "Treatment of the Ewing sarcoma family of tumors".)

Rarely, osteosarcomas can occur in soft tissue. There are conflicting data on their management as soft tissue sarcomas or osteosarcoma of bone [5,6]. These tumors are treated as soft tissue sarcomas at some institutions, with surgery and radiation alone or surgery, radiation, and soft tissue-based chemotherapy. At other institutions, they are treated as osteogenic sarcomas, with surgery, radiation, and doxorubicin plus cisplatin with or without methotrexate. The choice of chemotherapy is best determined by the availability of clinical trials and, otherwise, is decided on a patient-by-patient basis, balancing the risks and benefits of chemotherapy for this high-risk diagnosis.

PROGNOSIS AND EVOLUTION OF TREATMENT

The survival of patients with malignant bone sarcomas has improved dramatically over the past 40 years, largely as a result of the use of effective chemotherapy. Before the routine use of systemic therapy for conventional osteosarcoma, 80 to 90 percent of patients developed metastases, despite achieving local tumor control, and died of their disease. It was surmised (and subsequently demonstrated [7]) that subclinical metastatic disease was present at the time of diagnosis in the majority of patients and that chemotherapy can successfully eradicate these deposits if initiated at a time when disease burden is low. The benefits of chemotherapy are best illustrated by a systematic review of the literature, which showed that long-term survival after local tumor control without chemotherapy was only 16 percent (95% CI 9-23 percent) [8]. In contrast, the addition of systemic chemotherapy with three or more drugs provided a five-year overall survival rate of 70 percent.

                                   

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