Osteosarcoma

Osteosarcoma (also known as osteogenic sarcoma) is the most common primary malignant bone tumor, characterized by the production of osteoid (immature bone) by malignant mesenchymal cells. It predominantly affects children, adolescents, and young adults, with a second smaller peak of incidence in older adults over 60 years of age. The tumor most frequently arises in the metaphyseal regions of long bones, particularly around the knee (distal femur and proximal tibia) and the proximal humerus, though it can occur in any bone. Key symptoms include localized bone pain that may worsen at night or with activity, swelling or a palpable mass near the affected bone, limited range of motion in the adjacent joint, and occasionally pathologic fracture. Systemic symptoms such as fatigue and weight loss may occur, particularly in advanced disease. Approximately 15-20% of patients present with detectable metastases at diagnosis, most commonly to the lungs. The majority of osteosarcoma cases are sporadic, but certain hereditary cancer predisposition syndromes significantly increase risk. These include Li-Fraumeni syndrome (TP53 germline mutations), hereditary retinoblastoma (RB1 mutations), Rothmund-Thomson syndrome (RECQL4 mutations), Werner syndrome, and Bloom syndrome. Paget disease of bone and prior radiation therapy are recognized risk factors, particularly for osteosarcoma arising in older adults. The pathogenesis involves complex chromosomal abnormalities and genomic instability rather than a single driver mutation in most sporadic cases. The current standard of care for osteosarcoma involves a multimodal approach combining neoadjuvant (pre-surgical) chemotherapy, surgical resection of the primary tumor with wide margins, and adjuvant (post-surgical) chemotherapy. The most commonly used chemotherapeutic agents include high-dose methotrexate, doxorubicin, cisplatin, and ifosfamide (often referred to as the MAP regimen). Limb-salvage surgery has largely replaced amputation for most patients, with comparable oncologic outcomes. The five-year survival rate for localized disease is approximately 60-70%, but drops significantly to 20-30% for patients with metastatic or recurrent disease. Osteosarcoma is notably resistant to conventional radiation therapy. Research into targeted therapies, immunotherapy, and novel drug combinations is ongoing, though no major breakthrough has substantially changed survival outcomes in the past several decades.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Osteosarcoma