Osteosarcoma occurs in adolescents and young adults (10-20 years of age) and accounts for approximately 5% of childhood tumors. Osteosarcoma grows locally aggressively and is prone to metastasis. Historically, osteosarcoma has been evaluated and treated with radiographs, chest x-rays and amputations. Only 10-20% of patients treated in this way have survived long term. In the past 20 years, tremendous progress has been made in the diagnosis and treatment of osteosarcoma. The use of advanced imaging techniques (CT and MRI) can clearly show the local anatomy and growth pattern of the tumor. Spiral CT scanning of the chest is very sensitive in detecting occult lung metastases. Also, a modified grading system helps to determine the prognosis of patients. Multi-drug combination chemotherapy has greatly improved the long-term survival rate and the possibility of limb-sparing surgery. The most common complaint of patients with osteosarcoma is pain and swelling over a short period of time. By the time osteosarcoma is diagnosed, the patient’s symptoms have often lasted for several months (usually 3-4 months, but often more than 6 months). If the diagnosis is delayed, the skin on the surface of the tumor may be taut due to tumor swelling and superficial venous filling may be evident. Pathologic fractures most often occur after excisional biopsy. Laboratory tests are generally normal, except for a possible increase in ESR and elevated serum alkaline phosphatase (AKP) and lactate dehydrogenase (LDH). Osteosarcoma can occur in any bone, but usually occurs in the epiphysis of long bones. The knee is the most commonly affected site, accounting for about 50% of all sites, and about half of all osteosarcomas occur in the femur, followed by the tibia, humerus, pelvis, jaws, fibula, and ribs. 15% to 20% of patients have radiographically visible metastases at the time of presentation. However, approximately 80% of limited osteosarcomas develop metastases after surgical resection, so it is assumed that virtually all patients with osteosarcoma have subclinical micro-metastases. The most common site of metastasis is the lung. 2. Epidemiology Osteosarcoma accounts for 20% of primary malignant bone tumors and is second only to multiple myeloma in terms of incidence. The age distribution of patients with osteosarcoma has two peaks, the first one is between 10 and 20 years old (during the rapid growth and development of adolescents, the peak age is 16 years old for females and 18 years old for males). The second peak is in older adults. There are slightly more males than females. When a bone lesion is considered to be a possible osteosarcoma, the first step is to perform a plain radiograph (including both directions of projection) (the entire length of the lesion should be photographed frontally and laterally to avoid missing the diagnosis). Further imaging should include CT or MRI of the lesion to evaluate the extent of the bone and soft tissue involved in the tumor. CT has become the imaging modality of choice for the detection of pulmonary metastases, as MRI is superior to CT in showing soft tissue invasion. Puncture biopsy has some limitations and drawbacks. The puncture site must be located at the site of the final surgical incision line so that the needle tract can be removed during the final surgery. The most widely used staging system is the surgical staging system proposed by Enneking, which has a good correlation with the prognosis of the tumor. This system is based on the histologic grade of the tumor (low-grade malignant: stage I; highly malignant: stage II) and the local anatomic extent (A: intra-ventricular; B: extra-ventricular). Because most highly malignant osteosarcomas break through the bone cortex early in their natural course. In young patients, the vast majority of osteosarcomas are highly malignant, so virtually all young patients are stage IIB or III (depending on the presence or absence of metastases). Prior to the 1970s, osteosarcoma was treated by amputation or high-dose radiation therapy alone. In the 1970s, several studies of uncontrolled adjuvant chemotherapy regimens using adriamycin, methotrexate, and cisplatin after removal of the tumor or amputation were conducted and showed a tumor-free survival rate of 35% to 60%. Meanwhile, in two other randomized controlled studies at the time, patients treated with adjuvant chemotherapy had significantly better tumor-free survival and overall survival compared to patients treated without chemotherapy, with rates of (55%-63%):(12%-20%) and (71%-80%):48%, respectively. These studies are the basis for modern chemotherapy for osteosarcoma. Chemotherapy for osteosarcoma of the non-metastatic limb: Adjuvant chemotherapy: Adriamycin, cisplatin, high-dose MTX and more recently IFO are the most commonly used agents in osteosarcoma chemotherapy and have been extensively studied. When these drugs are used alone, the response rate is only close to 30%, whereas when combined with high doses of these drugs, a synergistic effect can be achieved, potentially leading to 100% tumor necrosis in vivo. The use of adjuvant drugs ensures the safe use of high doses of chemotherapeutic agents and more potent combinations, including: granulocyte colony-stimulating factor (G2CSF), erythropoietin (EPO), mesna (which prevents IFO-induced hemorrhagic cystitis), antiemetics, calcium formyl tetrahydrofolate (a folic acid analogue used to counteract MTX), dexrazoxane (a folic acid analogue used to counteract MTX), and dexrazoxane (a folic acid analogue used to counteract MTX). dexrazoxane (a cardioprotective agent, used in combination with adriamycin). Most current multidrug high-dose chemotherapy regimens have been reported to have a 5-year tumor-free survival rate of about 65%.