Osteosarcoma

What is Osteosarcoma?

Osteosarcoma is the second most common primary malignancy of bone behind multiple myeloma. Osteosarcoma accounts for 20% of primary bone malignancies. There is a preference for the metaphyseal region of tubular long bones. 50% of cases occur around the knee. It is a malignant connective (soft) tissue tumor whose neoplastic cells present osteoblastic differentiation and form tumoral bone.

Osteogenic Sarcoma is the 6th leading cancer in children under age 15. Osteogenic Sarcoma affects 400 children under age 20 and 500 adults (most between the ages of 15-30) every year in the USA. Approximately 1/3 of the 900 will die each year, or about 300 a year. A second peak in incidence occurs in the elderly, usually associated with an underlying bone pathology such as Paget's disease, medullary infarct, or prior irradiation. Although about 90% of patients are able to have limb-salvage surgery, complications, such as infection, prosthetic loosening and non-union, or local tumor recurrence may cause the need for further surgery or amputation.

Causes

The causes of osteosarcoma are not known. Several research groups are investigating cancer stem cells and their potential to cause tumors. The connection between osteosarcoma and fluoride has been investigated; there is no clear association between water fluoridation and deaths due to osteosarcoma.

Symptoms

Many patients first complain of pain that may be worse at night, and may have been occurring for some time. If the tumor is large, it can appear as a swelling. The affected bone is not as strong as normal bones and may fracture with minor trauma (a pathological fracture).

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Osteosarcoma Pathology

The tumor may be localized at the end of the long bones. Most often it affects the upper end of tibia or humerus, or lower end of femur. Osteosarcoma tends to affect regions around the knee in 60% of cases, 15% around the hip, 10% at the shoulder, and 8% in the jaw. The tumor is solid, hard, irregular ("fir-tree," "moth-eaten" or "sun-burst" appearance on X-ray examination) due to the tumor spicules of calcified bone radiating in right angles. These right angles form what is known as Codman's triangle. Surrounding tissues are infiltrated.

Microscopically: The characteristic feature of osteosarcoma is presence of osteoid (bone formation) within the tumour. Tumor cells are very pleomorphic (anaplastic), some are giant, numerous atypical mitoses. These cells produce osteoid describing irregular trabeculae (amorphous, eosinophilic/pink) with or without central calcification (hematoxylinophilic/blue, granular) - tumor bone. Tumor cells are included in the osteoid matrix. Depending on the features of the tumour cells present (whether they resemble bone cells, cartilage cells or fibroblast cells), the tumour can be subclassified. Osteosarcomas may exhibit multinucleated osteoclast-like giant cells.

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Osteosarcoma Diagnosis

Family physicians and orthopedists rarely see a malignant bone tumor (most bone tumors are benign). Thus, many patients are initially misdiagnosed with cysts or muscle problems, and some are sent straight to physical therapy without an x-ray.

The route to osteosarcoma diagnosis usually begins with an x-ray, continues with a combination of scans (CT scan, PET scan, bone scan, MRI) and ends with a surgical biopsy. Films are suggestive, but bone biopsy is the only definitive method to determine whether a tumor is malignant or benign.

The biopsy of suspected osteosarcoma should be performed by a qualified orthopedic oncologist. The American Cancer Society states: "Probably in no other cancer is it as important to perform this procedure properly. An improperly performed biopsy may make it difficult to save the affected limb from amputation."

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Osteosarcoma Treatment

Patients with osteosarcoma are best managed by a medical oncologist and an orthopedic oncologist experienced in managing sarcomas. Current standard treatment is to use neoadjuvant chemotherapy (chemotherapy given before surgery) followed by surgical resection. The percentage of tumor cell necrosis (cell death) seen in the tumor after surgery gives an idea of the prognosis and also lets the oncologist know if the chemotherapy regime should be altered after surgery.

Standard therapy is a combination of limb-salvage orthopedic surgery when possible (or amputation in some cases) and a combination of high dose methotrexate with leucovorin rescue, intra-arterial cisplatin, adriamycin, ifosfamide with mesna, BCD, etoposide, muramyl tri-peptite (MTP). Rotationplasty is also another surgical technique that may be used. Ifosfamide can be used as an adjuvant treatment if the necrosis rate is low.

Despite the success of chemotherapy for osteosarcoma, it has one of the lowest survival rates for pediatric cancer. The best reported 10-year survival rate is 92%; the protocol used is an aggressive intra-arterial regimen that individualizes therapy based on ateriographic response. Three-year event free survival ranges from 50% to 75%, and five-year survival ranges from 60% to 85+% in some studies. Overall, 65-70% patients treated five years ago will be alive today . These survival rates are overall averages and vary greatly depending on the individual necrosis rate.

Fluids are given for hydration, while drugs like Kytril and Zofran help with nausea and vomiting. Neupogen, epogen, Neulasta help with white blood cell counts and neutrophil counts. Blood transfusion helps with anemia.

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Osteosarcoma Prognosis

Prognosis is separated into three groups.

  • Stage I osteosarcoma is rare and includes parosteal osteosarcoma or low-grade central osteosarcoma. It has an excellent prognosis (>90%) with wide resection.
  • Stage IIb prognosis depends on the site of the tumor (proximal tibia, femur, pelvis, etc.) size of the tumor mass (in cm.), and the degree of necrosis from neoadjuvant chemotherapy (chemotherapy prior to surgery). Other pathological factors such as the degree of p-glycoprotein, whether the tumor is cxcr4-positive , or Her2-positive are also important, as these are associated with distant metastases to the lung. The prognosis for patients with metastatic osteosarcoma improves with longer times to metastases, (more than 12 months-24 months), a smaller number of metastases (and their resectability). It is better to have fewer metastases than longer time to metastases. Those with a longer length of time(>24months) and few nodules (2 or fewer) have the best prognosis with a 2-year survival after the metastases of 50% 5-year of 40% and 10 year 20%. If metastases are both local and regional, the prognosis is worse.
  • Initial Presentation of stage III osteosarcoma with lung metastates depends on the resectability of the primary tumor and lung nodules, degree of necrosis of the primary tumor, and maybe the number of metastases. Overall prognosis is about 30% .

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