Osteosarcoma

Osteosarcoma

Osteosarcoma is a cancerous tumor in a bone. Specifically, it is an aggressive malignant neoplasm that arises from primitive transformed cells of mesenchymal origin (and thus a sarcoma) and that exhibits osteoblastic differentiation and produces malignantosteoid.

Osteosarcoma is the most common histological form of primary bone cancer. It is most prevalent in children and young adults.

Signs and symptoms

Many patients first complain of pain that may be worse at night, and may have been occurring for some time. Also, teenagers who are active in sports tend to complain about pain in their lower femur, or right below the knee. If the tumor is large, it can appear as a swelling. Sometimes a sudden fracture of bone is the first symptom because affected bone is not as strong as normal bones and may fracture with minor trauma (a pathological fracture). According to Bone Cancer Research Trust, the pain may come and go and vary in intensity. The swelling will not be visible if it is not near the surface of the body such as on the pelvis.

Causes

Several research groups are investigating cancer stem cells and their potential to cause tumors. Radiotherapy for unrelated conditions may be a rare cause.

·         Familial cases where the deletion of chromosome '13q14' inactivates the retinoblastoma gene is associated with a high risk of osteosarcoma development.

·         Bone dysplasias, including Paget's disease, fibrous dysplasia, enchondromatosis, and hereditary multiple exostoses, increase the risk of osteosarcoma.

·         Li–Fraumeni syndrome (germline TP53 mutation) is a predisposing factor for osteosarcoma development.

·         Rothmund–Thomson syndrome (i.e. autosomal recessive association of congenital bone defects, hair and skin dysplasias, hypogonadism, and cataracts) is associated with increased risk of this disease.

Diagnosis

Family physicians and orthopedists rarely see a malignant bone tumor (most bone tumors are benign). 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. A characteristic often seen in an X-ray is Codman's triangle, which is basically a subperiosteal lesion formed when the periosteum is raised due to the tumor. 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." It may also metastasise to the lungs, mainly appearing on the chest X-ray as solitary or multiple round nodules most common at the lower regions.

 

Variants

·         Conventional: osteoblastic, chondroblastic, fibroblastic OS

·         Telangiectatic OS

·         Small cell OS

·         Low-grade central OS

·         Periosteal OS

·         Paraosteal OS

·         Secondary OS

·         High-grade surface OS

·         Extraskeletal OS

Treatment

A complete radical, surgical, en bloc resection of the cancer, is the treatment of choice in osteosarcoma. Although about 90% of patients are able to have limb-salvage surgery, complications, particularly infection, prosthetic loosening and non-union, or local tumor recurrence may cause the need for further surgery or amputation.

Mifamurtide is used after a patient has had surgery to remove the tumor and together with chemotherapy to kill remaining cancer cells to reduce the risk of cancer recurrence. Also, the option to have rotationplasty after the tumor is taken out exists.

Patients with osteosarcoma are best managed by a medical oncologist and an orthopedic oncologist experienced in managing sarcomas. Current standard treatment is to useneoadjuvant 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 regimen 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 leucovorinrescue, intra-arterial cisplatin, adriamycin, ifosfamide with mesna, BCD (bleomycin, cyclophosphamide, dactinomycin), etoposide, and muramyl tripeptide. Rotationplasty 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 arteriographic 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 antiemetic drugs (such as the 5-HT₃ receptor antagonists e.g. granisetron and ondansetron) help with nausea and vomiting. Filgrastim orpegfilgrastim help with white blood cell counts and neutrophil counts. Blood transfusions and epoetin alfa help with anemia.