Malignant bone tumours are rare, accounting for only 0.2% of all new cancers. Osteosarcoma is the commonest primary bone tumour and occurs predominantly in adolescence with a peak incidence coinciding with the growth spurt. Cases occurring over the age of 40 years are usually associated with:
♦ Irradiated bone
♦ Multiple hereditary exostosis
♦ Polyostotic fibrous dysplasia
The majority of tumours arise in the region of the metaphysis, most commonly in the tibia close to the knee joint. Other long bones may be involved, but presentation in the axial skeleton is relatively rare. Pain at the site of the tumour, often with overlying erythema and tenderness, is the usual mode of presentation. More rarely, fracture through a tumour site can occur. Serum alkaline phosphatase is elevated in 50% of cases.
Osteosarcomas are composed of malignant spindle cells and osteoblasts that produce osteoid or immature bone. The 'classic' subtype is a central medullary tumour but rarer types with a better prognosis exist— parosteal, periosteal, and low-grade intra-osseous osteosarcoma.
Plain X-rays of the affected area are usually sufficient to make a diagnosis of osteosarcoma. The classic features of osteosarcoma are:
♦ Poorly delineated or absent margins around the bone lesion
♦ Bone destruction
♦ New bone formation with calcification of the matrix
♦ Periosteal reaction, usually non-continuous and thin, with multiple laminations
Note: histological confirmation of the radiological diagnosis must be deferred until the patient is assessed by a surgeon with expertise in the management of bone malignancies.
Bone tumours disseminate almost exclusively via the bloodstream. Lymph node metastasis is rare (less than 5% of patients) and, if pre sent, represents a very poor prognosis. Metastases may be within the same bone (skip lesions) or to other organs, most commonly the lungs.
Several staging systems exist, the most commonly used being that described by Enneking. This stages patients from Ia-III. The stage is derived from a combination of the histological grade of the tumour, the presence or absence of distant metastases, and the extent of local spread of disease.
Surgical resection (usually amputation of a limb) alone was used to treat osteosarcomas until the 1970s. Overall survival was only 15-20%, largely because of the development of pulmonary metastases. Subsequent use of chemotherapy in the adjuvant (post-operative) or neo-adjuvant (pre- and post-operative) setting has improved the survival rate to 55-80%. Surgical management has also improved in the past 20 years, with amputation being replaced in the majority of patients by limb-sparing surgery.
When plain radiology suggests an osteosarcoma, staging should be performed prior to biopsy. Investigations include:
♦ Bone scan—determines multiple sites of involvement and provides a guide to the intra-osseous extension of disease.
♦ CT scanning of bone—this allows accurate determination of intra-and extra-osseous extension of disease. The entire bone and adjacent joint should be imaged and contrast used to identify vascular structures.
♦ MRI of bone—this provides excellent contrast discrimination and is particularly valuable for imaging the medullary marrow. It is the most useful method for detecting skip metastases.
♦ Angiography—this is used when limb-sparing procedures are planned to determine individual vascular patterns before resection. It is especially valuable in proximal tibial lesions.
♦ Biopsy—biopsies of suspected osteosarcomas must be performed by orthopaedic specialists with experience of this technique. Ideally, the biopsy should be performed by the surgeon who will undertake the definitive resection. Trephine or core biopsy is recommended. It must be assumed that there is potential tumour contamination of all tissue planes and compartments traversed by the biopsy needle. The site of biopsy must be carefully chosen as it will have to be removed en bloc during definitive resection. An incorrectly sited biopsy may necessitate amputation instead of limb-sparing surgery. Frozen section should be obtained during the biopsy to ensure that the tumour has been obtained. Clearance biopsies are normally taken during this procedure.
♦ CT scan of the thorax—to detect pulmonary metastases.
Sarcomas grow radially and produce a pseudo-capsule. The tumour invariably spreads through the capsule and expert surgery is necessary to ensure an adequate resection margin to remove all locally viable tumour. While previously amputation was almost always necessary, approximately 80% of osteosarcomas are now treated successfully with limb-sparing techniques. A wide variety of endo-prosthetic devices are available including extendable prostheses for growing children.
The outcome for patients with osteosarcomas has been markedly improved with the addition of chemotherapy to surgery. The most active agents are doxorubicin, cisplatin, ifosfamide, and high-dose methotrexate. Chemotherapy may be given pre-operatively and post-operatively (neo-adjuvant treatment). This has several potential benefits:
♦ Treatment starts without delay before surgery (time is taken obtaining a customized endoprosthesis).
♦ The bulk of viable tumour is reduced and thus, perhaps, the risk of dissemination of tumour at surgery.
♦ Reduction of tumour volume makes surgery technically simpler.
♦ It allows assessment of the pathological response to chemotherapy when examining the definitive resection specimen.
On the other hand, this approach delays the time of resection in patients who do not respond to chemotherapy. Post-operative adjuvant chemotherapy may be used instead with the advantages that only microscopic disease, if any, remains, and definitive local treatment with surgery is not delayed.
Clearly, pathological response to chemotherapy cannot be assessed and alternative regimens cannot therefore be considered in those failing to respond to first-line chemotherapy. The optimum regimen has not been defined and, wherever possible, patients with this rare tumour are included in clinical trials.
Osteosarcomas are relatively radio-resistant. Radiotherapy is rarely used in the primary treatment of this disease. Its use is limited to the palliative care of patients who refuse surgery, have lesions in axial sites which are not resectable, or have bone metastases.
The majority of patients developing recurrent disease will have pulmonary metastases. Up to 30% may be salvaged with surgical resection of the metastases. Metastasectomy may be considered on several occasions. Local recurrences are managed with surgical resection or palliative irradiation. The role of chemotherapy in relapsed disease is uncertain but patients with lung metastases at presentation undoubtedly benefit from combined modality treatment, and a few will be long-term survivors after chemotherapy and surgery for both the primary and residual metastases.
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