ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of osteosarcoma

G. Saeter

The Norwegian Radium Hospital, Montebello, Department of Oncology and Radiotherapy, Oslo, Norway


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The crude incidence is 0.3 cases/100 000/year. Peak incidence is in adolescence with a median age at diagnosis of 16 years. Sixty-five per cent of tumours are localised in the extremities; non-extremity tumours are more frequent in elderly patients. The mortality is ~0.15 cases/100 000/year.


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Patients with radiological findings suggesting a bone sarcoma should be referred without prior biopsy to a centre with particular bone sarcoma experience. Histological diagnosis is made by open surgical biopsy. Osteosarcoma is divided into osteoblastic, chondroblastic, fibroblastic, telangiectatic and mixed subtypes. Paraosteal osteosarcoma is a low-grade tumour arising on the bone surface.


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Prior to biopsy, the entire affected bone should be evaluated radiologically. Pulmonary metastases should be evaluated by CT scan and bone metastases should be ruled out by bone scintigraphy. Routine haematology with blood chemistry must include renal function (creatinine and glomerular filtration rate), electrolytes including Mg, transaminases, alkaline phosphatase (ALP) and LDH. If preoperative chemotherapy is given, evaluation of the primary tumour with all modalities should be repeated prior to surgery. Sperm banking should be considered.

Staging is most commonly carried out by the Enneking system, which is based on malignancy grade, extension through the bone surface and the presence of detectable metastases. Approximately 70% are in stage IIB (high-grade tumour extending into the adjacent soft tissue, but without detectable metastases).

Adverse prognostic factors include detectable metastases at diagnosis, age >40 years, non-extremity localisation, large tumour volume, elevated serum ALP or LDH and a poor histological response to preoperative chemotherapy [III, B].


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Localised tumours
Chemotherapy has significantly increased 5-year survival rates for patients with localised tumour from the 20% to the 60% range [II, A], as part of a multidisciplinary approach. Although most protocols include both pre- and postoperative chemotherapy, this has not been proven to add survival benefit over postoperative chemotherapy alone [II, C]. The evaluation of histological response after four to six courses of preoperative chemotherapy gives important prognostic information, but altering postoperative chemotherapy in poor responders has not been proven to improve outcome [IV, C].

Chemotherapy is intensive and based on combinations of doxorubicin and cisplatin, with many centres adding ifosfamide and high-dose methotrexate with leucovorin rescue for a total treatment time of 6–12 months.

In specialist centres, limb salvage procedures are performed in 80% of extremity tumours. A wide surgical margin is important to avoid local recurrence, regardless of tumour response [III, B].

Metastatic disease and recurrent disease
Metastatic disease should be treated with a combination of chemotherapy and metastasectomy, and repeated thoracotomies are often indicated. The options for second-line chemotherapy depend on the primary treatment but will often be based on high-dose methotrexate, ifosfamide and etoposide. With a limited pulmonary relapse; 40% 5-year survival may be obtained by complete surgical clearance of all metastases [IV, B].


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Patients should be followed at 3-month intervals until 3 years after the end of treatment, then at 6-month intervals until 5 years and at 8–12 month intervals until 10 years after the end of treatment. Pediatric patients should ideally be followed longer, due to long-term toxicity. Examinations must include chest radiological analyses.


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Levels of Evidence [I–V] and Grades of Recommendation [A–D] as used by the American Society of Clinical Oncology are given in square brackets. Statements without grading were considered justified standard clinical practice by the expert authors and the ESMO faculty.


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Coordinating author for the ESMO Guidelines Task Force: G. Saeter, The Norwegian Radium Hospital, Montebello, Department of Oncology and Radiotherapy, Oslo, Norway.

Approved by the ESMO Guidelines Task Force: August 2002.

Correspondence to:

ESMO Guidelines Task Force

ESMO Head Office

Via La Santa 7

CH-6962 Viganello-Lugano

Switzerland


    References
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 Staging and risk assessment
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 Literature
 References
 
1. Bramwell VH. The role of chemotherapy in the management of non-metastatic operable extremity osteosarcoma. Semin Oncol 1997; 24: 561–571.[ISI][Medline]

2. Sæter G, Bruland ØS, Follerås G et al. Extremity and non-extremity high-grade osteosarcoma. Acta Oncol 1996; 35 (Suppl 8): 129–134.

3. Picci P, Sangiorgi L, Rougraff BT et al. Relationship of chemotherapy-induced necrosis and surgical margins to local recurrence in osteosarcoma. J Clin Oncol 1994; 12: 2699–2705.[Abstract]

4. Sæter G, Høie J, Stenwig AE et al. Systemic relapse of patients with osteogenic sarcoma. Prognostic factors for long term survival. Cancer 1995; 75: 1084–1093.[ISI][Medline]