Figures 15.1 and 15.2 show imaging features of osteosarcoma. Box 15.2 shows prognostic factors in osteosarcoma. An overview of management is shown in Figure 15.3.

Figure 15.1 Coronal MRI of pelvis and thighs showing osteosarcoma of the left acetabulum (arrow). Note the change in bone texture compared with the normal side.

Figure 15.2 X-ray of left knee showing characteristic features of an osteosarcoma of the medial proximal tibia with bone destruction due to an expansile lesion (arrows) and periosteal elevation (arrow head).

(Courtesy of Mr Rob Grimer, Royal National Orthopaedic Hospital, Birmingham.)

Figure 15.3 Management of osteosarcoma.

Chemotherapy

As in the adjuvant setting, the most effective agents are cisplatin, doxorubicin, methotrexate and ifosfamide (Box 15.3). Response rates are between 20–40% although some tumours and metastases may not reduce in size. Apparent calcification of lung metastases can occur (Figure 15.5). If the presentation is with metastases, combination chemotherapy should be the primary treatment.

Figure 15.5 Axial CT of chest showing pleurally based and calcified metastases characteristic of osteosarcoma (arrow). These lung metastases can bleed giving rise to bloody pleural effusions.

High-dose treatment with stem cell rescue has shown no improvement in survival. Trials are underway to evaluate biological agents such as insulin like growth factor 1 receptor (IGF1-R) antagonists. Immunotherapy may have a role and the use of liposomal muramyl tripeptide-phosphatidyl-ethanolamine has been shown to produce a survival benefit in the adjuvant setting.

Surgery

Surgery in the metastatic setting should either be aimed at palliation of symptoms, e.g. resection of a large primary extremity tumour with low volume lung metastases, or with the intention of cure, e.g. resection of lung metastases.

Radiotherapy

Although osteosarcomas are relatively radio resistant tumours, radiotherapy has been successfully used in a number of clinical situations such as to control bone pain. It has also been used in addition to chemotherapy and surgery, e.g. following resection of lung metastases some groups advocate whole lung radiotherapy in addition to chemotherapy. It may provide local control for some patients with advanced metastatic disease for whom resection of the primary is inappropriate.

Recurrent osteosarcoma

Approximately 40% of patients treated with a primary osteosarcoma will recur either locally or with metastatic disease. Management of local recurrence can involve chemotherapy, surgery or radiotherapy. Chemotherapy drugs are the same as those used for metastatic disease. Surgery may be possible but limb sparing surgery is less likely for local recurrence of extremity tumours. Radiotherapy may be useful for local control but is less effective than surgery.

Ewing’s sarcoma

Presentation

Unlike osteosarcomas which present most often in the epiphyses of long bones, Ewing’s sarcomas occur within the diaphysis and are often associated with a soft tissue mass. The soft tissue reaction may be confused for infection and contribute to delay in diagnosis. The median delay from symptoms (Box 15.1) to diagnosis is 6–9 months. The most common sites are long bones (53%) or the axial skeleton (47%). 25% have a soft tissue primary. Systemic symptoms (fever, anorexia, weight loss, and lethargy) may be present and are associated with advanced disease. 25% patients have metastases at presentation. Subclinical metastases are present in 80–90% with apparently localized disease, necessitating multimodality treatment even in apparently small volume localized disease. Prognostic factors are listed in Box 15.4.

X-ray may show a characteristic destructive lesion within the bone with surrounding periosteal reaction known as an onion skin appearance (Figure 15.6). A soft tissue reaction may also be seen on X-ray and a pathological fracture is seen in 15%. Ewing’s sarcomas, like osteosarcomas, show intense tracer uptake in bone scan (Figure 15.7). Staging is given in Table 15.1 and Figure 15.8 shows an overview of management.

Figure 15.6 X-ray of Ewing’s sarcoma of right proximal femur with destructive lesion and onion skin appearance of periosteal reaction.

Courtesy of Mr Rob Grimer.

Figure 15.7 Bone scintigram of Ewing’s sarcoma of left proximal radius showing localized uptake at the site of the tumour.

Figure 15.8 Management of Ewing’s sarcomas (VIDE – vincristine, ifosfamide, doxorubicin & etoposide; VAI – vincristine, actinomycin-D & ifosfamide; VAC – vincristine, actinomycin-D & cyclophosphamide).

Management of localized disease

Chemotherapy

Combination chemotherapy is usually given pre- and postoperatively. Alkylating agents have the highest response rate and have been combined with doxorubicin, vincristine, actinomycin D and etoposide. Trials such as IESS-III showed that alternating ifosfamide and etoposide with vincristine, doxorubicin and cyclophosphamide (VAC) improved survival from 54 to 69% in localized disease. High-dose treatment in localized low-risk disease has not been shown to improve survival. Response to chemotherapy at the time of surgery reflects prognosis.

Stratifying treatment according to risk is under investigation in the EUROEWING99 trial (Figure 15.9). Low-risk patients are randomized between standard treatment and less intense treatment. High-risk/metastatic patients are randomized between standard treatment and high-dose with stem cell rescue.