Osteosarcoma

Osteosarcoma is a high grade primary malignant bone tumour in which malignant mesenchymal cells directly produce osteoid or immature bone.

It occurs most commonly in adolescents and young adults during periods of rapid skeletal growth.

Typical sites are the metaphyses of long bones, particularly:

• Distal femur
• Proximal tibia
• Proximal humerus

In older adults, osteosarcoma can arise secondary to:

• Paget disease
• Previous radiotherapy
• Preexisting abnormal bone

Conventional high grade intramedullary osteosarcoma is the dominant form.

Clinically relevant variants include:

• Conventional osteoblastic, chondroblastic or fibroblastic osteosarcoma
• Telangiectatic osteosarcoma
• Parosteal osteosarcoma, generally low grade
• Periosteal osteosarcoma, usually intermediate grade
• High grade surface osteosarcoma

The key staging distinction is localised versus metastatic disease.

The lungs are the commonest site of metastasis.

Typical presentation is progressive localised bone pain.

Pain may initially be activity related but becomes:

• Persistent
• Nocturnal
• Present at rest

A firm enlarging mass may develop.

Joint movement can become restricted when the tumour approaches a joint.

A pathological fracture can occur but is not the commonest presentation.

Do not repeatedly treat persistent focal bone pain in an adolescent as a sports injury when symptoms are progressive or associated with swelling.

Plain radiograph: first investigation; an aggressive metaphyseal destructive lesion with osteoid matrix and aggressive periosteal response should trigger urgent sarcoma referral.

MRI of the entire involved bone and adjacent joint: define intramedullary extent, soft tissue extension, neurovascular relationship and skip lesions.

CT chest: mandatory for pulmonary metastatic staging.

PET CT or bone scintigraphy can evaluate distant skeletal disease according to the treatment protocol.

Biopsy principle

Complete imaging and staging before biopsy.

Biopsy should be performed by, or planned with, the sarcoma surgeon who will undertake definitive resection.

The biopsy tract must:

• Pass directly through tissue that will be removed during definitive surgery
• Avoid crossing uninvolved anatomical compartments
• Avoid contaminating neurovascular structures
• Avoid transverse incisions that compromise future limb salvage

Core needle biopsy is usually sufficient.

An improperly planned biopsy can contaminate tissues that would otherwise have been preserved.

Treatment requires systemic chemotherapy plus complete surgical resection for conventional high grade osteosarcoma.

Neoadjuvant chemotherapy

A major reference regimen in children, adolescents and young adults is MAP:

Methotrexate

12 g/m² IV over approximately 4 hours

with:

• Aggressive IV hydration
• Urine alkalinisation
• Serial serum methotrexate concentrations
• Leucovorin rescue adjusted according to methotrexate clearance

Doxorubicin

37.5 mg/m² IV daily on days 1 and 2

Total 75 mg/m² per course.

Cisplatin

60 mg/m² IV daily on days 1 and 2

Total 120 mg/m² per course.

High dose methotrexate must only be delivered where therapeutic drug monitoring, leucovorin rescue, renal monitoring and intensive supportive care are available.

Monitor:

• Renal function
• Liver function
• Blood counts
• Cardiac function with anthracycline exposure
• Hearing with cisplatin

Surgery

Definitive resection usually follows neoadjuvant chemotherapy.

The objective is an R0 wide resection with an intact tumour specimen.

Do not enter the tumour.

Do not dissect directly along the pseudocapsule.

Remove:

• Tumour
• Biopsy tract
• Contaminated tissues

with an adequate cuff of normal tissue.

Limb salvage

Limb salvage is preferred when an oncologically adequate margin can be achieved while maintaining a useful functional extremity.

Reconstruction options include:

• Modular endoprosthetic replacement
• Biological allograft
• Autograft
• Allograft prosthetic composite
• Rotationplasty in selected children
• Vascularised fibular reconstruction in selected anatomical sites

Preservation of a limb is inappropriate if obtaining a safe margin would leave a nonfunctional extremity or uncontrollable tumour contamination.

Amputation

Indications include selected cases with:

• Major unreconstructible neurovascular involvement
• Extensive contamination
• Infection preventing safe tumour reconstruction
• Nonfunctional limb after required resection
• Recurrence unsuitable for further limb salvage

Histological response

The resected tumour is assessed for chemotherapy induced necrosis.

At least approximately 90% tumour necrosis represents a favourable histological response and is prognostically important.

A poor response does not justify arbitrary escalation to more toxic therapy. Adding ifosfamide and etoposide to postoperative MAP for poor responders did not improve outcome sufficiently to establish it as routine therapy.

Postoperative chemotherapy

Continue systemic chemotherapy after recovery from surgery according to the established protocol.

Do not omit postoperative systemic treatment merely because the tumour has been completely resected.

Pulmonary metastases

Patients with isolated resectable lung metastases can still be treated with curative intent.

Complete surgical resection of all detectable pulmonary disease is important when technically feasible.

Repeated pulmonary metastasectomy may be appropriate in carefully selected recurrent disease.

Radiotherapy

Conventional osteosarcoma is relatively radioresistant.

Radiotherapy has a limited role, including:

• Unresectable disease
• Positive margins when further surgery is impossible
• Palliation
• Selected axial tumours

Follow up

Surveillance must focus particularly on:

• Pulmonary metastasis
• Local recurrence
• Reconstruction failure
• Chemotherapy cardiotoxicity
• Cisplatin ototoxicity and renal toxicity
• Second malignancy