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Classic Osteosarcoma

- See:
     - Bone Tumor Menu  and Osteosarcoma Demonstration Project

- Discussion:
    - malignant tumor of bone in which neoplastic osteoid is produced by a proliferating spindle cell stroma;
    - most common primary malignant bone tumor of mesenchymal derivation;
    - arises in adolescents, and second or third decade;
    - affects males slightly more often than females.
    - affected sites:
            - occurs in region of knee (distal femur or proximal tibia) in 50% of pts;
            - other sites include proximal humerus, proximal femur, & pelvis;
            - most osteosarcomas occur in the metaphysis;
            - infrequently occurs in the spine
    - classification:
            - classic
            - telangiectatic
            - parosteal
            - periosteal

- Clinical Presentation:
     - initial symtom is a painful bony mass which hurts both day and night;
     - significant number of osteosarcomas in adults occur in assoc w/ Pagets disease;

- X-ray Studies and MRI: 
     - destructive lytic lesion
       - involves the metaphysis
     - new bone formation
     - periosteal reaction
     - visible soft-tissue mass
     - references:
             - Magnetic resonance imaging in planning limb-salvage surgery for primary malignant tumors of bone.
             - Imaging of intramedullary tumour spread in osteosarcoma. A comparison of techniques.

- Prognosis:
    - at time of dx, most osteosarcomas are stage IIb lesions that have infiltrated the soft tissue.
    - 70% of patients w/o detectable metastases will remain disease free with appropriate surgical resection and chemotherapy;
    - in 50% of adolescent pts, tumor penetrates growth plate into epiphysis.
    - metastasis:
            - metastatic spread is the single most important prognostic factor;
            - osteosarcoma tends to have early hematogenous metastasis;
            - pulmonary or lymph node metastases are detected at presentation in about 10% of patients;
            - pulmonary metastases are usually detected w/ in year after dx;
            - undetectable micrometastases are probably present in lungs of most patients at time they first seek medical attention;
            - w/o control of micrometastatic disease, there will be x-ray evidence of lung metastases in upto 80% of pts after 1-2 years;
            - following surgical resection, skip metastases are found in 25% of pts;
    - survival:
            - in the past suvival rate was around 15%, but w/ adjunctive therapy survival is greater than 50%.
            - metastatic disease evident at presentation also indicates presence of more aggressive disease & poor prognosis;
    - references

- Treatment of Classic Osteosarcoma;
    - surgery alone as a treatment yields only a 20% survival rate.
    - in contrast, non metastatic disease treated with chemotherapy and surgery, expected survival is 60-80%;
    - chemotherapy:
            - with adjuvant chemotherapy, the 5 year survival rate is > 50%;
            - some surgeons insist on preoperative chemotherapy in the management of osteosarcoma;
            - commonly used agents include doxorubicin, cisplatin, high-dose methotrexate, ifosfamide, cyclophosphamide, ifosfamide;
            - some authors recommend following serial alkaline phosphatase levels which can give a rough indication of response to
                     chemotherapy treatment;
            - good response to chemotherapy is indicated by 90% tumor necrosis on biopsy;
            - references:
                     - Neoadjuvant chemotherapy for osteosarcoma of the extremity.
                     - Neoadjuvant chemotherapy for nonmetastatic osteosarcoma of the extremities.
                     - Adjuvant chemotherapy of high-grade osteosarcoma of the extremity. Updated results of the Multi-Institutional Osteosarcoma Study.
                     - Local control and survival from the Cooperative Osteosarcoma Study Group studies of the German Society of Pediatric Oncology and the Vienna Bone Tumor Registry.
                     - Experience with multiagent chemotherapy for osteosarcoma. Improved outcome.
                     - Intraarterial cisplatin in the management of stage IIB osteosarcoma in the pediatric and adolescent age group.
                     - Impact of 2 cycles of chemo with cisplatin and doxorubicin on procedure for high-grade bone sarcomas of extremities.
                     - Adjuvant chemotherapy for osteosarcoma of the extremity. Long-term results of two consecutive prospective protocol studies.

    - limb salvage surgery does not seem to have a higher local recurrence rate than amputation;
    - limb salvage
    - relative indications for amputation:
            - associated pathologic fracture
            - tumors encasing the neurovascular bundle
            - tumors that enlarged during preoperative therapy that contact neurovascular bundle;
     - surgical resection of osteosarc pulmonary mets:
            - aggressive surgical resection will improve 5 yr surviva ratel;
            - resection of pulmonary mets, together with multiagent chemo, is assoc w/ long-term survival in about 20 percent of such pts;
            - pulmonary tumor resection requires good local disease control and no extra-pulmonary metastasis;
            - references:
    - osteosarcoma is not radiosensitive

- References:

  - references for prognostic features:
  - references for limb salvae:
  - references for chemotherapy

Medical Progress: Osteosarcoma: Fifteen Years Later.

Surgical treatment for osteosarcoma

Osteosarcoma of the spine

Limb-salvage treatment versus amputation for osteosarcoma of the distal end of the femur.

Functional performance after tibial rotationplasty.

Osteosarcomas arising on the surfaces of long bones.

Neoadjuvant chemotherapy for osteosarcoma of the extremity.

Osteosarcoma with small cells simulating Ewing's tumor.

Expression of P-glycoprotein in high grade osteosarcomas in relation to clinical outcome.

Experimental models for the study of drug resistance in osteosarcoma: P-glycoprotein positive, murine osteosarcoma cell lines.

A Comparison of Intramedullary and Juxtacortical Low-grade Osteogenic Sarcoma.

Current combined treatment of high grade osteosarcoma