Osteosarcoma

Osteosarcoma is the most common primary bone sarcoma affecting children and adolescents. It arises primarily from aggressive bone producing spindle cells.

What is Cause?

The etiology of osteosarcoma is unknown.

Various risk factors have been identified such as:

  • Age (growth spurt period, 10 to 30 years)
  • As a secondary tumor of bone related to Paget’s disease
  • Multiple osteochondromatosis
  • Radiation induced
  • Certain hereditary syndromes like Li-fraumeni syndrome (p53 gene), Retinoblastoma (Rb gene), Rothmund Thomson syndrome, Bloom syndrome, Werner syndrome and Diamond-blackfan anemia.

How is Osteosarcoma identified?

An individual affected by osteosarcoma presents with dull aching pain in involved region and seeks attention following trivial trauma or strenuous exercise for duration of 3 to 6 months. Pain at rest is an important indicator.

Loss of weight and appetite follow. The most common areas affected are metaphysis area of long bones especially around knee (nearly 50 %) and shoulder joint followed by pelvis and spine region.

How to know the extent & spread of Osteosarcoma in the body?

The individual suspected of having osteosarcoma is then evaluated with full physical examination, plain radiographs, MRI or CT scan followed by Biopsy (Needle biopsy) of involved region to confirm the diagnosis. Upon confirmation of Osteosarcoma by Pathologist (osteoblastic variety is commoner, followed by chondroblastic, fibroblastic and rarely telangiectatic and small cell variant according to WHO), a PET-CT (whole body) is performed to stage the disease (Enneking) and identify metastasis elsewhere in the body. The most common presentation (80%) is of primary site involvement without any distant or local metastasis. Due to its aggressive nature, distant metastases (most commonly in lungs) can be identified in 15 to 20 % of individuals at time of presentation or diagnosis. The work up is then discussed in a multi-disciplinary committee and treatment is individualized according to stage of sarcoma.

How is Osteosarcoma treated?

The treatment of osteosarcoma is multidisciplinary involving Medical Oncologist, Orthopaedic Oncosurgeon and infrequently Radiation Oncologist.

The historical treatment of osteosarcoma with surgery alone (amputation) or radiotherapy provided survival rates of 15-20 %.

After advent of chemotherapy and limb salvage surgery (1980 onwards), the rates of survival has increased to 65-74 % (5 years survival rate).

Does osteosarcoma require Neo-adjuvant chemotherapy?

Neoadjuvant chemotherapy is provided after staging for 3-4 cycles for 8-12 weeks(depending on the chemotherapy protocol i.e. cisplatin, doxorubicin and infrequently high dose methotrexate), followed by repeat MRI of involved region and CT scan of Thorax which helps evaluate the response to chemotherapy.

The individual after completion of chemotherapy will undergo definitive procedure (limb salvage surgery in majority of situations).

Parosteal type of osteosarcoma require no chemotherapy or radiotherapy and surgical removal of tumor is adequate whereas periosteal osteosarcoma require postoperative adjuvant chemotherapy to achieve complete cure.

How is Limb Salvage possible in Osteosarcoma?

Certain bones in our body are expendable and do not require any further reconstructive or salvage procedures like clavicle, rib, scapula, sternum, distal ulna and ilium. The disease can be removed or excised safely with adequate normal tissue margins. Limb salvage surgery is performed around knee, shoulder, wrist and hip joint, further individualized depending on the bone involved, extent of tumor, segment of bone remaining, age of individual and finally stage of disease. The two most important components of limb salvage surgery are surgical excision of primary tumor and Reconstruction of defect. The primary tumor is removed with adequate surrounding normal tissue margins always.

Reconstruction of the resultant defect is tackled by different reconstructive options due to complexity of musculoskeletal system. These are Bone Grafts (Autologous or Allogeneic) which can be segmental (intercalary) or osteoarticular aided with implants, Metallic Endoprosthesis (Megaprosthesis), Allograft-Prosthesis Composite (APC), Extracorporeal radiation and Re-implantation (ECRT), Vascularized fibula construct  and Allograft resurfacing.

In children and adolescents who have tumor involving growth plate and residual growth remaining, an APC or Expandable Endoprosthesis (invasive or non-invasive) are performed.

In individuals who have attained skeletal maturity, most common options are adult endoprosthesis and reconstruction using different modes of Bone grafts as outlined above. In case of involvement of shaft or diaphysis of long bones and pelvis, the removed tumor bone can be irradiated and reimplanted or substituted with allograft. This aspect is complex and beyond scope of this article, to summarize it is individualized to obtain maximum functionality.

Does osteosarcoma require post-operative adjuvant chemotherapy?

After removal of primary tumor and reconstruction, Adjuvant chemotherapy is provided (4-6 cycles) based on the pathological estimation of necrosis secondary to chemotherapy and clinical assessment of individual. This multi agent chemotherapy regimen may be altered in presence of either evidence of low necrosis percentage to chemotherapy or occurrence of distant metastasis.

What are the rehabilitation steps involved post limb salvage?

Rehabilitation post-surgery is dependent on the type of limb salvage. In case of bone graft reconstruction or APC, the involved limb is protected from bearing load or weight for duration of 6 – 9 months to allow sufficient healing and bone graft incorporation. When endoprosthesis reconstruction is performed in pelvis and lower limbs, protected weight bearing and walking is allowed from the second postoperative day.

How often should I visit the doctor?

The individual is followed up every 3 months for the first 2 years, followed by 6 months every 3 years (aggressive monitoring of the patient until 5 years).

An individual who does not have any adverse events such as distant metastases or local recurrence during 5 years from time of occurrence of primary tumor have 5 year survival rate of 65 – 75 %.

Can osteosarcoma reappear in the body?

Osteosarcoma can appear in the individual even after complete removal of tumor and process or completion of chemotherapy. They are defined as Distant or local metastases and Local recurrence.

In the situation of Lung metastases, if they are small in size and less in number they can be removed safely via thoracotomy or thoracoscopy during any stage of treatment. The treatment may be altered in case of widespread lung metastases. Distant metastases occurring in bone or soft tissue can also be considered for removal depending on extent of spread.

Local recurrence is the reappearance of tumor around area of initial excised primary tumor. This can occur in the bone or surrounding soft tissues and the characteristics of local recurrence help decide if they can be removed surgically with adequate margins.

Appearance of either distant lung and bone metastasis or local recurrence can affect survival. With aggressive treatment of lung metastases, nearly 40-45 % of such individuals survive for more than 5 years after relapse. But, the survival is reduced to 15-20 % post removal of local recurrence.

Does amputation still have a role in Osteosarcoma?

Amputation was the most common procedure performed before 1980’s to clear the body of tumor burden, but is used sparingly in specific indications currently.

Indications for amputation are:

  • Large size of primary tumor with fungation
  • Involvement of neurovascular structures which prevents a limb salvage surgery
  • Chronic infection
  • Large local recurrence or local metastases

Radiotherapy is reserved for inaccessible sites or for palliative treatment of advanced disease.