Pediatric Osteosarcoma Treatment & Management

Before the use of chemotherapy, which began in the 1970s, osteosarcoma was primarily treated with surgical resection, usually amputation. Despite good local control of the disease, more than 80% of patients subsequently developed recurrent disease that typically manifested as pulmonary metastases. The high recurrence rate indicates that most patients have micrometastatic disease at the time of diagnosis. Therefore, the use of adjuvant (postoperative) systemic chemotherapy is critical for the treatment of patients with osteosarcoma.^{[18, 19]}

Neoadjuvant (preoperative) chemotherapy not only facilitates subsequent surgical removal by shrinking the tumor but also provides oncologists with an important risk parameter. Patients who have a good histopathologic response to neoadjuvant chemotherapy (>95% tumor cell kill or necrosis) have a prognosis better than those whose tumors do not respond favorably. Therefore, an assessment of neoadjuvant tumor cell kill has been incorporated into current chemotherapy trials to provide risk-adapted treatment regimens to determine if dose-intensification can improve the survival of patients with a poor initial histologic response.

Osteosarcoma cells have a high level of resistance to radiotherapy; thus, this treatment modality is not incorporated into standard treatment regimens. Retrospective studies suggest it may be helpful in some cases, including in those with close or positive surgical margins^[20] or in the palliative setting. High doses, including those up to 80 Gy, are thought to be required to achieve some tumor kill. Localized proton beam therapy may be useful to achieve high tumor doses and spare normal surrounding tissue for unresectable lesions.^[21] The bone seeking isotope, Samarium-153-EDTMP, may be helpful for palliation of metastases positive on bone scan findings, but this treatment requires hematopoietic stem cell rescue due to its hematologic toxicity.^[22]

The orthopedic surgeon is of paramount importance in the care of patients with osteosarcoma. However, surgery should be conducted only in collaboration with a pediatric oncologist familiar with and knowledgeable about ongoing clinical trials to facilitate optimal care. Patients with suspected osteosarcoma are often referred to the orthopedic surgeon first for diagnosis.

In addition, because osteosarcomas are not particularly responsive to radiotherapy, surgery is the only option for definitive tumor removal (ie, local control). In addition, prosthesis or bone stabilization may be required after surgical resection. Therefore, close involvement of the orthopedic surgeon at diagnosis and during and after therapy is critical.

• Biopsy

  • Open biopsy is preferred because it avoids sampling error and provides adequate tissue for biologic studies. Other options include trephine biopsy, which is preferred for vertebral bodies and iliac crests. Fine-needle aspiration is not recommended.
  • Incision for an open biopsy should be carefully planned to avoid tumoral contamination of neurovascular structures and to allow for en bloc removal during eventual definitive surgery.
  • Regardless of the technique chosen, a frozen section should be examined to be certain that the tumor was sampled accurately. If possible, extraosseous components should be sampled rather than bone to decrease the risk of fracture.
  • Bone holes should be sealed with polymethacrylate, and extraosseous holes should be sealed with absorbable gelatin sponge (Gelfoam) to decrease the risk of hematoma and tumoral spread.
  • Drains should be closed suction (to prevent infection) in line with the skin incision (to prevent tumor contamination in adjacent tissue).
• Definitive resection

  • The primary aim of definitive resection is the patient's survival. As such, margins on all sides of the tumor must contain normal tissue (ie, wide margin).
  • The width of the margin is important only for the marrow; an adequate margin is thought to be 5-7 cm from the edge of the abnormality, as shown on MRI or bone scans.
  • Radical margins, defined as removal of the entire compartment involved (joint to joint for bone and origin to insertion for muscle), are not usually required to achieve a cure.
  • A marginal or intralesional margin may be functionally helpful as debulking therapy, but it is not locally curative.
  • Amputation may be the treatment of choice.
  • Patients usually prefer limb-salvage reconstruction (if possible) over amputation, but studies of late effects reveal that patients with amputations may have long-term quality of life equivalent to that of patients undergoing limb salvage. These data are largely based on patients who underwent limb-salvage decades ago; therefore, the effect of modern limb-salvage techniques on this assessment is not clear.
  • The reconstruction technique must be chosen on the basis of individual considerations, as described below.
    • Autologous bone grafting: Advantages include no rejection and a low rate of infection. This technique should be used only in skeletally mature patients because periosteal infusion inhibits epiphyseal growth.
    • Allografting: Graft healing and infection can be problematic with this technique, particularly during chemotherapy. Rejection can also occur.
    • Prosthetic: Prosthetic joints can be solitary or expandable. They are usually expensive, and their longevity is unknown.
    • Rotationplasty: This technique is suitable for tumors of the distal femur or proximal tibial when the knee cannot be spared and particularly for large tumors for which high amputation is the only alternative. Young or athletic patients may functionally benefit from this procedure. After tumoral resection, vessels are repaired or looped and kept in continuity. The distal portion of the leg is rotated 180° and reattached to the thigh at the proximal resected edge. The rotation allows the ankle to become a functional knee joint; the length of the leg should be adjusted to match the contralateral knee. The foot acts as the anchor for the prosthesis. Patients can learn to use the leg effectively.
• Resection of pulmonary nodules

  • Metastatic lung nodules can be cured by means of complete surgical resection, most often wedge resection. Lobar resection or pneumonectomy is occasionally required to achieve clear margins. This procedure should be done at the time of primary tumor resection.
  • Although bilateral nodules can be resected by using a median sternotomy, surgical exposure is superior with a lateral thoracotomy. Therefore, staged bilateral thoracotomy procedures are recommended for bilateral disease (ie, 2 lateral thoracotomy procedures separated by a few weeks).
  • For osteosarcoma that recurs as only lung lesions more than 1 year after the patient completion therapy, surgical resection alone can be curative because the likelihood of metastases to other sites is low.^[13] If disease recurs sooner than 1 year after therapy, chemotherapy is warranted because the risk of other micrometastatic disease is high.

As is usual for any child with cancer, consultations with an oncologist and with any subspecialist related to the specific clinical circumstances are strongly recommended. Social service professions, psychologist, dentists, dietitians, and child-life specialists are usually involved with patients and their families throughout the course of their treatment.

Patients receiving methotrexate should not be given folate supplementation or prophylaxis with trimethoprim-sulfamethoxazole (Bactrim). Diet is not otherwise restricted.

Restrictions on activity vary with the location of the tumor and on the type of surgical procedure required for treatment.