Metastatic Osteosarcoma

Overview

Osteosarcoma that has spread from the initially affected bone to one or more sites in the body, distant from the site of origin, is called metastatic. The most common site to which osteosarcoma spreads, or metastasizes, is the lungs. Metastatic osteosarcoma is typically difficult to control, though patients with lung metastases have a better prognosis than patients with distant metastases. Historically, less than 20% of patients with metastatic osteosarcoma survived without recurrence of their cancer. However, survival has improved with the development of more effective chemotherapy.

The following is a general overview of treatment for metastatic osteosarcoma. Treatment may consist of surgery, radiation, chemotherapy, biological therapy, or a combination of these treatment techniques. Multi-modality treatment, which is treatment using two or more techniques, is increasingly recognized as an important approach for increasing a patient’s chance of cure or prolonging survival. In some cases, participation in a clinical trial utilizing new, innovative therapies may provide the most promising treatment. Circumstances unique to each patient’s situation may influence how these general treatment principles are applied and whether the patient decides to receive treatment. The potential benefits of multi-modality care, participation in a clinical trial, or standard treatment must be carefully balanced with the potential risks. The information on this website is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating cancer physician.

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Chemotherapy for Metastatic Osteosarcoma

The main improvement in the treatment of osteosarcoma over the past 30 years has been the development of chemotherapy. Historically, chemotherapy was administered as an adjuvant, or after surgery. Clinical trials have shown that treatment of osteosarcoma with adjuvant chemotherapy improves the patient’s chance of survival and decreases the risk of cancer recurrence compared to local therapy alone. More recently, neoadjuvant chemotherapy has been developed. This is the administration of chemotherapy before surgery in order to shrink the cancer.

Chemotherapy using multiple drugs, called combined chemotherapy, followed by surgery to remove as much of both the primary and metastatic cancer as possible, may be the most promising treatment for metastatic osteosarcoma. However, three studies conducted by the Pediatric Oncology Study Group suggest that further research is needed to identify the optimal chemotherapy combination for patients with metastatic osteosarcoma. The three chemotherapy combinations evaluated were an Ifex®-based treatment, high dose Ifex® supported by Neupogen®, and neoadjuvant Paraplatin® with adjuvant high-dose methotrexate, Ifex®, doxorubicin, and Platinol®. Surgery was performed in all three studies.

Of the three chemotherapy combinations evaluated, the Ifex®-based treatment was considered tolerable and provided the longest survival among patients. Approximately 53% of the patients lived 5 years or more after treatment and approximately 47% did not experience a recurrence of their cancer for 5 years or longer. Patients with fewer metastases in their lungs, or metastases in only one lung, lived longer after treatment.[1] High-dose Ifex® chemotherapy supported by Neupogen® was more effective, resulting in a partial response in 49% of the 43 patients treated, and a complete response in 10%.[2]

The third treatment evaluated was neoadjuvant Paraplatin® chemotherapy followed by surgery, when feasible, and then 40 weeks of adjuvant chemotherapy. This combination appears to be less effective than the Ifex®–based treatment. Of the 37 patients treated, approximately 32% lived more than 3 years or more and 24% did not experience a recurrence of their cancer for more than 3 years.

Researchers from St Jude Children’s Research Hospital reported outcomes of 29 patients with metastatic osteosarcoma treated between 1986 and 1997 with ifosfamide, cisplatin, doxorubicin and high-dose methotrexate.[3] The five-year survival for patients with lung metastases only was 46% with the better results in those with unilateral lung metastases (metastases in only one lung), no more than three nodules and those in surgical remission. They also concluded that cisplatin was probably superior to carboplatin.

Researchers from Italy treated 57 patients with metastatic osteosarcoma between 1995 and 2000 with neoadjuvant (before surgery) chemotherapy.[4] These patients were treated with primary chemotherapy, restaging, simultaneous surgical removal of the primary tumor and metastatic lesions and maintenance chemotherapy after recovery from surgery. Thirty-five of the 57 patients achieved remission after neoadjuvant chemotherapy. The two year event-free survival was 21% and overall survival was 55%.

Researchers from France have reviewed their experience with treating 78 pediatric patients with metastatic osteosarcoma.[5] These patients were treated between 1987 and 200. Fifty-nine percent of patients had only one metastatic site with 35 being in the lung. After combination chemotherapy 36% of patients were in a complete remission. Event-free survival at five years was 14% and the overall survival was 19%. Patients who had more than one metastatic site had a worse outcome.

Role of Surgery

As a generality, patients with metastatic osteosarcoma have the same primary surgery performed as patients with localized disease. It is important to gain local control in order to better treat metastatic disease. Every attempt is made to perform limb sparing surgery but this is not always possible. In addition all accessible metastatic lesions are usually surgically removed after neoadjuvant (before surgery) chemotherapy.

Role of Radiation Therapy

Radiation therapy has a limited role in the treatment of metastatic osteosarcoma. The standards and options for use of radiation therapy in the management of patients with osteosarcoma have been reviewed.[6] Radiation therapy may be indicated for relief of symptoms in patients with inoperable lesions. There is no apparent benefit from whole lung radiation in patients with lung metastases.

Strategies to Improve Treatment

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References


[1]Harris MB, Gieser P, Goorin AM, et al. Treatment of metastatic osteosarcoma at diagnosis: a Pediatric Oncology Group Study. Journal of Clinical Oncology 1998;16: 3641-3648.

[2]Goorin AM, Harris MB, Bernstein M, et al. Phase II/III Trial of Etoposide and High-Dose Ifosfamide in Newly Diagnosed Metastatic Osteosarcoma: A Pediatric Oncology Group Trial. Journal of Clinical Oncology 2002;20: 426-433.

[3] Daw NC, Billups CA, Rodriquez-Galindo C, et al. Metastatic osteosarcoma. Cancer 2006;106:403-412.

[4] Bacci G, Briocoli M et al, Neoadjuvant chemotherapy for osteosarcoma of the extremities with metastases at presentation: recent experience at the Rizzoli Institute in 57 patients treated with cisplatin, doxorubicin, and a high dose of methotrexate and ifosfamide. Annals of Oncology 2003;14:1126-1134.

[5] Metastatic osteosarcoma at diagnosis: Prognostic factors and long-term outcome-The French pediatric experience. Cancer 2005;104:11001109.

[6] Claude L, Rousmano S, Carrie C. Standards and options for use of radiation therapy in the management of patients with osteosarcoma. Update 2004. Bulletin of Cancer 2005;92:891-906.

[7] Fagioli F, Aglietta M, Tienghi A, et al. High-dose chemotherapy in the treatment of relapsed osteosarcoma: an Italian sarcoma group study. J Clin Oncol 2002;20:2150-6.

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