- In an international series of 370 patients with localized extraskeletal osteosarcoma, the combination of definitive surgery and radiation therapy was associated with significantly decreased risk of local recurrence
- Chemotherapy did not decrease the risk of either local or systemic recurrence
- Neither disease-free nor overall survival was improved by radiation therapy, chemotherapy or the combination
- Chemotherapy should not be routinely used for locally resectable extraskeletal osteosarcoma; rather, local therapy with surgery and radiation therapy should be considered
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Extraskeletal osteosarcoma is very rare, accounting for only 4% of cases of osteosarcoma, itself a rare disease. Accordingly, there's no consensus about the role of chemotherapy or radiation therapy or the effect of treatment on oncologic outcomes.
By pooling data from 25 sarcoma specialty centers worldwide, Marilyn Heng, MD, MPH, orthopaedic trauma surgeon (who trained as an orthopaedic oncologist) in the Department of Orthopaedics at Massachusetts General Hospital, and colleagues were able to determine that radiation therapy, but not chemotherapy, is a beneficial adjunct to definitive surgery for patients with extraskeletal osteosarcoma. They published their findings in the European Journal of Cancer.
The researchers identified 370 adults in prospective databases maintained by high-volume sarcoma centers in Canada, the United States, Japan, China, South Korea, France, Taiwan and Germany. They were diagnosed between 1971 and 2016 with high-grade, non-metastatic extraskeletal osteosarcoma at an extremity or truncal site and underwent definitive surgical resection.
There was a fairly even distribution between patients who underwent surgery alone (33%), surgery plus adjuvant chemotherapy (26%), surgery plus radiation (19%) or surgery plus both treatments (22%).
The type of chemotherapy regimen was categorized as doxorubicin plus either cisplatin and/or methotrexate ("osteosarcoma type," 48%) or doxorubicin plus any agent other than cisplatin or methotrexate ("soft-tissue sarcoma-type," 33%). The other patients received something else or the regimen was unknown.
Forty-seven percent of the patients developed recurrent disease: local recurrence (9%), metastases (28%) or both (10%). There was no difference in systemic recurrence between patients who received chemotherapy and those who did not.
The 211 patients who were not known to have died during the study period had a median follow-up of 4.5 years (range, 0–40 years).
The five-year disease-free survival rate was 50% and the overall survival rate was 56%. The disease-free survival rate was 50% for patients who did not receive chemotherapy, 57% for those who received osteosarcoma-type chemotherapy and 43% for those treated with a soft-tissue sarcoma-type regimen (P = NS).
Factors Predicting Outcomes
On multivariate analysis:
- Radiation therapy was significantly associated with decreased risk of local recurrence (HR, 0.46; 95% CI, 0.26–0.80; P = .01)
- Use of chemotherapy was not significantly associated with decreased risk of either local or systemic recurrence
- Survival was not significantly improved by radiation therapy, chemotherapy or the combination
This study spanned 45 years, and there were surely changes in treatment approaches, including radiation therapy techniques. However, even when the year of treatment was tested as a continuous variable, the benefit of radiation therapy on the risk of local recurrence remained significant.
This study confirms the view that extraskeletal osteosarcoma behaves more like soft-tissue sarcoma than like conventional osteosarcoma of the bone, which responds to chemotherapy and is well known to be resistant to radiation. Chemotherapy should not be routinely used for locally resectable extraskeletal osteosarcoma; rather, local therapy with surgery and radiation therapy should be considered.
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