Surgery and Radiation Therapy

In a retrospective data analysis of 120 patients with multifocal metastatic Ewing sarcoma, patients who received local treatment to both the primary tumor and metastases had better outcomes than patients who received local treatment to the primary tumor only or with no local treatment (3-year EFS rate, 39% vs. 17% and 14%, respectively; P < .001).[12]

A similar trend for better outcomes with irradiation of all sites of metastatic disease was seen in three retrospective analyses of smaller groups of patients who received radiation therapy to all tumor sites.[13-15] These results must be interpreted with caution. The patients who received local-control therapy to all known sites of metastatic disease were selected by the treating investigator, not randomly assigned. Patients with so many metastases that radiation to all sites would result in bone marrow failure were not selected to receive radiation to all sites of metastatic disease. Patients who did not achieve control of the primary tumor did not go on to have local control of all sites of metastatic disease. There was a selection bias. While all patients in these reports had multiple sites of metastatic disease, the patients who had surgery and/or radiation therapy to all sites of clinically detectable metastatic disease had better responses to systemic therapy and fewer sites of metastasis than patients who did not undergo similar therapy of metastatic sites.

Bone and soft tissue. Stereotactic body radiation therapy has been used to treat metastatic sites in bone and soft tissue. The median total curative/definitive stereotactic body radiation therapy dose delivered was 40 Gy in five fractions (range, 30–60 Gy in 3–10 fractions). The median total palliative stereotactic body radiation therapy dose delivered was 40 Gy in five fractions (range, 16–50 Gy in 1–10 fractions). These short-course regimens with large-dose fractions are biologically equivalent to higher doses delivered with smaller-dose fractions given over longer treatment courses.[17][Level of evidence C1]

Pulmonary. For all patients with pulmonary metastases, whole-lung irradiation should be considered, even if complete resolution of overt pulmonary metastatic disease has been achieved with chemotherapy.[4,5,18] Radiation doses are modulated based on age, the amount of lung to be irradiated, and pulmonary function. Doses between 12 Gy and 15 Gy are generally used if whole lungs are treated. No randomized trial has been done to prove radiation therapy improves survival in this group of patients. An early trial from the intergroup Ewing sarcoma group in the 1970s showed that radiation to the lung improved survival in patients with nonmetastatic disease when added to vincristine, actinomycin, and cyclophosphamide (VAC) compared with VAC alone.[19] However, the addition of doxorubicin to the therapy produced better EFS than the VAC/radiation therapy regimen.