Local Control (Surgery and Radiation Therapy) for Ewing Sarcoma

Treatment approaches for Ewing sarcoma and therapeutic aggressiveness must be adjusted to maximize local control while also minimizing morbidity.

Surgery is the most commonly used form of local control.[30] Radiation therapy is an effective alternative modality for local control in cases where the functional or cosmetic morbidity of surgery is deemed too high by experienced surgical oncologists. However, in the immature skeleton, radiation therapy can cause subsequent deformities that may be more morbid than deformities from surgery. When complete surgical resection with pathologically negative margins is not anticipated, surgery is not typically performed, and definitive radiation is used instead. When pathologically positive margins are found, then postoperative radiation therapy is indicated. A multidisciplinary discussion between the experienced radiation oncologist and the surgeon is necessary to determine the best treatment options for local control for a given case. For some marginally resectable lesions, a combined approach of preoperative radiation therapy followed by resection can be used.

Timing of local control may impact outcome. A retrospective review from the National Cancer Database identified 1,318 patients with Ewing sarcoma.[31] Patients who initiated local therapy at 6 to 15 weeks had a 5-year OS rate of 78.7% and a 10-year OS rate of 70.3%, and patients who initiated local therapy after 16 weeks had a 5-year OS rate of 70.4% and a 10-year OS rate of 57.1% (P < .001). The difference in OS according to time to local therapy was more important in patients who received radiation therapy alone.

For patients with metastatic Ewing sarcoma, any benefit of combined surgery and radiation therapy compared with either therapy alone for local control is relatively less substantial because the overall prognosis of these patients is much worse than the prognosis of patients who have localized disease.

Randomized trials that directly compare surgery and radiation therapy do not exist, and their relative roles remain controversial. Although retrospective institutional series suggest better local control and survival with surgery than with radiation therapy, most of these studies are compromised by selection bias. An analysis using propensity scoring to adjust for clinical features that may influence the preference for surgery only, radiation only, or combined surgery and radiation demonstrated that similar EFS is achieved with each mode of local therapy.[30] Data for patients with pelvic primary Ewing sarcoma from a North American intergroup trial showed no difference in local control or survival based on local-control modality—surgery alone, radiation therapy alone, or surgery plus radiation therapy.[32]

The EURO-EWING-INTERGROUP-EE99 (NCT00020566) trial prospectively treated 180 patients with pelvic primary tumors without clinically detectable metastatic disease.[33][Level of evidence B4] A retrospective analysis of outcomes for these patients showed improved survival for patients whose tumors were treated with combined radiation therapy and surgery. The study did not prospectively define criteria for the selection of local-control modalities, and the investigators did not have access to information that would allow them to clarify how decisions for local-control modalities were made. In nonsacral tumors, combined local treatment was associated with a lower local recurrence probability (14% [95% CI, 5%–23%] vs. 33% [95% CI, 19%–47%] at 5 years; P = .015) and a higher OS probability (72% [95% CI, 61%–83%] vs. 47% [95% CI, 33%–62%] at 5 years; P = .024), compared with surgery alone. Even in a subgroup of patients with wide surgical margins and a good histological response to induction treatment, the combined local treatment was associated with a higher OS probability (87% [95% CI, 74%–100%] vs. 51% [95% CI, 33%–69%] at 5 years; P = .009), compared with surgery alone. In patients with bone tumors who underwent surgical treatment—after controlling for tumor site in the pelvis, tumor volume, and surgical margin status—those who did not undergo complete removal of the affected bone (HR, 5.04; 95% CI, 2.07–12.24; P < .001), those with a poor histological response to induction chemotherapy (HR, 3.72; 95% CI, 1.51–9.21; P = .004), and those who did not receive additional radiation therapy (HR, 4.34; 95% CI, 1.71–11.05; P = .002) had a higher risk of death.

For patients who undergo gross-total resection with microscopic residual disease, a radiation therapy dose of 50.4 Gy is recommended. For patients treated with primary radiation therapy, the radiation dose is 55.8 Gy (45 Gy to the initial tumor volume and an additional 10.8 Gy to the postchemotherapy volume).[14,34]

Evidence (postoperative radiation therapy):