(P 023) FACTORS ASSOCIATED WITH LOCAL CONTROL AND SURVIVAL IN LOCALIZED EWING SARCOMA PATIENTS TREATED WITH SURGERY ON AEWS1031: A REPORT FROM THE CHILDRENS ONCOLOGY GROUP

Objective: To evaluate clinical and treatment variables associated with local failure (LF) risk and event-free survival (EFS) for Ewing sarcoma (ES) patients treated with surgery as a component of primary site local control on AEWS1031.

Methods: 429 eligible patients who underwent surgery for local control were considered. 403 with complete surgical records are reported herein. Surgery was performed with the goal of achieving a negative margin of resection (R0). Those with microscopically involved margins (R1) were to receive adjuvant radiation therapy. Local failure (LF), defined as local recurrence only or combined local and distant recurrence was analyzed. EFS and cumulative incidence (CI) of LF from the time of local control surgery for those treated with surgery alone and from the start of adjuvant radiation was estimated using the Kaplan-Meier and Gray method, respectively. P-values were calculated using the logrank or Gray’s test, as appropriate. 5-year estimates of EFS and CI of LF are reported. A two-sided p-value of 0.05 or less was considered significant; no adjustment was made for number of tests performed.

Results: There were 403 patients that underwent surgery for local tumor control (303 surgery alone; 100 surgery plus radiation therapy). The analytic cohort consisted of 42 pelvis tumors, 133 lower extremity tumors (defined femur or distal in the lower extremity), 60 upper extremity tumor (defined clavicle or distal in the upper extremity), 16 spine tumors, 73 axial non-spine tumors, and 79 extraosseous tumors. Tumor locations and surgical reconstruction type are listed in Table 1. 205 tumors had a maximum tumor dimension (MTD) ≥ 8cm at diagnosis and more likely to involve the lower extremity. 63 patients were ≥18 years of age. Of patients with extremity and pelvic tumors, 21 underwent amputation and 214 limb salvage surgery. 143 patients had > 99% tumor necrosis (no viable tumor), 90 had 90-99% tumor necrosis, and 77 had less than 90% tumor necrosis (see Table 2).

After a median follow up of 67.7 months, five-year EFS was 76% (95% CI, 72-80) and cumulative incidence of LF was 5.2% (95% CI, 3.4-7.9). LF was 4.6% (95% CI, 2.7-7.8%) in the surgery alone patients and LF was 7.1% (95% CI, 3.4-14) in patients who received both surgery and radiation therapy (p=0.63). By tumor site, the LF incidence was 13.6% for pelvis, 1.54% for lower extremities, 3.4% for upper extremities, 6.3% for spine, 13.7% for axial non-spine, and 8.8% for extraosseous tumors (p=0.039; Figure 1). The LF incidence was 4.9% in patients < 18 years versus 6.5% in patients ≥18 years (P=0.35); 4.4% for tumors < 8cm and 6.0% for tumors ≥8cm (p=0.13). There were no LF in patients that underwent amputation, while 3.8% (95% CI, 1.9-7.4) of patients undergoing limb salvage surgery had LF (p=0.34). The LF incidence was 4.3% for tumors with > 99% necrosis, 7.4% for tumors with 90-99% necrosis and 6.6% for less than 90% necrosis (p=0.45). There was no significant difference in tumor necrosis based on tumor location. LF in negative margin resections was 6.0% versus 12.9% in positive margin resections (p=0.07; Figure 2).

Conclusion: Five-year EFS was 76% and cumulative incidence of LF was 5.2% in localized ES patients treated with surgery as a component of primary site local control. LF was most common in axial non-spine tumors and pelvic tumors. Patients treated with surgery alone or surgery plus radiotherapy (typically due to positive margins) had low rates of LF. Further efforts should focus on evaluating complications and functional outcomes for patients undergoing surgery for local control.

Surgery for Local Control_Table 1.docx

Surgery for Local Control_Table 2.docx

Surgery for local control_Figure 1.docx

Surgery for local control_Figure 2.docx