1. LOCAL CONTROL MODALITY AND OUTCOME IN EWING SARCOMA OF THE FEMUR: A REPORT FROM THE CHILDREN’S ONCOLOGY GROUP Najat C. Daw, Nadia N. Laack, Elizabeth J. McIlvaine, Mark Krailo, Richard B. Womer, Linda Granowetter, Holcombe E. Grier, Neyssa M. Marina, Mark L. Bernstein, Richard G. Gorlick, R. Lor Randall CTOS 2014, Berlin Germany

2. The femur is the most frequently involved bone by Ewing sarcoma and has the greatest structural significance. Reported 5-year overall survival for localized disease 31% - 64%. Survival of patients treated with surgery with or without radiotherapy is better than that of patients treated with radiotherapy alone. Local control modality at this site is controversial. Background

3. To describe the treatment and outcome of patients with localized Ewing sarcoma of the femur treated on 3 consecutive cooperative group trials To determine the effect of local control modality on tumor local control and patient outcome Study Objectives

4. Review of patients with localized Ewing sarcoma of femur treated on INT-0091, INT-0154, and AEWS0031. Included only patients who received vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide (VDC/IE) every 3 weeks and local therapy after neoadjuvant chemotherapy. Analysis of disease outcome in relation to local control modality: surgery, surgery plus radiotherapy (RT), RT. Differences in survival curves were assessed using log- rank tests. Cumulative incidence was calculated using the method of Fine. Patients and Methods

5. Results CharacteristicNo. of patients% Median age in yr (range)13 (1-33) Gender Male Female 69 46 60% 40% Race Caucasian Black Latino/Hispanic Other Missing 98 4 10 1 2 85% 4% 9% 1% 2% Location in femur Proximal Mid Distal Unknown 49 26 19 21 43% 23% 17% 18% Tumor size > 8 cm ≤ 8 cm Not reported 29 26 60 25% 23% 52% 131 patients with localized EWS of femur identified 16 excluded for incomplete data on local control 115 had complete data on local control

6. Treatment N% Treatment regimen INT-0091 experimental arm INT-0154 standard arm AEWS0031 standard arm 33 50 32 29% 44% 28% Local control modality Surgery only Surgery + RT RT only 84 17 14 73% 15% 12% Type of surgery/reconstruction (n=101) Amputation Prosthesis/allograft prosthetic composite Allograft Vascularized autograft Rotationplasty Unknown 5 35 37 7 2 15 5% 35% 37% 7% 2% 15%

7. Patient Outcome (N=115) 5-yr EFS 65%, 95% CI (55%, 73%) 5-yr OS 70%, 95% CI (61%, 78%)

8. Event-Free Survival by Tumor Size

9. EFS by Local Control Modality

10. Overall Survival by Local Control Modality

11. Cumulative Incidence of Local Failure not Associated with Type of Local Control p=0.57

12. Ewing sarcoma of the femur arises most commonly in the proximal aspect of the bone. Most common local treatment was surgery alone. Patients treated with VDC/IE every 3 weeks appear to have an EFS comparable to that of patients with Ewing sarcoma in general. The local control modality did not significantly affect disease outcome. Further study of treatment complications and functional outcome of the limb is needed to determine the optimal local control modality. Conclusions

13. COG Bone Sarcoma Committee members Treating physicians/investigators and CRAs at participating sites Participating patients and their families Acknowledgements

15. Outcome by Surgery vs Any RT EFS Overall Survival