1. Danny Indelicato, MD CTOS 2012 Ewing Sarcoma of the Axial Skeleton: Early Outcomes from the University of Florida Proton Therapy Program

2. Spine: 89% Chest wall: 60% Pelvis: 86% Local control Head/Neck: 87% Axial Ewing sarcoma at the University of Florida: 1965-2007

3. Spine: 37% Chest wall: 20% Pelvis: 25% Grade 3+ Complications Head/Neck: 45% Axial Ewing sarcoma at the University of Florida: 1965-2007

4. 80% treated with radiation Risk of second malignant neoplasms 9%, mostly breast and thyroid Compared to siblings, 6X risk of severe, life threatening, or disabling chronic health conditions Comprehensive report of long term Ewing survivors (1970-1986) Today, only 35% of Ewing patients treated with radiation

5. “From the most unexpected source, experimental physics, a new and powerful weapon has been brought into play.” - James Ewing, 1922 “Cancer Man Ewing”

6. A Dosimetric Comparison of Conformal Radiotherapy for Ewing Sarcoma of the Skull Base (Indelicato DJ et al, ASTRO 2011) Proton therapy may minimize neurocognitive deficits, neuroendocrine dysfunction, chronic otitis media, and radiation-induced second malignancies

7. Dosimetric Comparison of Proton Therapy and IMRT for Ewing Sarcoma of the Spine and Chest Wall (Su Z, Indelicato DJ et al, ASTRO 2012) Depending on the chest wall sub-region, proton therapy has the potential to minimize cardiac, pulmonary, and renal toxicity. In long term survivors, there may be lower risks of radiation-induced second malignancies, particularly breast cancer. Proton IMRT

8. Dosimetric Comparison of Highly Conformal Photon and Proton Radiotherapy for Unresectable Ewing Sarcoma of the Pelvis (Roca M, Indelicato DJ et al ASTRO 2012) Proton therapy may reduce gastrointestinal toxicity, musculoskeletal complications, and second malignancies in patients with pelvic Ewing sarcoma IMRT Proton IMRT Proton IMRTProton

9. Clinical Outcomes at the University of Florida Proton Therapy Institute

10. Since 2006, 24 patients with primary localized Ewing sarcoma of the axial skeleton were treated at UFPTI Chest wall9Pelvis5 Skull base7Spine3 Median maximum tumor dimension at diagnosis: 7 cm (range, 3-18 cm) Median patient age: 5.9 y/o (range, 1-21 years) Race: Caucasian: 20 Asian: 3 Hispanic: 1 13 patients were male Patient Characteristics

11. Patient Distribution

12. Treatment Chemotherapy: –Arm B of COG AEWS0031: 12 –EURO-EWING 99: 12 Gross total resection at diagnosis: 2 following neoadjuvant chemotherapy: 3 –2 had <90% necrosis 19 patients had gross disease at the start of radiotherapy Median RT dose –PTV1: 45 CGE (range, 30.6-50.4 CGE) –PTV2: 50.4 CGE (range, 44-57.6 CGE). –4 chest wall tumors with high-risk features received a component of hemithorax RT (median, 12 CGE)

13. Results Median followup of 2 years (range, 0.7-6 yrs) 22/24 patients remain disease free –One patient with a skull base tumor died of local progression 6 months following treatment –One patient is living following local progression of a pelvic tumor 1.8 years after treatment. –Both local failures occurred within the 100% isodose line

14. Pattern of Failure 0.5 years1.8 years

15. Axial Ewing sarcoma at the University of Florida: 2006-2012 Toxicity 6 patients with skull base or medial chest wall tumors required temporary percutaneous or nasogastric enteral nutrition support for mucositis No other radiation- related grade 3 acute or late complications

16. Conclusions In this cohort of young patients with unfavorable axial tumors, proton therapy allows highly conformal radiation delivery and minimal toxicity without compromising early tumor control Further followup is necessary to assess late effects Provides the foundation for the long-term institutional and cooperative group outcome studies necessary to accurately characterize the therapeutic ratio of proton therapy