1. Local Control in Ewing Sarcoma of the Chest Wall Benedetta Bedetti Andreas Ranft Heribert Jürgens Karsten Wiebe Uta Dirksen

2. The story behind...... Is there a benefit from combined modality local treatment? Who needs additional radiotherapy? ? Large Tumor ? Pre-Chemo Resection ? Poor Response to Inductionchemotx ? Shaved Margin What is an appropriate surgical procedure? ewing@ukmuenster.de

3. CESS EURO E.W.I.N.G.- 99 cohort 198 patients July 1998- April 2009 119 male (60 %), 79 female (40 %) Age at diagnosis: 13,9 (0,5-60) Localized disease only Primary: 134 Rib 28 Scapula 23 Soft Tissue 12 Clavicula 1 Sternum Cohort

4. Local treatment modalities Surgery in 191 patients: Surgery only (OP): 85 pts, 43 % Radiotherapy only (RT): 7 pts, 3,5 % OP + RT: 106 pts, 53,3% 130 complete en bloc resections 81 reconstructions of the thoraxic wall

5. Local treatment modalities 5y-EFS (OP) = 0,75 (SE =,07) 5Y-EFS (RT) = 0,63 (SE =,05) 5y-EFS (OP+RT) = 0,65 (SE =,07) RecurrenceGroup OP+RTGroup OP - Local26 %29,5 % - Systemic53 %41 % - Combined relapse21 %29,5 % Years Survival p=.233

6. Is there a group of patients that benefit from combined modality local treatment? Tumorvolume < 200 ml Tumorvolume > 200 ml OP= 39 OP + RT = 60 ALL= 99 5y-EFS (OP) = 0,56 (SE =,05) 5y-EFS (OP+RT) = 0,55 (SE =,07) OP = 44 OP+ RT = 51 ALL= 95 5y-EFS (OP) = 0,86 (SE =,05) 5y-EFS (OP+RT) = 0,73 (SE =,07) Years Survival

7. Surgical margin: R1&R2Surgical margin: R0 OP = 77 OP + RT = 58 ALL= 99 5y-EFS (OP) = 0,74 (SE =,05) 5y-EFS (OP+RT) = 0,62 (SE =,07) OP = 8 OP + RT = 48 ALL = 56 5y-EFS (OP) = 0,57 (SE =,19) 5y-EFS (OP+RT) = 0,64 (SE =,07) Years Survival

8. Good histological response Poor histological response OP = 59 OP + RT = 81 ALL= 140 5y-EFS (OP) = 0,75 (SE =,07) 5y-EFS (OP+RT) = 0,65 (SE =,07) OP = 8 OP + RT = 20 ALL= 28 5y-EFS (OP) = 0,46 (SE =,07) 5y-EFS (OP+RT) = 0,41 (SE =,07) Survival Years

9. Risk Factor N3y-EFS5y-EFSP value Surgical Margins(n=191) 0.142 - R013573 %69 % - R14870 %65. 5% - R2843 % Histological tumor response(n=145) <0.001 - Good10476 %70 % - Poor4145 % Tumor size(n=194) 0.007 - < 200 ml9579 % - >= 200 ml9963 %55 % Not malignant pleural effusion(n=198) 0.041 No13276 %72 % Yes6660 %56 % Local treatment(n=198)0.233 Radiotherapy863% Surgery8576%75% Surgery & Radiotherapy10666%65% Univariate analysis

10. Multivariate analysis Tumor size ( =200ml), Surgical margins (R0/R1 and R2) Pleura effusion Local therapy modality (OP/OP&RT) Poor histological response (Hazard Ratio=2.74; 95 %CI 1.54-4.89)

11. Complete versus partial resection of the affected rib Unknown 5Y-EFS complete resection= 0,63 (SE=,07) 5y-EFS partial resection = 0,65 (SE =,06) P=0.685

12. Complications after surgery Prosthetic MaterialNComplicationN Non rigid46 Pneumothorax after chest drain removal 7 - Gore Tex28Paralysis after surgery involving vertebra 1 - Prolene 5 Bleeding1 - Vicryl12Anemia2 - Biopatch1Pneumonia 1 Spontaneous pneumothorax1 Rigid5Phrenic nerve paralysis1 - Stratos1Subcutanous emphysema 2 - Marlex4Tension pneumothorax2 Pleural effusion3 Combined with or without muscular flap 20Wound dehiscence 3 NoSeroma1

13. Late effectNRadiotherapyNo Radiotherapy Secondary malignancies7 7 Thyroid cancer312 AML 2 21 Tongue cancer1 1 Colorectal cancer1 1 Thoracic bone hypoplasia331 Myelopathy111 Heart /valular disease63 3 Lung function impairment14 Restricitive 11 56 Obstructive 3 2 1 Late effects

14. 95 patients INT-0091 & POG 9354 “The 5-year event-free survival was 56% (SE 7%) for the chest wall lesions compared with 64% (SE 2.4%) for the entire cohort of patients.”

15. Conclusions In patients with close margins additional radiotherapy seems recommended (small number of pts w/o additional RT) No added value in patients with other risk factors such as large tumorvolume, poor histological response Surgery should be done by an experienced team in the technique that seems appropriate

16. Münster Team

18. 36 patients, St. Judes “The 15-year estimates of EFS and survival were 56.3% ± 11.2% and 65.6% ± 10.7%, respectively.” Five year EFS app. 65%.