1. PREOPERATIVE HYPOFRACTIONED RADIOTHERAPY IN LOCALIZED EXTREMITY/TRUNK WALL SOFT TISSUE SARCOMAS EARLY STUDY RESULTS Hanna Kosela; Milena Kolodziejczyk; Tadeusz Morysinski; Wirginiusz Dziewirski; Marcin Zdzienicki; Piotr Rutkowski Department of Soft Tissue/Bone Sarcoma and Melanoma, Department of Radiotherapy Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology Warsaw, Poland

2. Background  Primary treatment of majority of localized soft tissue sarcoma is surgical resection of the tumor with adequate margins combined with radiotherapy  Using radiotherapy in the local setting increases local control of the disease (with suggested survival benefit for patients with high grade tumors * ) * Koshy M, et al.. Improved survival with radiation therapy in high-grade soft tissue sarcomas of the extremities: a SEER analysis. Int J Radiat Oncol Biol Phys. 2010 May 1;77(1):203-9

3. Background – preoperative radiotherapy vs postoperative setting No differences in local recurrence rate, regional and distant failure rates*; *O'Sullivan B, et al.. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial.2002 Jun 29;359(9325):2235-41. BenefitsDrawbacks Lower doses and smaller treatment field size; Possible improvement in tumor resectability; Smaller incidence in long term radiation- related complications; Increased risk of wound complications;

4. Background Can we shorten the overall treatment time by using hypofractionated radiotherapy and immediate surgery in STS as in rectal carcinoma? Potential benefits Lower risk of tumor clonogens repopulation Convenience Lower cost Radiobiological rationale: low α/β ratio: -0,5-5 Gy* *Gunderson LL, Tepper JE. Clinical Radiation Oncology. London, UK: Churchill Livingstone; 2007 *

5. AIM OF THIS PILOT STUDY Incidence of late complicatons and local recurrences compared to those observed after conventionally fractionated preoperative radiotherapy. Overall survival;

6. Patients and methods In the years 2006-2010, 262 patients received 5x5 Gy according to uniform internal preoperative protocol and underwent tumor resection within a consecutive week. In our analysis we included only patients with diagnosis of localized, resectable soft tissue sarcoma of the extremities or trunk wall (confirmed pathologically): primary or recurrent; deep seated and/or intermediate/high grade

7. Patients and methods 225 patients 122 (54%) women, 103 (46%) men Median age 54 years (range 18-82) Median follow up 34 months (range 1-80) Bioethical committee approval

8. Patients and methods  140 patients (62.2%)- primary tumors 75 patients (33%) – clinical local recurrence after previous surgery in another center 10 patients (4.4%)- after non-radical surgery in another center, but without clinical recurrence (scar)  56 (24.9%) patients received preoperative chemotherapy 75% of these patients had high grade tumors (G3)

9. Patients and methods

10. Synovial sarcoma

11. Patients and methods * 16 patients had also postoperative radiotherapy Tumor sizeMedian size 9cm (range 0,5-41cm) 45%>10cm Tumor grade29- G1 54-G2 136- G3 (60%) 6- unknown Final resection margin176- R0 (78%) 41- R1* 2-R2

12. Results 51 (22.6%) patients were dead at the time of analysis 93 (41.3%) recurrences of the disease 46 - local recurrence (20% local recurrence = 80% local control rate) - in 10 patients after local recurrence amputation was performed 78 (34.7%)- distant metastases 31 (13.8%) patients had local and distant recurrence of the disease

13. ~70%

14. ~80%

15. Factors influencing survival (univariate analysis) OS: -Tumor size (p = 0.05) -Tumor grade (p = 0.0002) LRFS: - Tumor grade (p = 0.007)

18. p=0.05

21. `~80% ~~60%

22. ~75% ~~57%

26. Complications of the treatment 97 patients (43%) had postoperative wound complications including 9 patients (4%) who required an additional surgical procedure 33.6% of patients with complications received preoperative chemotherapy 87 patients with wound complications (89.6%) had tumor localized on the lower limb

27. Early local complications 38 (16.9%) patients had prolonged healing of the wound (>1 month) 28 (12.4%) patients had wound dehiscence 9 (4%) patients required prolonged punctures of the collecting lymph fluid 6 (2.7%) patients had an increased acute skin toxicity

28. Late complications 2 (0.8%) patients severe fibrosis leading to contracture of the limb 24 (10.7%) patients prolonged edema of the operated limb 6 (2.7%) patients - fracture of the treated limb (median time from treatment to fracture 18 months)

29. Discussion

31. Conclusions Local control rates an overall survival similar to those seen in patients treated with preoperative radiotherapy conventionally fractionated; Our series comprises majority of high risk patients with large high grade tumors; Wound complication - quite high rate of early complications but low percentage of severe complications; Late complications - similar to those seen in patients treated with preoperative radiotherapy conventionally fractionated

32. Clinical trial? „Short-course” preoperative radiotherapy vs conventional radiotherapy

33. Cancer Center – Institute; Warsaw: K. Wiater, S. Falkowski, A. Klimczak, T. Świtaj, K. Ptaszyński, U. Grzesiakowska, E. Bylina, A, Głuszcz,… Our patients and their families ACKNOWLEDGEMENTS

34. Thank you for your attention! Cancer Center, Warsaw, Poland