1. Effectiveness of Radiotherapy in Myxoid Sarcomas is Associated with a Dense Vascular Pattern Ronald de Vreeze, research physician Daphne de Jong Fiona Stewart Rick Haas Frits van Coevorden

2. Liposarcoma 20% of all malignancies in adults Localisation –extremities (75%) –retroperitoneal (10%) –trunk (10%) Introduction

3. Target area limitation easier Lower dose Canadian SR2 trial (Lancet 2002) PrePost Pre vs post operative radiotherapy 50 Gy 66 Gy –comparable local control 93% 92% –early complications35%17% –late complications23% 36% Pre operative radiotherapy Introduction

4. Target area limitation easier Lower dose Canadian SR2 trial (Lancet 2002) PrePost Pre vs post operative radiotherapy 50 Gy 66 Gy –comparable local control 93% 92% –early complications35%17% –late complications23% 36% Pre operative radiotherapy Introduction

5. 2 studies myxoid liposarcoma show volume reduction after pre-operative radiotherapy –Pitson et al 2004 –Engström et al 2007 Mechanism is unknown Pre operative radiotherapy Introduction

6. To investigate histopathological response to preoperative radiotherapy Purpose Introduction

7. 70 yr male Progressive circumference calf No pain or neuro-vascular disability Patiënt P. Introduction

8. 70 yr male Progressive circumference calf No pain or neuro-vascular disability MLS WLS-like Patiënt P. Introduction

9. Biopsy Myxoid Liposarcoma  intermediate grade  Pre-operative 50Gy radiotherapy Introduction

10. Methods All pre-operative irradiated sarcomas 2002 - 2006 Intermediate/high grade sarcomas No prior therapy 50 Gy Study pre-operative radiotherapy Methods

11. Results 31 Patiënts 15 ♂ / 16 ♀ Localisation leg24 (78%) Median tumor Ø 9 cm (3-18) Grade intermediate/high19 / 12 Early complications2 Study pre-operative radiotherapy Results

12. PtHistologyResponse 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 MLS MLS/ALT-like Pleomorphic MFH Synovial sarcoma Fibromyxo sarcoma Pleomorphic MFH MPNST Pleomorfic liposarcoma 100 100/0 90 80 Pathologic respons after radiotherapy Results PtHistologyresponse 21 22 23 24 25 26 27 28 29 30 31 MLS/RLS Leiomyosarcoma Pleomorphic MFH Synovial sarcoma Chondro sarcoma Clear cell sarcoma 66/66 50 40 10 0

13. All pure MLS 100% pathologic response 20 of 31 sarcomas > 80% pathologic response Arteriolar vascular damage in areas of response Similar MLS-like vascular damage in all responding sarcomas Results

14. MLS WLS-like Patiënt P. Results

15. MLS pre and post radiotherapy Results

16. Vascular changes Results Arteriolar damage

17. Thrombosis and arteriolar damage

18. Histology border MLS/WLS Viable Non-Viable Results

19. Pre-operative radiotherapy in vascular sarcomas results in effective pathologic response MLS is a radio sensitive sarcoma –All MLS-like sarcomas are sensitive The sensitivity seems associated to vascular structure of sarcomas Conclusions

20. 1)O'Sullivan B, Davis AM, Turcotte R, Bell R, Catton C, Chabot P, Wunder J, Kandel R, Goddard K, Sadura A, Pater J, Zee B. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet 2002 June 29;359(9325):2235-41. 2) Pitson G, Robinson P, Wilke D, Kandel RA, White L, Griffin AM, Bell RS, Catton CN, Wunder JS, O'Sullivan B. Radiation response: an additional unique signature of myxoid liposarcoma. Int J Radiat Oncol Biol Phys 2004 October 1;60(2):522-6. 3)Engstrom K, Bergh P, Cederlund CG, Hultborn R, Willen H, Aman P, Kindblom LG, Meis-Kindblom JM. Irradiation of myxoid/round cell liposarcoma induces volume reduction and lipoma-like morphology. Acta Oncol 2007;46(6):838-45. References

21. Extra Figures