Effectiveness of Radiotherapy in Myxoid Sarcomas is Associated with a Dense Vascular Pattern

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

3. Pre operative radiotherapy • Target area limitation easier • Lower dose • Canadian SR2 trial (Lancet 2002) Pre Post Pre vs post operative radiotherapy 50 Gy 66 Gy • comparable local control 93% 92% • early complications 35% 17% • late complications 23% 36% Introduction

4. Pre operative radiotherapy • Target area limitation easier • Lower dose • Canadian SR2 trial (Lancet 2002) Pre Post Pre vs post operative radiotherapy 50 Gy 66 Gy • comparable local control 93% 92% • early complications 35% 17% • late complications 23% 36% Introduction

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

6. Purpose • To investigate histopathological response to preoperative radiotherapy Introduction

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

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

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

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

11. Study pre-operative radiotherapy Results • 31 Patiënts 15 ♂ / 16 ♀ • Localisation leg 24 (78%) • Median tumor Ø 9 cm (3-18) • Grade intermediate/high 19 / 12 • Early complications 2 Results

12. Pathologic respons after radiotherapy Results

13. Results • 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. Patiënt P. MLS WLS-like Results

15. MLS pre and post radiotherapy Results

16. Vascular changes Arteriolar damage Results

17. Thrombosis and arteriolar damage

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

19. Conclusions • 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. References 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.

21. Extra Figures