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

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

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

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

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

To investigate histopathological response to preoperative radiotherapy Purpose Introduction

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

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

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

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

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

PtHistologyResponse MLS MLS/ALT-like Pleomorphic MFH Synovial sarcoma Fibromyxo sarcoma Pleomorphic MFH MPNST Pleomorfic liposarcoma / Pathologic respons after radiotherapy Results PtHistologyresponse MLS/RLS Leiomyosarcoma Pleomorphic MFH Synovial sarcoma Chondro sarcoma Clear cell sarcoma 66/

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

MLS WLS-like Patiënt P. Results

MLS pre and post radiotherapy Results

Vascular changes Results Arteriolar damage

Thrombosis and arteriolar damage

Histology border MLS/WLS Viable Non-Viable Results

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

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): ) 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): )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): References

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