1. CTOS 14.11.08 Soft Tissue Sarcoma of the Extremity Comparison of Conformal Post-operative Radiotherapy (CRT) and Intensity Modulated Radiotherapy (IMRT) 1 Joint Department of Physics, Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK 2 St Luke’s Cancer Centre, Royal Surrey County Hospital, Guildford, Surrey, UK 3 Department of Radiotherapy, Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK Young K Lee 1, Alexandra J Stewart 2, Frank H Saran 3

2.  Background  Materials and Methods  Results  Summary CRT and IMRT for extremity STS

3.  Background  Materials and Methods  Results  Summary CRT and IMRT for extremity STS

4. Background  Limb-sparing surgery in combination with focal radiotherapy - standard of care in patients with intermediate and high grade limb and limb girdle soft tissue sarcomas (STS)  Normal tissue toxicity increases with escalating total and integral dose  Dose prescription limited by organs-at-risk (OAR) surrounding the PTV

5. Aims  To define a reproducible and comparable target volume definition for CT planning  To define reproducible prospective planning dose volume constraints  To assess the ability of inversely-planned IMRT plans to minimise the dose to surrounding OAR  To assess efficacy of ‘simple’ IMRT compared to ‘complex’ IMRT planning

6.  Background  Materials and Methods  Results  Summary CRT and IMRT for extremity STS

7. Patient data  T 2 and G 2/3 STS of the thigh (n=10)  No tumours invading bone  Entire surgical scar and all drain sites marked  Planning CT scan (GE HiSpeed QX/i, Milwaukee, WI) pelvic brim to below knee pelvic brim to below knee customised immobilisation customised immobilisation slice thickness = 2.5mm slice thickness = 2.5mm

8. Target volume definition  Phase I volume PTV 1 = tumour bed + 5cm SI and 3cm circumferentially  Phase II volume PTV 2 = tumour bed + 2cm isotropically  OAR defined as whole femur, neurovascular bundle, normal tissue corridor and normal tissue outside PTV 1

9. Planning target volumes PTV 1 PTV 2

10. normal tissue outside PTV 1 PTV 1 whole femur PTV 2 tissue corridor neurovascular bundle Organ definition

11. Radiotherapy planning  Primary planning objective PTV dosePTV dose femurfemur skin corridorskin corridor  Other planning objectives neurovascular bundle soft tissue outside PTV

12. Dose prescription  Pinnacle 3 v7.4f (Philips Radiation Oncology Systems, Madison, WI)  2-phase 3D-CRT Ph I - 50 Gy/25# (5 weeks)Ph I - 50 Gy/25# (5 weeks) Ph II - 16 Gy/8# (1½ weeks)Ph II - 16 Gy/8# (1½ weeks)  IMRT with simultaneous integrated boost (SIB) Ph I - 50 Gy/25# (5 weeks)Ph I - 50 Gy/25# (5 weeks) Ph II - 62.5 Gy/25# (5 weeks) (  /  = 10 Gy)Ph II - 62.5 Gy/25# (5 weeks) (  /  = 10 Gy)

13. Analysis  cumulative dose volume histograms (DVH)  D mean, D max, D min  Conformity Index (CI)  Heterogeneity Index (HI)

14.  Background  Materials and Methods  Results  Summary CRT and IMRT for extremity STS

15. Conformal Radiotherapy 2-3 field (simple) IMRT 4-5 field IMRT

16. conformal 2-3f 4-5f IMRT sagittal view

17. conformal 2-3f IMRT 4-5f IMRT coronal view

18. Conformity and Heterogeneity Mean Conformity Index (range) p-value Mean Heterogeneity Index (range) p-value 3DCRT 1.76 (1.48-2.47) 1.052 (1.031-1.065) 2/3f IMRT 1.59 (1.15-2.67)0.02 1.045 (1.029-1.063) 0.06 4/5f IMRT 1.33 (1.08-1.84)0.0002 1.036 (1.027-1.049) 0.001

19. DVH summary

20. ‘Simple’ 2-3f IMRT?  Median number of segments 26 (range 13-37) for 2-3f IMRT26 (range 13-37) for 2-3f IMRT 36 (range 34-56) for 4-5f IMRT36 (range 34-56) for 4-5f IMRT  Both IMRT plans were more conformal and less heterogeneous than 3D-CRT  Both IMRT delivered significantly lower femur V 45 compared to 3D-CRT plans  HOWEVER, 4/5f IMRT resulted in significantly lower femur V 45 when compared directly to 2/3f IMRT (p=0.04)

21.  Background  Materials and Methods  Results  Summary CRT and IMRT for extremity STS

22. Summary  Reproducible, comprehensive planning guidelines and dose-volume constraints for 3D planning for extremity sarcomas devised  4/5f IMRT plan - lowest clinically relevant doses to OAR whilst delivering conformal doses to PTV  Large primary tumour 4/5f preferable to a 2/3f IMRT approach4/5f preferable to a 2/3f IMRT approach  Small, superficial disease 3D-CRT may provide adequate treatment without added cost and complexity3D-CRT may provide adequate treatment without added cost and complexity

23.  Results from this study may not be directly translated to all other primary locations of STS of the extremity  IMRT approach should be assessed prospectively with respect to late toxicity within the confines of a prospective clinical trial Further work

24. Radiotherapy Department Royal Marsden NHS Foundation Trust Acknowledgment