1. IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA

2. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone (n=71) LSS + External Radiotherapy (n=70) Ext. Radiotherapy: 45Gy (WF) + 18Gy (Boost) Median FU: 115mths Local Control LSS Alone: 76% LSS + External Radiotherapy: 98% p=0.0001 +ve impact in high grade as well as low grade sts Level I Evidence

3. MSKCC Trial (Pisters PWT et al, JCO 1996) Extremity / Superficial Trunk STS (n=164) LSS Alone (n=86) LSS + Interstitial Brachytherapy (n=78) Brachytherapy: 42-45Gy in 4-6 days Median FU: 76mths Local Control LSS Alone: 69% LSS + Interstitial Brachytherapy: 82% p=0.04 +ve impact in 119 pts. with high grade sts only no improvement in 45 pts. with low grade sts Level I Evidence BRACHYTHERAPY FOR STS

6. Three prospective trials investigating the impact of limited radiation volumes on toxicity rates and local control RTOG 0630 United Kingdom VORTEX trial COG ARST 0332 trial Radiation volume reduction aims at sparing healthy surrounding tissues to potentially decrease treatment toxicities Lymphedema Subcutaneous Fibrosis Joint Stiffness TRIALS ADRESSING TARGET VOLUME

7. Local Control Complications Functional Outcomes QOL Duration of Treatment Cost of Treatment

8. Dept of Radiation Onology, MSKCC, USA Cancer July 2011

9. PATIENTS & METHODS January 1995 – December 2006 134 Adult Patients Inclusion Criteria: Primary Presentation Extremity High Grade Limb Sparing Surgery at MSKCC Adj. Brachyherapy / IMRT at MSKCC Brachytherapy (Jan 1995 – Nov. 2003), n = 71 (53%) IMRT (Feb 2002 – Dec 2006), n = 63 (47%)

10. BRACHYTHERAPY LDR Brachytherapy: Dose Rate – 0.41Gy / Hour Total Dose – 45Gy Started – Post op Day ≥ 5

11. Intensity Modulated Radiation Therapy Pre – Operative N = 10 Dose : 50Gy/ 25 # @ 2Gy/# WLE : 4-6 wks after RT CTV : Gross Tumor + 3cm long 0.5cm bone 1.5cm Radial PTV : CTV + 2cm Post – Operative N = 53 Dose : 63Gy (Median) Started 4–6 wks after Sx CTV : Sx bed + 3cm expansion 0.5cm bone 1.5cm Radial PTV : CTV + 2cm

12. PROGNOSTIC FACTORS

13. 5 YEAR LOCAL CONTROL (Actuarial) Median FU: 46 mths Whole Group: 86% IMRT: 92% BRT: 81% Significant Wound Complications IMRT: 19% BRT: 11%p=0.6

14. AUTHORS INFERENCE Post-op adjuvant RT using IMRT technique results in Superior outcomes compared to Brachytherapy for Local Disease Control Should be considered the treatment of choice for extremity sts

15. PRE-OP VS. POST-OP RADIOTHERAPY Randomized Trial O’Sullivan et al, Lancet 2002 Extremity STS (n=190) Pre-op RT + LSS (n=94) LSS + Post-op Ext. RT(n=96) Pre-op Ext. RT Dose: 50Gy/ 25# Post-op Ext. RT Dose: 66Gy/ 33# Primary endpoint: Complication rate within 120 days Median FU: 3.3 years Pre-opPost-op Wound Complications 35%17% p=0.011 Local Control91%(3yr)90%(3yr) p=0.711 Overall Survival84%(3yr)74%(3yr) p=0.048 Level I Evidence

16. O’Sullivan Cancer 2013

17. Local Control: 65 – 89% Complications: 1 – 50% RESULTS WITH LDR BRACHY ALONE

18. RESULTS WITH HDR BRACHY ALONE Local Control: 50 – 100% Adverse Effects: 0 – 50%

19. Laskar et al, Ann Surg Oncology 2007

20. RESULTS

21. TOXICITIES S Laskar Annals of Surgical Oncolog 2007

22. CENTERPTSBRACHYLC(%) MSKCC (Pister et al.)164LDR/HDR89 Tata Memorial Hosp. (1983-92)151LDR71 Fox Chase130LDR/HDR82 MSKCC (Harrison et al.)126LDR82 Inst. Claudius Regaud112LDR/HDR89 MSKCC (Alekhteyar et al.)105LDR86 Institute Gustave Roussy50LDR62 Tata Memorial Hospital (1990-2003)155LDR/HDR71 LITERATURE REVIEW

23. 10 year local control - 91.7% LONG TERM DATA TMH (TMH – UNPUBLISHED 2012)

24. Laskar et al, Pediatric Blood & Cancer 2007

25. RESULTS

26. INTERSTITIAL BRACHYTHERAPY IN THE ERA of IMRT / IGRT / DOSE PAINTING WITH NUMBERS Hong et al., IJROBP 2004 Lancet Oncology 2006

27. IMAGE GUIDED BRACHYTHERAPY

28. 2500 INR = 40 USD 300INR – 6 USD Brachy: 450 USD (At TMH) IMRT: 1400 USD (At TMH) Protons: 100-200,000 USD

29. IMRTBRTVerdict Local Control***** Complications***** Functional Outcome ** QOLNo Data Treatment Duration***** Treatment Cost***** Similar BRT Randomised Clinical Trial: IMRT vs. BRT SUMMARY