imrt vs. brachytherapy for soft tissue sarcoma. external rt in sts nci trial (yang jc et al, jco...

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IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA

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Page 1: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

IMRT vs. BRACHYTHERAPY

FOR

SOFT TISSUE SARCOMA

Page 2: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

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 ControlLSS Alone: 76% LSS + External Radiotherapy: 98%

p=0.0001

+ve impact in high grade as well as low grade sts

Level I Evidence

Page 3: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

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 ControlLSS Alone: 69% LSS + Interstitial Brachytherapy: 82%

p=0.04

+ve impact in 119 pts. with high grade sts onlyno improvement in 45 pts. with low grade sts

Level I Evidence

BRACHYTHERAPY FOR STS

Page 4: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone
Page 5: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone
Page 6: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

• 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

Page 7: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

• Local Control

• Complications

• Functional Outcomes

• QOL

• Duration of Treatment

• Cost of Treatment

Page 8: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

Dept of Radiation Onology, MSKCC, USA

Cancer July 2011

Page 9: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

PATIENTS & METHODS

January 1995 – December 2006

134 Adult Patients

Inclusion Criteria:

Primary PresentationExtremityHigh GradeLimb Sparing Surgery at MSKCCAdj. Brachyherapy / IMRT at MSKCC

Brachytherapy (Jan 1995 – Nov. 2003), n = 71 (53%)

IMRT (Feb 2002 – Dec 2006), n = 63 (47%)

Page 10: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

BRACHYTHERAPY

LDR Brachytherapy: Dose Rate – 0.41Gy / Hour

Total Dose – 45Gy

Started – Post op Day ≥ 5

Page 11: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

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

Page 12: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

PROGNOSTIC FACTORS

Page 13: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

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

Page 14: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

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

Page 15: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

PRE-OP VS. POST-OP RADIOTHERAPYRandomized 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-op Post-opWound Complications 35% 17% p=0.011Local Control 91%(3yr) 90%(3yr) p=0.711Overall Survival 84%(3yr) 74%(3yr) p=0.048

Level I Evidence

Page 16: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

O’Sullivan Cancer 2013

Page 17: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

Local Control: 65 – 89%

Complications: 1 – 50%

RESULTS WITH LDR BRACHY ALONE

Page 18: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

RESULTS WITH HDR BRACHY ALONE

Local Control: 50 – 100%

Adverse Effects: 0 – 50%

Page 19: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

Laskar et al, Ann Surg Oncology 2007

Page 20: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

RESULTS

Page 21: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

TOXICITIES

S Laskar Annals of Surgical Oncolog 2007

Page 22: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

CENTER PTS BRACHY LC(%)

MSKCC (Pister et al.) 164 LDR/HDR 89

Tata Memorial Hosp. (1983-92) 151 LDR 71

Fox Chase 130 LDR/HDR 82

MSKCC (Harrison et al.) 126 LDR 82

Inst. Claudius Regaud 112 LDR/HDR 89

MSKCC (Alekhteyar et al.) 105 LDR 86

Institute Gustave Roussy 50 LDR 62

Tata Memorial Hospital (1990-2003) 155 LDR/HDR 71

LITERATURE REVIEW

Page 23: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

10 year local control - 91.7%

LONG TERM DATA TMH (TMH – UNPUBLISHED 2012)

Page 24: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

Laskar et al, Pediatric Blood & Cancer 2007

Page 25: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

RESULTS

Page 26: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

INTERSTITIAL BRACHYTHERAPY IN THE ERA of

IMRT / IGRT / DOSE PAINTING WITH NUMBERS

Hong et al., IJROBP 2004Lancet Oncology 2006

Page 27: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

IMAGE GUIDED BRACHYTHERAPY

Page 28: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

2500 INR = 40 USD

300INR – 6 USD

Brachy: 450 USD (At TMH)IMRT: 1400 USD (At TMH)Protons: 100-200,000 USD

Page 29: IMRT vs. BRACHYTHERAPY FOR SOFT TISSUE SARCOMA. EXTERNAL RT IN STS NCI Trial (Yang JC et al, JCO 1998) Extremity / Superficial Trunk STS (n=141) LSS Alone

IMRT BRT Verdict

Local Control *** **

Complications ** ***

Functional Outcome

** **

QOL No Data No Data

Treatment Duration

* ****

Treatment Cost ** ***

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