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Tumor Perfusion or Metabolism for Predicting Early and Late Treatment Response in Advanced Rectal Cancer? - PowerPoint PPT Presentation


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Tumor Perfusion or Metabolism for Predicting Early and Late Treatment Response in Advanced Rectal Cancer? . Avinash Kambadakone Ramesh 1 Anna Galluzzo 1 Onofrio Catalano 1 Lawrence Blaszkowsky 2 C G Willett 3 Dushyant Sahani* 1.

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slide1

Tumor Perfusion or Metabolism for Predicting Early and Late Treatment Response in Advanced Rectal Cancer?

AvinashKambadakone Ramesh1

Anna Galluzzo1

Onofrio Catalano1

Lawrence Blaszkowsky2

C G Willett3

Dushyant Sahani*1

1Department of Abdominal Imaging and Intervention, 2Department of Oncology, Massachusetts General Hospital

3 Department of Radiology, Duke University

disclosures
Disclosures
  • Dushyant Sahani MD has received Research Grants from GE healthcare
  • NCI grants (R21 CA099237 to CGW and PO1 CA80124 to RKJ)"
slide3

Advanced stage Rectal Cancer (T3>) conventionally treated preoperative chemo-radiation followed by curative resection

Targeted therapies (anti-angiogenic drug) in a neo-adjuvant setting (+C-XRT) have shown to improve the patient outcome in rectal cancer.

Background

Howe et al J Natl Cancer Inst 2001, Lindmark et al Dis Colon Rectum 1994, Willett et al Nat Med 2004

Introduction • Objectives • Materials and Methods • Results • Conclusion

slide4

Background

  • Evaluation of treatment response to targeted therapies by measuring changes in tumor burden using morphological assessment is not reliable
  • Perfusion CT (CTp) has shown to be a validated surrogate to measure early treatment changes
  • 18 FDG-PET/CT - effective modality to measure metabolic response following chemo-radiation in rectal cancer

RECIST

WHO

540 mm

598mm

350 mm

180mm

Sahani et al Radiology 2005, Bellomi et al Radiology 2007, Sahani et al Radiology 2008

Zhu et al The Oncologist 2008, Rosenberg et al Int J Colorect 2009

Introduction • Objectives • Materials and Methods • Results • Conclusion

slide5

Locally advanced rectal cancer

To EVALUATE and COMPARE treatment effects with CTp and 18FDG-PET

EARLY changes after Bevacizumab therapy

LATE changes following chemoradiation (C-XRT)

To assess if the baseline tumor perfusion and SUV values can PREDICT treatment response and long term outcome

To CORRELATE the baseline tumor perfusion and SUV values with nodal stages and tumor volume

Aims and Objectives

Introduction • Objectives • Materials and Methods • Results • Conclusion

study design
Study Design

HIPPA Compliant IRB approved Prospective Study

Pre operative staging

19 patients (2003 - 2008)

13M:6F (Mean age 56 yrs, range 38-69yrs)

Locally advanced Rectal cancer

(Stage T3 or above) and no distant metastases

MRI (n=17) and EUS (n=2)

18 patients - T3

1 patient - T4

Introduction • Objectives • Materials and Methods • Results • Conclusion

slide7

Study Design

6-10 weeks

2 weeks

6 weeks

16 patients

9M:6F

Mean-55yrs

CTp1

CTp2

CTp3

4-6 weeks after

treatment

completion

10-14 days after

start of BVZ

Baseline

PET1

PET 3

PET 2

3 patients

3M

Mean-57yrs

Introduction • Objectives • Materials and Methods • Results • Conclusion

slide8

Scanning Technique

BV

MTT

PS

CT perfusion

18 FDG PET

BF

  • Fasting 6 hrs
  • 10-20 mCi of 18-FDG, delay 45 min
  • Static and emission scans
  • Section thickness of 2.5-3.5mm.
  • IV contrast (370mgI/ml) – 70 ml @ 7cc/sec
  • Delay = 7-10 sec
  • First pass - Cine acquisition for 45 sec
  • Delayed phase
    • Limited acquisition (15)
    • kVp 80-100 and mA 200-240
  • Metabolic quantification
  • Standardized uptake value (SUV)
  • GE deconvolution method
  • Advantage Windows 4.0, CT perfusion 3.0

Introduction • Objectives • Materials and Methods • Results • Conclusion

slide9

Data Analysis

  • Response Assessment
  • Responders – Tumor downstaging at surgery
  • Non responders – Tumor staging unchanged at surgery
  • Long term outcome (follow up of 24 months)
  • - Evaluation of recurrence and metastases
  • Nodal staging
  • N0- No Nodal metastases
  • N1- Metastasis to 1-3 regional nodes
  • N2- 4 or more regional nodes
  • Tumor L-T product

Introduction • Objectives •Materials and Methods • Results • Conclusion

slide10

Results

Early CTp vs SUV changes 2 weeks following start of therapy

32%

5%

21%

10%

16%

(p=0.5)

(p=0.01)

(p=0.4)

(p=0.07)

(p=0.05)

No change in SUV

Drop in BF and PS

Introduction • Objectives • Materials and Methods • Results • Conclusion

slide11

Results

Late CTp vs SUV changes following completion of treatment

77%

59%

87%

37%

54%

(p<0.01)

(p<0.01)

Substantial drop in tumor perfusion and metabolism

Introduction • Objectives • Materials and Methods • Results • Conclusion

slide12

BVZ

Post CXRT

Baseline

Sag

Sag

Sag

18FDG PET

2.5

12.4

12.5

Ax

Ax

Ax

CTP

26 ml/100g/min

117 ml/100g/min

63 ml/100g/min

Introduction • Objectives • Materials and Methods • Results • Conclusion

slide13

Results

Responders (n=10) vs Non-responders (n=9)

  • No significant difference in baseline tumor CTp and tumor SUV between R & NR
  • After C-XRT, higher drop in perfusion values and SUV values in R than NR

Baseline 18 FDG PET

Baseline CTp

Introduction • Objectives • Materials and Methods • Results • Conclusion

slide14

Results

Long Term Outcome (Mean Follow up -32 months)

Favorable LT outcome

- Lower baseline perfusion (BF, PS) values

- Higher baseline SUV values

Introduction • Objectives • Materials and Methods • Results • Conclusion

slide15

Results

Nodal Stage

Tumor L-T product

N2- 12 patients, N1- 5 patients, N0- 2 patients

L-T product >10 (18.8)= 11 patients

L-T product <10 (6.5) = 8 patients

  • No significant association between
  • the perfusion parameters, SUV values and tumor L-T product at baseline

Advanced nodal disease - higher perfusion

Introduction • Objectives • Materials and Methods • Results • Conclusion

conclusion
Conclusion

CT perfusion is a more robust surrogate to evaluate early antiangiogenic activity in advanced rectal cancer

Both CT perfusion and FDG PET can be used as reliable indicators to measure late tumor response following completion of treatment.

Responders show substantially greater drop in perfusion and metabolic activity compared to non responders.

Introduction • Objectives • Materials and Methods • Results • Conclusion

conclusion1
Patients with favorable LT outcome show lower baseline perfusion (BF, PS) values and higher baseline SUV values

Tumors with advanced nodal stage have higher perfusion values

There is no significant association between tumor L-T product, perfusion parameters and tumor metabolic activity

Conclusion

Introduction • Objectives • Materials and Methods • Results • Conclusion