Multi-parametric MRI for Radiotherapy Response Prediction in Rectal Cancer

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1 Multi-parametric MRI for Radiotherapy Response Prediction in Rectal Cancer Dr Trang Pham Radiation Oncologist PhD Supervisors: Prof Barton, A/Prof Liney, Dr K Wong

2 Current Status in Locally Advanced Rectal T2-weighted MRI Cancer Advances Chemoradiotherapy and TME surgery LRR (20-30% 7-10%) pcr = 15%-27% MRI (morphologic) - soft tissue definition and local staging Limitations Variable treatment response (25-45% minimal response) 45% require permanent colostomy McCarthy Cochrane Review 2012 Valentini IJROBP 2001, JCO 2011 Zeestraten Sem Rad Onc 2012

3 Functional MRI for Radiotherapy Response Prediction Diffusion MRI Tumour Cellularity Perfusion MRI Tumour Vascularity 3D Analysis Tumour Heterogeneity Radiotherapy Response Prediction Good Responder Poor Responder Avoid Surgery Wait-and-watch Intensification/ Alteration treatment

4 Clinical complete response Wait-and-watch Study Median follow-up Local recurrence UK OnCoRe* (2015) 33 months 44/129 (34%) Brazil* (Habr-Gama 2011) 65 months 8/173 (5%) Netherlands (Maas 2011) 25 months 1/21 (5%) US MSKCC (2012) 28 months 6/32 (19%) *Complete response: DRE and Endoscopy Absence of residual ulceration, stenosis, or mass MRI normal imaging of (meso)rectum not standardized

5 Diffusion Weighted Imaging (DWI) Movement of water in tissue Tumour Restricted Diffusion Low Normal Tissue Free Diffusion High Tumour Cellularity Distinguish between viable tumour and necrosis Radiotherapy response prediction

6 DWI Prediction of Radiotherapy Response Meta-analyses: van der Paardt Radiology 2013 DWI better than T2-W MRI (Sensitivity 84% vs 50%) DWI Sensitivity 84%, Specificity 84% Joye et al Radioth Oncol 2014 Prediction of pcr pre sensitivity 69%, specificity 68% post sens 78%, spec 72%

7 Dynamic Contrast Enhanced (DCE) Tumour microvascular environment Tumour Angiogenesis Hypoxia Radiotherapy response prediction Zahra et al pre-treatment: high value - predictive of good response - Orbeholzer (2013), Intven (2014), George (2001) MVD, VEGF (De Lussanet, Yeo, George)

8 Microvascular Architecture Heterogeneity Normal Adenocarcinoma Heterogeneity in tumour vascularity

9 Purpose Prospectively evaluate multi-parametric MRI (DWI and DCE) for therapeutic response prediction in locally advanced rectal cancer Good responders vs. Poor responders Multi-parametric histogram analysis technique: 3D Tumour function and heterogeneity

10 MRI 1. T2-Weighted 2. DWI RESOLVE 3. DCE TWIST In-plane resolution: 1.1 x 1.1 Thickness: 4mm Methods Patient Eligible ct3-4/n+ rectal Ca chemoradiotherapy and surgery Accrual Target 35 DWI+DCE =29 DWI only =2 Dropout=1 Unanalyzable data=1 Commence CRT Complete CRT MRI-Sim Liverpool Hospital Surgery

11 DCE Analysis Strategy 1. Commercial Software 3D, Tissue 4D Siemens 2. In-house Code Matlab 3. WIP Software OncoTreat Siemens Native T1 Map 4. map Define volume of interest Signal intensity curve TWIST High temporal resolution 5s Tissue 4D

12 Motion Buscopan Peristalsis Patient Motion Registered

13 Multi-parametric MRI Complete responder AJCC TRG0 - no viable cancer cells (pcr) Pre-CRT Week 3 CRT Post-CRT T2-weighted DWI-RESOLVE Minimal distortion DWI calculated b=1400 map DCE

14 Voxel-by-voxel Map and Histograms Complete Responder (pcr, TRG0) Pre- 57% Median 929x10-6 During 59% Median1404x10-6 Post Median 1582x %

15 Voxel-by-voxel Maps and Histograms Complete Responder (pcr, TRG0) Pre- 80% 20% Median 71 x 10-3 Median 74 x 10-3 During 71% 29% Post 98% Median 48 x 10-3

16 Maps and Histograms: Poor Responder (TRG2) Pre- During Post Necrosis Viable 54% 59% 62% Median 985 x 10-6 Median 1167 x 10-6 Median 1362 x 10-6

17 Pre- During Maps and Histograms Poor Responder (TRG 2) Median 118 x % Median 100 x % Post 39% Median 4342 x 10-3

18 Perfusion Tumour Function for Poor Responder (TRG2) Tumour Perfusion?Angiogenesis maps T1 PRE T2 WEEK 3 T3 POST TUMOUR HYPOXIA

19 Multi-parametric Assessment Pre- During Post 0% 0% 0% 0% 0% 0% 0% 0% 0% Complete Responder (pcr, TRG0) 14% 5% 1% 43% 31% 6% 3% 20% 6% 4% 39% 28% 0% 1% 1% 1% 34% 63% Poor Responder (TRG2) 2% 0% 0% 29% 24% 0.8% 1% 0.8% 0.2% 10% 30% 8% 2% 28% 9% 1% 22% 14% 23% 21% 0.2% 14% 29% 7% 4% 13% 7%

20 Tumour Physiology Summary - Quantifying Tumour Function and Heterogeneity Intratumour Heterogeneity Multi-parametric Prediction of Response Pre DWI-MRI Cellularity 3D Histograms Week 3 Post DCE-MRI Perfusion Cellularity maps Perfusion maps Good Responder AJCC TRG1

21 Acknowledgements PhD Supervisors Prof Michael Barton, A/Prof Gary Liney, Dr Karen Wong Ms. R. Rai, Dr M. Lee, Dr D Moses, Prof.C.Henderson, Mr D. Roach, Dr J. Shin, Dr S. Lim, Dr M. Lin RANZCR Withers and Peters Grant 2014