Disclosures Paid Consultant, MedQIA LLC Paid Consultant, Agios Pharmaceuticals, Inc. Consultant, Genentech Consultant, Siemens Medical Systems B.M. Ellingson,

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Presentation transcript:

Disclosures Paid Consultant, MedQIA LLC Paid Consultant, Agios Pharmaceuticals, Inc. Consultant, Genentech Consultant, Siemens Medical Systems B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011

Apparent diffusion coefficient (ADC) measured clinically reflects extracellular water ADC is dependent on tumor cell density (Ellingson, 2010; Sugahara, 1999; Lyng, 2000; Chenevert, 2000; Gaurain, 2001; Nonomura, 2001; Guo, 2002; Chen, 2005; Hayashida, 2006; Manenti, 2008; Kinoshita, 2008 –  Cell Density (hypercellular) =  ADC –  Cell Density (hypocellular) =  ADC Diffusion MR Characteristics of the Central Nervous System Viable Tumor (Dark) Necrotic Core Edema ADC Map From: Ellingson, J Magn Reson Imaging, 2010 B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011

The Functional Diffusion Map (fDM) (Moffat, 2005; 2006; Hamstra, 2005; 2008; Ellingson, 2010) From: Ellingson, JMRI, 2010 B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011

Graded fDMs Allow Visualization and Quantification of Growing Tumor + Hypercellular+ Hypocellular Biological Calibration From: Ellingson, JMRI, 2010 B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011

Graded fDMs Allow Better Visualization of Growing Tumor + Hypercellular+ Hypocellular B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011

What about anti-angiogenic therapy? B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011

What about anti-angiogenic therapy? B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011

What about anti-angiogenic therapy? B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 Apparent diffusion coefficient (ADC) measured clinically reflects extracellular water Large changes in ADC after anti-angiogenic therapy reflect (largely) reduction in edema Subtle decreases in ADC after anti-angiogenic treatment are likely to contain solid / infiltrating tumor

What about anti-angiogenic therapy? B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011

What about anti-angiogenic therapy? B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011

What about anti-angiogenic therapy? B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011

What about anti-angiogenic therapy? B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 Hypotheses: 1. Traditional fDMs (single threshold)  edema changes + tumor growth  greater risk of failure

What about anti-angiogenic therapy? B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 Hypotheses: 1. Traditional fDMs (single threshold)  edema changes + tumor growth  greater risk of failure 2. Graded fDMs  tumor growth  greater risk of failure

What about anti-angiogenic therapy? B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 Hypotheses: 1. Traditional fDMs (single threshold)  edema changes + tumor growth  greater risk of failure 2. Graded fDMs  tumor growth  greater risk of failure 3. Graded fDMs + pre-treatment ADC + T1+C  active tumor burden  GREATEST RISK (BEST PREDICTOR) Pope, Radiology, 2009; Pope, AJNR, 2011

Methods B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 Patients N = 77 patients - Pathology confirmed GBM with recurrence confirmed via histology or clinical features - Regularly treated every 2 weeks per cycle with becacizumab (5-10 mg/kg) - Baseline & minimum of one follow-up with high-quality diffusion MRI MRI Clinical MR sequences on 1.5T T2w, FLAIR, T1w, T1+C 3-5mm slice thickness Diffusion MRI w/ twice refocused spin echo preparation ADC calculated from b=0 and b=1000 s/mm 2

Methods B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 Image Registration All images registered to Baseline T1 weighted images Mutual information + 12 dof transformation Graded fDM Calculation - Voxel-wise subtraction - Each voxel classified according to relative difference from previous calibration studies From: Ellingson, JMRI, 2010

Methods B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 Traditional fDM  ΔADC beyond 0.4 um 2 /ms

Methods B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 Traditional fDM  ΔADC beyond 0.4 um 2 /ms Graded fDM  ΔADC between 0.25 and 0.4 um 2 /ms (7.5% probability of occurring randomly)

Results B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011

From: Ellingson, Neuro Onc, 2011 Results Conventional response does not predict survival

Results B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 Conventional response does not predict survival

Results B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 Graded fDM regions are localized to post-treatment contrast enhancement

Results B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 Traditional and graded fDMs both predict survival

Results B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 T1+C is better than FLAIR

Results B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 Graded fDMs are better than traditional fDMs

Results B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 Graded fDMs in T1+C

Results B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 ADC distribution for graded fDMs is different than traditional fDMs and contrast-enhancing regions Chi-squared goodness of fit, P < 0.05 Between CE and graded fDMs For 46 of 77 patients

Results B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 ADC distribution for graded fDMs is different than traditional fDMs and contrast-enhancing regions Chi-squared goodness of fit, P < 0.05 Between CE and graded fDMs For 46 of 77 patients

Results B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 ADC distribution for graded fDMs is different than traditional fDMs and contrast-enhancing regions Chi-squared goodness of fit, P < 0.05 Between T1+C and graded fDMs For 46 of 77 patients Graded fDMs  FILTER

Results B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 Graded fDMs + Pre-Tx ADC Characteristics

Results B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 Graded fDMs + Pre-Tx ADC Characteristics in T1+C  BEST PREDICTOR

Results B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 Graded fDMs + Pre-Tx ADC Characteristics in T1+C  BEST PREDICTOR

Summary B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 Graded fDMs + Pre-Tx ADC Characteristics in T1+C  BEST PREDICTOR

Summary B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 Graded fDMs + Pre-Tx ADC Characteristics in T1+C  BEST PREDICTOR

Conclusions Both traditional and graded fDMs in FLAIR and T1+C were predictive of OS B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011

Conclusions Both traditional and graded fDMs in FLAIR and T1+C were predictive of OS Subtle changes in ADC after anti-angiogenic therapy w/in T1+C may reflect active tumor burden B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011

Conclusions Both traditional and graded fDMs in FLAIR and T1+C were predictive of OS Subtle changes in ADC after anti-angiogenic therapy w/in T1+C may reflect active tumor burden Graded fDMs + Pre-Tx ADC Characteristics in T1+C BEST PREDICTOR Median Survival Advantage of 7 months B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011

Radiology Whitney Pope, M.D., Ph.D. Dieter Enzmann, M.D. Jonathan Goldin, M.D. MedQIA Neurology/Neuro-Oncology Timothy Cloughesy, M.D. Albert Lai, M.D., Ph.D. Phioanh (Leia) Nghiemphu, M.D. Thank You! B.M. Ellingson, Ph.D., Dept. of Radiological Sciences, David Geffen School of Medicine at UCLAISMRM, Montreal, 2011 Neurosurgery Linda Liau, M.D. Bob Shafa, M.D. Antonio DeSalles, M.D. Pathology Paul Mischel, M.D. Bill Yong, M.D. David Geffen School of Medicine Taryar Zaw, B.S. Korosh Neini, M.D. Bobby Harris, B.S. Carissa White, B.S. Medical College of Wisconsin Kathleen Schmainda, Ph.D. Peter LaViolette, B.S.