Feasibility and initial dosimetric findings for a randomized trial using dose painted multi-parametric-mri defined targets in prostate cancer

Transcription

1 Feasibility and initial dosimetric findings for a randomized trial using dose painted multi-parametric-mri defined targets in prostate cancer Thoughts on the use of MRI in the treatment of prostate cancer and the HEIGHT Trial Presented at the FLAAPM Fall Chapter Meeting, September 9, 2016 Elizabeth L. Bossart, Ph.D., Radka Stoyanova, Ph.D., Kiri Sandler, M.D., Matthew Studenski, Ph.D., Amber Orman, M.D., Matthew Abramowitz, M.D., Alan Pollack, M.D., Ph.D. Disclosures None 1

2 Dose Painting of Prostate MP-MRI Lesions HEIGHT: HYPOFRACTIONATED EXTERNAL BEAM IMAGE-GUIDED HIGHLY TARGETED RT HEIGHT Radiotherapy randomized trial comparing a dose painted boost to the MP MRI defined tumor volume(s) with standard treatment. 2

3 HEIGHT Trial Standard Arm of Treatment 80Gy in 40 fractions to the prostate PTV HEIGHT Arm of Treatment 76Gy in 38 fractions to the prostate PTV 89.3Gy in 38 fractions to the MP-MRI indicated prostate lesion Dose Painting of Prostate MP-MRI Lesions MULTI-PARAMETRIC MRI (MP-MRI) 3

4 Multiparametric MRI MP-MRI is essentially any functional form of imaging used to supplement standard anatomical T1 and T2- weighted imaging. Dynamic Contrast-Enhanced (DCE) MRI Diffusion-weighted imaging (DWI) including apparent diffusion coefficient (ADC) maps MR Spectroscopy Multiparametric MRI MP-MRI is essentially any functional form of imaging used to supplement standard anatomical T1 and T2- weighted imaging. Dynamic Contrast-Enhanced (DCE) MRI Diffusion-weighted imaging (DWI) including apparent diffusion coefficient (ADC) maps) MR Spectroscopy 4

5 MP-MRI Typically on 3T scanner i. Axial T2w-MRI of the pelvis resolution 0.7x0.7x2.5 mm no gap; rectangular FOV (360x264); 72 slices; TR = 6300 ms/te = 112ms; flip angle = 120 degrees ii. Axial T1w GRE MR images with identical resolution and spacing as above (TR = 5.1ms/TE = 2.3ms; flip angle = 10 degrees) iii. DWI single-shot echo-planar imaging using diffusionmodule and fat-suppression pulses. Water diffusion is measured in 3D using b = 50, 500, 1000 s/mm 2. (TR = 5700 ms/te = 80 ms; parallel imaging factor of 3, 38 sections, 2.5mm thick sections and in-plane resolution of 2.25x2.25mm. ADC maps created from these. iv. DCE-MRI collected every seconds post contrast injection Bowel Preparation Avoid gas producing foods for 2 days Drink a 10oz bottle of magnesium citrate at 6pm the night before Do a Fleet enema 2 hours prior to leaving home for the scan Drink 16oz of water minutes prior to the scan 5

6 Multi-Parametric MRI (MP-MRI) T2- weighted DWI T1-precontrast T1-early enhancement T1-late washout Dynamic Contrast Enhanced-MRI T1-early enhancement T1-late washout 6

7 T2-weighted DWI DCE 7

8 Planning Constraints Structure SIMRT HTIMRT Bladder No more than 25% receives 65Gy No more than 25% receives 61.75Gy No more than 50% receives 40Gy No more than 50% receives 38Gy No more than 17% receives 65Gy No more than 17% receives 61.75Gy Rectum/Anus No more than 35% receives 40Gy No more than 35% receives 38Gy L/R Femur Maximum point dose of 50Gy Maximum point dose of 47.5Gy Bowel Less than 150cc to receive 40Gy Less than 150cc to receive 38Gy PTV (prostate) At least 95% of the volume to receive a dose of 80Gy At least 95% of the volume to receive a dose of 76Gy GTV (small At least 95% of the volume to receive imaging Same as PTV (prostate) a dose of 89.3Gy (2.35Gy/fx) volume) Example Plan Comparison for the This image cannot currently be displayed. Pre study 8

9 Patient Statistics for the Pre-Study # Patients 20 Age Range years (Mean: 66.7 years) #Patients with Gleason Score of # Patients with Tumor Category T1 T2 T Initial PSA ng/ml (Mean: 8.3 ng/ml) Prostate Volume cc (Mean: 37.1 cc) Patients with Risk Category Low Intermediate High GTV Volume cc (Mean: 3.9 cc) Normal Tissue Sparing between arms of the trial for the pre-study Standard Arm (n=20) HTIMRT Arm (n=20) p value % Volume a Dose in Gy Mean (Min, Max) % Volume receiving a particular dose %V40 (Rectum/Anus) 28.7 (20.8, 34.5) 26.8 (20.4, 36.0) %V65 (Rectum/Anus) 11.3 (6.7, 19.8) 9.6 (4.6, 12.3) %V80 (Rectum/Anus) 3.4 (0.5, 8.3) 0.8 (0.1, 2.4) < %V40 (Bladder) 36.2 (12.1, 53.9) 33.3 (10.4, 51.5) %V65 (Bladder) 16.0 (5.4, 36.1) 13.9 (4.8, 33.0) %V80 (Bladder) 8.0 (3.0, 25.3) 3.7 (1.0, 12.3) < V50cc (Bowel) 2.7 (0.0, 18.9) 2.6 (0.0, 17.8)

10 Normal Tissue Sparing between arms of the trial for the pre-study Standard Arm (n=20) HTIMRT Arm (n=20) p value Dose to Volume (Gy) Mean (Min, Max) doses to targets GTV (Gy) 83.8 (77.1, 87.2) 91.7 (87.0, 94.8) < GTV + 3mm (Gy) 83.8 (79.4, 88.1) 89.2 (79.0, 94.8) < P CTV (Gy) 83.8 (78.4, 88.8) 84.4 (73.7, 94.8) <0.48 P PTV (Gy) 84.1 (69.6, 90.3) 82.1 (66.7, 95.5) < Dose to 95% of target (Gy) Mean (Min, Max) coverage dose to 95% of the target GTV (Gy) 81.4 (79.9, 84.9) 89.7 (89.3, 90.3) < GTV + 3mm (Gy) 81.3 (80.0, 84.6) 84.7 (82.9, 87.0) < P CTV (Gy) 81.2 (79.8, 84.0) 78.2 (76.5, 81.1) < P PTV (Gy) 80.4 (80.0, 80.8) 76.5 (76.0, 78.4) < Patient Statistics for the Trial (so far) # Patients 15 Age Range years (Mean: 71 years) #Patients with Gleason Score of # Patients with Tumor Category T1 T2 T Initial PSA ng/mL (Mean: 6.9 ng/ml) Prostate Volume cc (Mean: 60.1 cc) Patients with Risk Category Low Intermediate High GTV Volume cc (Mean: 2.5 cc) 10

11 Normal Tissue Sparing between arms of the trial Standard Arm (n=8) HTIMRT Arm (n=7) HTIMRT Replan % Volume a Dose in Gy Mean (Min, Max) % Volume receiving a particular dose %V40 (Rectum/Anus) 23.1 (17.6, 27.9) 16.3 (6.7, 28.3) 18.9 (14.5, 24.4) %V65 (Rectum/Anus) 8.1 (4.3, 11.1) 4.0 (1.0, 8.8) 3.8 (2.5, 5.7) %V80 (Rectum/Anus) 1.5 (0.4, 3.0) 0.1 (0.0, 0.2) 0.3 (0.0, 0.7) %V40 (Bladder) 26.7 (15.7, 37.8) 16.9 (3.9, 26.4) 25.0 (20.2, 31.9) %V65 (Bladder) 10.3 (7.0, 13.5) 6.7 (1.4, 11.2) 9.4 (8.1, 10.8) %V80 (Bladder) 4.1 (2.7, 5.6) 1.3 (0.0, 4.5) 2.5 (1.6, 3.7) V50cc (Bowel) 0.0 (0.0, 1.5) 0.0 (0.0, 0.0) 0.0 (0.0, 1.4) Normal Tissue Sparing between arms of the trial Standard Arm (n=8) HTIMRT Arm (n=7) HTIMRT Replan Dose to Volume (Gy) Mean (Min, Max) doses to targets GTV (Gy) 82.9 (81.1, 84.7) 91.5 (86.8, 94.7) 94.6 (93.9, 96.9) GTV + 3mm (Gy) N/A 86.8 (77.3, 94.7) 92.8 (92.4, 93.3) P CTV (Gy) 83.2 (75.5, 85.6) 80.6 (76.0, 94.7) 85.0 (83.9, 86.7) P PTV (Gy) 83.0 (71.3, 87.6) 79.7 (68.0, 94.7) 82.4 (81.3, 84.0) Dose to 95% of target (Gy) Mean (Min, Max) coverage dose to 95% of the target GTV (Gy) 81.7 (81.3, 82.8) 89.0 (88.9, 89.4) 93.2 (92.6, 94.4) GTV + 3mm (Gy) N/A 81.0 (79.5, 82.7) 89.4 (89.3, 89.9) P CTV (Gy) 81.8 (80.9, 82.6) 77.8 (76.7, 79.4) 80.3 (77.9, 81.7) P PTV (Gy) 80.2 (79.9, 80.6) 76.4 (75.9, 77.1) 76.3 (76.1, 76.6) 11

12 Favorable To High Risk A Phase II Randomized Trial of MRI Guided Prostate Boosts Via Initial Lattice Stereotactic vs Daily Moderately Hypofractionated Radiotherapy The Miami BLaStM Trial M P - M R I Stratify Risk group L Ki-67 e Length ADT s i o n R A N D O M I Z E Stereotactic Lattice (LEAD) GTV: Gy in 1 Fx, Day 1 CTV1: 76 Gy in 38 (2.0 Gy) Fxs Moderate Hypofractionation (HEIGHT) CTV1 76 Gy in 38 (2.0 Gy) Fxs GTV: 91.2 Gy (2.4 Gy/Fx) 98.5 Gy 2.0 Equiv 2 BLaStM Trial schema now in use Thank you for your attention! 12

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