advances in prostate learning objectives mr · pdf filedjavan j urol (2001); roehl j urol...
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Jelle Barentsz
Prostate MR Center of Excellence
Department of RadiologyRadboud University Nijmegen Medicaal CenterThe Netherlands
Advances in Prostate Advances in Prostate MR imagingMR imaging Learning Objectives
•• to show theto show the potentialpotential of of new new MRMRI I developments developments in in PCaPCa
•• to illustrate this from a to illustrate this from a clinicalclinical((radiation oncologyradiation oncology ) perspective) perspective
Learning Objectives
Learning ObjectivesMulti-parametic MRI
1. High resolution 1. High resolution T2T2WI: WI: anatomyanatomy
2. 2. DDiffusioniffusion WWeightedeighted IImaging: maging: functionfunction
3. 3. HHydrogenydrogen MRMR--SSpectroscopy: pectroscopy: functionfunction
4.4. DDynamic ynamic CContrast ontrast EEnhanced:nhanced: functionfunction
T2WI MRI: anatomy
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MRI: high soft tissue contrast Delineation of CTV:CT > MRI
CT Image MR Image
c. Villiers
Delineation of CTVAdditional Use of MRI
•• Smaller Smaller CTV (6.5%CTV (6.5%--34%)34%)
•• InterInter--observer variability observer variability ↓↓ (~63%)(~63%) at: at: -- Apex : Apex : ↓ ↓ ↓ ↓↓ ↓ ↓ ↓-- Base : Base : ↓ ↓↓ ↓-- SV : SV : ↓↓-- MidMid--gland : gland : -- RoachRoach IJROPB 1996, IJROPB 1996,
RashRash IJROPB 1999, IJROPB 1999, VilliersVilliers, , StrahlentherStrahlenther OnkoOnko 20062006
PCa, hematoma, fibrosis, prostatitis: low SI
MR-anatomy of PCa
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Patient 57 y, PSA 7; TRUS Bx: negative
1. 1. nnormalormal2. 2. BPHBPH3. 3. prostatitisprostatitis4. 4. ventralventral TZTZ tumortumor
YourYour diagnosis?diagnosis?
T2WI: PCa anatomy
“Erased Charcoal drawing sign”
T2WI: PCa anatomy
BPH: organised chaosBPH: organised chaos
• prostatectomy vs radiotherapy• decrease R+• nerve sparing• local therapy
• prostatectomy vs radiotherapy• decrease R+• nerve sparing• local therapy
T2WI: Local Staging
3T ERC:3T ERC:se se 87% 87% spsp 96%96%
3T ERC:3T ERC:se se 87% 87% spsp 96%96%
Futterer, Invest Radiol 2006, Heijmink, Radiology 20 07
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DWI:DWI: PCaPCa restrictedrestricted HH 22O O movementmovement
Multi-parametric MRI: DWI
Tightly packed cellular tissueTightly packed cellular tissueOrganised Organised galandulargalandular tissuetissue
Specificity, aggression!
Pearson Pearson CorrelationCorrelation
r = r = 0.73 0.73
p <p < 0.010.01
DWI: ADC-value versus Gleason score
HambrockHambrock, Radiology, in press, Radiology, in press
AlvaresAlvares, Radiology, in press , Radiology, in press
DWI: ADC-value vs Gleason score Multi-parametric MRI: DCE
DCE MRI: DCE MRI: PCaPCa increasedincreased vascularvascular permeabilitypermeability
SensitivitySensitivity!!
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Creatine
Creatine
Creatine
Creatine
CitrateCitrateCitrateCitrate
0.37 / 0.37 / 0.640.64
Cho + Cho + Cr Cr ↑↑CitCit
Metabolite Metabolite ratioratio
MR Spectroscopy MR Spectroscopy
For Ferrari drivers only?
You need EXPERIENCE how to drive
MR Spectroscopy
•• PSAPSA: : non non specificspecific marker : marker :
>4 >4 ngng/L: /L: senssens.: 80%, .: 80%, specspec.: 36%.: 36%
Djavan J Urol (2001); Roehl J Urol (2002); Pepe Uro l (2007), Schroeder JNCI (1998) Djavan J Urol (2001); Roehl J Urol (2002); Pepe Uro l (2007), Schroeder JNCI (1998)
Clinical Problems
•• DRE DRE is is notnot sensitivesensitive
-- senssens.: 37%.: 37%,, specspec.: 91%.: 91%
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•• Clinically Clinically insignificant insignificant cancers cancers are identified by are identified by chancechance
•• Important Important cancers are cancers are incorrectly incorrectly classified as classified as unimportant unimportant or areor are missedmissed
•• 3636-- 46% 46% undergradingundergrading of of Gleason scoreGleason score
Problems: TRUS Problems: TRUS BxBx Be aware! Be aware! EU Urologists are getting thereEU Urologists are getting there
Sciarra, European Urology 2011Sciarra, European Urology 2011
IntraprostaticIntraprostatic LocalizationLocalization AccuracyAccuracy::
T2T2--w : w : 70%70%
DWIDWI--MRI: MRI: 86%86%
HH--MRS: MRS: 81%81%
DCEDCE-- MRI: MRI: 85%85%
Jager AJR 1996; Scheidler Radiol 1999Jager AJR 1996; Scheidler Radiol 1999
Haider AJR 2007; Miao Eur J Rad 2007Haider AJR 2007; Miao Eur J Rad 2007
Futterer Radiol 2006, Reinsberg AJR 2007Futterer Radiol 2006, Reinsberg AJR 2007
Ito Br J Radiol 2003, Futterer Radiol 2006Ito Br J Radiol 2003, Futterer Radiol 2006
Multi- modality MRI: MR-guided biopsy
Gleason score 4+3
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• After ≥2 - biopsies: TRUS is + in 5-19% • After ≥2 - biopsies: TRUS is + in 5-19%
• with MR ~ 4 cores instead of ~ 12• with MR ~ 4 cores instead of ~ 12
• 93% (37/40) clinically significant tumors• 93% (37/40) clinically significant tumors
• MR-guided biopsy of TSR: + in 59% (40/68) • MR-guided biopsy of TSR: + in 59% (40/68)
3T MR-biopsy (n=68)
• 57% anterior tumors • 57% anterior tumors
Hambrock, J Urol 2010
Learning ObjectivesWhat is beyond the horizon?
1.1. ImprovementImprovement of of mpmp--MR MR directeddirectedbiopsybiopsy techniquestechniques
2. 2. AActive ctive SSurveillance, urveillance, ScreeningScreening
3. Will 3. Will mpmp--MRI MRI replacereplace Gleason?Gleason?
4. 4. FocalFocal therapytherapy
5. 5. NodesNodes: : nanonano--particlesparticles + + DWIDWI
Learning ObjectivesWhat is beyond the horizon?What is beyond the horizon?
1.1. ImprovementImprovement of of mpmp--MR MR directeddirectedbiopsybiopsy techniquestechniques
2. Active Surveillance, Screening2. Active Surveillance, Screening
3. Will 3. Will mpmp--MRI MRI replace Gleason?replace Gleason?
4. 4. FocalFocal therapytherapy
5. Nodes: 5. Nodes: nanonano--particles particles + + DWIDWI
Learning ObjectivesWhat is beyond the horizon?What is beyond the horizon?
1.1. ImprovementImprovement of of mpmp--MR MR directeddirectedbiopsybiopsy techniquestechniques
2. Active Surveillance, Screening2. Active Surveillance, Screening
3. Will 3. Will mpMRImpMRI replacereplace GleasonGleason??
4. 4. FocalFocal therapytherapy
5. 5. NodesNodes: : nanonano--particlesparticles + DWI+ DWI
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Biopsy with TRUS - mp-MRI fusion
with with TRUS TRUS –– MR MR ((ADCmap) ADCmap) fusionfusionwith with TRUS TRUS –– MR MR ((ADCmap) ADCmap) fusionfusion
Hit the most aggressive lesion
Learning ObjectivesFuture Potential
•• MRMR--robotrobot with MR guided with MR guided remote remote controlcontrol
Case: 59 y.o., PSA 10, 3x negative TRUS sessionsCase: 59 y.o., PSA 10, 3x negative TRUS sessions
DCEDCEDWIDWIT2T2--weightedweighted
First, diagnostic sessionFirst, diagnostic session
TSR 2TSR 2
MR-robot
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Perform biopsyPerform biopsy
HistopathologyHistopathologyGleason Gleason 4+34+3
Learning ObjectivesWhat is beyond the horizon?
1.1. Improvement of Improvement of mpmp--MRMR--directed directed biopsy techniquesbiopsy techniques
2. Active Surveillance, Screening2. Active Surveillance, Screening
3. Will 3. Will mpmp--MRI MRI replace Gleason?replace Gleason?
4. 4. FocalFocal therapytherapy
5. 5. NodesNodes: : nanonano--particlesparticles + DWI+ DWI
PZ PZ PCaPCa withwith focalfocal“hot spot” “hot spot” (Gl (Gl 4+34+3))
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Focal therapy
- Focal laser ablation
- HDR Brachytherapy / DIL IMRT
- Focal laser ablation
- HDR Brachytherapy / DIL IMRT
DWI with b values 0, 50, 600 ADC map showing restricted diffusion
Focal therapy
c. J. Feller, Palm Springs USA
Treatment temperature map Irreversible damage estimate
Laser Doses
Treatment #1177s @ 8.00W
Visible Damage10mm by 12mm
Animation – not in real-time
Focal therapy
c. J. Feller, Palm Springs USA
Damage Estimate
Irreversible damage estimate Post-treatment MRIT2 Pre-treatment Image
Axial Images
Thermal AblationTarget Area
Laser Fiber Trajectory
Prostate Capsule
Focal therapy
c. J. Feller, Palm Springs USA
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Focal therapy
- Focal laser ablation
- HDR Brachytherapy / DIL IMRT
- Focal laser ablation
- HDR Brachytherapy / DIL IMRT
Marker fusion CT- MRI
inaccuracy < 1 mminaccuracy < 1 mmat at peripheryperiphery of prostateof prostate
Huisman Radiology 2005
f-MR-based DIL IMRT Planning
van Lin IJROBP 2006IMRT: Partial boost to 90 Gy
Learning ObjectivesWhat is beyond the horizon?
1.1. Improvement of Improvement of mpmp--MRMR--directed directed biopsy techniquesbiopsy techniques
2. Active Surveillance, Screening2. Active Surveillance, Screening
3. Will 3. Will mpmp--MRI MRI replace Gleason?replace Gleason?
4. 4. FocalFocal therapytherapy
5. Nodes: 5. Nodes: nanonano--particles particles + + DWIDWI
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Pathway of spread
MRL detected in 41% patients Positive nodes outside routine PLND
Heesakkers et al Radiology 2009
SVIDetecting Nodal metastasis
in PCa
• Imaging (CT, MRI etc)- Less invasive- Inaccurate size
criterion
• Surgery (PLND)- Invasive, costly- Limited in coverage
• Imaging (CT, MRI etc)- Less invasive- Inaccurate size
criterion
• Surgery (PLND)- Invasive, costly- Limited in coverage
Vincent van GoghVincent van GoghSorrowing old manSorrowing old man
FeFe--nanoparticlesnanoparticles(20 nm)(20 nm)
FerumoxtranFerumoxtran--1010
(Combidex/Sinerem(Combidex/Sinerem))
FeFe--nanoparticlesnanoparticles(20 nm)(20 nm)
FerumoxtranFerumoxtran--1010
(Combidex/Sinerem(Combidex/Sinerem))
PatientPatient--toto--patientpatient correlationcorrelation (n=375)(n=375)CTCT MRL MRL
accuracyaccuracy 86% 86% → → 9191%%specificityspecificity 97%97% →→ 9393%%sensitivitysensitivity 34% 34% →→ 9393%%NPVNPV 89% 89% →→ 9797%%
ProbabilityProbability of of correct diagnosiscorrect diagnosis : : MRL MRL 91%91%PLND + CT PLND + CT 89%89%
Dutch study: 13 centres
Heesakkers et al Lancet Oncology 2008
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PSA ≥PSA ≥0.2 0.2 ngng/ml /ml 6 w. postop. + 6 w. postop. + 1 1 higher higher value, or a single PSA value, or a single PSA ≥≥0.5 0.5 ngng/ml; /ml; no bone no bone metastasesmetastases
•• 72% 72% (47/65) ≥1 (47/65) ≥1 ⊕⊕ node, node, 66/275/275 nodes >1 cmnodes >1 cm•• 6262% % had ≥had ≥1 1 ⊕⊕ node node with with low PSA low PSA ((<1.0<1.0))•• 77%77% and and 61%61% ≥≥1 1 ⊕⊕ node in regions node in regions not in CTV not in CTV for elective for elective
pelvic irradiation pelvic irradiation by the by the RTOGRTOG
Post Px recurrence: MRLMeijer, IJROPB in preparation
4. Many nodes are 4. Many nodes are not in CTVnot in CTV
Nodal Roach Formula: Low PPV
Deserno, IJROPB 2010
IMRT planning
• Accurate mapping of positive MRL nodes for IMRT has the potential:
- to reduce toxicity in normal tissue
- allows higher doseson the positive nodes
• Accurate mapping of positive MRL nodes for IMRT has the potential:
- to reduce toxicity in normal tissue
- allows higher doseson the positive nodes
IJROPB 2010IJROPB 2010
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Case
•• 60 60 yryr; ; initialinitial PSAPSA 66; ; GleasonGleason 4+34+3
•• DecDec 2005: Da Vinci 2005: Da Vinci PxPx: : T3B N1 T3B N1 MxMx R+ R+ •• FebFeb 2006: PSA 2006: PSA 0.220.22
WhatWhat treatmenttreatment: : hormonalhormonal palliativepalliativewholewhole pelvicpelvic radiationradiationparapara--aorticaortic nodesnodes??
March 2005 Combidex/Sinerem MRI
Case
•• MarchMarch 20052005 Combidex/Sinerem MRI: Combidex/Sinerem MRI:
•• 6 6 positivepositive pelvicpelvic nodesnodes
→ ADT + → ADT + 4D4D--IGIG--IMRTIMRT: : dosedose paintingpainting
Case 1Case 1
c M Dattoli
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Case
•• PSAPSA: : Nov 06:Nov 06: 0.00060.0006Apr 07:Apr 07: 0.0030.003
July 07: Stop ADTJuly 07: Stop ADT
•• PSAPSA:: AugAug 07:07: <0.01*<0.01*MarchMarch 08:08: <0.003<0.003MarchMarch 09:09: <0.003<0.003MarchMarch 10:10: <0.01*<0.01*
Combidex/Sinerem MRI November 2009
Due to approval Due to approval problems, problems, development development of of CombidexCombidexis is discontinueddiscontinued
But
But there is hope: DWI? Ferumoxytol? P904?
DWI helps to findbone and nodal metas
Future: Future: ferumoxytolferumoxytol: WIP: WIP24 24 hrshrs post post ferumoxytolferumoxytol24 24 hrshrs post Combidexpost Combidex
CTACTA post post ferumoxytolferumoxytol post post ferumoxytolferumoxytol + + GdGd
c. S Bravo, Orlandoc. S Bravo, Orlando
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•• Bone: Bone: DWI DWI MRI of MRI of pelvis pelvis & & spinespine•• Bone: Bone: DWI DWI MRI of MRI of pelvis pelvis & & spinespine
PSA Relapse: Imaging Protocol
•• Nodes: Nodes: Nanoparticle MRI (n.a.)Nanoparticle MRI (n.a.)DWI MRI of pelvis & spineDWI MRI of pelvis & spine
•• Nodes: Nodes: Nanoparticle MRI (n.a.)Nanoparticle MRI (n.a.)DWI MRI of pelvis & spineDWI MRI of pelvis & spine
•• Local: Local: DCEDCE-- and DWI MRI and DWI MRI •• Local: Local: DCEDCE-- and DWI MRI and DWI MRI
Learning ObjectivesPost-Brachy, PSA recurrence (1.8)
Post-Brachy, PSA recurrence
bone + X: bone + X: se 63% sp 64%se 63% sp 64%bone + X: bone + X: se 63% sp 64%se 63% sp 64% MRI: MRI: se 100% sp 88%se 100% sp 88%MRI: MRI: se 100% sp 88%se 100% sp 88%
Spine and pelvis is enough Lecouvet JCO 2007
Post-Brachy, PSA recurrence
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• Bone: DWI MRI of pelvis & spine• Bone: DWI MRI of pelvis & spine
PSA Relapse: Imaging Protocol
• Nodes: Nanoparticle MRI (n.a.)DWI MRI of pelvis & spine
• Nodes: Nanoparticle MRI (n.a.)DWI MRI of pelvis & spine
• Local: DCE- and DWI MRI • Local: DCE- and DWI MRI
StephensonStephenson nomogramnomogram accurately predicted accurately predicted ⊕⊕ MRL result MRL result →can be used to →can be used to identify patients identify patients
for pelvic radiationfor pelvic radiationbutbut
We need We need better imaging better imaging to to decrease the CTVdecrease the CTV
Post Post PxPx recurrencerecurrence: MRL: MRLMeijer,Meijer, IJROPBIJROPB inin preparationpreparation
Meijer, IJROPB Meijer, IJROPB 20102010
Future: MRL or 11C Choline PET/CT?
MRL• 151 positive nodes in 23/29 patients
mean size 4.9 mm*
11C Choline PET/CT• 34 positive nodes in 13/29 patients
mean size 8.4 mm*
MRL• 151 positive nodes in 23/29 patients
mean size 4.9 mm*
11C Choline PET/CT• 34 positive nodes in 13/29 patients
mean size 8.4 mm*
* p<0.001 more and smaller nodes detected
Future: MRL or 11C Choline PET/CT?
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USPIOUSPIO--MRIMRIUSPIOUSPIO--MRIMRI Choline PET/CTCholine PET/CTCholine PET/CTCholine PET/CT
Negative PET/CT: post-RP (T3b N0 M0)
• Bone: DWI MRI of pelvis & spine• Bone: DWI MRI of pelvis & spine
PSA Relapse: Imaging Protocol
• Nodes: Nanoparticle MRI (n.a.)DWI MRI of pelvis & spine
• Nodes: Nanoparticle MRI (n.a.)DWI MRI of pelvis & spine
• Local: DCE- and DWI MRI • Local: DCE- and DWI MRI
post Pxpost Px DCE MRI!DCE MRI!
T2T2--w w DCE KDCE K transtrans
Local post radiotherapy Local post radiotherapy recurrence: DCErecurrence: DCE-- MRIMRI
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•• MRI MRI is the best technique to show the is the best technique to show the prostate and its tumor localization and prostate and its tumor localization and aggressionaggression
•• MRI MRI is the best technique to show the is the best technique to show the prostate and its tumor localization and prostate and its tumor localization and aggressionaggression
Take home messages
•• MRI MRI is a superior technique in showing is a superior technique in showing small small nodal nodal and bone and bone metastatesmetastates
•• MRI MRI is a superior technique in showing is a superior technique in showing small small nodal nodal and bone and bone metastatesmetastates
•• integration of Rth and MRI still needs a integration of Rth and MRI still needs a lot of lot of research research but offers but offers great potentialgreat potential
•• integration of Rth and MRI still needs a integration of Rth and MRI still needs a lot of lot of research research but offers but offers great potentialgreat potential
Thank you for your attention
Bomers, Debats, Fütterer, Bomers, Debats, Fütterer, Hambrock, Huisman, Hambrock, Huisman, Heijmink, Heerschap, Heijmink, Heerschap, Hoeks, Scheenen, Yakar.Hoeks, Scheenen, Yakar.
HulsbergenHulsbergen, van Lin, , van Lin, van Oort, Witjes, Dattolivan Oort, Witjes, Dattoli