igrt in gynecologic malignancies
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IGRT in Gynecologic MalignanciesArno J. Mundt MD
Professor and ChairDepartment of Radiation OncologyUniversity of California San Diego
La Jolla CA
Image-Guided RT?
“Image guided” is non-informativeRT has always been guided by imagesDefinition of IGRT is not standardized and is open to various interpretationsGlobal definition might include any aspect of RT involving imaging, from fluoroscopic simulation to CT-based planning, to weekly port films
RTOG Research Plan 2002-2006IGRT Committee ReportMichalski J, Purdy JA, Gaspar L, et al.
Int J Radiat Oncol Biol Phys 2001;51:60-5
“IGRT refers broadly to treatment delivery using modern imaging methods, such as CT, MRI, PET and Ultrasound, in target and non-target structures and in RT definition, design and delivery…”
“IGRT includes, but is not limited to, 3DCRT, IMRT, stereotactic radiosurgery, stereotactic RT, and brachytherapy….”
IntroductionRecommend a more focused definition
Highlight the 2 most important roles of imaging in modern RT:
Improved Target DelineationImproved Treatment Delivery
IGRT DefinitionUse of modern imaging modalities, especially those incorporating functional or biological information, to
augment target delineation
and
Use of imaging, particularly in-room approaches, to adjust for target motion and positional uncertainty,
and, potentially, to adapt treatment to tumor response
New FrontierImage-Guided Radiotherapy
Strong rationale in gynecologic tumors, particularly when IMRT is used
CT is not ideal for imaging tumors and normal tissues Gynecology patients often difficult to setupConsiderable organ motion existsTumors shrink rapidly
Target DelineationTraditional method planar (flouroscopic) x-raysExternal beam fields based on visualized bony anatomyContrast used to define normal tissuesBrachytherapy doses prescribed to specified “Points” based on applicator position
2D planning → Poor target coverage and excess normaltissue exposure compared to 3D planning
Red Journal2006
43 cervical cancer ptsEvaluated adequacy of coverage of pelvic vesselsSurrogate for lymph nodesAdequate: >15 mm vessel to block edge
41/43 (95%) inadequate coverage with 2D based fields24/43 (56%) too generous (> 2 cm)Excess normal tissue exposure
Beyond CT ImagingInterest now focused on more sophisticated imaging for treatment planning
Magnetic Resonance Imaging (MRI)With ultra-small iron oxide particles (USPIO)Positron Emission Tomography (PET)18F-Deoxyglucose (FDG)Or combined PET/CT units
Red Journal (2005)
Fe Oxide nano-particleTaken up in benign lymph nodes by macrophages
7 mm margin around vessels encompassed 99% of pelvic nodes
FDG-PET particularly useful to identify involved nodesBoost to higher doses with IMRT
Ahmed Red Journal (2004)PET+ nodes: 60 Gy/2.4 Gy fxPET- nodes: 45 Gy/1.8 Gy fx
Mutic Red Journal (2003)PET+ Nodes: 59.4 Gy/1.8 Gy fx
PET- Nodes: 50.4 Gy/1.53 Gy fx
More Advanced Imaging
Dynamic-Contrast MRI (tumor hypoxia)
Cooper et al. RadiotherOncol (2000)
1H-MR spectroscopy (tumor vs normal tissue)
Okada et al. J MRI (2001)Okada (2001)
Alternative PET TracersMetabolic Abnormalities or Hypoxia11C-Choline (tumor vs normal tissue)11C-Methionine (amino acid transport)60Cu-ATSM (hypoxia)
Torizuka J Nucl Med (2003)11C-Choline imaging
MRI FDG-PET 11C-Choline PET
Less uptake in normal tissues
Tumor hypoxia inversely correlated with DFS and OS3y PFS normoxic (71%) and hypoxix (28%)Could be used to dose paint during external beam and brachytherapy
Normal Tissue DelineationNovel imaging techniques also valuable for normal tissue delineation
Roeske (2003)MR-Spectroscopy to identify active(red) marrow sites
Roeske (2005)SPECT also useful for
active bone marrow delineation
SPECT-Guided BM Delineation
Roeske (2005)
T2* Pulse Echo MRI“Fat Fraction”
Used to differentiate between redand yellow marrow
Information then used to dose paintIMRT plans minimizing red marrowirradiation
Loren Mell MDUC San Diego
ASCO Young InvestigatorAward
Image-Guided Target DelineationBrachytherapy
Growing interest in using imaging to break away from Point AMost attention on MRI
Radiother Oncol (2006)
PET-Guided Brachytherapy
MalyapaRed Journal (2002)
Intravenous FDG+ FDG inserted into tandem and ovoids
Used to conform dose to shape of the cervix and uterusExcellent correlation with MRI
Image-GuidedTreatmentDelivery
Cancer Center Corridor
Strong RationaleImage-Guided Treatment Delivery
Patient setup is difficult
Tumors and normal tissues move
Tumors shrink
RationaleAll 3 issues are a problem for IMRTRapid dose gradients very unforgivingInaccurate setup, organ motion and regression all may lead to underdosageof the tumor and overdosage of the normal tissuesIGRT has the potential to overcome all three problems
Image-Guided Treatment DeliveryImaging Modalities
IGRT Technologies
UltrasoundBAT
SonArrayI-BeamRestitu
VideoVideo subtractionAlignRTPhotogrammetryC-Rad
VolumetricIn-Room CT (FOCAL)CT-on-Rails
Primatom, EXaCTTomotherapyMobile C-ArmSiemens (MVCT)Elekta, Varian (kVCT)
PlanarEPID
CyberKnifeNovalis
RTRTVarian, Elekta
Ultrasound-Based IGRTCervical Cancer
Little dataSurprising given popularity in prostate cancerBut useful for difficult implants
Good Bad
Video-Based IGRTCervical Cancer
No dataAppealing given ability to monitor intra-fraction patient position in real-time without x-raysClinical trial planned at UCSD
Align RT systemCeiling-mounted camerasReal-time 3D surface image
Popular in breast and lung cancer
Planar-Based IGRTCervical Cancer
Most studied IGRT approach in cervical cancerLong history using electronic portal imaging devices (EPID) to monitor patient setupMV image of bony anatomy or implanted markers
Antonuk (2002)
EPID-Based IGRTImplanted Fiducials on Cervix
Kaatee (2002)10 cervical cancer ptsRadiopaque tantalum markers on cervix
Used to track cervix positionImage quality good-excellent½ lost before end of RT
Red J (2000)14 gynecology ptsOn-line EPID IGRTBased on boney landmarksAction level > 4 mm
57% re-positionedAverage time ~ 3 minutesAcquisition and adjustment
↓PTV margins to 5 mm
Real-Time Tumor Tracking (RTRT)
Four sets of diagnostic x-raytubes and imagers
1.5 MHU x-ray tube and a fixedfloor-mounted collimator
Corresponding ceiling-mountedimager
Mitsubishi Electronics Co Ltd, Tokyo, Japanhttp://global.mitsubishielectric.com/
RTRT System
Harada (2002)
During treatment,2 of the 4 x-ray systemsTrack an implanted markerUsing motion tracking software
Tracking is continuous
If the marker coordinates arewithin a permitted distance,the beam is triggered on
Marker position calculated0.03 seconds
Green Journal (2004)10 gynecology patients with implanted fiducials
Necessary CTV-PTV margin using real-time RTRT tracking:6.9 mm (right-left), 6.7 mm (sup-inf), 8.3 mm (ant-post)
No data using other popular planar systems(CyberKnife, Novalis)
Planar-IGRT SystemsSeveral vendors have mounted kV sources on gantry opposite amorphous silicon (aSi) flat panel detectorsCapable of generating high quality kV planar imagesBetter image quality and less dose than EPIDEmerging data using both approachesNone focused solely on gynecology patients
Commercial Gantry-Mounted SystemsPlanar IGRT
Varian On-Board Imaging (OBI)www.varian.com
Elekta Synergywww.elekta.com
kV SourceEPID aSI Detector
Varian OBI planar-IGRT systemOn-line patient setup correction based on bony landmarksVariety of tumor sites including gynecologyFeasibleEntire process < 1 additional minute
Planar kV Commercial Systems
Planar IGRT On-Line Setup
Process FlowPlanar IGRT (Gynecology-Pelvis)
Day 1MD and RTTs meet at console
Discuss anatomy, special issues, etc.
Day 2 thru Completion
All shifts ≤ 1 mm LR shift > 15 mmSI or AP shift > 15 mm
Any concerns
Other shifts
Make no shiftsand treat Call MD
Make all shiftsand treat
Offer the potential to trackImplanted fiducials
Analogous to on-line techniques popularized in prostate cancer
Potentially useful to deliver a high dose conformal boost in patients unable to receive brachytherapy
Planar kV Commercial Systems
Volumetric-Based IGRTInterest is now turning to volumetricIGRTSeveral vendors offer volumetric solutions using the MV treatment beam
Tomotherapy, SiemensOthers generate kV cone-beam CT (CBCT) scans by reconstructing multiple planar kV images
Varian, Elekta
Volumetric-IGRTHigh quality kV CBCT scans can be producedUseful now to monitor target coverageIn future, opens door to adaptive RT
Planar KV Imaging Align boney anatomy(↓CTV-PTV margins around NodesGenerous margins around cervix)
↓Video Imaging Monitor Patient Position during Tx
↓Volumetric ImagingOff-line monitoring of target CoverageAdjust margins if necessary
On-Line Planar, Off-line Volumetric IGRTCervical Cancer
Day 1 Day 2
Day 3 Day 4
Day 5
Day 1
Day 3
Day 2
Day 4
Day 5
Day 3Day 4
Day 595%90%85%80%
Day 1 Day 2
Day 1
Day 3
Day 2
Day 4
Day 5
Volumetric-based IGRTCervical Cancer
Off-line monitoring of target coverage is very useful Particularly important if modest margins are used around the cervix and fundusWe used 1.7 cm marginsModifications are still common to ensure coverage
CBCT Cervical Cancer StudyMargin % Fx Volume Location(mm) CTV Missed Missed Fundus Cervix0 100% 45.3 cc 100% 95.2%3 98.7% 24.8 cc 89.0% 79.5%5 95.4% 20.3 cc 83.6% 65.1%7 87.2% 13.9 cc 71.2% 50.0%10 59.3% 9.3 cc 54.0% 35.6%15 32.1% 4.0 cc 24.0% 18.5%20 19.3% 1.7 cc 11.6% 10.9%25 14.0% 0.7 cc 7.5% 6.9%30 6.7% 0.3 cc 4.1% 0.7%
Image-GuidedAdaptive RT
Aerial View, Inner Garden and Cafe
Adaptive IGRTTumors shrinkAnd often quite quickly with chemotherapy plus RTShrinkage is a double-edged sword
Reduces the conformity of the
original plan
Reduces the chance of a
geographic miss
Tumor ResponseMany investigators have quantified the rate of response in cervical cancersUniversity of Utah used physical exam measurements and found by 30.8 Gy tumors reduced by 50%MD Anderson used weekly conventional CT and noted a mean reduction of 64%Others have used IMRT to better calculate tumor regressionLee et al. Red Journal 2005;58:625Beadle et al. ASTRO 2006Mayr et al. Am J Roentgenol 2006;187:65Van de Bunt et al. Red Journal 2006;64:189
14 cervical cancer patientsMRI prior to RT and after 30 Gy external beamGTV decreased (on average) by 46% Decrements in CTV and PTV were 18% and 9%
Does Re-Planning Help?Re-optimizing the IMRT plan at 30 Gyimproved the sparing of the rectumAverage rectal volume receiving ≥ 95% of the prescription dose
75 cc (range, 20-145 cc) (No Re-planning)67 cc (range, 15-106 cc) (Re-planning)P = 0.009
Improved bowel sparing seen in women with bulky (> 30 cc) tumors
Does Re-Planning Help?
Currently analyzing a large dataset of daily CBCT in cervical cancer patients undergoing IMRT and chemotherapy
Daily imaging data allows us to not only ask whether re-planning helps, but the optimal frequency and timing of re-planning
Adaptive IGRTMany technical obstacles stand in the way of adaptive IGRT, particularly if performed on-lineNew software tools: image deformation and automated segmentationBetter quality CBCT imagingNew rapid, accurate QA approaches
Adaptive IGRTOnce technical obstacles are overcome, numerous clinical questions remain
Does adaptive IGRT help? Does it hurt?Should it be performed on-line or off-line?How often should it be done? Weekly? Daily?
Such questions can only be addressed in carefully designed clinical trials
Bladder
Rectum
Tumor
Bladder
Tumor
Rectum
Week 1 Week 3
Adapt to What?
Adaptive IGRTNecessary tools being developed at UCSD in collaboration with the San Diego Super-Computer Center and Varian Medical Systems
On-Line Setup, Off-Line Adapt On-Line Setup, On-Line Adapt
Setup to Marks
On-LinePlanar IGRT
Deliver TreatmentReal-time Video
IGRT
Off-LineAnalysis
Re-Plan asneeded
On-LineCBCT
Re-plan if necessary
Deliver TreatmentReal-time Video IGRT
“Re-Plan If Necessary”Need to decide on the table within minutes!Not an simple taskCould involve target and normal tissue delineation, re-planning and evaluating potential benefitA more elegant solution may be to use the CBCT image itselfAnalyzed using Machine Learning
Machine LearningRapid Interpretation of 3D Image
Machine LearningRapid Interpretation of 3D Image
Yes Yes No YesYes No
Adapt????
On-Line AdaptationDeform simulation CT anatomy into all potential anatomical changesGenerate 1000+ IMRT plans using supercomputer computational powerImage patient on the table each day and select most similar planTreat with new plan
Daily Re-PlanningHigh speed computer processing is essentialNeed to move from sequential processing to parallel processingNever been applied to radiation oncology
1.5 M Grant Awarded
Acknowledgement
UCSDCome Visit!
= Original space (2 vaults, 1 CT sim)
Southbay
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