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Igrt In Gynecologic Malignancies

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Information about Igrt In Gynecologic Malignancies
Health & Medicine

Published on February 27, 2009

Author: fovak

Source: slideshare.net

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IGRT in Gynecologic Malignancies Arno J. Mundt MD Professor and Chair Department of Radiation Oncology University of California San Diego La Jolla CA

Image-Guided RT? “Image guided” is non-informative RT has always been guided by images Definition of IGRT is not standardized and is open to various interpretations Global definition might include any aspect of RT involving imaging, from fluoroscopic simulation to CT-based planning, to weekly port films

RTOG Research Plan 2002-2006 IGRT Committee Report Michalski 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….”

Introduction Recommend a more focused definition Highlight the 2 most important roles of imaging in modern RT: Improved Target Delineation Improved Treatment Delivery

IGRT Definition Use 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 Frontier Image-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 setup Considerable organ motion exists Tumors shrink rapidly

Target Delineation Traditional method planar (flouroscopic) x-rays External beam fields based on visualized bony anatomy Contrast used to define normal tissues Brachytherapy doses prescribed to specified “Points” based on applicator position

2D planning → Poor target coverage and excess normal tissue exposure compared to 3D planning Red Journal 2006 43 cervical cancer pts Evaluated adequacy of coverage of pelvic vessels Surrogate for lymph nodes Adequate: >15 mm vessel to block edge 41/43 (95%) inadequate coverage with 2D based fields 24/43 (56%) too generous (> 2 cm) Excess normal tissue exposure

Beyond CT Imaging Interest 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

Fe Oxide nano-particle Taken up in benign lymph nodes by macrophages 7 mm margin around vessels encompassed 99% of pelvic nodes Red Journal (2005)

FDG-PET particularly useful to identify involved nodes Boost to higher doses with IMRT Mutic Red Journal (2003) PET+ Nodes: 59.4 Gy/1.8 Gy fx PET- Nodes: 50.4 Gy/1.53 Gy fx Ahmed Red Journal (2004) PET+ nodes: 60 Gy/2.4 Gy fx PET- nodes: 45 Gy/1.8 Gy fx

More Advanced Imaging Dynamic-Contrast MRI (tumor hypoxia) Cooper et al. Radiother Oncol (2000) 1H-MR spectroscopy (tumor vs normal tissue) Okada et al. J MRI Okada (2001) (2001)

Alternative PET Tracers Metabolic Abnormalities or Hypoxia 11C-Choline (tumor vs normal tissue) 11C-Methionine (amino acid transport) 60Cu-ATSM (hypoxia) MRI FDG-PET 11C-Choline PET Less uptake in normal tissues Torizuka J Nucl Med (2003) 11C-Choline imaging

Tumor hypoxia inversely correlated with DFS and OS 3y PFS normoxic (71%) and hypoxix (28%) Could be used to dose paint during external beam and brachytherapy

Normal Tissue Delineation Novel 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 red and yellow marrow Information then used to dose paint IMRT plans minimizing red marrow irradiation Loren Mell MD UC San Diego ASCO Young Investigator Award

Image-Guided Target Delineation Brachytherapy Growing interest in using imaging to break away from Point A Most attention on MRI Radiother Oncol (2006)

PET-Guided Brachytherapy Malyapa Red Journal (2002) Intravenous FDG + FDG inserted into tandem and ovoids

Used to conform dose to shape of the cervix and uterus Excellent correlation with MRI

Image-Guided Treatment Delivery Cancer Center Corridor

Strong Rationale Image-Guided Treatment Delivery Patient setup is difficult Tumors and normal tissues move Tumors shrink

Rationale All 3 issues are a problem for IMRT Rapid dose gradients very unforgiving Inaccurate setup, organ motion and regression all may lead to underdosage of the tumor and overdosage of the normal tissues IGRT has the potential to overcome all three problems

Image-Guided Treatment Delivery Imaging Modalities Ultrasound Video BAT Video subtraction SonArray AlignRT IGRT I-Beam Photogrammetry Technologies Restitu C-Rad Planar Volumetric EPID In-Room CT (FOCAL) CyberKnife CT-on-Rails Novalis Primatom, EXaCT RTRT Tomotherapy Varian, Elekta Mobile C-Arm Siemens (MVCT) Elekta, Varian (kVCT)

Ultrasound-Based IGRT Cervical Cancer Little data Surprising given popularity in prostate cancer But useful for difficult implants Bad Good

Video-Based IGRT Cervical Cancer No data Appealing given ability to monitor intra-fraction patient position in real-time without x-rays Clinical trial planned at UCSD Align RT system Ceiling-mounted cameras Real-time 3D surface image Popular in breast and lung cancer

Planar-Based IGRT Cervical Cancer Most studied IGRT approach in cervical cancer Long history using electronic portal imaging devices (EPID) to monitor patient setup MV image of bony anatomy or implanted markers Antonuk (2002)

EPID-Based IGRT Implanted Fiducials on Cervix Kaatee (2002) 10 cervical cancer pts Radiopaque tantalum markers on cervix Used to track cervix position Image quality good-excellent ½ lost before end of RT

Red J (2000) 14 gynecology pts On-line EPID IGRT Based on boney landmarks Action level > 4 mm 57% re-positioned Average time ~ 3 minutes Acquisition and adjustment ↓PTV margins to 5 mm

Real-Time Tumor Tracking (RTRT) Four sets of diagnostic x-ray tubes and imagers 1.5 MHU x-ray tube and a fixed floor-mounted collimator Corresponding ceiling-mounted imager Mitsubishi Electronics Co Ltd, Tokyo, Japan http://global.mitsubishielectric.com/

RTRT System During treatment, 2 of the 4 x-ray systems Track an implanted marker Using motion tracking software Tracking is continuous If the marker coordinates are within a permitted distance, the beam is triggered on Marker position calculated 0.03 seconds Harada (2002)

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 Systems Several vendors have mounted kV sources on gantry opposite amorphous silicon (aSi) flat panel detectors Capable of generating high quality kV planar images Better image quality and less dose than EPID Emerging data using both approaches None focused solely on gynecology patients

Commercial Gantry-Mounted Systems Planar IGRT Varian On-Board Imaging (OBI) www.varian.com EPID aSI Detector kV Source Elekta Synergy www.elekta.com

Planar kV Commercial Systems Varian OBI planar-IGRT system On-line patient setup correction based on bony landmarks Variety of tumor sites including gynecology Feasible Entire process < 1 additional minute

Planar IGRT On-Line Setup

Process Flow Planar IGRT (Gynecology-Pelvis) Day 1 MD and RTTs meet at console Discuss anatomy, special issues, etc. Day 2 thru Completion Other shifts All shifts ≤ 1 mm LR shift > 15 mm SI or AP shift > 15 mm Any concerns Make all shifts Make no shifts Call MD and treat and treat

Planar kV Commercial Systems Offer the potential to track Implanted 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

Volumetric-Based IGRT Interest is now turning to volumetric IGRT Several vendors offer volumetric solutions using the MV treatment beam Tomotherapy, Siemens Others generate kV cone-beam CT (CBCT) scans by reconstructing multiple planar kV images Varian, Elekta

Volumetric-IGRT High quality kV CBCT scans can be produced Useful now to monitor target coverage In future, opens door to adaptive RT

On-Line Planar, Off-line Volumetric IGRT Cervical Cancer Planar KV Imaging Align boney anatomy (↓CTV-PTV margins around Nodes Generous margins around cervix) ↓ Video Imaging Monitor Patient Position during Tx ↓ Volumetric Imaging Off-line monitoring of target Coverage Adjust margins if necessary

Day 2 Day 1 Day 2 Day 1 Day 3 Day 4 Day 4 Day 3 Day 5 Day 5

Day 2 Day 1 Day 1 Day 2 Day 3 Day 4 Day 3 Day 4 Day 5 95% 90% Day 5 85% 80%

Volumetric-based IGRT Cervical Cancer Off-line monitoring of target coverage is very useful Particularly important if modest margins are used around the cervix and fundus We used 1.7 cm margins Modifications are still common to ensure coverage

CBCT Cervical Cancer Study Margin % Fx Volume Location (mm) CTV Missed Missed Fundus Cervix 0 100% 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-Guided Adaptive RT Aerial View, Inner Garden and Cafe

Adaptive IGRT Tumors shrink And often quite quickly with chemotherapy plus RT Shrinkage is a double-edged sword Reduces the Reduces the chance of a conformity of the geographic miss original plan

Tumor Response Many investigators have quantified the rate of response in cervical cancers University 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 regression Lee et al. Red Journal 2005;58:625 Beadle et al. ASTRO 2006 Mayr et al. Am J Roentgenol 2006;187:65 Van de Bunt et al. Red Journal 2006;64:189

14 cervical cancer patients MRI prior to RT and after 30 Gy external beam GTV 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 Gy improved the sparing of the rectum Average 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 IGRT Many technical obstacles stand in the way of adaptive IGRT, particularly if performed on-line New software tools: image deformation and automated segmentation Better quality CBCT imaging New rapid, accurate QA approaches

Adaptive IGRT Once 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

Adapt to What? Bladder Bladder Tumor Tumor Rectum Rectum Week 1 Week 3

Adaptive IGRT Necessary 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-Line Planar IGRT On-Line Deliver Treatment CBCT Real-time Video IGRT Re-plan if necessary Off-Line Deliver Treatment Analysis Real-time Video Re-Plan as IGRT needed

“Re-Plan If Necessary” Need to decide on the table within minutes! Not an simple task Could involve target and normal tissue delineation, re-planning and evaluating potential benefit A more elegant solution may be to use the CBCT image itself Analyzed using Machine Learning

Machine Learning Rapid Interpretation of 3D Image

Machine Learning Rapid Interpretation of 3D Image Adapt???? Yes Yes No Yes No Yes

On-Line Adaptation Deform simulation CT anatomy into all potential anatomical changes Generate 1000+ IMRT plans using supercomputer computational power Image patient on the table each day and select most similar plan Treat with new plan

Daily Re-Planning High speed computer processing is essential Need to move from sequential processing to parallel processing Never been applied to radiation oncology

1.5 M Grant Awarded

Acknowledgement

UCSD Come Visit! Encinitas Proton Center Basic Science Mexico Institute = Original space (2 vaults, 1 CT sim) Colima Southbay

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