Disclosures. What Is So Hard? End of ITV: Gating is the Best ITV Killer 8/3/2016. Daniel A. Low, Ph.D. UCLA. Varian Grant Siemens Grant Accuray Grant

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Real Timefullness 8/3/2016 End of ITV: Gating is the Best ITV Killer Daniel A. Low, Ph.D. UCLA Varian Grant Siemens Grant Accuray Grant Disclosures What Is So Hard? Light Ultrasound MRI X Ray Planar X Ray Planar + Fiducial Touch CBCT Soft Tissue Imaging 1

*Respiratory Motion* Lung Liver Pancreas, etc. Liver motion typically greater than lung, penumbra also sharper, so consequence of missing is worse MR+RT 3 companies formed, one academic investigational device ViewRay Elekta/Philips University of Alberta MagnetTx (6/21/16) Australian Program Can MR+RT Eliminate ITV? Excellent soft tissue contrast Systems have or will have at least rapid (>= 4fps) planar imaging Can this be used to eliminated ITV? 2

Anterior posterior 8/3/2016 Liver Breast Pancreas IMRT with breath hold gating Superior Heart Liver Stomach Pancreatic Tumor Radiation Target Bowel Loops Inferior Sagittal View Courtesy Michael Bassetti 3

Recent ViewRay Patient Treating HCC metastasis to adrenal. Poor definition vs. liver on noncontrast CT Easily visible on 0.35T MR w/ Eovist contrast injected prior to every Tx. > 1 cm motion during normal breathing. SBRT 8 Gy x 5 fx, gated treatment. *Free Breathing* Typically exhale phase longer than other phases More efficient to gate at exhalation If gating at 50% of time, most efficient at exhale Decreases motion by more than half 4

ViewRay Gating Accuracy - Methods Target rod film insert (MRI w/dose) Target rod film insert (jpeg) CIRS Gating Phantom Courtesy Jim Lamb Actual tumor trajectories from MRI-guided treatments. ViewRay Gating Accuracy - Results Courtesy Jim Lamb Gamma pass rate vs. static plan - 3%/3mm Trajectory Ungated Gated- 3 mm margin, 5% ROI Breath hold 49.9% 95.2% Free breathing 1 25.0% 91.7% Free breathing 2 32.9% 98.6% 32 combinations of trajectory and gating parameter were evaluated, this is a representative subset. What About The Rest Of Us? Most of us don t have MR+RT machines Can we eliminate ITV? Examine ITV from breathing motion 5

Breathing Motion Management Typical Workflow 1) Get 4DCT to determine motion 2) Motion? Plan ITV for gating or non-gating 3) (non marker) Get CBCT at Linac 4) Position tumor and treat/gate What s Wrong With That? 4DCT provides inferior images with respect to noise and sorting artifacts 4DCT provides no quantitative information regarding its own quality/accuracy Treatment planning with 4DCT does not provide guidance as to tradeoffs between motion mitigation strategies What s Wrong With That? Breathing patterns & lung tumor positions change day to day At the machine, 4DCBCT provides similar artifact ridden information that has no quantitative assessment and sensitivity to irregular breathing patterns 6

And During Treatment? How to translate mediocre 4DCT data to real time? Solution: Model-Based CT Breathing is irregular in TIME Develop a biologically-guided motion model Breathing motion is not irregular in AMPLITUDE Hysteresis can be a function of breathing RATE Our model takes amplitude and rate and converts to position in time Mathematically: Our Model ( 5D ) amplitude rate 7

Model Data Useless unless we can measure tumor position (and other lung structures) during free breathing and correlate against amplitude and rate Fast Helical Free Breathing CT (FHFBCT) All modern CT scanners can do this! Monitor breathing during scan acquisition Take scans back and forth until required number reached (10-ish) Steps Fast helical CT scans have no sorting artifacts Relatively few and small motion artifacts Deformably map fast helical CT scans to single reference scan Assign breathing phase to each slice Use deformation maps to fit model 8

Output Unlike 4DCT: No sorting artifacts Use most or all of dose (low noise) Can create image at any breathing phase Verification of accuracy (rebuild original helical CT scans and compare) Courtesy Dylan O Connell Error Distribution by the Scans 3 mm Factor of 8! Plan CT Simulation Dosimetry Treatment Room Model Based CT Automated Treatment Planning Model Updating (MBCBCT) Positioning Treating Gating 9

Conclusions For those of us that MR+RT ITV is dead For those of us that don t have MR+RT ITV may be dying for breathing motion Will require further development and commercialization Daniel A. Low, Ph.D. John Lewis, Ph.D. Tai Dou, Ph.D. Dylan O Connell Lisa Yang James Lamb, Ph.D. Dan Ruan, Ph.D. David Thomas, Ph.D. Anand Santhanam, Ph.D. Hao Gao, Ph.D, Jiulong Li Minsong Cao Yingi Yang Percy Lee, M.D. Thank You! 10