Potential conflicts-of-interest. Respiratory Gated and Four-Dimensional Tumor Tracking Radiotherapy. Educational objectives. Overview.

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Respiratory Gated and Four-Dimensional Tumor Tracking Radiotherapy Potential conflicts-of-interest I am PI of a sponsored research agreement between Stanford University and Varian Medical Systems P Keall 1,2, S Vedam 2,3 and M Murphy 2 1 Stanford University 2 Virginia Commonwealth University 3 UT MD Anderson Cancer Center Educational objectives Understand the rationale for accounting for respiratory motion during imaging, treatment planning and radiation delivery Learn about respiratory gated radiotherapy and 4D tumor tracking radiotherapy Understand the advantages and disadvantages of respiratory gated and tumor tracking radiotherapy Effects of poor Measurement of respiratory motion Effects of poor

Measurement of lung tumor motion Measurement of other sites The tumor moves with time Distorted images, incorrect anatomical positions, volumes or shapes Tumor Conventional With 4D imaging Treatment Planning: Large margins are added to the clinical target volume IMRT Delivery: Interplay between anatomy and MLC leaf motion leads to motion artifacts Increases normal tissue dose and limits target dose PTV CTV Conventional PTV CTV Account for motion Dose Planned dose Delivered dose Position

Motion during treatment Geometric error translates to dosimetric error Courtesy Slobodan Devic Geometric error translates to dosimetric error Effects of poor Clinical rationale An RTOG retrospective analysis of 1290 NSCLC patients demonstrates that every 10-Gy increase in BED results in an 18% decrease in the risk of death Martel et al. estimate that 85 Gy is needed to achieve 50% local progression-free survival at 30 months The cost of dose escalation is normal tissue toxicity, which has been shown to be dose dependent for lung, heart, esophagus and bronchus Improved targeting will allow improved tumor control Wulf, Rad Onc, 2005

Improved targeting will allow improved tumor control Improved targeting will allow reduced treatment toxicity Wulf, Rad Onc, 2005 Marks, IJROBP editorial, 2002 Clinical rationale Simultaneously increase tumor dose and reduce normal tissue dose? Increase treatment accuracy Other methods Improve dose calculation accuracy Improve IMRT Increase degrees of freedom in delivery Normal tissue displacement Particles Synergistic biologic modifiers Clinical rationale The skeletal, respiratory, GU, GI and cardiac systems cause tumor motion The magnitude of motion is variable and unpredictable Respiratory variability Case study: T1 NSCLC; non-operative operative due to COPD 3 minutes later Courtesy Sonja Dieterich, Georgetown University

Case study: Gated IMRT 70Gy in 2Gy/fx Effects of poor Prior to gated IMRT 3 wks after 70 Gy gated IMRT Respiration signals Surrogate choices External Optical Spirometer Strain gauge Nasal thermistor Pressure sensors Internal Fluoroscopy EPID Indoor GPS EM MRI US Surrogate External respiration signal Implanted markers 4D CT MRI/US The good Real time Real time Large dimensionality Large dimensionality, real time The bad Limited dimensionality, no positional information, variable tumor correlation Limited dimensionality, migration, invasive Not real time Not yet commercially available Surrogate vs. tumor motion Organ/respiratory signal correlation

Effects of poor Target position Action threshold Action controller Action thresholds Beam hold state Beam on/off Continuously receive position information Beam on if position < threshold Beam hold if position > threshold Gated control Respiratory gating Target signal Gating controller Beam hold state Beam on/off Gating thresholds Similar to action threshold but applicable to periodic motion Continuously receive position information Beam on if position < threshold Beam hold if position > threshold Respiratory gated treatment Respiratory gated treatment Motion inclusive treatment

RPM system components IR Illuminator Infra-red light source CCD Camera Obtains real-time images of IR reflective marker block motion IR Reflective marker block Markers reflect IR light making them appear as bright areas on CCD camera images Junction Box Power supply source and routing center for signals Gating switch box Enable/Disable gated treatments at Linac Video distribution amplifier Amplify video signals In room View Finder Ensure markers are within field of view of CCD camera Motion tracking Dynamic motion compensation Couch tracking Open loop- move beam Robotic control of the linear accelerator (clinically available) Block motion (used clinically at one center) DMLC (proof of principle but not clinical) Closed loop- move patient Couch motion (proof of principle but not clinical) Schematic Courtesy Warren D Souza University of Maryland No tracking Tracking Beam tracking Block tracking Courtesy Accuray

DMLC tracking (CRT) DMLC tracking (IMRT) Tracking patient-derived motion Displacement vs. time Tracking error vs. time PDF of corrected and uncorrected motion Target Beam Beam (RT corr) Comparison of motion compensation methods Effects of poor

Summary Position monitoring devices provide useful information This information can be used in several ways A targeted radiotherapy control system can minimize geometric error Geometric errors translate to dosimetric errors Engineering and implementation issues remain Integrated position monitoring and targeted radiotherapy systems can Significantly reduce systematic and random treatment errors Reduce set-up time Reduce operator error Integrated position monitoring and targeted radiotherapy systems are limited by Accuracy of position monitoring system Relationship of surrogate to target Deformation Rotation Migration Anatomic and physiologic changes Tracking of normal anatomy Radiotherapy challenge? Courtesy Steve Jiang Massachusetts General Hospital