Sudden cardiac death (SCD) caused by ventricular tachycardia (VT) results in >150,000 deaths/year in the U.S. Noninvasive Stereotactic Cardiac Radiosurgery (NSCR) was recently reported as a novel and alternative noninvasive treatment option to treat VT refractory to standard drug and catheter ablation therapy (Cuculich and Robinson, NEJM, Dec. 2017). The initial results for five patients resulted in a 99.9% reduction of VT episodes after 6 weeks, leading to a Phase I/II clinical trial in 2016-2018 (ClinicalTrials.gov NCT02919618). The preliminary results of Phase I/II trial showed similar efficacy (publication is pending) to the initial pilot study. Currently, the target volume is ~3 times larger than the arrhythmogenic tissue to ensure the therapeutic dose is delivered to the cardiac lesion in the presence of cardiac and respiratory motion. Despite evidence supporting efficacy, it is essential to minimize the volume of healthy cardiac tissue unnecessarily treated to high radiation doses to reduce the likelihood of late complications (including pericarditis, angina, myocardial infarction and accelerated atherosclerosis). Our clinical goals of this study are to: 1) Improve the accuracy of directing the radiation beam to the diseased myocardial tissue; 2) Reduce radiation toxicity to the surrounding healthy tissues of the heart, lungs and esophagus; and 3) Improve the overall NSCR treatment efficacy. These goals will be accomplished using novel radiation treatment processes, target definition, imaging, image guidance, target motion tracking and prediction, and radiation delivery gating methods. New MRI and cone beam CT (CBCT) image acquisition and reconstruction methods will be developed to characterize and compensate for cardiac and respiratory motion, and to dramatically improve target definition and motion management components of NSCR. New NSCR treatment processes will be developed to reduce the patient setup uncertainties on the treatment day, and to improve the radiation delivery accuracy by tracking the target motion and gating the radiation beam based on the real-time target position and the respiratory + ECG signals. The new treatment and imaging methods developed and tested under this study will be applicable to both MRI-guided radiation delivery systems (MR-Linacs) and CBCT image guided radiation delivery systems (CBCT-Linacs).

Public Health Relevance

Sudden cardiac death (SCD) caused by ventricular tachycardia (VT) results in >150,000 deaths/year in the U.S. Noninvasive Stereotactic Cardiac Radiosurgery (NSCR) was recently developed as a novel noninvasive treatment for treatment-resistant VT, resulting in >95% reduction in VT episodes. In this R01 project, we will implement enhancements to NSCR that will: 1) Reduce the radiation toxicity to the surrounding healthy tissues of the heart and chest to minimize complications from radiation; and 2) Improve the accuracy and efficacy of the radiation dose delivered to the heart lesion that is causing the VT.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL148210-02
Application #
9998017
Study Section
Imaging Guided Interventions and Surgery Study Section (IGIS)
Program Officer
Fenton, Kathleen Nelle
Project Start
2019-08-17
Project End
2023-07-31
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Washington University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130