Stereotactic Arrhythmia Radioablation for Ventricular Tachycardia (StAR-VT)
Study Details
Study Description
Brief Summary
In 2017 a novel treatment approach to a series of 5 patients with refractory VT was introduced, using ablative radiation with a stereotactic body radiation therapy (SBRT) technique to arrhythmogenic scar regions defined by noninvasive cardiac mapping. More recently, Robinson et al. reported on the results of their Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia (ENCORE-VT) trial, also using a similar SBRT technique in a series of 17 patients with refractory VT. Both studies report a marked reduction in VT burden, a decrease in antiarrhythmic drug use, and an improvement in quality of life. Since then, numerous other centres have detailed their initial experience with this technique. These initial results suggest that this new treatment paradigm has the potential to improve morbidity and mortality for patients suffering from treatment-refractory VT by means of a minimally invasive technique, but requires further validation for widespread use.
The appropriate dose for therapeutic effect of this new treatment is not well established as only a single dose prescription of 25 Gy in 1 fraction has been described with benefit. In this phase 2 trial, the investigators plan on expanding the experience with this technique but also by contributing to understanding the relationship between dose-effect relationship through a dose de-escalation stratification, to 20 Gy in 1 fraction, with the goal of minimizing possible adverse events and radiation dose to surrounding healthy tissue while maintaining a clinical benefit.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Detailed Description
Ventricular tachycardia (VT) is a potentially life-threatening arrhythmia characterized by electrical re-entry within patches of heterogeneous myocardial fibrosis leading to sustained consecutive ventricular beats at a rate > 100 per minute. VT is classified based on hemodynamic stability, duration (less than or greater than 30 seconds), morphology (monomorphic or polymorphic), and mechanism (scar-related re-entry, automaticity, triggered activity.
In patients with monomorphic VT, implantable cardioverter-defibrillators (ICDs) have become the cornerstone of therapy in decreasing mortality, through the prevention of sudden death from potentially lethal sustained arrhythmia in select patients. However, ICDs have no effect on the underlying arrhythmogenic substrate or fibrotic scar and thus are primarily a symptom-control therapy; patients may develop recurrent and debilitating shocks associated with an increase in mortality. Currently, catheter ablation (CA) for VT is used as an adjunctive therapy for patients who are refractory to medical therapy. A recent systematic review and meta-analysis of randomized controlled trials and observation studies comparing medical therapy and catheter ablation for VT shows that CA is superior to medical therapy for scar-related VT with respect to VT recurrence and the life-threatening VT storm. Despite this, there is still a high reported incidence of VT recurrence in both medically-treated (48%) and ablation-treated (39%) patients, suggesting that the current treatment paradigm is suboptimal for good control of this debilitating arrhythmia.
In 2017, Cuculich et al. introduced a novel treatment approach to a series of 5 patients with refractory VT, using ablative radiation with a stereotactic body radiation therapy (SBRT) technique to arrhythmogenic scar regions defined by noninvasive cardiac mapping. More recently, Robinson et al. reported on the results of their Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia (ENCORE-VT) trial, also using a similar SBRT technique in a series of 17 patients with refractory VT. Both studies report a marked reduction in VT burden, a decrease in antiarrhythmic drug use, and an improvement in quality of life. These initial results suggest that this new treatment paradigm has the potential to vastly improve morbidity and mortality for patients suffering from VT by means of a minimally invasive technique, but requires further validation for widespread use.
Additionally, the appropriate dose for therapeutic effect of this new treatment is not well established as only a single dose prescription of 25 Gy in 1 fraction has been described with benefit. In this phase 2 trial, the investigators plan on expanding the experience with this technique but also by contributing to understanding the relationship between dose-effect relationship through a dose de-escalation stratification, to 20 Gy in 1 fraction, with the goal of minimizing possible adverse events and radiation dose to surrounding healthy tissue while maintaining a clinical benefit.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Radiation: 20 Gy in 1 fraction External beam, stereotactic body radiotherapy of 20 Gy delivered in 1 fraction to the planning target volume (PTV) of the arrhythmogenic substrate |
Radiation: stereotactic body radiotherapy, 20 Gy in 1 fraction
A single dose of focused radiation therapy of 20 Gy in 1 fraction to the PTV of the arrhythmogenic substrate
Other Names:
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Outcome Measures
Primary Outcome Measures
- Change in arrhythmia burden measured by the number of VT events [6 months and 12 months following study intervention]
Changes in arrhythmia burden measured by the number of VT events comparing the 12-month period after a single fraction of 20 Gy SBRT with a single fraction of 25 Gy in historical controls
- Change in arrhythmia burden measured by the number of ICD events [6 months and 12 months following study intervention]
Changes in arrhythmia burden measured by the number of ICD events comparing the 12-month period after a single fraction of 20 Gy SBRT with a single fraction of 25 Gy in historical controls
- Acute radiation toxicity within the first 90 days measured by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [90 days following study intervention.]
Rate of severe adverse events at less than or equal to 90 days that were treatment related (possibly, probably, or definitely) as defined using the CTCAE v5.0
Secondary Outcome Measures
- Late radiation toxicity occurring after the first 90 days until 5 years measured by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [90 days - 5 years following study intervention]
Severe adverse events as defined by CTCAE v5.0 occuring after the first 90 days following treatment
- Changes in number and doses of antiarrhythmic drugs [1 year, 3 years, and 5 years following study intervention]
Changes in number and doses of all antiarrhythmic drugs that are used before and in the 5 year follow-up after the study intervention
- Patient-Reported Quality of life as measured by the short form-36 questionnaire [6 months, 1 year, 3 years, and 5 years following study intervention]
Patient-Reported Quality of life as measured by the short form-36 questionnaire
- Patient-Reported Quality of life as measured by the Arrhythmia-specific questionnaire in Tachycardia and arrhythmia (ASTA) [6 months, 1 year, 3 years, and 5 years following study intervention]
Patient-Reported Quality of life as measured by the Arrhythmia-specific questionnaire in Tachycardia and arrhythmia (ASTA)
Other Outcome Measures
- Overall Survival [5 years following radiation therapy]
The overall survival of participants following the intervention
Eligibility Criteria
Criteria
Inclusion Criteria:
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18 years of age
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Ishemic or non-ischemic cardiomyopathy
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Recurrent episodes of monomorphic ventricular tachycardia having failed standard treatment with at least 1 antiarrhythmic drug
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Previous endocardial and/or epicardial electrophysiology study and ablation.
Participants who have a contraindication to electrophysiology studies (ventricular thrombus, absence of vascular access, valvular heart disease or mechanical heart valve that precludes left-ventricular access) may be eligible for the protocol provided the arrhythmic substrate can be defined through non-invasive methods.
Exclusion Criteria:
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Previous RT in the treatment field that precludes furth RT
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Active connective tissue disease
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Interstitial pulmonary fibrosis
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Pregnant or breastfeeding individuals
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Participants who plan to become pregnant or breast feed during the study duration
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Cedars Cancer Center, McGill University Health Centre | Montreal | Quebec | Canada | H4A3J1 |
Sponsors and Collaborators
- McGill University Health Centre/Research Institute of the McGill University Health Centre
Investigators
- Principal Investigator: Joanne Alfieri, MD, MUHC division of radiation oncology/RIMUHC
- Principal Investigator: Martin L Bernier, MD, MUHC division of cardiology
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- AlKalbani A, AlRawahi N. Management of monomorphic ventricular tachycardia electrical storm in structural heart disease. J Saudi Heart Assoc. 2019 Jul;31(3):135-144. doi: 10.1016/j.jsha.2019.05.001. Epub 2019 May 11. Review.
- Amino M, Yoshioka K, Fujibayashi D, Hashida T, Furusawa Y, Zareba W, Ikari Y, Tanaka E, Mori H, Inokuchi S, Kodama I, Tanabe T. Year-long upregulation of connexin43 in rabbit hearts by heavy ion irradiation. Am J Physiol Heart Circ Physiol. 2010 Mar;298(3):H1014-21. doi: 10.1152/ajpheart.00160.2009. Epub 2010 Jan 8.
- Anderson RD, Ariyarathna N, Lee G, Virk S, Trivic I, Campbell T, Chow CK, Kalman J, Kumar S. Catheter ablation versus medical therapy for treatment of ventricular tachycardia associated with structural heart disease: Systematic review and meta-analysis of randomized controlled trials and comparison with observational studies. Heart Rhythm. 2019 Oct;16(10):1484-1491. doi: 10.1016/j.hrthm.2019.05.026. Epub 2019 May 29.
- Aziz Z, Tung R. Novel Mapping Strategies for Ventricular Tachycardia Ablation. Curr Treat Options Cardiovasc Med. 2018 Mar 23;20(4):34. doi: 10.1007/s11936-018-0615-1. Review.
- Blanck O, Bode F, Gebhard M, Hunold P, Brandt S, Bruder R, Grossherr M, Vonthein R, Rades D, Dunst J. Dose-escalation study for cardiac radiosurgery in a porcine model. Int J Radiat Oncol Biol Phys. 2014 Jul 1;89(3):590-8. doi: 10.1016/j.ijrobp.2014.02.036. Epub 2014 Apr 18. Erratum in: Int J Radiat Oncol Biol Phys. 2014 Dec 1;90(5):1264.
- Chiu MH, Mitchell LB, Ploquin N, Faruqi S, Kuriachan VP. Review of Stereotactic Arrhythmia Radioablation Therapy for Cardiac Tachydysrhythmias. CJC Open. 2020 Nov 13;3(3):236-247. doi: 10.1016/j.cjco.2020.11.006. eCollection 2021 Mar. Review.
- Cuculich PS, Schill MR, Kashani R, Mutic S, Lang A, Cooper D, Faddis M, Gleva M, Noheria A, Smith TW, Hallahan D, Rudy Y, Robinson CG. Noninvasive Cardiac Radiation for Ablation of Ventricular Tachycardia. N Engl J Med. 2017 Dec 14;377(24):2325-2336. doi: 10.1056/NEJMoa1613773.
- Desai MY, Windecker S, Lancellotti P, Bax JJ, Griffin BP, Cahlon O, Johnston DR. Prevention, Diagnosis, and Management of Radiation-Associated Cardiac Disease: JACC Scientific Expert Panel. J Am Coll Cardiol. 2019 Aug 20;74(7):905-927. doi: 10.1016/j.jacc.2019.07.006.
- Duane F, Aznar MC, Bartlett F, Cutter DJ, Darby SC, Jagsi R, Lorenzen EL, McArdle O, McGale P, Myerson S, Rahimi K, Vivekanandan S, Warren S, Taylor CW. A cardiac contouring atlas for radiotherapy. Radiother Oncol. 2017 Mar;122(3):416-422. doi: 10.1016/j.radonc.2017.01.008. Epub 2017 Feb 21.
- Gerard IJ, Bernier M, Hijal T, Kopek N, Pater P, Stosky J, Stroian G, Toscani B, Alfieri J. Stereotactic Arrhythmia Radioablation for Ventricular Tachycardia: Single Center First Experiences. Adv Radiat Oncol. 2021 Apr 20;6(4):100702. doi: 10.1016/j.adro.2021.100702. eCollection 2021 Jul-Aug.
- Hanna GG, Murray L, Patel R, Jain S, Aitken KL, Franks KN, van As N, Tree A, Hatfield P, Harrow S, McDonald F, Ahmed M, Saran FH, Webster GJ, Khoo V, Landau D, Eaton DJ, Hawkins MA. UK Consensus on Normal Tissue Dose Constraints for Stereotactic Radiotherapy. Clin Oncol (R Coll Radiol). 2018 Jan;30(1):5-14. doi: 10.1016/j.clon.2017.09.007. Epub 2017 Oct 13.
- Hohnloser SH, Kuck KH, Dorian P, Roberts RS, Hampton JR, Hatala R, Fain E, Gent M, Connolly SJ; DINAMIT Investigators. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med. 2004 Dec 9;351(24):2481-8.
- Knutson NC, Samson PP, Hugo GD, Goddu SM, Reynoso FJ, Kavanaugh JA, Mutic S, Moore K, Hilliard J, Cuculich PS, Robinson CG. Radiation Therapy Workflow and Dosimetric Analysis from a Phase 1/2 Trial of Noninvasive Cardiac Radioablation for Ventricular Tachycardia. Int J Radiat Oncol Biol Phys. 2019 Aug 1;104(5):1114-1123. doi: 10.1016/j.ijrobp.2019.04.005. Epub 2019 Apr 16.
- Lee J, Bates M, Shepherd E, Riley S, Henshaw M, Metherall P, Daniel J, Blower A, Scoones D, Wilkinson M, Richmond N, Robinson C, Cuculich P, Hugo G, Seller N, McStay R, Child N, Thornley A, Kelland N, Atherton P, Peedell C, Hatton M. Cardiac stereotactic ablative radiotherapy for control of refractory ventricular tachycardia: initial UK multicentre experience. Open Heart. 2021 Nov;8(2). pii: e001770. doi: 10.1136/openhrt-2021-001770.
- Pinta C, Besse R. Stereotactic ablative body radiotherapy for ventricular tachycardia: An alternative therapy for refractory patients. Anatol J Cardiol. 2021 Dec;25(12):858-862. doi: 10.5152/AnatolJCardiol.2021.187. Review.
- Robinson CG, Samson PP, Moore KMS, Hugo GD, Knutson N, Mutic S, Goddu SM, Lang A, Cooper DH, Faddis M, Noheria A, Smith TW, Woodard PK, Gropler RJ, Hallahan DE, Rudy Y, Cuculich PS. Phase I/II Trial of Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia. Circulation. 2019 Jan 15;139(3):313-321. doi: 10.1161/CIRCULATIONAHA.118.038261.
- Sharma A, Wong D, Weidlich G, Fogarty T, Jack A, Sumanaweera T, Maguire P. Noninvasive stereotactic radiosurgery (CyberHeart) for creation of ablation lesions in the atrium. Heart Rhythm. 2010 Jun;7(6):802-10. doi: 10.1016/j.hrthm.2010.02.010. Epub 2010 Feb 13.
- Shenthar J. Unusual Incessant Ventricular Tachycardia: What Is the Underlying Cause and the Possible Mechanism? Circ Arrhythm Electrophysiol. 2015 Dec;8(6):1507-11. doi: 10.1161/CIRCEP.115.002886.
- Walfridsson U, Arestedt K, Stromberg A. Development and validation of a new Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA) with focus on symptom burden. Health Qual Life Outcomes. 2012 Apr 30;10:44. doi: 10.1186/1477-7525-10-44.
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