Abstract and Introduction
Abstract
The EU Horizon 2020 Framework-funded Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) consortium has been established as a large research network for investigating STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia (VT). The aim is to provide a pooled treatment database to evaluate patterns of practice and outcomes of STAR and finally to harmonize STAR within Europe. The consortium comprises 31 clinical and research institutions. The project is divided into nine work packages (WPs): (i) observational cohort; (ii) standardization and harmonization of target delineation; (iii) harmonized prospective cohort; (iv) quality assurance (QA); (v) analysis and evaluation; (vi, ix) ethics and regulations; and (vii, viii) project coordination and dissemination. To provide a review of current clinical STAR practice in Europe, a comprehensive questionnaire was performed at project start. The STOPSTORM Institutions' experience in VT catheter ablation (83% ≥ 20 ann.) and stereotactic body radiotherapy (59% > 200 ann.) was adequate, and 84 STAR treatments were performed until project launch, while 8/22 centres already recruited VT patients in national clinical trials. The majority currently base their target definition on mapping during VT (96%) and/or pace mapping (75%), reduced voltage areas (63%), or late ventricular potentials (75%) during sinus rhythm. The majority currently apply a single-fraction dose of 25 Gy while planning techniques and dose prescription methods vary greatly. The current clinical STAR practice in the STOPSTORM consortium highlights potential areas of optimization and harmonization for substrate mapping, target delineation, motion management, dosimetry, and QA, which will be addressed in the various WPs.
Introduction
Cardiovascular disease is one of the leading causes of death in Europe (45%).[1] In patients with structural heart disease (SHD), ventricular tachycardia (VT) and ventricular fibrillation play a decisive role in sudden cardiac death, and anti-arrhythmic medication and implantable cardioverter-defibrillators (ICDs) are used to minimize the risks.[2] Patients with refractory VT often undergo minimally invasive catheter ablation. However, many patients with advanced heart disease have secondary diagnoses that make invasive procedures difficult or impossible. Another limitation for performing ablation is the accessibility of the corresponding VT region. Deep intramural areas or subepicardial locations, especially in the vicinity of structures such as coronary arteries, make effective ablation difficult so that ~20–50% of the patients develop recurrent VT after catheter ablation.[3,4] For refractory VT patients without other interventional options, cardiac stereotactic body radiation therapy (SBRT), called STereotactic Arrhythmia Radioablation (STAR), is now a new promising form of therapy.[5,6]
Preclinical studies on STAR were already realized in 2010,[7] while the first clinical STAR treatments for VT were accomplished as early as 2012[8] and 2014.[9] STAR treatments are based on a complex, interdisciplinary interaction of various diagnostic procedures, as well as quality assurance (QA) methods, and require a great amount of clinical experience in the respective areas.[10] A schematic presentation of the STAR process is shown in Figure 1. First, pre-planning takes place, in which an electrophysiologist defines the VT substrate. This is usually done based on electroanatomical mapping (EAM) data, which can be obtained, for example, from previous ablation procedures or dedicated non-invasive mapping systems, combined with anatomical scar imaging. The latter is performed through the assessment of echocardiography, computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET)/scintigraphy imaging. The defined VT substrate must then be transferred to the contrast-enhanced cardiac CT and the planning CT for delineation of the target volume (TV) by the radiation oncologists for treatment planning.[11–13] Radiotherapy treatment delivery is another challenge in the case of STAR treatments because of respiratory and cardiac motion of the target area.[13] Furthermore, the indication for STAR treatment is often given at a short notice due to incessant VT or electrical storm.
Figure 1.
Schematic presentation of the individual parts of a STAR treatment underlining the complexity of this procedure and its need for QA, exchange of experience, and cooperation between electrophysiologists, radiation oncologists, and medical physicists.
Little is currently known about the possible acute and late radiation-related effects of STAR on the whole heart or on individual substructures. Furthermore, the exact radiobiological processes in healthy as well as diseased cardiac tissue are also not yet fully understood, though recent data suggest that STAR at lower doses (20–25 Gy) may quickly induce reprogramming of cardiac conduction, whereas radioablation at higher doses (> 30 Gy) may induce scar formation.[14–17] These different mechanisms further complicate accurate recommendations for the prescription dose, desired dose (in)homogeneity, and the maximum dose. Nevertheless, the first clinical data for STAR showed promising results with markedly reduced VT burden after treatment.[10,18–21] The first prospective clinical trial by Robinson et al. (NCT 02919618) evaluated the safety and efficacy of STAR. Limited acute toxicities were observed, with a 1-year survival rate which is comparable with survival rates of similar patients and an improvement in quality of life (QoL) over time with a marked reduction in VT burden.[20]
That said, the complexity of STAR with regard to substrate identification by EAM, target volume delineation, cardiac and respiratory motion management, and the application of high-dose single-fraction irradiation requires a high-quality standard for optimal safety and efficacy. Further multi-centre evaluation of this novel procedure is urgently needed,[22,23] despite several ongoing clinical trials for STAR currently recruiting in Europe (e.g. NCT 03867747,[23] NCT 04642963,[24] and NCT 04066517).[25] A novel programme investigating STAR is the EU-funded Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary project (STOPSTORM consortium, Horizon 2020, GA No. 945119). The aim of this project is to establish a pooled STAR treatment database to evaluate efficacy and safety and to eventually harmonize STAR within Europe. Herein, in the first part of the article, we present an outline of the STOPSTORM project, followed by a review of current clinical STAR practice in Europe based on a comprehensive survey of the participating centres.
Europace. 2023;25(4):1284-1295. © 2023 Oxford University Press
Copyright 2007 European Heart Rhythm Association of the European Society of Cardiology (ESC). Published by Oxford University Press. All rights reserved.
