Chronic therapy of patients with sustained VA included ICD, antiarrhythmic drugs, catheter ablation, and/or surgery. For patients with recurrent VA refractory to antiarrhythmic medication therapy, current guideline recommended radiofrequency catheter ablation.
The VISTA randomized multicenter trial showed that an extensive substrate-based ablation approach is superior to ablation targeting only clinical and stable VTs in patients with ICM presenting with tolerated VTs . Systematic review and meta-analysis of non-randomized trials suggested significantly lower rates of recurrent VT following a combined endocardial/epicardial ablation compared with endocardial ablation alone . Therefore, comprehensive and extensive substrate elimination is the best catheter ablation strategy for recurrent VT. However, there are some potential etiologies that might lead to failure of catheter ablation, for example, inability to accurately identify VT substrate, extensive substrate not amenable for ablation, or inaccessible VT substrates, such as mid-myocardial, LV summit or intraseptal area. In patients who failed with catheter ablation, SBRT is an emerging treatment under investigation.
To our knowledge, this is first reported case series in Asia-Pacific which included 7 patients with 5 different VA etiologies. This case series is also the first one to compare pre-treatment and post-treatment imaging.
The first reported case series of five patients who received noninvasive cardiac radiation for VT have suggested the efficacy of cardiac radioablation for VT using SBRT . The same group published the first prospective phase I/II trial of electrophysiology-guided noninvasive cardiac radioablation for VT (ENCORE VT study) of 19 patients, which showed that the procedure was safe and well-tolerated and markedly reduced VT burden . These 2 studies used noninvasive electrocardiographic imaging to map the VT circuit. In our study, every patient received 3D electroanatomic mapping either by activation mapping during VTs or voltage mapping for hemodynamically unstable VTs or polymorphic VTs. To identify the substrates accurately, in additional to 3D electroanatomic mapping, every patient received pre-treatment contrast enhanced dual energy CT and DE-MRI (unless contraindicated) to identify the scar areas in order to delineate the target region precisely. The fundamental concept of this approach is to eliminate the potential arrhythmogenic substrates thoroughly rather than just the exit site and adjacent areas of clinical VTs which might be far from the critical isthmus.
Regarding the SBRT, compared with the published studies, our report is different in several aspects. First, we used simultaneous integrated boost strategy to deliver 25 Gy to GTV and 20 Gy to PTV in a single fraction, while other studies prescribed a single dose of 25 Gy to the PTV [6, 7, 10]. Our clinical results demonstrated that this strategy in treating refractory VT is as effective as previous studies. Second, we used linear accelerator Varian TrueBeam System with flattening filter-free photon beam, which is similar to ENCORE VT study  (16% treated by Varian TrueBeam and 84% by Varian Edge) but different from Neuwirth study  in which the robotic treatment system CyberKnife was used. According to published reports [7, 11, 13], CyberKnife system however contributed to smaller planning target volume (22.2cc in Neuwirth CyberKnife study vs. 98.9cc in ENCORE VT study vs. 52.0cc in our study) and lesser Gr3+ late toxicities (10% late cardiac late toxicity in Neuwirth CyberKnife study vs. 39% late cardiac or pulmonary toxicity in ENCORE VT study) and caused longer treatment time (68.0 min in Neuwirth CyberKnife study vs 15.3 min in ENCORE VT study vs 12.7 in our study). As yet, linear accelerator–based radiotherapy system is currently the main strategy for treating refractory VT in our facility.
In all previously reported case series [6, 7, 10-12] VT episodes decreased significantly after 6-week blanking period. In our study, VT episodes decreased 91%, and ICD shock therapy decreased 86%. All patients responded to SBRT. Besides, all VT patients showed acute effect of SBRT with no recurrence in blanking period. In previous reports, three studies [6, 7, 10] with linear accelerator Varian TrueBeam System revealed better efficacy on VT reduction than the other two studies [11, 12] with CyberKnife system. In TrueBeam system group, 94% of patients responded to SBRT in ENCORE VT study ; 87.5% of patients responded to SBRT in Lloyd study . In CyberKnife system group, 80% of patients responded to SBRT and 20% of patients showed delayed effects in Neuwirth study ; all patients (5 patients) experienced clinically significant mid- to late-term VA recurrence in Gianni study . Delivering ablative dose to heart by TrueBeam system seems more effective than by Cyberknife system. However, dosimetry study comparing the two systems and quality assurance study approving consistency between delivered doses and planned doses should be carried out, in order to reasoning a suggestion to use TrueBeam system as the major delivery strategy.
In ENCORE VT study, 2 patients with PVC-related cardiomyopathy were enrolled and 1 showed an increased PVC burden at 6-week and decreased in the 3-month during follow-up. In our patient 3, the PVC burden was stationary at 6-week, increased in the 4th month and decreased in the 7th and 12th month. The effect of SBRT to PVC was more delayed than the previous study. Since the response on PVC burden to radioablation was less reported, it needs further study to clarify the time course of response after SBRT.
Previous studies have demonstrated the radiobiological mechanisms of SBRT. Recent evidence indicates that SBRT causes direct cell death due to DNA damages and indirect cell death through vascular damage . Garcia-Barros et al.  reported that irradiation of tumors with doses higher than 8-10 Gy rapidly caused ceramide-mediated apoptotic death in endothelial cells, thereby leading to vascular occlusion and tumor cell death. Cuculich et al.  demonstrated the first postmortem cardiac samples 3 weeks after SBRT, which showed prominent ectatic blood vessels at the interface of dense scar and viable myocardium (scar border zone). This study is the first report to compare pre- and post-SBRT images. Images of most of the patients showed denser or more extensive scar after SBRT as expected. In patient 4, both pre-and post-treatment images didn’t identify obvious scar. This patient received SBRT with only 4.6cc of PTV and 14.4cc GTV. Although CMR theoretically could detect the myocardium scar as little as 1 cm3, it was probable that the biological effects prompted by exposure to radiation cannot be precisely predicted, and the scar might be too small to be detected by CMR in this patient. In patient 5, post-treatment scar at RV basal septum was stationary without enlargement. The radiation effects may be correlated with the nature of exposure and their extents, and also the microenvironment of the target tissues. Whether the septum (thicker myocardium) is more radioresistant and needs higher doses is unknown.
No severe acute adverse event was reported by previous studies [6, 7, 10-12]. Radiation pneumonitis and pericardial effusions were most common reported clinical relevant adverse events. In our study, no radiation pneumonitis was noted by post-treatment chest X ray and CT. In patient 2, the post treatment CT 6 months after SBRT revealed Grade 1 pericardial effusion, which was absent in the previous follow-up transthoracic echocardiography. The pericardial effusion persisted in the latest transthoracic echocardiography follow-up.
Patient 6 in this study died of hepatic failure. He was a HCV carrier without previous follow up history. His baseline liver function was normal. One month after SBRT, he came to ER due to progressive jaundice and dyspnea. HCV viral load was 205000 IU/mL. GTV of this patient was 35.5 cc and PTV was 83.4 cc. The liver mean dose was 41.5 cGy. Radiation related hepatic failure was not likely. Heart failure symptoms and slow VT (in blanking period) were also presented at ER. Heart failure with comorbid hepatitis C was proposed to be related to his hepatic failure. In the 2 largest reports [7, 10], most of the mortality cases were related to heart failure, and none was radiation related.
In our study, the mean age was young (mean 55 years, range 23-80 years). We enrolled young patients because that patients receiving SBRT reported overall good quality of life in general, associated with better global health status and lower indirect costs of productivity loss [15, 16], which are much more important in young rather than old patients. In children and young adults, SBRT prolonged overall survival without significant toxicities . The maturation of SBRT contributed to decades of technical and clinical advancement, including managing cardiac and respiratory motions, defining safe radiation dosing levels for critical organs, and setting quality assurance standards globally. Before large-scale long-term follow-up data emerges, we recommended that SBRT could be given to patients only with life-threatening or severely symptomatic VAs refractory to medications and traditional ablation procedures. As long as the SBRT organs at risks (OARs) constraints by the report of AAPM Task Group 101 were cautiously satisfied , we could minimize long-term complications in patients undergoing SBRT.
This is a small, single-center, retrospective analysis with limited follow-up time. The long-term efficacy and safety of this treatment is still not known.