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Cardiac radioablation (CRA) is an emerging treatment for high-risk refractory ventricular tachycardia (VT). Despite a fixed prescription dose to the planning target volume (PTV) there is still considerable heterogeneity in the radiotherapy dose distribution due to planning technique, proximity to organs at risk, and radiation oncologist preference. The hypothesis is that plans with an inherently "hotter" internal dose to the PTV may lead to improved VT outcomes. Single-center, IRB-approved retrospective case series of patients with refractory VT who had failed at least one prior CA (or were unfit for CA) treated with CRA. All patients were treated with a single fraction of 25 Gy prescribed to the PTV. Maximum dose to PTV was collected from each plan and stratified as high vs low above and below the median. Maximum dose was defined as the highest dose delivered to the "hottest" 0.035 cc of the PTV to avoid known variability in reporting of dose to single voxels within the treatment planning system. Rates of survival (OS), freedom from shock and/or storm (FFSS), and freedom from death, shock, and/or storm (FFDSS) were collected, and stratified by maximum dose to the PTV. Formal statistical comparisons were not performed due to limited patient numbers. From 2015-2020, 22 patients were treated with CRA (18 with prior CA, 4 unfit for CA) for high-risk refractory VT. Median age was 64.5 years (range, 49-84), and 90.9% were male. 50% had ICM, with a median NYHA class of 3 (range, 1-4) and median EF of 25% (range, 15-58%). Median follow-up was 31.3 months. 2-year OS was 54.5%, FFSS was 42.4%, and FFDSS was 27.3%. Median maximum dose to the PTV was 42.2 Gy (range, 29.2-45.8 Gy). PTV maximum dose (high vs low) discriminated 2-year OS (63.6% vs 45.5%), FFSS (50% vs 30%) and FFDSS (36.4% vs 18.2%). For all endpoints, Kaplan-Meier curves overlapped for the first 6 months, and then diverged. In patients with high-risk refractory VT treated with CRA, survival and VT outcomes were similar between both groups out to 6 months, with improved OS and VT control noted after that with higher maximum doses. With a prescription dose of 25 Gy to the PTV, adjusting planning parameters to maintain maximum doses > 42 Gy may improve durable outcomes and requires validation in a larger cohort. [ABSTRACT FROM AUTHOR]

Ventricular tachycardia (VT) is a life-threatening rhythm disturbance of the heart that has been shown to be amenable to treatment with SBRT, known as non-invasive cardiac radioablation (CRA). The metabolic impact of directly targeting arrhythmogenic regions of scarred left ventricle (LV) is unknown. Herein the relationship between RT dose and 18FDG uptake in LV segments following CRA was interrogated. Patients in the ENCORE–VT trial received a 25 Gy single-fraction CRA to an electrophysiology-guided gross target volume (GTV), planned on 4D-CT. Patients underwent PET-CT, troponin–I and MRI at baseline, day 3 (D3) & day 90 (D90). Auto-segmentation of LV into the AHA 17-segment model was performed on planning CTs & PET-CTs, allowing median RT dose and standardized uptake value (SUV) to be extracted. Change in segment median SUV was correlated with dose, clinical outcomes (ICD shock, death) & biomarkers. 19 patients received CRA. Median VT episodes were reduced from 119 in the 6 months before compared to 3 in the six months after CRA (p<0.001). In the first 90 days, 2/19 patients (10.5%) developed a treatment-related SAE. Overall survival was 89% at 6 months. Targeted LV segments had lower baseline SUV than non-targeted segments (p<0.001). Median SUV of targeted segments at baseline, D3 & D90 were 1.43, 1.67 & 2.52 (P = 0.012). There were time-dependent decreases in troponin–I, and from as early as D3 (P = 0.332). At D3, greater SUV increases were observed in cardiac segments that received lower doses (0–10Gy SUV +37.2% vs 20–40Gy SUV +8.0%, P = 0.004). At D90, the opposite trend was seen; greater SUV increases were seen in segments that received higher doses (20–40Gy SUV +106.7% vs 0–10Gy SUV +79.0%, P = 0.012). At D3, a ≥20% SUV increase in targeted segments (n = 7/19) was associated with improved survival (P = 0.006). At D90, increased median whole myocardium SUV was weakly associated with improved LVEF (R2 = 0.355, P = 0.158). In logistic regression models, SUV values, together with cardiomyopathy type, VT storm, and amiodarone use predicted shocks (AUC 0.828, P = 0.027) and death (AUC 0.847, P = 0.016). Metabolic activity of the GTV increased after CRA. Late (D90) SUV increases were observed in targeted segments, consistent with VT burden reduction. Which cell populations (e.g. cardiomyocytes, immune cells, fibroblasts) have become more metabolically active remains to be determined. Unexpectedly, early SUV changes (D3) were observed in segments in the low dose bath outside the GTV, and were associated with both reduced troponin–I and improved survival. Further longitudinal studies with PET-CT after CRA will define how SUV dynamics can be optimally incorporated as a biomarker in practice, and the potential therapeutic functional impact of low-dose RT in the setting of cardiomyopathy warrants further investigation. [ABSTRACT FROM AUTHOR]

Radiation therapy is a well-established approach for safely and non-invasively treating solid tumours and benign diseases with high precision and accuracy. Cardiac radiation therapy has recently emerged as a non-invasive treatment option for the management of refractory ventricular tachycardia. Here we summarise existing clinical and preclinical literature surrounding cardiac radiobiology and discuss how these studies may inform basic and translational research, as well as clinical treatment paradigms in the management of arrhythmias. [ABSTRACT FROM AUTHOR]