Radiation therapy in refractory ventricular tachycardia

Advancement in medicine and cardiology has led to more numbers of patients now living longer with cardiac morbidities, and many patients now reach advanced stage of cardiac condition where cardiac arrhythmias represent a serious complication of the disease.[1,2] Available treatment options {antiarrhythmic drugs, invasive cardiac ablation and implantable cardioverter defibrillators (ICDs)} are effective in preventing arrhythmic event thus saving life but many patients progress and become refractory for these treatment modalities. Moreover, these modalities are with significant adverse events and invasive and sometimes not feasible in end-stage patient. Therefore, non-invasive therapeutic options are warranted. High-dose radiation therapy with precision to a well-define targets potentially guided by cardiac diagnostic tools is now evolving with satisfactory and sometimes substantially improved outcomes. Radiation therapy effect on cardiac tissues is understood by scattered dose and dose as organ at risk to cardia during thoracic radiotherapy but radiation is seldom used directly for cardiac pathology. In the first decade of twenty-first century, case reports were published to manage cardiac metastases and cardiac sarcoma by then evolving image-guided high-precision radiotherapy (radiosurgery).[3,4] Preclinical and feasibility studies in human established safety as well as efficacy with single-fraction stereotactic body ablative radiation therapy (SABR). Sharma et al.[5] demonstrate the feasibility of using stereotactic radiosurgery (SRS) to produce targeted cardiac lesions without causing injury to nearby tissues. Contemporarily, Guerra et al. and Perez-Castellano demonstrated cardiac radiation effect of blocking electrical conduction in porcine and canine models using beta radiation seeds in a catheter directly applied to cardiac tissue.[6,7] Myocardial scar after infarction or fibrosis replacement is a usual substrate of monomorphic ventricular tachycardia (VT) in patients with structural heart disease. The extent of the myocardial necrosis and the degree of left ventricular dysfunction are predominant factors in determining the risk of arrhythmia after an infarction. While risk of ventricular tachycardia in general population is quite low and stable, the incidence of post-infarction ventricular tachycardia is established at about 3%–5%. But it has estimated to decline to around 1% due to better and timely management of myocardial infarction.[8] However, it might be increasing as a result of improved post-infarction survival and the possibility of VT appearing years after the initial infarction combined with the progressive aging of the population. Cardiac target motion compensation is a crucial component to cardiac radiotherapy that enhances the complexity of radiotherapy treatment planning and patient positioning prior and during treatment. Combine respiratory and myocardial motion might lead to erroneous delivery of radiation doses to target and normal tissue resulting into more adverse events. Though cardiac motion does not result in translational movement requiring significant motion management, since severe cardiomyopathy leads to even less heart motion due to decreased contractility.[9] Respiratory motion resulting in craniocaudal movement accounts for most of intrafraction motion of targets of interest, i.e., post-infarct scar.[10] Various techniques are used in thoracic SABR for motion management. The respiratory motion compensation techniques used during radiation delivery are; respiratory gating (the dose is delivered only when the target is in a specific part of the respiratory cycle), respiratory tracking (the radiation beam follows the target throughout the respiratory cycle), respiratory inhibition systems (the respiratory motion is limited by abdominal compression or breath-hold). Furthermore, radio-opaque fiducial meticulously placed adjacent to the cardiac target and moves synchronously can add accuracy in localizing and tracking a moving target; potentially any radio-opaque structure that moves synchronously with the target can be used as a surrogate for the target position and used to image movement with X-ray or CT imaging. Intra or extracardiac structures-like artificial (mechanical valves, stents, pacemaker or ICD leads) or natural radio-opaque structures (vessels or valvular calcifications) are usually used in place of fiducial markers to maintain the non-invasiveness of the radiation treatment procedure. An appropriate definition of internal target volume (ITV) with the help of four-dimensional CT simulation while delineating and planning, in addition to above-mentioned strategies, further enhances radiation delivery accuracy. Since gating and targeting a moving organ is routine now in advanced radiation oncology setup, targeting cardiac lesion well delineated by modern cardiac diagnostic tool is quite feasible with submillimetre accuracy. When multidisciplinary team including radiation oncologist and cardiologist decides to treat the refractory VT by radioablation, patient undergoes non-invasive electrocardiographic imaging during induced VT to precisely map the tachycardia circuit. Additional cardiac imaging such as resting single-photon emission CT (SPECT) or contrast-enhanced cardiac MRI are used to identify regions of anatomical scarring. Both imaging and electrical information are combined to construct a volumetric target. ICD if in situ is used as fiducial marker guiding the planning and for real-time tracking system. Patient undergoes a respiration-correlated CT simulation scan (four-dimensional CT) to assess the total sum of cardiac and pulmonary motion after body immobilization with a vacuum-assisted device. Volume of interest is delineated as CTV (clinical target volume) with the help of cardiac imaging and electrocardiographic imaging fusion and an ITV is drawn based on 4D imaging. Eventually, a planning target volume (PTV) is built by expanding the target to account for motion, setup uncertainty, and delivery uncertainty. A robust PTV is used based on setup error of individual departmental facilities. Radiation dose is prescribed to PTV with specific dose constraints to surrounding normal structure with aim to achieve at least 95% of volume receiving 95% of dose prescribed and achieving dose constraints of normal structure to reduce adverse events. Treatment planning system by iterative process provides best possible solution, and best possible plan is selected for execution. For the treatment, the patient is placed supine similar to simulation scan on the treatment table and made comfortable to minimize movement for the duration of treatment delivery (the treatment can be interrupted if needed and restarted after repositioning). Treatment is delivered with the use of an image-guided radiotherapy unit equipped with cone beam computerised tomography (CBCT) system or biplane X-ray imaging cameras system to acquire images of the thorax, which can be directly registered to the planning CT. Ablation target volumes ranged from 10 to 80 cc in previous studies and the efficacy of the treatment has been demonstrated in all cases, evidencing the reduction or disappearance of the arrhythmia without patients complications and very low toxicity rate (mild inflammatory changes in the adjacent lung tissue and pericardium resolving withing few months). Patient can return home immediately after treatment without acute symptoms. A case series published in 2017 and later first phase I/II clinical trial for arrythmia radioablation in 2019 and STARNL-1 trial found significant reduction in ventricular arrhythmias and improvement in the clinical conditions allowing to reduce the use of antiarrhythmic drugs and to improve the quality of life.[11-13] 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 of this consortium is to provide a pooled treatment database to evaluate patterns of practice and outcomes of cardiac radiotherapy and finally to harmonize it.[14] Two other outcomes of interest that further warrant to study arrythmia radioablation in refractory VT patients are, a) improvement in myocardial function in recent revelation of results of a prospective study[15] and elucidation of mechanism of single fraction of 25 Gy that leads to immediate improvement in arrythmia episode before development in fibrosis. Perhaps STOPSTORM consortium and further research can provide answer to these questions and improve the outcome of refractory tachycardias. Moreover, fractionation effect can also be studied but till now, a single fraction (25Gy) is used for arrhythmia radioablation. In conclusion, high-dose single-fraction radiotherapy with help of motion management techniques is quite effective treatment option for cardiac arrythmias especially in patients with refractory ventricular tachycardias.