Histopathological Examination of an Explanted Heart in a Long-Term Responder to Cardiac Stereotactic Body Radiotherapy (STereotactic Arrhythmia Radioablation).
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SUBMITTER: Miszczyk M
PROVIDER: S-EPMC9302025 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Cardiac tachyarrhythmias are a major cause of morbidity and mortality. Treatments for these tachyarrhythmias include antiarrhythmic drugs, catheter ablation, surgical ablation, cardiac implantable electronic devices, and cardiac transplantation. Each of these treatment approaches is effective in some patients but there is considerable room for improvement, particularly with respect to the most common of the tachydysrhythmias, atrial fibrillation, and the most dangerous of the tachydysrhythmias, ventricular tachycardia (VT) or ventricular fibrillation. Noninvasive stereotactic ablative radiation therapy is emerging as an effective treatment for refractory tachyarrhythmias. Animal models have shown successful ablation of arrhythmogenic myocardial substrates with minimal short-term complications. Studies of stereotactic radioablation involving patients with refractory VT have shown a reduction in VT recurrence and promising early safety data. In this review, we provide the background for the application of stereotactic arrhythmia radioablation therapy along with promising results from early applications of the technology.
| S-EPMC7984992 | biostudies-literature
Project description:BackgroundStereotactic arrhythmia radioablation (STAR) is delivered with a planning target volume (PTV) prescription dose of 25 Gy, mostly to the surrounding 75-85% isodose line. This means that the average and maximum dose received by the target is less than 35 Gy, which is the minimum threshold required to create a homogenous transmural fibrosis. Similar to catheter ablation, the primary objective of STAR should be transmural fibrosis to prevent heterogenous intracardiac conduction velocities and the occurrence of sustained ventricular arrhythmias (sVA) caused by reentry. We hypothesize that the current dose prescription used in STAR is inadequate for the long-term prevention of sVA and that a significant increase in dose is necessary to induce transmural scar formation.ObjectiveA single arm, multi-center, phase II, dose escalation prospective clinical trial employing the i3 + 3 design is being conducted to examine the safety of a radiation dose-escalation strategy aimed at inducing transmural scar formation. The ultimate objective of this trial is to decrease the likelihood of sVA recurrence in patients at risk.MethodsPatients with ischemic or non-ischemic cardiomyopathy and recurrent sVA, with an ICD and history of ≥ 1 catheter ablation for sVA will be included. This is a prospective, multicenter, one-arm, dose-escalation trial utilizing the i3 + 3 design, a modified 3 + 3 specifically created to overcome limitations in traditional dose-finding studies. A total of 15 patients will be recruited. The trial aims to escalate the ITV dose from 27.0 Gy to an ITV prescription dose-equivalent level of maximum 35.1 Gy by keeping the PTV prescription dose constant at 25 Gy while increasing the dose to the target (i.e. the VT substrate without PTV margin) by step-wise reduction of the prescribing isodose line (85% down to 65%). The primary outcome of this trial is safety measured by registered radiation associated adverse events (AE) up to 90 days after study intervention including radiation associated serious adverse events graded as at least 4 or 5 according to CTCAE v5, radiation pneumonitis or pericarditis requiring hospitalization and decrease in LVEF ≥ 10% as assessed by echocardiography or cardiac MRI at 90 days after STAR. The sample size was determined assuming an acceptable primary outcome event rate of 20%. Secondary outcomes include sVA burden at 6 months after STAR, time to first sVA recurrence, reduction in appropriate ICD therapies, the need for escalation of antiarrhythmic drugs, non-radiation associated safety and patient reported outcome measures such as SF-36 and EQ5D.DiscussionDEFT-STAR is an innovative prospective phase II trial that aims to evaluate the optimal radiation dose for STAR in patients with therapy-refractory sVA. The trial has obtained IRB approval and focuses on determining the safe and effective radiation dose to be employed in the STAR procedure.Trial registrationNCT05594368.
| S-EPMC10634182 | biostudies-literature
Project description:AimsStereotactic arrhythmia radioablation (STAR) is a novel therapeutic approach for cardiac arrhythmias. The aim of this trial is to investigate the feasibility of STAR for the treatment of paroxysmal atrial fibrillation (AF) in elderly patients.Methods and resultsInclusion criteria were age >70 years, symptomatic AF, antiarrhythmic drugs failure, or intolerance. All patients underwent to 4D cardiac computed tomography simulation. The clinical target volume was identified in the area around pulmonary veins (PV). Stereotactic arrhythmia radioablation was performed with a total dose of 25 Gy (single fraction) delivered in 3 min. Twenty patients were enrolled and 18 underwent STAR. One patient withdrew informed consent before treatment and one patient was excluded due to unfavourable oesophagus position. With a median follow-up (FU) of 16 months (range 12-23), no acute toxicity more than Grade 3 was reported. Five patients had a Grade 1 oesophagitis 24 h after STAR; eight patients had an asymptomatic Grade 1 pericardial effusion, and one patient had a torsade de pointes treated effectively by electrical cardioversion and subsequent cardiac implantable cardioverter-defibrillator implantation. Most patients had a significant reduction in AF episodes. Five patients, due to arrhythmias recurrences after STAR, performed electrophysiological study documenting successful PV isolation. Finally, a significant improvement of quality of life was documented (48 ± 15 at enrolment vs. 75 ± 15 at 12 months FU; P < 0.001).ConclusionThe present phase II trial demonstrated the feasibility of STAR in paroxysmal AF elderly patients and its potential role in increasing the quality of life. Surely, more robust data are needed about safety and efficacy.Trial registrationClinicalTrials.gov: NCT04575662.
| S-EPMC10700012 | biostudies-literature
Project description:Stereotactic body radiotherapy is the technique of accurately delivering high doses of radiotherapy to small volume targets in a single or small number of sessions. The high biological effective dose of this treatment is reflected in the high rates of local control achieved across multiple tumour sites. Toxicity of the treatment can be significant and ongoing prospective trials will help define the utility of this treatment as an alternative to surgery in treating primary tumours and oligometastatic disease. Longer follow-up and survival data from prospective trials will be essential in determining the value of this resource-intensive treatment. The opportunity to combine this treatment with systemic therapies and its potential synergy with immunotherapy opens up interesting avenues for research in the future.
| S-EPMC6316669 | biostudies-other
Project description:Introduction: Although catheter ablation is the current gold standard treatment for refractory ventricular arrhythmias, sometimes its efficacy is not optimal and it's associated with high risks of procedural complication and death. Stereotactic arrhythmia radioablation (STAR) is increasingly being adopted for such clinical presentation, considering its efficacy and safety. Case Presentation: We do report our experience managing a case of high volume of left ventricle for refractory ventricular tachycardia in advanced heart failure patient, by delivering a single fraction of STAR through an highly personalization of dose delivery applying repeated inter- and continuous intra-fraction image guidance. Conclusion: According to the literature reports, we recommend considering increasing as much as possible the personalization features and safety technical procedure as long as that is not significantly affecting the STAR duration. Moreover, the duration in itself shouldn't be the main parameter, but balanced into the frame of possibly obtainable outcome improvement. At best of our knowledge, this is the first report applying such specific technology onto this clinical setting. Future studies will clarify these issues.
| S-EPMC7719630 | biostudies-literature
Project description:Prostate cancer remains the most common and second most deadly cancer diagnosed amongst U.S. men. External beam radiotherapy is a standard-of-care definitive treatment option for localized prostate cancer and historically constituted an 8-9-week treatment course comprised of 39-45 doses of 1.8-2.0 Gy each (conventional fractionation, CF). Based on the notion that prostate cancer may respond favorably to a higher dose per day, considerable research efforts have been focused on characterizing the safety and efficacy profile of shorter and shorter radiation courses. Ultrahypofractionation (UHF) involves condensing the radiation course into just 5-7 treatments of 6-8 Gy each. When utilizing modern techniques that allow the precise sculpting of a dose distribution that delivers high doses to the prostate and lower doses to surrounding normal tissues over five or fewer treatments, this treatment is called stereotactic body radiotherapy (SBRT). Two randomized trials (HYPO-RT-PC and PACE-B) have compared UHF to longer radiation courses. The former demonstrated that UHF and CF have similar long-term toxicity and efficacy, while the latter demonstrated that modern SBRT has equivalent short-term toxicity as well. A separate report from a consortium of studies data provides prospective, albeit nonrandomized, data supporting the longer-term safety and efficacy of SBRT specifically. Thus, mounting high-level evidence suggests that SBRT is an acceptable standard care of option for men with localized prostate cancer.
| S-EPMC7278320 | biostudies-literature
Project description:Prostate cancer is the most common non-cutaneous cancer in males. There are a number of options for patients with localized early stage disease, including active surveillance for low-risk disease, surgery, brachytherapy, and external beam radiotherapy. Increasingly, external beam radiotherapy, in the form of dose-escalated and moderately hypofractionated regimens, is being utilized in prostate cancer, with randomized evidence to support their use. Stereotactic body radiotherapy, which is a form of extreme hypofractionation, delivered with high precision and conformality typically over 1 to 5 fractions, offers a more contemporary approach with several advantages including being non-invasive, cost-effective, convenient for patients, and potentially improving patient access. In fact, one study has estimated that if half of the patients currently eligible for conventional fractionated radiotherapy in the United States were treated instead with stereotactic body radiotherapy, this would result in a total cost savings of US$250 million per year. There is also a strong radiobiological rationale to support its use, with prostate cancer believed to have a low ?/? ratio and therefore being preferentially sensitive to larger fraction sizes. To date, there are no published randomized trials reporting on the comparative efficacy of stereotactic body radiotherapy compared to alternative treatment modalities, although multiple randomized trials are currently accruing. Yet, early results from the randomized phase III study of HYPOfractionated RadioTherapy of intermediate risk localized Prostate Cancer (HYPO-RT-PC) trial, as well as multiple single-arm phase I/II trials, indicate low rates of late adverse effects with this approach. In patients with low- to intermediate-risk disease, excellent biochemical relapse-free survival outcomes have been reported, albeit with relatively short median follow-up times. These promising early results, coupled with the enormous potential cost savings and implications for resource availability, suggest that stereotactic body radiotherapy will take center stage in the treatment of prostate cancer in the years to come.
| S-EPMC6069023 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Dose prescription in stereotactic body radiotherapy (SBRT) for liver tumors is often limited by the mean liver dose. We explore the concept of spatiotemporal fractionation as an approach to facilitate further dose escalation in liver SBRT. MATERIALS AND METHODS:Spatiotemporal fractionation schemes aim at partial hypofractionation in the tumor along with near-uniform fractionation in normal tissues. This is achieved by delivering distinct dose distributions in different fractions, which are designed such that each fraction delivers a high single fraction dose to complementary parts of the tumor while creating a similar dose bath in the surrounding noninvolved liver. Thereby, higher biologically effective doses (BED) can be delivered to the tumor without increasing the mean BED in the liver. Planning of such treatments is performed by simultaneously optimizing multiple dose distributions based on their cumulative BED. We study this concept for five liver cancer patients with different tumor geometries. RESULTS:Spatiotemporal fractionation presents a method of increasing the ratio of prescribed tumor BED to mean BED in the noninvolved liver by approximately 10-20%, compared to conventional SBRT using identical fractions. CONCLUSIONS:Spatiotemporal fractionation may reduce the risk of liver toxicity or facilitate dose escalation in liver SBRT in circumstances where the mean dose to the non-involved liver is the prescription-limiting factor.
| S-EPMC5705331 | biostudies-literature
Project description:Stereotactic body radiotherapy (SBRT) has become a standard treatment option for early stage, node negative non-small cell lung cancer (NSCLC) in patients who are either medically inoperable or refuse surgical resection. SBRT has high local control rates and a favorable toxicity profile relative to other surgical and non-surgical approaches. Given the excellent tumor control rates and increasing utilization of SBRT, recent efforts have focused on limiting toxicity while expanding treatment to increasingly complex patients. We review toxicities from SBRT for lung cancer, including central airway, esophageal, vascular (e.g., aorta), lung parenchyma (e.g., radiation pneumonitis), and chest wall toxicities, as well as radiation-induced neuropathies (e.g., brachial plexus, vagus nerve and recurrent laryngeal nerve). We summarize patient-related, tumor-related, dosimetric characteristics of these toxicities, review published dose constraints, and propose strategies to reduce such complications.
| S-EPMC4491695 | biostudies-literature
Project description:Purpose: Approaching treatment for elderly patients with atrial fibrillation is difficult. A prospective phase II trial evaluating LINAC-based stereotactic arrhythmia radioablation (STAR) safety in this population started in 2021. Dosimetric and planning data were reported. Materials and Methods: A vac-lock bag was used for immobilization in the supine position and a computed tomography (CT, 1 mm) was performed. The clinical target volume (CTV) was defined as the area around the pulmonary veins. An internal target volume (ITV) was added to the CTV to compensate heart and respiratory movement. The planning target volume (PTV) was defined by adding 0-3 mm to the ITV. STAR was performed during free-breathing with a PTV prescription total dose (Dp) of 25 Gy/1 fraction. Flattening filter-free volumetric-modulated arc therapy plans were generated, optimized, and delivered by TrueBeamTM. Image-guided radiotherapy with cone-beam CT and surface-guided radiotherapy with Align-RT (Vision RT) were employed. Results: From May 2021 to March 2022, 10 elderly patients were treated. Mean CTVs, ITVs, and PTVs were 23.6 cc, 44.32 cc, and 62.9 cc, respectively; the mean prescription isodose level and D2% were 76.5% and 31.2 Gy, respectively. The average heart and left anterior descending artery (LAD) Dmean were 3.9 and 6.3 Gy, respectively; the mean Dmax for LAD, spinal cord, left and right bronchus, and esophagus were 11.2, 7.5, 14.3, 12.4, and 13.6 Gy, respectively. The overall treatment time (OTT) was 3 min. Conclusions: The data showed an optimal target coverage, sparing surrounding tissue, in 3 min of OTT. LINAC-based STAR for AF could represent a valid non-invasive alternative for elderly patients who were excluded from catheter ablation.
| S-EPMC10143465 | biostudies-literature