Background: Stereotactic radiosurgery is a form of radiotherapy that is performed in a single session and focuses high-dose ionizing radiation beams from a collimated radiation source to a small, localized area of the body. Recently, stereotactic radiosurgery has been applied to arrhythmias (stereotactic arrhythmia radioablation - STAR), with promising results reported in patients with refractory, scar-related ventricular tachycardia (VT), a cohort with known high morbidity and mortality. Objective: Herein, we describe our experience with the use of CyberKnife, a frameless image-guided linear accelerator stereotactic radiosurgery system, in conjunction with CardioPlan, a cardiac specific radiotherapy planning software, to treat patients with scar-related VT, detailing its early and mid- to long-term results. Methods: This is a pilot, prospective study of patients undergoing STAR for refractory VT. The anatomical target for radioablation was defined based on the clinical VT morphology, electroanatomical mapping, and study-specific pre-procedural imaging with cardiac computed tomography. The target volume delineated with the aid of CardioPlan was treated with a prescription radiation dose of 25 Gy delivered in a single fraction by CyberKnife in an outpatient setting. Ventricular arrhythmias and radiation-related adverse events were monitored at follow-up to determine STAR efficacy and safety. Result: Five patients (100 % male, 63 ± 12 years old, 80 % ischemic cardiomyopathy, left ventricular ejection fraction 34 ± 15 %) with refractory VT underwent STAR between January and June 2018. Radioablation was delivered in 82 ± 11 minutes without acute complications. During a mean follow-up of 12 ± 2 months, all patients experienced clinically significant mid- to late-term ventricular arrhythmia recurrence; two patients died of complications associated with their advanced heart failure. There were no clinical or imaging evidence of radiation necrosis or other radiation-induced complications in the organs at risk surrounding the scar targeted by radioablation. Conclusion: Despite good initial results, STAR did not result in effective ventricular arrhythmia control in the long term in a selected, high-risk population of patients with scar-related VT. The safety profile was confirmed to be favorable, with no radiation-related complications observed during follow-up. Further studies are needed to explain these disappointing results.

doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

PURPOSE In the treatment of uveal melanomas, the optimal prescribed dose to maximize disease control, but minimize radiation-related complications is unknown. Historically our institution has treated uveal melanomas to doses less than 85 Gy to the tumor apex even if the apex was less than 5mm in height. Here, we investigate how tumor control and visual outcomes are affected by the radiation dose at the tumor apex. METHODS AND MATERIALS A retrospective review was performed to evaluate patients treated for uveal melanoma with Iodine-125 plaques between 1988 and 2010. Radiation dose is reported as dose to tumor apex and dose to 5 mm. Primary end points included time to local failure, distant failure, and death. Secondary end points included eye preservation, visual acuity, and radiation-related complications. Univariate and multivariate analyses were performed to determine association between radiation dose and the end point variables. RESULTS One hundred ninety patients with sufficient data to evaluate the end points were included. The 5 year local control (LC) rate was 91%. The 5 year distant metastases (DM) rate was 10%. The 5 year overall survival (OS) rate was 84%. There were no differences in outcome (LC, DM, OS) when dose was stratified by apex dose quartile (<69 Gy, 69–81 Gy, 81–89 Gy, >89 Gy). However, increasing apex dose and dose to 5 mm depth were correlated with greater visual acuity loss (p=0.02, p=0.0006), worse final visual acuity (p=0.02, p<0.0001) and radiation complications (p<0.0001, p=0.0009). In addition, enucleation rates were worse with increasing quartiles of dose to 5 mm (p=0.0001). CONCLUSIONS Doses at least as low as 69 Gy prescribed to the tumor apex achieve rates of local control, distant metastasis free survival, and overall survival that are similar to radiation doses of 85 Gy to the tumor apex, but with improved visual outcomes.

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ImportanceHypofractionated radiation therapy (RT) for prostate cancer has been associated with greater acute grade 2 gastrointestinal (GI) toxic effects compared with conventionally fractionated RT.ObjectiveTo evaluate whether a hyaluronic acid rectal spacer could (1) improve rectal dosimetry and (2) affect acute grade 2 or higher GI toxic effects for hypofractionated RT.Design, Setting, and ParticipantsThis randomized clinical trial was conducted from March 2020 to June 2021 among 12 centers within the US, Australia, and Spain, with a 6-month follow-up. Adult patients with biopsy-proven, T1 to T2 prostate cancer with a Gleason score 7 or less and prostate-specific antigen level of 20 ng/mL or less (to convert to μg/L, multiply by 1) were blinded to the treatment arms. Of the 260 consented patients, 201 patients (77.3%) were randomized (2:1) to the presence or absence of the spacer. Patients were stratified by intended 4-month androgen deprivation therapy use and erectile quality.Main Outcomes and MeasuresFor the primary outcome, we hypothesized that more than 70% of patients in the spacer group would achieve a 25% or greater reduction in the rectal volume receiving 54 Gy (V54). For the secondary outcome, we hypothesized that the spacer group would have noninferior acute (within 3 months) grade 2 or higher GI toxic effects compared with the control group, with a margin of 10%.ResultsOf the 201 randomized patients, 8 (4.0%) were Asian, 26 (12.9%) Black, 42 (20.9%) Hispanic or Latino, and 153 (76.1%) White; the mean (SD) age for the spacer group was 68.6 (7.2) years and 68.4 (7.3) years for the control group. For the primary outcome, 131 of 133 (98.5%; 95% CI, 94.7%-99.8%) patients in the spacer group experienced a 25% or greater reduction in rectum V54, which was greater than the minimally acceptable 70% (P &amp;lt; .001). The mean (SD) reduction was 85.0% (20.9%). For the secondary outcome, 4 of 136 patients (2.9%) in the spacer group and 9 of 65 patients (13.8%) in the control group experienced acute grade 2 or higher GI toxic effects (difference, −10.9%; 95% 1-sided upper confidence limit, −3.5; P = .01).Conclusions and RelevanceThe trial results suggest that rectal spacing with hyaluronic acid improved rectal dosimetry and reduced acute grade 2 or higher GI toxic effects. Rectal spacing should potentially be considered for minimizing the risk of acute grade 2 or higher toxic effects for hypofractionated RT.Trial RegistrationClinicalTrials.gov Identifier: NCT04189913