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Background: Noninvasive cardiac radioablation is reported to be effective and safe for the treatment of ventricular tachycardia (VT). Objective: This study aimed to analyze the acute and long-term effects of VT radioablation. Methods: Patients with intractable VT or premature ventricular contraction (PVC)–induced cardiomyopathy were included in this study and treated using a single-fraction 25-Gy dose of cardiac radioablation. To quantitatively analyze the acute response after treatment, continuous electrocardiography monitoring was performed from 24 hours before to 48 hours after irradiation and at the 1-month follow-up. Long-term clinical safety and efficacy were assessed 1-year follow-up. Results: From 2019 to 2020, 6 patients were treated with radioablation for ischemic VT (n = 3), nonischemic VT (n = 2), or PVC-induced cardiomyopathy (n = 1). In the short-term assessment, the total burden of ventricular beats decreased by 49% within 24 hours after radioablation and further decreased by 70% at 1 month. The VT component decreased earlier and more dramatically than the PVC component (decreased by 91% and 57% at 1 month, respectively). In the long-term assessment, 5 patients showed complete (n = 3) or partial (n = 2) remission of ventricular arrhythmias. One patient showed recurrence at 10 months, which was successfully suppressed with medical treatment. The posttreatment PVC coupling interval was prolonged (+38 ms at 1 month). Ischemic VT burden decreased more markedly than nonischemic VT burden after radioablation. Conclusion: In this small case series of 6 patients, without a comparison group, cardiac radioablation appeared to decrease the intractable VT burden. A therapeutic effect was apparent within 1–2 days after treatment but was variable by etiology of cardiomyopathy.

Purpose: We conducted a prospective, in silico study to evaluate the feasibility of cone-beam computed tomography (CBCT)-guided stereotactic adaptive radiation therapy (CT-STAR) for the treatment of ultracentral thoracic cancers (NCT04008537). We hypothesized that CT-STAR would reduce dose to organs at risk (OARs) compared with nonadaptive stereotactic body radiation therapy (SBRT) while maintaining adequate tumor coverage. Methods and Materials: Patients who were already receiving radiation therapy for ultracentral thoracic malignancies underwent 5 additional daily CBCTs on the ETHOS system as part of a prospective imaging study. These were used to simulate CT-STAR, in silico. Initial, nonadaptive plans (PI) were created based on simulation images and simulated adaptive plans (PA) were based on study CBCTs. 55 Gy/5 fractions was prescribed, with OAR constraint prioritization over PTV coverage under a strict isotoxicity approach. PI were applied to patients’ anatomy of the day and compared with daily PA using dose-volume histogram metrics, with selection of superior plans for simulated delivery. Feasibility was defined as completion of the end-to-end adaptive workflow while meeting strict OAR constraints in ≥80% of fractions. CT-STAR was performed under time pressures to mimic clinical adaptive processes. Results: Seven patients were accrued, 6 with intraparenchymal tumors and 1 with a subcarinal lymph node. CT-STAR was feasible in 34 of 35 simulated fractions. In total, 32 dose constraint violations occurred when the PI was applied to anatomy-of-the-day across 22 of 35 fractions. These violations were resolved by the PA in all but one fraction, in which the proximal bronchial tree dose was still numerically improved through adaptation. The mean difference between the planning target volume and gross total volume V100% in the PI and the PA was –0.24% (–10.40 to 9.90) and –0.62% (–11.00 to 8.00), respectively. Mean end-to-end workflow time was 28.21 minutes (18.02-50.97). Conclusions: CT-STAR widened the dosimetric therapeutic index of ultracentral thorax SBRT compared with nonadaptive SBRT. A phase 1 protocol is underway to evaluate the safety of this paradigm for patients with ultracentral early-stage NSCLC.

Purpose: Hippocampal volume (HV) is an established predicting factor for neurocognitive function (NCF) in neurodegenerative disease. Whether the same phenomenon exists with hippocampal-avoidant whole brain radiation therapy is not known; therefore, we assessed the association of baseline HV with NCF among patients enrolled on RTOG 0933. Methods and Materials: Hippocampal volume and total brain volume were calculated from the radiation therapy plan. Hippocampal volume was correlated with baseline and 4-month NCF scores (Hopkins Verbal Learning Test–Revised [HVLT-R] Total Recall [TR], Immediate Recognition, and Delayed Recall [DR]) using Pearson correlation. Deterioration in NCF was defined per the primary endpoint of RTOG 0933(mean 4-month relative decline in HVLT-R DR). Comparisons between patients with deteriorated and nondeteriorated NCF were made using the Wilcoxon test. Results: Forty-two patients were evaluable. The median age was 56.5 years (range, 28-83 years), and 81% had a class II recursive partitioning analysis. The median total, right, and left HVs were 5.4 cm3 (range, 1.9-7.4 cm3), 2.8 cm3 (range, 0.9-4.0 cm3), and 2.7 cm3 (range, 1.0-3.7 cm3), respectively. The median total brain volume was 1343 cm3 (range, 1120.5-1738.8 cm3). For all measures of corrected HV, increasing HV was associated with higher baseline HVLT-R TR and DR scores (ρ: range, 0.35-0.40; P-value range, .009-.024) and 4-month TR and DR scores (ρ: range, 0.29-0.40; P-value range, .009-.04), with the exception of right HV and 4-month DR scores (ρ: 0.29; P = .059). There was no significant association between HV and NCF change between baseline and 4 months. Fourteen patients (33.3%) developed NCF deterioration per the primary endpoint of RTOG 0933. There was no significant difference in HV between patients with deteriorated and nondeteriorated NCF, although in all instances, patients with deteriorated NCF had numerically lower HV. Conclusions: Larger HV was positively associated with improved performance on baseline and 4-month HVLT-R TR and DR scores in patients with brain metastases undergoing hippocampal-avoidant whole brain radiation therapy but was not associated with a change in NCF.

Purpose: NRG Oncology's RTOG 0933 demonstrated benefits to memory preservation after hippocampal avoidant whole-brain radiation therapy (HA-WBRT), the avoidance of radiation dose to the hippocampus (using intensity modulated radiation planning and delivery techniques) during WBRT, supporting the hypothesis of hippocampal radiosensitivity and associated memory specificity. However, some patients demonstrated cognitive decline, suggesting mechanisms outside hippocampal radiosensitivity play a role. White matter injury (WMI) has been implicated in radiation therapy–induced neurocognitive decline. This secondary analysis explored the relationship between pretreatment WMI and memory after HA-WBRT. Methods and Materials: Volumetric analysis of metastatic disease burden and disease-unrelated WMI was conducted on the pretreatment magnetic resonance image. Correlational analyses were performed examining the relationship between pretreatment WMI and Hopkins Verbal Learning Test-Revised (HVLT-R) outcomes at baseline and 4 months after HA-WBRT. Results: In the study, 113 patients received HA-WBRT. Of 113 patients, 33 underwent pretreatment and 4-month posttreatment HVLT testing and pretreatment postcontrast volumetric T1 and axial T2/fluid-attenuated inversion recovery magnetic resonance imaging. Correlation was found between larger volumes of pretreatment WMI and decline in HVLT-R recognition (r = 0.54, P

Purpose: Stereotactic radiosurgery (SRS) in combination with immunotherapy (IMT) or targeted therapy is increasingly being used in the setting of melanoma brain metastases (MBMs). The synergistic properties of combination therapy are not well understood. We compared the distant intracranial failure rates of intact MBMs treated with SRS, SRS + IMT, and SRS + targeted therapy. Methods and materials: Combination therapy was defined as delivery of SRS within 3 months of IMT (anti-CTLA-4 /anti-PD-1 therapy) or targeted therapy (BRAF/MEK inhibitors). The primary endpoint was distant intracranial failure after SRS, which was defined as any new MBM identified on brain magnetic resonance imaging. Outcomes were evaluated using the Kaplan Meier method and Cox proportional hazards. Results: A total of 72 patients with melanoma with 233 MBMs were treated between April 2006 and April 2016. The number of MBMs within each treatment group was as follows: SRS: 121; SRS + IMT: 48; and SRS + targeted therapy: 64. The median follow-up was 8.9 months. One-year distant intracranial control rates for SRS, SRS + IMT, and SRS + targeted therapy were 11.5%, 60%, and 10%, respectively (P

Purpose: Magnetic resonance image guided radiation therapy (MR-IGRT) has been used at our institution since 2014. We report on more than 2 years of clinical experience in treating patients with the world's first MR-IGRT system. Methods and materials: A clinical service was opened for MR-IGRT in January 2014 with an MR-IGRT system consisting of a split 0.35T magnetic resonance scanner that straddles a ring gantry with 3 multileaf collimator-equipped 60Co heads. The service was expanded to include online adaptive radiation therapy (ART) MR-IGRT and cine gating after 6 and 9 months, respectively. Patients selected for MR-IGRT were enrolled in a prospective registry between January 2014 and June 2016. Patients were treated with a variety of radiation therapy techniques including intensity modulated radiation therapy and stereotactic body radiation therapy (SBRT). When applicable, online ART was performed and gating on sagittal 2-dimensional cine MR was used. The charts of patients treated with MR-IGRT were reviewed to report on the clinical and treatment characteristics of the initial patients who were treated with this novel technique. Results: A total of 316 patients have been treated with the MR-IGRT system, which has been integrated into a high-volume clinic. The cases were most commonly selected for improved soft tissue visualization, ART, and cine gating. Seventy-six patients were treated with 3-dimensional conformal radiation therapy, 146 patients with intensity modulated radiation therapy, and 94 patients with SBRT. The most commonly treated disease sites were the abdomen (28%), breast (26%), pelvis (22%), thorax (19%), and head and neck (5%). Sixty-seven patients were treated with online ART over a total of 244 adapted fractions. Cine treatment gating was used for a total of 81 patients. Conclusions: MR-IGRT has been successfully implemented in a high-volume radiation clinic and provides unique advantages in the treatment of a variety of malignancies. Additional clinical trials are in development to formally evaluate MR-IGRT in the treatment of multiple disease sites with techniques such as SBRT and ART.

Purpose: Treatment planning factors are known to affect the risk of severe acute esophagitis during thoracic radiation therapy. We tested a previously published model to predict the risk of severe acute esophagitis on an independent data set. Methods and materials: The data set consists of data from patients who had recoverable treatment plans and received definitive radiation therapy for non–small cell carcinoma of the lung at a single institution between November 2004 and January 2010. Complete esophagus dose-volume and available clinical information was extracted using our in-house software. The previously published model was a logistic function with a combination of mean esophageal dose and use of concurrent chemotherapy. In addition to testing the previous model, we used a novel, machine learning-based method to build a maximally predictive model. Results: Ninety-four patients (81.7%) developed Common Terminology Criteria for Adverse Events, Version 4, Grade 2 or more severe esophagitis (Grade 2: n = 79 and Grade 3: n = 15). Univariate analysis revealed that the most statistically significant dose-volume parameters included percentage of esophagus volume receiving ≥40 to 60 Gy, minimum dose to the highest 20% of esophagus volume (D20) to D35, and mean dose. Other significant predictors included concurrent chemotherapy and patient age. The previously published model predicted risk effectively with a Spearman's rank correlation coefficient (rs) of 0.43 (P < .001) with good calibration (Hosmer-Lemeshow goodness of fit: P = .537). A new model that was built from the current data set found the same variables, yielding an rs of 0.43 (P < .001) with a logistic function of 0.0853 × mean esophageal dose [Gy] + 1.49 × concurrent chemotherapy [1/0] − 1.75 and Hosmer-Lemeshow P = .659. A novel preconditioned least absolute shrinkage and selection operator method yielded an average rs of 0.38 on 100 bootstrapped data sets. Conclusions: The previously published model was validated on an independent data set and determined to be nearly as predictive as the best possible two-parameter logistic model even though it overpredicted risk systematically. A novel, machine learning-based model using a bootstrapping approach showed reasonable predictive power.