The use of cardiac stereotactic body radiation therapy for the treatment of ventricular tachycardia (VT), also termed stereotactic ablative radiation therapy or, increasingly, stereotactic arrhythmia radioablation (STAR), is increasingly used in select patients. STAR has emerged as a promising alternative to invasive catheter ablation (CA) for patients with high-risk refractory VT who have failed prior medical therapy or catheter ablation. Since the publication of the first case series using STAR, our understanding of the mechanisms of STAR, longer-term clinical outcomes, potential side effects, and barriers to widespread adoption of cardiac radioablation has become increasingly clear. In this review, we discuss these topics, the increased adoption of STAR, as well as the challenges that lie ahead for this therapy. In addition, as data strongly suggest that fibrosis alone cannot account for the early decreases in VT events observed post-STAR, we propose adopting the STAR acronym to instead stand for stereotactic arrhythmia radiation therapy.

Top 5 gene ontology pathways enriched in each cell type upon chemoradiation related to Figure 3D

The objective of this study was to quantify and characterize the presence of non-tumor size features among non-small cell lung cancer (NSCLC) patients in a surgical cohort versus those in a nonsurgical cohort and assess the potential impact of key features on staging. A total of 22,876 patients aged 66 years and older with newly diagnosed (2010-2015) stage I-III NSCLC (T1-T3, N0/N1, M0) without prior or concurrent primary cancer were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare Database. Reported T stage data (American Joint Committee on Cancer 7th Edition) were compared with a hypothetical tumor size only T stage (Tsize-Only), which did not account for non-tumor size defining characteristics. Frequencies of key non-tumor size features were analyzed among surgical and non-surgical cohorts. In the surgical cohort, a lower Tsize-Only vs. SEER-reported T stage was observed in 2,531 patients (20.8%). Specifically, T stage would be lower in 1,542 (32.6%) patients with T2 disease and in 989 (66.4%) patients with T3 disease. In the non-surgical cohort, lower Tsize-Only vs. Reported T was observed in 1,446 patients (13.5%) [342 (8.8%) patients with T2 disease and 1,104 (60.1%) patients with T3 disease]. The largest disparity between cohorts was in T2 disease and visceral pleural invasion (VPI): VPI was identified in 87.5% of surgically resected patients with lower Tsize-Only versus only 37.4% in nonsurgical patients. Our findings highlight the need for better T stage characterization in non-surgical patients. Development of predictive models or standardized radiographic methods to accurately identify VPI in the non-surgical NSCLC population are recommended in light of the established impact of VPI on clinical outcomes. Trial investigators should consider the potential impact of un-identified VPI on their effect size estimates and sample size calculations. Attention towards non-tumor size related features, particularly VPI, may lead to improved treatment decisions and outcomes

Stereotactic arrhythmia radioablation (STAR) has emerged as a novel, noninvasive therapeutic option for patients with drug- and ablation-refractory ventricular tachycardia (VT). Derived from stereotactic body radiotherapy (SBRT), STAR enables the delivery of a single, high-dose fraction of ionizing radiation to arrhythmogenic myocardial tissue with submillimeter precision while minimizing exposure to surrounding cardiac and extracardiac structures. This review summarizes current evidence regarding mechanisms of action, patient selection, treatment planning, and clinical outcomes of STAR. Preclinical and early clinical studies suggest that STAR exerts rapid antiarrhythmic effects through modulation of cardiac conduction proteins and potential structural remodeling, though long-term efficacy remains under investigation. Clinical trials and prospective registries report substantial reductions in VT burden with acceptable short-term safety, yet recurrence rates and late toxicities require further evaluation. The European STOPSTORM consortium has been established to standardize treatment protocols, harmonize target delineation, and coordinate multicenter clinical validation. As STAR continues to evolve, multidisciplinary collaboration between radiation oncologists, cardiologists, and medical physicists will be essential to define optimal practice standards, ensure patient safety, and assess long-term outcomes. STAR represents a promising paradigm shift in the management of refractory VT, offering a noninvasive alternative when conventional therapies are ineffective or infeasible.

Supplementary Figure 2: Forest plot of univariate Cox proportional hazards regression analyses comparing the prognostic value of ctFE and Max VAF as continuous measures in the LA-WU cohort from pre- and mid-treatment timepoints. Hazard ratios for OS and PFS per absolute one percentage point increase in ctFE or Max VAF are shown as squares; horizontal bars denote 95% CIs. CI, confidence interval; ctFE, circulating tumor fraction estimate; HR, hazard ratio; LA-WU, locally advanced NSCLC Washington University cohort (n = 24 pre-treatment, n = 26 mid-treatment); Max VAF, maximum variant allele frequency; OS, overall survival; PFS, progression-free survival.

The Radiation Oncology-Biology Integration Network (ROBIN) initiative addresses critical gaps in radiation oncology by integrating advanced biological research, technologic innovation, and clinical practice. ROBIN leverages "omics" technologies, data science, and integrative analyses to elucidate the mechanisms governing tumor and normal tissue responses to radiotherapy (RT). Through five specialized centers-OligoMET, ImmunoRad, GenRad, METEOR, and KIDSROBIN-the network covers a broad spectrum of cancer and radiation biology research. Each center conducts translational programs linked to clinical trials, targeting key domains, including metastasis biology, RT-immune system interactions, and genomic determinants of treatment response. KIDSROBIN assures the invaluable inclusion of pediatric cancers to the consortium. By collecting clinically annotated human biospecimens and applying single-cell and spatially resolved omics, ROBIN enables mechanistic insights into radiation effects directly in patients. A central pillar of the initiative is its commitment to data standardization and sharing, using cloud-based platforms to generate accessible and interoperable datasets. ROBIN also prioritizes education and cross-disciplinary training to cultivate the next generation of scientists in radiation biology and oncology. This integrated approach positions ROBIN to drive transformative advances in radiation oncology and multimodal cancer therapy, informing personalized treatment strategies and improving patient outcomes. This review provides an overview of the ROBIN program and its key strategies, research activities, and contributions to advancing radiation biology and oncology. The vision and leadership of Dr. Norman Coleman have been foundational to the development of the ROBIN initiative, inspiring a collaborative ecosystem that bridges science and clinical practice to drive meaningful impact in patient care.

Introduction The cardiovascular toxicity of radiation therapy (RT) remains incompletely understood in patients with NSCLC. Our objective was to define changes in echocardiographic parameters of structure and function with RT and their associations with cardiac dose-volume metrics. Methods This multicenter, longitudinal, prospective cohort study included participants with NSCLC who received standard, curative-intent thoracic RT. Dose-volume metrics were extracted from centrally contoured cardiac substructures. Echocardiograms at baseline, end of RT, 6 months post-RT, and 12 months post-RT were core laboratory-quantified. Repeated-measures multivariable linear regression via generalized estimating equations estimated changes in echocardiographic measures and associations with dose-volume metrics. Results Across 125 participants, there was a modest worsening in left ventricular ejection fraction (LVEF) (p = 0.019), global longitudinal strain (p < 0.001), circumferential strain (p < 0.001), and Ea/Ees (p = 0.011) post-RT that largely recovered by 12 months. Cardiac dysfunction, defined as LVEF declines of at least 10% from baseline to a threshold value of less than 50%, occurred in 7.2% of participants at a median of 1.7 months after RT initiation. Mean heart dose was associated with LVEF declines (-1.1%, 95% confidence interval: -2.2 to 0.0 per interquartile range increase, p = 0.044), as was whole heart V30 (-1.4%, 95% confidence interval: -2.5 to -0.3 per interquartile range increase, p = 0.015); with multiple comparison adjustment, whole heart V30 remained significant (p = 0.030). Conclusions On average, there were modest changes in cardiac function immediately after RT in patients with NSCLC, with a subset experiencing clinically relevant cardiac dysfunction. Although whole heart V30 was associated with LVEF declines, suggesting its relevance in RT planning, there is also a need for newer dose-volume measures.

Mid-treatment ctDNA variant-level data per patient in the prospective LA-WU cohort.

Supplementary Figure 5: Kaplan-Meier curves showing survival outcomes based on the presence or absence of one or more nonsynonymous-mutated canonical driver genes in NSCLC (EGFR, KRAS, ERBB2, MET, RET, BRAF, ROS1, NTRK1/2/3, ALK, and NRG1). A) OS in LA-WU, B) PFS in LA-WU, C) OS in LA-RW. Hazard ratios from univariate Cox regression analysis and log-rank p-values are shown. HR, hazard ratio; KM, Kaplan-Meier; LA-WU, locally-advanced NSCLC Washington University cohort (n = 24); LA-RW, locally-advanced real-world NSCLC validation cohort (n = 94); OS, overall survival; PFS, progression-free survival.

Supplementary Figure 3: Forest plot of multivariate Cox proportional hazards regression analysis comparing the prognostic value of ctFE and Max VAF as continuous measures in the LA-RW cohort. Hazard ratios for ctFE and Max VAF (calculated per increase of 0.1) and covariates are shown as squares; horizontal bars denote 95% CIs. Reference levels for categorical variables were as follows: Histology: LUAD, Sex: Male, Smoking: Never. CI, confidence interval; ctFE, circulating tumor fraction estimate; HR, hazard ratio; LA-RW, locally advanced real-world NSCLC cohort (n = 94); Max VAF, maximum variant allele frequency; OS, overall survival; PFS, progression-free survival.

Supplementary Figure 10: KM survival curves showing (A) OS and (B) PFS based on pre-treatment Max VAF levels in the LA-WU cohort (n = 24). Hazard ratios from univariate Cox analysis and log-rank p-values are shown. High Max VAF is defined as Max VAF >0.0138; low Max VAF as Max VAF ≤0.0138 (Methods). HR, hazard ratio; KM, Kaplan-Meier; LA-WU, locally advanced NSCLC cohort from Washington University (n = 24); Max VAF, maximum variant allele frequency; OS, overall survival; PFS, progression-free survival.

BACKGROUND:Stereotactic arrhythmia radiotherapy (STAR) treats ventricular tachycardia (VT) but requires internal target volume (ITV) expansions to compensate for cardiorespiratory motion. Respiratory 4D CTs (r4DCT) are commonly acquired for STAR patients to assess respiratory motion and determine the ITV expansion margin. Current clinical r4DCT imaging methods are limited, and the reconstructed r4DCTs suffer from unmanaged cardiac motion artifacts that affect the quantitative assessment of respiratory motion of the heart and substructures. PURPOSE:To develop a novel image-processing method that accurately quantifies the respiratory motion of the heart and substructures in r4DCTs corrupted by cardiac motion artifacts. METHODS:A groupwise surface-to-surface deformable image registration (DIR) algorithm, named gCGF, was developed by combining the Coherent Point Drift (CPD) algorithm with Gaussian Mixture Models (GMM) and a Finite Element Model (FEM). A novel principal component filtering (PCF) mechanism and a spatial smoothing mechanism were developed and incorporated into gCGF to iteratively register heart contours of ten r4DCT phases while removing random cardiac motion from the cyclic respiratory motion. The performance of the groupwise DIR was quantitatively validated using eight digital phantoms with simulated cardiac artifacts. An ablation study was conducted to compare gCGF to another comparable state-of-the-art groupwise DIR method. gCGF was applied to r4DCTs of 20 STAR patients to analyze the respiratory motion of the heart, which was computed for individual respiratory phases, with the average position of registered heart shapes as the reference position. RESULTS:Validation on digital phantoms showed that gCGF achieved target registration errors (TRE) of 0.63 ± 0.51 mm for the heart surface while successfully achieving phase smoothness and reducing cardiac motion artifacts. TREs of 0.69 to 0.95 mm were achieved for the cardiac substructures. For each STAR patient, the heart contours of ten phases of r4DCT were registered with gCGF. Among all STAR patients, the heart's maximum and mean respiratory motion magnitudes ranged from 3.6 to 7.9 mm and 1.0 to 2.6 mm. The peak-to-peak motion range was from 6.2 to 14.7 mm. For VT targets, the max and mean motion magnitude ranges were 3.0 to 6.7 mm and 0.8 to 2.9 mm, respectively. The peak-to-peak range was from 4.7 to 11.8 mm. Significant dominance of the first principal component of the motion direction was observed (p = 0). Respiratory motion was found to be patient-specific and predominantly in the first principal component direction. CONCLUSIONS:The gCGF surface-to-surface deformable registration algorithm was confirmed to be robust to quantify respiratory motion of the heart in the r4DCTs while mitigating cardiac motion artifacts. The gCGF algorithm and the results of this study can be useful to enable personalized motion management for STAR treatments and patient-specific optimization of the ITV margins.

NRG Oncology RTOG 0539 was a prospective phase II trial of risk-adapted radiotherapy for patients with WHO grade 1-3 meningioma. Low-risk (group 1, n = 60) was defined as a grade 1 tumor after gross total resection or subtotal resection (GTR/STR) and prospectively monitored. Intermediate-risk (group 2, n = 52) was defined as recurrent grade 1 or newly diagnosed grade 2 tumor after GTR and treated with radiotherapy (54 Gy). High-risk (group 3, n = 53) included a newly diagnosed grade 2 tumor after STR, newly diagnosed grade 3 tumor, or recurrent grade 2 or 3 tumor and treated with radiotherapy (60 Gy). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The median follow-up times for the low-, intermediate-, and high-risk cohorts were 12.1, 12.0, and 11.1 years, respectively. The 10-year PFS and OS rates for the low-, intermediate-, and high-risk cohorts were 85.2% and 94.1%, 72.2% and 84.7%, and 42.5% and 51.1%, respectively. Five patients (9.6%) and eight patients (15.1%) had a grade 3+ toxicity attributed to radiotherapy in the intermediate- and high-risk cohorts, respectively. The long-term outcomes using this risk-adapted approach support observation for low-risk patients, inform radiotherapy patient selection and practice standards for intermediate- and high-risk patients, and provide comparative benchmarks for future trials.

Baseline patient characteristics in the prospective LA-WU cohort.

Ventricular tachycardia is a life-threatening cardiac arrhythmia that can potentially be treated using stereotactic body radiation therapy given as a single fraction. Given these characteristics, along with the delicate nature of irradiating a portion of the heart, accuracy of dose calculation in the treatment planning system is imperative. Two such calculation methods employed are superposition-convolution-based algorithms, such as Varian’s Analytical Anisotropic Algorithm (AAA) and Linear Boltzmann Transport Equation solvers, such as Varian’s Acuros XB (AXB). The purpose of this work is to compare these calculation algorithms in this treatment setting. Forty-eight patient plans with a nominal planning target volume prescription dose of 25 Gy that were initially calculated using AAA were recalculated using AXB without re-optimization. A third recalculation was conducted using Radformation’s standalone Monte Carlo (MC) algorithm as a gold standard. Both AAA and AXB dose distributions were then compared to MC using 3D gamma analysis. Various target dose metrics in the AAA, AXB, and MC plans were compared along with organ-at-risk (OAR) dose points. Relative to MC, the median agreement rate for AAA was 89.1% and for AXB was 98.3%. The minimum agreement rate over the patient cohort was 70.4% and 93.2% for AAA and AXB, respectively. The overall gamma agreement rates were significantly higher for AXB than for AAA. With respect to the target and OAR dose comparisons, in every case, the differences in dose metrics were significantly different between AAA/MC and AXB/MC, with AXB having the superior agreement with MC. The mean differences between MC for both algorithms were lower in each case for AXB. By every metric evaluated, including target dose coverage, OAR dose endpoints, and 3D gamma dose evaluation, AXB resulted in a more precise agreement with the MC dose calculation benchmark for cardiac radioablation of ventricular tachycardia.