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Automatic segmentation of 3D objects in computed tomography (CT) is challenging. Current methods, based mainly on artificial intelligence (AI) and end-to-end deep learning (DL) networks, are weak in garnering high-level anatomic information, which leads to compromised efficiency and robustness. This can be overcome by incorporating natural intelligence (NI) into AI methods via computational models of human anatomic knowledge.We formulate a hybrid intelligence (HI) approach that integrates the complementary strengths of NI and AI for organ segmentation in CT images and illustrate performance in the application of radiation therapy (RT) planning via multisite clinical evaluation.The system employs five modules: (i) body region recognition, which automatically trims a given image to a precisely defined target body region; (ii) NI-based automatic anatomy recognition object recognition (AAR-R), which performs object recognition in the trimmed image without DL and outputs a localized fuzzy model for each object; (iii) DL-based recognition (DL-R), which refines the coarse recognition results of AAR-R and outputs a stack of 2D bounding boxes (BBs) for each object; (iv) model morphing (MM), which deforms the AAR-R fuzzy model of each object guided by the BBs output by DL-R; and (v) DL-based delineation (DL-D), which employs the object containment information provided by MM to delineate each object. NI from (ii), AI from (i), (iii), and (v), and their combination from (iv) facilitate the HI system.The HI system was tested on 26 organs in neck and thorax body regions on CT images obtained prospectively from 464 patients in a study involving four RT centers. Data sets from one separate independent institution involving 125 patients were employed in training/model building for each of the two body regions, whereas 104 and 110 data sets from the 4 RT centers were utilized for testing on neck and thorax, respectively. In the testing data sets, 83% of the images had limitations such as streak artifacts, poor contrast, shape distortion, pathology, or implants. The contours output by the HI system were compared to contours drawn in clinical practice at the four RT centers by utilizing an independently established ground-truth set of contours as reference. Three sets of measures were employed: accuracy via Dice coefficient (DC) and Hausdorff boundary distance (HD), subjective clinical acceptability via a blinded reader study, and efficiency by measuring human time saved in contouring by the HI system. Overall, the HI system achieved a mean DC of 0.78 and 0.87 and a mean HD of 2.22 and 4.53 mm for neck and thorax, respectively. It significantly outperformed clinical contouring in accuracy and saved overall 70% of human time over clinical contouring time, whereas acceptability scores varied significantly from site to site for both auto-contours and clinically drawn contours.The HI system is observed to behave like an expert human in robustness in the contouring task but vastly more efficiently. It seems to use NI help where image information alone will not suffice to decide, first for the correct localization of the object and then for the precise delineation of the boundary.

Background Three- and five-year progression-free survival (PFS) for low-risk meningioma managed with surgery and observation reportedly exceeds 90%. Herewith we summarize outcomes for low-risk meningioma patients enrolled on NRG/RTOG 0539. Methods This phase II trial allocated patients to one of three groups per World Health Organization grade, recurrence status, and resection extent. Low-risk patients had either gross total (GTR) or subtotal resection (STR) for a newly diagnosed grade 1 meningioma and were observed after surgery. The primary endpoint was 3-year PFS. Adverse events (AEs) were scored using Common Terminology Criteria for Adverse Events (CTCAE) version 3. Results Among 60 evaluable patients, the median follow-up was 9.1 years. The 3-, 5-, and 10-year rates were 91.4% (95% CI, 84.2 to 98.6), 89.4% (95% CI, 81.3 to 97.5), 85.0% (95% CI, 75.3 to 94.7) for PFS and 98.3% (95% CI, 94.9 to 100), 98.3%, (95% CI, 94.9 to 100), 93.8% (95% CI, 87.0 to 100) for overall survival (OS), respectively. With centrally confirmed GTR, 3/5/10y PFS and OS rates were 94.3/94.3/87.6% and 97.1/97.1/90.4%. With STR, 3/5/10y PFS rates were 83.1/72.7/72.7% and 10y OS 100%. Five patients reported one grade 3, four grade 2, and five grade 1 AEs. There were no grade 4 or 5 AEs. Conclusions These results prospectively validate high PFS and OS for low-risk meningioma managed surgically but raise questions regarding optimal management following STR, a subcohort that could potentially benefit from adjuvant therapy.

OBJECTIVE The internal high-dose volume varies widely for a given prescribed dose during stereotactic radiosurgery (SRS) to treat brain metastases (BMs). This may be altered during treatment planning, and the authors have previously shown that this improves local control (LC) for non–small cell lung cancer BMs without increasing toxicity. Here, they seek to identify potentially actionable dosimetric predictors of LC after SRS for melanoma BM. METHODS The records of patients with unresected melanoma BM treated with single-fraction Gamma Knife RS between 2006 and 2017 were reviewed. LC was assessed on a per-lesion basis, defined as stability or a decrease in lesion size. Outcome-oriented approaches were utilized to determine optimal dichotomization for dosimetric variables relative to LC. Univariable and multivariable Cox regression analysis was implemented to evaluate the impact of collected parameters on LC. RESULTS Two hundred eighty-seven melanoma BMs in 79 patients were identified. The median age was 56 years (range 31–86 years). The median follow-up was 7.6 months (range 0.5–81.6 months), and the median survival was 9.3 months (range 1.3–81.6 months). Lesions were optimally stratified by volume receiving at least 30 Gy (V30) greater than or equal to versus less than 25%. V30 was ≥ and < 25% in 147 and 140 lesions, respectively. For all patients, 1-year LC was 83% versus 66% for V30 ≥ and < 25%, respectively (p = 0.001). Stratifying by volume, lesions 2 cm or less (n = 215) had 1-year LC of 82% versus 70% (p = 0.013) for V30 ≥ and < 25%, respectively. Lesions > 2 to 3 cm (n = 32) had 1-year LC of 100% versus 43% (p = 0.214) for V30 ≥ and < 25%, respectively. V30 was still predictive of LC even after controlling for the use of immunotherapy and targeted therapy. Radionecrosis occurred in 2.8% of lesions and was not significantly associated with V30. CONCLUSIONS For a given prescription dose, an increased internal high-dose volume, as indicated by measures such as V30 ≥ 25%, is associated with improved LC but not increased toxicity in single-fraction SRS for melanoma BM. Internal dose escalation is an independent predictor of improved LC even in patients receiving immunotherapy and/or targeted therapy. This represents a dosimetric parameter that is actionable at the time of treatment planning and warrants further evaluation.

Radiation therapy is an important component of cancer therapy for many malignancies. With improvements in cardiac-sparing techniques, radiation-induced cardiac dysfunction has decreased but remains a continued concern. In this review, we provide an overview of the evolution of radiotherapy techniques in thoracic cancers and associated reductions in cardiac risk. We also highlight data demonstrating that in some cases radiation doses to specific cardiac substructures correlate with cardiac toxicities and/or survival beyond mean heart dose alone. Advanced cardiac imaging, cardiovascular risk assessment, and potentially even biomarkers can help guide post-radiotherapy patient care. In addition, treatment of ventricular arrhythmias with the use of ablative radiotherapy may inform knowledge of radiation-induced cardiac dysfunction. Future efforts should explore further personalization of radiotherapy to minimize cardiac dysfunction by coupling knowledge derived from enhanced dosimetry to cardiac substructures, post-radiation regional dysfunction seen on advanced cardiac imaging, and more complete cardiac toxicity data., Central Illustration, Highlights • Despite improvements in radiation techniques, radiation-induced cardiac dysfunction can occur in those with thoracic cancers. • Newer studies have examined associations between cardiac substructure doses and cardiac outcomes and/or survival. • Advanced cardiac imaging allows assessment of regional dysfunction after cardiac radiation exposure. • Enhanced dose tracking, imaging, and comprehensive clinical data hold promise for personalized approaches to minimize cardiotoxicity.

Determine the dosimetric quality and the planning time reduction when utilizing a template-based automated planning application.A software application integrated through the treatment planning system application programing interface, QuickPlan, was developed to facilitate automated planning using configurable templates for contouring, knowledge-based planning structure matching, field design, and algorithm settings. Validations are performed at various levels of the planning procedure and assist in the evaluation of readiness of the CT image, structure set, and plan layout for automated planning. QuickPlan is evaluated dosimetrically against 22 hippocampal-avoidance whole brain radiotherapy patients. The required times to treatment plan generation are compared for the validations set as well as 10 prospective patients whose plans have been automated by QuickPlan.The generations of 22 automated treatment plans are compared against a manual replanning using an identical process, resulting in dosimetric differences of minor clinical significance. The target dose to 2% volume and homogeneity index result in significantly decreased values for automated plans, whereas other dose metric evaluations are nonsignificant. The time to generate the treatment plans is reduced for all automated plans with a median difference of 9' 50″ ± 4' 33″.Template-based automated planning allows for reduced treatment planning time with consistent optimization structure creation, treatment field creation, plan optimization, and dose calculation with similar dosimetric quality. This process has potential expansion to numerous disease sites.

Purpose: To provide a new insight on a novel safe cardiac radioablation using deep inspiration breath-hold (DIBH) to reduce gastrointestinal dose.Materials and Methods: For treating incessant ventricular tachycardia (VT) originated from left ventricle inferior scar abutting the stomach, a target delineation and treatment planning for cardiac radioablation was performed. With four different computed tomography (CT) scan protocols—DIBH, full expiration breath-hold, four-dimensional (4D) CT without and with abdominal compression, the distances between the target and the stomach were compared.Results: Among the protocols, the CT scan with DIBH showed largest distance between the target and the stomach and selected for the treatment planning. The prescribed dose was 25 Gy in a single fraction, and satisfactory dosimetric parameters were achieved with the DIBH. The patient was successfully treated with the DIBH, and experienced no acute toxicity. Conclusion: To gain the best benefit from cardiac radioablation, understanding the possible toxicity in the adjacent organs is crucial. By moving the heart with thoraco-diaphragmatic movement by DIBH, the target could be physically separated from the stomach.

The American Cancer Society has recently reported an increase in the percentage of patients with localized lung cancer from 2004 to 2018, coinciding with the initial lung cancer screening guidelines issued in 2013. We conducted a National Cancer Database (NCDB) study to further evaluate the trends in stage I according to patient and tumor characteristics.We selected patients with lung cancer from the NCDB Public Benchmark Report diagnosed between 2010 and 2017. Patients with stages I to IV according to the AJCC seventh edition were evaluated according to the year of diagnosis, histology, age, sex, race, and insurance.Among the 1,447,470 patients identified in the database, 56,382 (3.9%) were excluded due to stage 0 or unknown, or incorrect histology, leaving 1,391,088 patients eligible. The percentage of patients with stage I increased from 23.5% in 2010 to 29.1% in 2017 for all lung cancers, from 25.9% to 31.8% in non-small-cell lung cancer (NSCLC), and from 5.0% to 5.4% in small-cell lung cancer (SCLC). Patients younger than 70 years, males and blacks had lower percentages of stage I compared to older patients, females, and nonblacks respectively. Patients with no insurance had the lowest percentage of stage I.There has been a significant increase in the percentage of stage I lung cancer at diagnosis from 2010 to 2017, which occurred mostly in NSCLC. Although the staging shift was observed in all subsets of patients, there were noticeable imbalances according to demographic factors.

Background To identify factors predictive of developing symptomatic radiation necrosis (sRN) among patients with either intact or resected brain metastases undergoing five-fraction stereotactic radiosurgery (5fSRS). Methods Multi-institutional retrospective review of 117 brain metastases from 83 patients treated with 5fSRS. The cumulative incidence of sRN and predictors of sRN were calculated using Gray’s competing risks and Cox regression. Results The median dose of 5fSRS was 30 Gy (range: 25–40), and 21 lesions (18%) had prior SRS. After a median follow-up of 10.3 months (range: 3–52), the cumulative sRN incidence was 15%, with a median time to sRN of 6.9 months (range: 1.8–31.7). sRN incidence was significantly higher among the lesions treated with prior SRS: hazard ratio (HR): 7.48 [95% confidence interval: 2.57–21.8]. Among lesions without prior SRS, higher volume of uninvolved brain receiving 25 Gy (BrainV25; HR: 1.07 [1.02–1.12]) and 30 Gy (BrainV30; HR: 1.07 [1.01–1.33]) were the most significant factors associated with sRN. Similar results were also observed among the patients with prior SRS. For lesions without prior SRS, BrainV25 > 16 cm3 (HR: 11.7 [1.47–93.3]) and BrainV30 > 10 cm3 (HR: 7.08 [1.52–33.0]) were associated with significantly higher risk of sRN. At two years, the sRN incidence was 21% if violating either dosimetric threshold and 2% if violating neither (p = .007). Conclusion BrainV25 and BrainV30 are significant dosimetric predictors of sRN of brain metastases treated with 5fSRS. In the absence of prior SRS, maintaining BrainV25Gy

PURPOSE: Stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) is a standard of care for medically inoperable patients. Our aim was to compare Common Terminology Criteria for Adverse Events (CTCAE) thoracic grade 3 or higher adverse events (AEs) of 30 Gy in one fraction (arm 1) vs. 60 Gy in 3 fractions (arm 2). METHODS: This was a randomized multi-institutional, phase II, two-arm, clinical trial. Medically inoperable patients with biopsy-proven peripheral T1/T2N0M0 NSCLC tumors were enrolled. Patients were randomized to arm 1 or arm 2 and stratified by performance status. The primary endpoint was CTCAE thoracic grade 3 or higher AEs. Secondary end points were local control (LC), progression-free survival (PFS), overall survival (OS), and quality of life (QOL). RESULTS: Between September, 2008 and April, 2015, 98 patients were randomized. Median follow-up was 53.8 months. 10 patients were lost to follow-up; 1 in arm 1 and 9 in arm 2. Thoracic grade 3 AEs were experienced by 8 (16%) patients on arm 1 and 6 (12%) patients on arm 2 there were no grade 4 or 5 AEs.. There were no differences in LC, PFS or OS (p= 0.68, 0.86 and 0.94, respectively). Arm 1 reported better social functioning (p=0.006) with less dyspnea (p=0.016) in follow-up at 6 months. CONCLUSIONS: This randomized phase II study demonstrated 30 Gy in one fraction was equivalent to 60 Gy in three fractions in terms of toxicity, LC, PFS and OS. QOL measures of social functioning and dyspnea favored single fraction SBRT.

We conducted a prospective, in silico imaging clinical trial to evaluate the feasibility and potential dosimetric benefits of computed tomography-guided stereotactic adaptive radiotherapy (CT-STAR) for the treatment of locally advanced pancreatic cancer (LAPC).Eight patients with LAPC received five additional CBCTs on the ETHOS system before or after their standard of care radiotherapy treatment. Initial plans were created based on their initial simulation anatomy (PCT-STAR was feasible in silico for LAPC and improved OAR and/or target dosimetry in 100% of fractions. Use of the PCT-STAR for the treatment of LAPC cancer proved feasible and was dosimetrically superior to non-adapted CT-stereotactic body radiotherapy.

A kV imager coupled to a novel, ring-gantry radiotherapy system offers improved on-board kV-cone-beam computed tomography (CBCT) acquisition time (17-40 seconds) and image quality, which may improve CT radiotherapy image-guidance and enable online adaptive radiotherapy. We evaluated whether inter-observer contour variability over various anatomic structures was non-inferior using a novel ring gantry kV-CBCT (RG-CBCT) imager as compared to diagnostic-quality simulation CT (simCT).Seven patients undergoing radiotherapy were imaged with the RG-CBCT system at breath hold (BH) and/or free breathing (FB) for various disease sites on a prospective imaging study. Anatomy was independently contoured by seven radiation oncologists on: 1. SimCT 2. Standard C-arm kV-CBCT (CA-CBCT), and 3. Novel RG-CBCT at FB and BH. Inter-observer contour variability was evaluated by computing simultaneous truth and performance level estimation (STAPLE) consensus contours, then computing average symmetric surface distance (ASSD) and Dice similarity coefficient (DSC) between individual raters and consensus contours for comparison across image types.Across 7 patients, 18 organs-at-risk (OARs) were evaluated on 27 image sets. Both BH and FB RG-CBCT were non-inferior to simCT for inter-observer delineation variability across all OARs and patients by ASSD analysis (p 0.001), whereas CA-CBCT was not (p = 0.923). RG-CBCT (FB and BH) also remained non-inferior for abdomen and breast subsites compared to simCT on ASSD analysis (p 0.025). On DSC comparison, neither RG-CBCT nor CA-CBCT were non-inferior to simCT for all sites (p 0.025).Inter-observer ability to delineate OARs using novel RG-CBCT images was non-inferior to simCT by the ASSD criterion but not DSC criterion.

Rationale: Because of improvements in screening, there is an increasing number of patients with early-stage non-small-cell lung cancer (NSCLC) who are making treatment decisions.Objectives: Among patients with suspected stage I NSCLC, we evaluated longitudinal patient-centered outcomes (PCOs) and the association of changes in PCOs with treatment modality, stereotactic body radiotherapy (SBRT) compared with surgical resection.Methods: We conducted a multisite, prospective, observational cohort study at seven medical institutions. We evaluated minimum clinically important differences of PCOs at four time points (during treatment, 4-6 wk after treatment, 6 mo after treatment, and 12 mo after treatment) compared with pretreatment values using validated instruments. We used adjusted linear mixed models to examine whether the association between treatment and European Organization for Research and Treatment of Cancer global and physical quality-of-life (QOL) scales differed over time.Results: We included 127 individuals with stage I NSCLC (53 surgery, 74 SBRT). At 12 months, approximately 30% of patients remaining in each group demonstrated a clinical deterioration on global QOL from baseline. There was a significant difference in slopes between treatment groups on global QOL (-12.86; 95% confidence interval [CI], -13.34 to -12.37) and physical QOL (-28.71; 95% CI, -29.13 to -28.29) between baseline and during treatment, with the steeper decline observed among those who underwent surgery. Differences in slopes between treatment groups were not significant at all other time points.Conclusions: Approximately 30% of patients with stage I NSCLC have a clinically significant decrease in QOL 1 year after SBRT or surgical resection. Surgical resection was associated with steeper declines in QOL immediately after treatment compared with SBRT; however, these declines were not lasting and resolved within a year for most patients. Our results may facilitate treatment option discussions for patients receiving treatment for early-stage NSCLC.

Failure of drugs and catheter ablation procedures for the treatment of ventricular arrhythmias is still extremely relevant. Recently, stereotactic body radiotherapy has been introduced to treat therapy refractory patients. In this systematic review (International Prospective Register of Systematic Reviews, CRD42019133212), we aimed to summarize electrophysiological and histopathological effects of radioablation in animals, patients, and extracted and perfused hearts. A systematic search was performed in OVID MEDLINE, OVID Embase, the Cochrane Central Register of Controlled Trials, Web of Science, Google Scholar, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) from inception to September 2019. Identified records were independently screened for eligibility by 2 reviewers. Risk of bias and methodological quality were assessed using the SYRCLE, ROBINS-I, or Murad tool and tailored to the different study designs. We included 13 preclinical and 10 clinical publications. Large heterogeneity in study designs prompted a narrative synthesis approach. Baseline, (pre-)procedural details, outcome, target tissue analyses, and safety data were extracted and summarized. In animal studies evaluating electrophysiological parameters, radioablation induced a reduction in voltage/potential amplitude or bidirectional block in target areas in 93.2% of animals. Atrioventricular block (first to third degree) was induced in 78.3% of animals, and in studies evaluating ventricular arrhythmia inducibility, 75% reduction was achieved. In patients, predominantly ventricular tachycardias were targeted with >85% reduction in arrhythmia episodes during follow-up with an encouraging short-term safety profile. Preclinical and clinical evidence on the efficacy and safety of radioablation is limited in both quantity and quality. The results of radioablation for therapy refractory patients with ventricular tachycardia are promising, but further research is needed.

The medical necessity of stereotactic radiosurgery (SRS) is nonuniform across insurance policies. The American Society for Radiation Oncology (ASTRO) created a model policy based on the consensus of the radiation oncology community to communicate medically necessary indications for SRS. We compared the current insurance policies for SRS with those of the ASTRO model policy.We identified 58 insurance payers and 3 national benefits managers with SRS policies. Among these, 7 insurance payers were excluded for policies that were not reviewed after 2015 and for not detailing individual medically necessary indications. For each of the indications listed in ASTRO's model policy, we determined the proportion of payers that considered SRS medically necessary. We compared these proportions for national versus regional payers and policies updated in the last 12 months versus those updated less often using Fisher exact and χAll insurance policies reviewed considered SRS as medically necessary for brain metastases, medically refractory trigeminal neuralgia, and arteriovenous malformations. Compared with national payers, regional payers were less likely to deem other schwannomas, and a boost for large cranial or spinal lesions medically necessary (P.05). The indication with the lowest coverage was medically refractory movement disorders (44.4%), followed by medically refractory epilepsy (33.3%). However, policies that were updated within the last year were more likely to deem medical necessity for epilepsy, movement disorders, hemangioblastoma, pineal gland tumors, and other schwannomas.Significant discrepancy remains among insurance policies for several indications in ASTRO's model policy for SRS; however, national payers and those with recent policy updates have a greater concordance with the ASTRO model policy.

Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer and the leading cause of cancer-related death. Although durable local control rates are high after surgical resection or definitive radiotherapy for early-stage disease, a substantial proportion of these patients eventually experience regional and/or distant failure and succumb to their metastatic disease. The discovery of immunotherapeutics and targeted biologics has revolutionized the treatment of locally advanced and metastatic disease, improving progression-free and overall survival when incorporated with the current standards of care. Notably, post-hoc analyses and early clinical trials provide a growing body of evidence to support a synergistic effect between radiation and immunotherapy for the treatment of NSCLC from early-stage to metastatic disease. Radiotherapy appears to be capable of not only potentiating the effect of immunotherapy in targeted lesions, but also eliciting an antitumor response in distant lesions without any direct exposure to radiation. This review explores the biologic basis of immunotherapy, targeted biologics, and radiotherapy as well as the preclinical and clinical data that support the combined use of radioimmunotherapy for early-stage, locally advanced, and metastatic NSCLC.

BACKGROUND: Phase 2 cooperative group meningioma trial assessing the safety and efficacy of risk-adaptive management strategies. This is the initial analysis of the high-risk cohort. METHODS AND MATERIALS: High-risk patients were those with a new or recurrent World Health Organization (WHO) grade III meningioma of any resection extent, recurrent WHO grade II of any resection extent, or new WHO grade II after subtotal resection. Patients received intensity-modulated radiotherapy (IMRT) using a simultaneous integrated boost technique (60 Gy high dose and 54 Gy low dose in 30 fractions). Three-year progression-free survival (PFS) was the primary endpoint. Adverse events (AEs) were scored per NCI Common Terminology Criteria for Adverse Events version 3. RESULTS: Of 57 enrolled patients, 53 received protocol treatment. Median follow-up was 4.0 years (4.8 years for living patients). Two patients withdrew without progression before year 3; for the remaining 51 patients, 3-year PFS was 58.8%. Among all 53 protocol-treated patients, 3-year PFS was 59.2%. Three-year local control was 68.9%, and overall survival was 78.6%. Of 51 patients, 1 patient (1.9%) experienced a late grade-5 necrosis-related AE. All other acute (23 of 53 patients) and late (21 of 51 patients) AEs were grades 1 to 3. CONCLUSIONS: Patients with high-risk meningioma treated with IMRT (60 Gy/30) experienced 3-year PFS of 58.8%. Combined acute and late AEs were limited to grades 1 to 3, except for a single necrosis-related grade 5 event. These results support postoperative IMRT for high-risk meningioma and invite ongoing investigations to improve outcomes further. © 2019 Elsevier Inc. All rights reserved.

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Introduction Lattice stereotactic body radiotherapy (SBRT) is a form of spatially fractionated radiotherapy that potentially allows for the safe delivery of ablative radiation doses to bulky tumors. Tumor lysis syndrome (TLS) is most often seen in patients with hematologic malignancies treated with chemotherapy. Radiation-induced TLS in patients with solid tumor malignancies is uncommon. We describe a case of a patient who presented with radiation-induced TLS following Lattice SBRT. Case Report A 85-year-old-female with chronic kidney disease (CKD) stage III and metastatic clear cell endometrial cancer was treated with Lattice SBRT to 20Gy in 5 fractions with 66.7Gy delivered simultaneously to spherical vertices spaced within the GTV on a phase 2 clinical trial. Treatment was delivered every other day. 13 days following completion of radiotherapy the patient presented with syncope and possible seizure and was found to have bradycardia, shock, acute renal failure, and biochemical abnormalities consistent with TLS. She was admitted to the intensive care unit and discharged to hospice shortly after. Discussion The traditional definition of TLS requires presentation within 7 days of initiation of chemotherapy. In this case, the constellation of biochemical derangements associated with a 28% tumor shrinkage over two weeks status post radiotherapy is suggestive of TLS. Risk factors for TLS for this patient included a relatively radiosensitive tumor histology and baseline CKD. As a result of this sentinel event, the phase II clinical trial has been amended to monitor for TLS following treatment with Lattice SBRT.

Cardiac radiotherapy (RT) may be effective in treating heart failure (HF) patients with refractory ventricular tachycardia (VT). The previously proposed mechanism of radiation-induced fibrosis does not explain the rapidity and magnitude with which VT reduction occurs clinically. Here, we demonstrate in hearts from RT patients that radiation does not achieve transmural fibrosis within the timeframe of VT reduction. Electrophysiologic assessment of irradiated murine hearts reveals a persistent supraphysiologic electrical phenotype, mediated by increases in NaV1.5 and Cx43. By sequencing and transgenic approaches, we identify Notch signaling as a mechanistic contributor to NaV1.5 upregulation after RT. Clinically, RT was associated with increased NaV1.5 expression in 1 of 1 explanted heart. On electrocardiogram (ECG), post-RT QRS durations were shortened in 13 of 19 patients and lengthened in 5 patients. Collectively, this study provides evidence for radiation-induced reprogramming of cardiac conduction as a potential treatment strategy for arrhythmia management in VT patients., Noninvasive cardiac radiotherapy may effectively manage ventricular tachycardia in refractory patients, but its radiobiologic mechanisms of action are unclear. Here, the authors show that photon radiation durably and favourably reprograms cardiac conduction in the absence of transmural fibrosis suggesting this could be the mechanism through which cardiac radiotherapy to modulates arrhythmia susceptibility.

Purpose To develop and evaluate deep learning based auto-segmentation of cardiac substructures from non-contrast planning computed tomography (CT) images in patients undergoing breast cancer radiotherapy and to investigate the algorithm sensitivity to out-of-distribution data such as CT image artifacts. Methods Nine substructures including Aortic Valve (AV), Left Anterior Descending (LAD), Tricuspid Valve (TV), Mitral Valve (MV), Pulmonic Valve (PV), Right Atrium (RA), Right Ventricle (RV), Left Atrium (LA) and Left Ventricle (LV) were manually delineated by a radiation oncologist on non-contrast CT images of 129 patients with breast cancer; among them 90 were considered in-distribution data, also named 'clean' data. The image/label pairs of 60 subjects were used to train a 3D deep neural network while the remaining 30 were used for testing. The rest of the 39 patients were considered out-of-distribution ('outlier') data which were used to test robustness. Random rigid transformations were used to augment the dataset during training. We investigated multiple loss functions, including Dice Similarity Coefficient (DSC), Cross-entropy (CE), Euclidean loss as well as the variation and combinations of these, data augmentation, and network size on overall performance and sensitivity to image artifacts due to infrequent events such as the presence of implanted devices. The predicted label maps were compared to the ground truth labels via DSC and mean and 90th percentile symmetric surface distance (90th -SSD). Results When using modified Dice combined with cross-entropy (MD-CE) as the loss function, the algorithm achieved a mean DSC = 0.79±0.07 for chambers and a mean DSC = 0.39±0.10 for smaller substructures (valves and LAD). The mean and 90th -SSD for chambers was 2.7±1.4 mm and 6.5±2.8 mm and was 4.1±1.7 mm and 8.6±3.2 mm for smaller substructures. Models with MD-CE, Dice-CE, MD, and weighted CE loss had highest performance, and were statistically similar. Data augmentation did not affect model performances on both clean and outlier data and model robustness was susceptible to network size. For a certain type of outlier data, robustness can be improved via incorporating them into the training process. The execution time for segmenting each patient was on average 2.1s. Conclusions A deep neural network provides a fast and accurate segmentation of large cardiac substructures in non-contrast CT images. Model robustness to two types of clinically common outlier data were investigated and potential approaches to improve them were explored. Evaluation of clinical acceptability and integration into clinical workflow are pending. This article is protected by copyright. All rights reserved.

Radiation therapy (RT) is an essential component of effective cancer care and is used across nearly all cancer types. The delivery of RT is becoming more precise through rapid advances in both computing and imaging. The direct integration of magnetic resonance imaging (MRI) with linear accelerators represents an exciting development with the potential to dramatically impact cancer research and treatment. These impacts extend beyond improved imaging and dose deposition. Real-time MRI-guided RT is actively transforming the work flows and capabilities of virtually every aspect of radiation therapy. It has the opportunity to change entirely the delivery methods and response assessments of numerous malignancies. This review intends to approach the topic of MRI-based RT guidance from a vendor neutral and international perspective. It also aims to provide an introduction to this topic targeted towards oncologists without a specialty focus in radiation therapy. Specialty implications, areas for physician education, and research opportunities are identified as they are associated with MRI-guided RT. The uniquely disruptive implications of MRI-guided RT are discussed and placed in context. We further aim to describe and outline important future changes to the specialty of radiation oncology that will occur with MRI-guided RT. The impacts on radiation therapy caused by MRI-guidance include target identification, radiation therapy planning, quality assurance, treatment delivery, training, clinical workflow, tumor response assessment, and treatment scheduling. In addition, entirely novel research areas that may be enable by MRI-guidance are identified for future investigation.

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 Characterize the intra‐fraction motion management (IFMM) system found on the Gamma Knife Icon (GKI), including spatial accuracy, latency, temporal performance, and overall effect on delivered dose. Methods A phantom was constructed, consisting of a three‐axis translation mount, a remote motorized flipper, and a thermoplastic sphere surrounding a radiation detector. An infrared marker was placed on the translation mount secured to the flipper. The spatial accuracy of the IFMM was measured via the translation mount in all Cartesian planes. The detector was centered at the radiation focal point. A remote signal was used to move the marker out of the IFMM tolerance and pause the beam. A two‐channel electrometer was used to record the signals from the detector and the flipper when motion was signaled. These signals determined the latency and temporal performance of the GKI. Results The spatial accuracy of the IFMM was found to be

Purpose This study aimed to evaluate the feasibility of using a single-institution, knowledge-based planning (KBP) model as a dosimetric plan quality control (QC) for multi-institutional clinical trials. The efficacy of this QC tool was retrospectively evaluated using a subset of plans submitted to Radiation Therapy Oncology Group (RTOG) study 0617. Methods and Materials A single KBP model was created using commercially available software (RapidPlan; Varian Medical Systems, Palo Alto, CA) and data from 106 patients with non-small cell lung cancer who were treated at a single institution. All plans had prescriptions that ranged from 60 Gy in 30 fractions to 74 Gy in 37 fractions and followed the planning guidelines from RTOG 0617. Two sets of optimization objectives were created to produce different trade-offs using the single KBP model predictions: one prioritizing target coverage and a second prioritizing lung sparing (LS) while allowing an acceptable variation in target coverage. Three institutions submitted a high volume of clinical plans to RTOG 0617 and provided data on 25 patients, which were replanned using both sets of optimization objectives. Model-generated, dose-volume histogram predictions were used to identify patients who exceeded the lung clinical target volume (CTV) V20Gy >37% and would benefit from the LS objectives. Overall plan quality differences between KBP-generated plans and clinical plans were evaluated at RTOG 0617–defined dosimetric endpoints. Results Target coverage and organ at risk sparing was significantly improved for most KBP-generated plans compared with those from clinical trial data. The KBP model using prioritized target coverage objectives reduced heart Dmean and V40Gy by 2.1 Gy and 5.2%, respectively. Similarly, using LS objectives reduced the lung CTV Dmean and V20Gy by 2.0 Gy and 2.9%, respectively. The KBP predictions correctly identified all patients with lung CTV V20Gy > 37% (5 of 25 patients) and significantly reduced the dose to the lung CTV by applying the LS optimization objectives. Conclusions A single-institution KBP model can be applied as a QC tool for multi-institutional clinical trials to improve overall plan quality and provide decision-support to determine the need for anatomy-based dosimetric trade-offs.

Wide variation is seen in the dosage of preoperative induction radiation therapy for esophageal cancer. We investigated associations between outcomes after esophagectomy and dosage of induction radiation therapy.Patients undergoing induction radiation therapy (30 to 70 Gy), followed by esophagectomy, were identified from the National Cancer Database and classified as low (40 Gy), standard (40 to 50.4 Gy), and high dose (50.4 Gy). Perioperative outcomes and overall survival were compared. Subgroup analysis compared two common dosages: 45 Gy and 50.4 Gy.From 2004 to 2014, 10,738 patients (84.7%) received standard-dose radiation, increasing from 69.7% in 2004 to 93.6% in 2014 (p0.001), 1,329 (10.5%) received low-dose radiation, and 608 (4.8%) received high-dose radiation. Higher rates of pathologic complete response (pCR; low: 11.7%, standard: 16.2%, high: 21.0%; p0.001) and downstaging (low: 52.0%, standard: 56.4%, high: 63.1%, p = 0.001) were observed as the dosage increased. On multivariable analysis, compared with standard-dose, high-dose radiation was associated with higher 30-day mortality (odds ratio [OR], 2.11; p0.001) without a higher likelihood of downstaging or pCR. Low-dose radiation was associated with lower likelihood of downstaging (OR, 0.85; p = 0.04) and pCR (OR, 0.67; p 0.001) without lowering the risk of 30-day mortality. The dose of 50.4 Gy was associated with higher likelihood of pCR (OR, 1.12; p = 0.04), without affecting 30-day mortality, compared with 45 Gy.High-dose induction radiation (50.4 Gy) is associated with increased perioperative death after esophagectomy, without a significant improvement in tumor response. Low-dose radiation (30 Gy) is associated with worse tumor response without a lower risk of perioperative death. Within standard dosages, 50.4 Gy is associated with higher likelihood of pCR without adversely affecting perioperative mortality compared with 45 Gy.

Purpose Stereotactic body radiation therapy (SBRT) is an effective treatment for oligometastatic or unresectable primary malignancies, although target proximity to organs at risk (OARs) within the ultracentral thorax (UCT) limits safe delivery of an ablative dose. Stereotactic magnetic resonance (MR)–guided online adaptive radiation therapy (SMART) may improve the therapeutic ratio using reoptimization to account for daily variation in target and OAR anatomy. This study assessed the feasibility of UCT SMART and characterized dosimetric and clinical outcomes in patients treated for UCT lesions on a prospective phase 1 trial. Methods and Materials Five patients with oligometastatic (n = 4) or unresectable primary (n = 1) UCT malignancies underwent SMART. Initial plans prescribed 50 Gy in 5 fractions with goal 95% planning target volume (PTV) coverage by 95% of prescription, subject to strict OAR constraints. Daily real-time online adaptive plans were created as needed to preserve hard OAR constraints, escalate PTV dose, or both, based on daily setup MR image set anatomy. Treatment times, patient outcomes, and dosimetric comparisons were prospectively recorded. Results All initial and daily adaptive plans met strict OAR constraints based on simulation and daily setup MR imaging anatomy, respectively. Four of the 5 patients received ≥1 adapted fraction. Ten of the 25 total delivered fractions were adapted. A total of 30% of plan adaptations were performed to improve PTV coverage; 70% were for reversal of ≥1 OAR violation. Local control by Response Evaluation Criteria in Solid Tumors was 100% at 3 and 6 months. No grade ≥3 acute (within 6 months of radiation completion) treatment-related toxicities were identified. Conclusions SMART may allow PTV coverage improvement and/or OAR sparing compared with nonadaptive SBRT and may widen the therapeutic index of UCT SBRT. In this small prospective cohort, we found that SMART was clinically deliverable to 100% of patients, although treatment delivery times surpassed our predefined, timing-based feasibility endpoint. This technique is well tolerated, offering excellent local control with no identified acute grade ≥3 toxicity.