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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.

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.

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.

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.

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.

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.

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.

Purpose Stereotactic body radiation therapy (SBRT) has demonstrated clinical benefits for patients with metastatic and/or unresectable cancer. Technical considerations of treatment delivery and nearby organs at risk can limit the use of SBRT in large tumors or those in unfavorable locations. Spatially fractionated radiation therapy (SFRT) may address this limitation because this technique can deliver high-dose radiation to discrete subvolume vertices inside a tumor target while restricting the remainder of the target to a safer lower dose. Indeed, SFRT, such as GRID, has been used to treat large tumors with reported dramatic tumor response and minimal side effects. Lattice is a modern approach to SFRT delivered with arc-based therapy, which may allow for safe, high-quality SBRT for large and/or deep tumors. Methods and Materials Herein, we report the results of a dosimetry and quality assurance feasibility study of Lattice SBRT in 11 patients with 12 tumor targets, each ≥10 cm in an axial dimension. Prior computed tomography simulation scans were used to generate volumetric modulated arc therapy Lattice SBRT plans that were then delivered on clinically available Linacs. Quality assurance testing included external portal imaging device and ion chamber analyses. Results All generated plans met the standard SBRT dose constraints, such as those from the American Association of Physicists in Medicine Task Group 101. Additionally, we provide a step-by-step approach to generate and deliver Lattice SBRT plans using commercially available treatment technology. Conclusions Lattice SBRT is currently being tested in a prospective trial for patients with metastatic cancer who need palliation of large tumors ( NCT04553471 , NCT04133415 ).

Background Consolidation durvalumab improved overall survival (OS) in locally advanced non-small cell lung cancer (LA-NSCLC) treated with chemoradiotherapy (CRT) in the PACIFIC trial; however, pneumonitis was increased with durvalumab. We sought to examine real-world outcomes with the PACIFIC paradigm, especially factors associated with pneumonitis, using a multi-institutional review. Methods Patients with LA-NSCLC treated with CRT followed by durvalumab from January 2017-February 2019 were identified at 2 institutions. We characterized demographics, tumor factors, radiotherapy, and duration of durvalumab. We examined pneumonitis outcomes including re-challenge success, with secondary endpoints of progression-free survival (PFS) and OS. Results Thirty-four patients were included with median follow-up of 12 months (range, 3 to 20 months); 94% had stage III disease. The cumulative grade >2 pneumonitis rate was 26.5% with 2 patients developing grade 3 pneumonitis and no grade 4/5 events. Median time to pneumonitis after RT was 2.4 months (range, 0 to 4.9 months). Pneumonitis management included median prednisone dose of 60 mg for median taper of 6 weeks with durvalumab held for median of 4.5 weeks (range, 2 to 8 weeks); 70% of pneumonitis patients received durvalumab re-challenge, with pneumonitis recurring in 14% of patients. 3-month and 6-month pneumonitis-free-survival were 76.9% and 73.6%, respectively; 9- and 12-month OS were 96% (75.1-99.8%), 86.6% (63.5-95.5%), respectively; 9- and 12-month PFS were 68% (47.5-82.5%), 48.7% (25.3-68.3%). Pneumonitis development did not significantly impact PFS or OS (P>0.05). Conclusions Among LA-NSCLC patients treated with CRT followed by consolidation durvalumab, more than 25% developed symptomatic pneumonitis. In this small case series, pneumonitis did not appear to negatively impact survival, and durvalumab re-challenge appeared feasible after pneumonitis treatment with steroids.

PURPOSE/OBJECTIVE(S) Outcomes of low-risk meningioma from NRG/RTOG-0539. MATERIALS/METHODS Outcomes of the intermediate and high-risk cohorts from this phase II trial have been previously reported. Low-risk (Group 1: new WHO grade 1) patients were observed after gross total (GTR) or subtotal resection (STR). Progression-free (PFS) and overall (OS) were estimated using Kaplan-Meier. CTCAE v3 AE grading was employed. RESULTS Group 1 enrolled 65 patients. 56/60 (93.4%) evaluable patients had investigator-reported GTR. Sufficient imaging for central confirmation was available for 48: GTR in 35 and STR in 13. Median follow-up for living patients was 9.1 years (y). For all evaluable patients 5 and 10 y PFS and OS rates were 89.4 and 85.0%, and 98.3 and 93.8%, respectively. For patients with centrally-confirmed STR, 5/10 y PFS rates were 72.7/72.7%, with 100% 10 y OS. For patients with centrally-confirmed GTR, 5/10 y PFS and OS rates were 94.3/87.6 and 97.1/90.4%, respectively. For combined study cohorts (Groups 1–3) with central-review (n=104), the median centrally-measured largest pre-operative tumor dimension was 4.3 cm (range 0.4 - 14.4); this was significantly associated with OS (hazard ratio [HR]=1.03, p=0.021) and PFS (HR=1.03, p=0.003). No grade 4 or 5 protocol-related adverse events were reported. There were 1 grade 3 (infection), 4 grade 2 (neurologic, pulmonary, gastrointestinal, and pain), and 5 grade 1 (3 neurologic, 1 occulovisual, 1 constitutional) events from 5 patients. CONCLUSION These results prospectively validate high OS and PFS outcomes for low-risk meningioma managed with surgery followed by observation, but raise questions regarding optimal management following STR (5 y PFS 72.7%), a subcohort that could potentially benefit from adjuvant therapy. However, we identified considerable discordance between local and central assessments of resection extent. Pre-operative tumor size has a significant impact on OS and PFS. Supported by: U10CA180868 and U10CA180822 from the National Cancer Institute (NCI)

BackgroundTo explore if early perfusion-weighted magnetic resonance imaging (PWI) may be a promising imaging biomarker to predict local recurrence (LR) of brain metastases after stereotactic radiosurgery (SRS).MethodsThis is a prospective pilot study of adult brain metastasis patients who were treated with SRS and imaged with PWI before and 1 week later. Relative cerebral blood volume (rCBV) parameter maps were calculated by normalizing to the mean value of the contralateral white matter on PWI. Cox regression was conducted to explore factors associated with time to LR, with Bonferroni adjusted pResultsTwenty-three patients were enrolled from 2013 through 2016, with 22 evaluable lesions from 16 patients. After a median follow-up of 13.1 months (range: 3.0-53.7), 5 lesions (21%) developed LR after a median of 3.4 months (range: 2.3-5.7). On univariable analysis, larger tumor volume (HR 1.48, 95% CI 1.02-2.15, p = 0.04), lower SRS dose (HR 0.45, 95% CI 0.21-0.97, p = 0.04), and higher rCBV at week 1 (HR 1.07, 95% CI 1.003-1.14, p = 0.04) had borderline association with shorter time to LR. Tumors >2.0cm3 had significantly higher LR than if ≤2.0cm3: 54% vs 0% at 1 year, respectively, p = 0.008. A future study to confirm the association of early PWI and LR of the high-risk cohort of lesions >2.0cm3 is estimated to require 258 patients.ConclusionsPWI at week 1 after SRS may have borderline association with LR. Tumors

Purpose/Objectives Before definitive stereotactic body radiation therapy (SBRT) for presumably node-negative, early-stage NSCLC, many patients are staged with PET/CT alone. In patients undergoing PET/CT prior to SBRT, the role of invasive nodal staging (INS) with endobronchial ultrasound (EBUS) or mediastinoscopy is uncertain. We sought to characterize the impact of nodal staging modality on outcomes. Materials/Methods Patients receiving definitive SBRT for T1-2N0 NSCLC deemed node-negative by either PET/CT plus INS (EBUS or mediastinoscopy) or PET/CT alone were identified. Patients with initially equivocal or positive nodes on PET/CT were excluded from this analysis. All patients received 3–5 fraction SBRT according to institutional guidelines. Control was assessed by at least one follow-up CT in all patients. Multivariable logistic regression (MVA) was performed to identify variables independently associated with use of INS. Results We identified 651 eligible patients at our institution from 2005–2016. INS was performed in 15.2% of patients (n = 99) with EBUS (n = 78) or mediastinoscopy (n = 21). Median follow-up was 19.4 months (0.2–135.1). Median survival was 28.5 months (0.6–140). Factors predictive of increased likelihood of INS after negative PET/CT on MVA were age (OR for decreasing age 1.033; 95% CI 1.058–1.010), Caucasian race (OR vs. non-white 1.852; 1.044–3.289), male sex (1.629; 1.031–2.575), central location (1.978; 1.218–3.211) and squamous histology (2.564; 1.243–5.287). Nodal and/or distant control at 2 years was similar between PET/CT alone (78%, 95% CI 74–82%) and INS + PET/CT (75%, 95% CI 65–85%) (p = 0.877) as well as on MVA. Overall survival did not differ based on staging modality. Conclusions In patients with early-stage NSCLC deemed node-negative by PET/CT, addition of INS did not appreciably alter patterns of failure or survival after definitive SBRT. This study does not question the established value of INS for equivocal or suspicious nodes.

The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a pandemic affecting healthcare centers across the globe. Patients with cancer have been reported to be particularly vulnerable to infection, morbidity, and severe events. Given the high proportion of asymptomatic carriers and concerns regarding speed and availability of laboratory testing, novel detection strategies are necessary to supplement traditional screening methods and facilitate mitigation of viral transmission. Recent data support the diagnostic consistency and potential value of computed tomography (CT) scans to aid early diagnosis of COVID-19. Volumetric CT image-guidance is commonly employed in patients undergoing radiotherapy and presents a unique opportunity to screen for COVID-specific lung changes. This case series describes the presentation of SARS-CoV-2 infections among three patients undergoing thoracic radiotherapy across multiple institutions. We highlight their clinical symptoms, imaging findings, potential confounders, and clinical workflow to triage these patients to the next level of care.

Purpose During the coronavirus 2019 disease (COVID-19) pandemic, alternative methods of care are needed to reduce the relative risk of transmission in departments. Also needed is the ability to provide vital radiation oncological care if radiation oncologists (RO) are reallocated to other departments. We implemented a novel remote RO stereotactic body radiation therapy (SBRT) coverage practice, requiring it to be reliable, of high audio and visual quality, timely, and the same level of specialty care as our current in-person treatment coverage practice. Methods and Materials All observed failure modes were recorded during implementation over the first 15 sequential fractions. The time from cone beam computed tomography to treatment was calculated before and after implementation to determine timeliness of remote coverage. Image quality metrics were calculated between the imaging console screen and the RO’s shared screen. Comfort levels with audio and visual communication as well as overall comfort in comparison to in-person RO coverage was evaluated using Likert scale surveys after treatment. Results Remote RO SBRT coverage was successfully implemented in 14 of 15 fractions with 3 observed process failures that were all corrected before treatment. Average times of pretreatment coverage before and after implementation were 8.74 and 8.51 minutes, respectively. The cross correlation between the imaging console screen and RO’s shared screen was r = 0.96 and lag was 0.05 seconds. The average value for all survey questions was more than 4.5, approaching in-person RO coverage comfort levels. Conclusion Our novel method of remote RO SBRT coverage permits reduced personnel and patient interactions surrounding radiation therapy procedures. This may help to reduce transmission of COVID-19 in our department and provides a means for SBRT coverage if ROs are reallocated to other areas of the hospital for COVID-19 support.

Purpose The 2019 coronavirus disease pandemic has placed an increased importance on physical distancing to minimize the risk of transmission in radiation oncology departments. The pandemic has also increased the use of hypofractionated treatment schedules where magnetic resonance-guided online adaptive radiation therapy (ART) can aid in dose escalation. This specialized technique requires increased staffing in close proximity, and thus the need for novel coverage practices to increase physical distancing while still providing specialty care. Methods and Materials A remote-physician ART coverage practice was developed and described using commercially available software products. Our remote-physician coverage practice provided control to the physician to contour and review of the images and plans. The time from completion of image registration to the beginning of treatment was recorded for 20 fractions before remote-physician ART coverage and 14 fractions after implementation of remote-physician ART coverage. Visual quality was calculated using cross-correlation between the treatment delivery and remote-physician computer screens. Results For the 14 fractions after implementation, the average time from image registration to the beginning of treatment was 24.9 ± 6.1 minutes. In comparison, the 20 fractions analyzed without remote coverage had an average time of 29.2 ± 9.8 minutes. The correlation between the console and remote-physician screens was R = .95. Conclusions Our novel remote-physician ART coverage practice is secure, interactive, timely, and of high visual quality. When using remote physicians for ART, our department was able to increase physical distancing to lower the risk of virus transmission while providing specialty care to patients in need.

Importance: The COVID-19 pandemic is currently accelerating. Patients with locally advanced non-small cell lung cancer (LA-NSCLC) may require treatment in locations where resources are limited and the prevalence of infection is high. Patients with LA-NSCLC frequently present with comorbidities that increase the risk for severe morbidity and mortality from COVID-19. These risks may be further increased by treatments for LA-NSCLC. Observation: We present expert thoracic oncology multidisciplinary (radiation oncology, medical oncology, surgical oncology) consensus of alternative strategies for the treatment of LA-NSCLC during a pandemic. The overarching goals of these approaches are to reduce the number of visits to a healthcare facility, reduce the risk of SARS-CoV-2 exposure, and attenuate the immunocompromising effects of lung cancer therapies. Patients with resectable disease can be treated with definitive non-operative management if surgical resources are limited or the risks of perioperative care are high. Non-operative options include chemotherapy, chemoimmunotherapy, and radiation therapy with sequential schedules. The order of treatments may be based on patient factors and clinical resources. Whenever radiation therapy is delivered without concurrent chemotherapy, hypofractionated schedules are appropriate. For patients who are confirmed to have COVID-19, usually cancer therapies may be withheld until symptoms have resolved with negative viral test results. Conclusions and Relevance: The risk of severe treatment-related morbidity and mortality is significantly elevated for patients undergoing treatment for LA-NSCLC during the COVID-19 pandemic. Adapting alternative treatment strategies as quickly as possible may save lives and should be implemented through communication with the multidisciplinary cancer team.

INTRODUCTIONDuring the COVID-19 pandemic, alternative methods of care are needed to reduce the relative risk of transmission in departments. Also needed is the ability to provide vital radiation oncological care if radiation oncologists (RO) are reallocated to other departments. We implemented a novel remote RO SBRT coverage practice, requiring it to be reliable, of high audio and visual quality, timely, and the same level of specialty care as our current in-person treatment coverage practice.METHODSAll observed failure modes were recorded during implementation over the first 15 sequential fractions. The time from CBCT to treatment was calculated before and after implementation to determine timeliness of remote coverage. Image quality metrics were calculated between the imaging console screen and the RO’s shared screen. Comfort levels with audio/visual communication as well as overall comfort in comparison to in-person RO coverage was evaluated using Likert scale surveys after treatment.RESULTSRemote RO SBRT coverage was successfully implemented in 14/15 fractions with 3 observed process failures that were all corrected before treatment. Average times of pre-treatment coverage before and after implementation were 8.74 and 8.51min, respectively. The cross correlation between the imaging console screen and RO’s shared screen was r=0.96 and lag was 0.05s. The average value for all survey questions was above 4.5, approaching in-person RO coverage comfort levels.CONCLUSIONSOur novel method of remote RO SBRT coverage permits reduced personnel and patient interactions surrounding RT procedures. This may help to reduce transmission of COVID-19 in our department and provides a means for SBRT coverage if ROs are reallocated to other areas of the hospital for COVID-19 support.

The coronavirus disease 2019 (COVID-19) pandemic is currently accelerating. Patients with locally advanced NSCLC (LA-NSCLC) may require treatment in locations where resources are limited, and the prevalence of infection is high. Patients with LA-NSCLC frequently present with comorbidities that increase the risk of severe morbidity and mortality from COVID-19. These risks may be further increased by treatments for LA-NSCLC. Although guiding data is scarce, we present an expert thoracic oncology multidisciplinary (radiation oncology, medical oncology, surgical oncology) consensus of alternative strategies for the treatment of LA-NSCLC during a pandemic. The overarching goals of these approaches are the following: (1) reduce the number of visits to a health care facility, (2) reduce the risk of exposure to severe acute respiratory syndrome-coronavirus-2, (3) attenuate the immunocompromising effects of lung cancer therapies, and (4) provide effective oncologic therapy. Patients with resectable disease can be treated with definitive nonoperative management if surgical resources are limited or the risks of perioperative care are high. Nonoperative options include chemotherapy, chemoimmunotherapy, and radiation therapy with sequential schedules that may or may not affect long-term outcomes in an era in which immunotherapy is available. The order of treatments may be on the basis of patient factors and clinical resources. Whenever radiation therapy is delivered without concurrent chemotherapy, hypofractionated schedules are appropriate. For patients who are confirmed to have COVID-19, usually, cancer therapies may be withheld until symptoms have resolved with negative viral test results. The risk of severe treatment-related morbidity and mortality is increased for patients undergoing treatment for LA-NSCLC during the COVID-19 pandemic. Adapting alternative treatment strategies as quickly as possible may save lives and should be implemented through communication with the multidisciplinary cancer team.

Stereotactic body radiotherapy (SBRT) has demonstrated clinical benefit for patients with metastatic and/or unresectable cancer. Technical considerations of treatment delivery and sensitive organs at risk (OARs) limit the use of SBRT in large tumors or those in unfavorable locations. Spatially fractionated radiotherapy (SFRT) delivers high-dose radiation to discrete sub-volume vertices within a tumor target while restricting the remainder of the target to low dose. SFRT has been utilized for treatment of large tumors with reported dramatic tumor response and minimal side effects. Lattice is a modern approach to SFRT that can be delivered with arc-based therapy, which allows for the rapid dose fall-off required for high quality SBRT. In order to overcome the limitations of SBRT for large tumors, we developed Lattice SBRT. Here we report the results of a dosimetry and quality assurance (QA) feasibility study of Lattice SBRT in 11 patients with 12 tumor targets, each ≥ 10 cm in an axial dimension. Prior CT simulation scans were used to generate volumetric-modulated arc therapy (VMAT) Lattice SBRT plans that were then delivered on clinically available Linacs. QA testing included external portal imaging device (EPID) and ion chamber (IC) analysis. All generated plans were able to meet the standard SBRT dose constraints, such as those from AAPM Task Group 101. Additionally, we provide a step-by-step approach for generating and delivering Lattice SBRT plans using commercially available treatment technology. Lattice SBRT is currently being tested in a prospective trial for patients with metastatic cancer needing palliation of large tumors (NCTXXXX).

PURPOSE RTOG 0617 compared standard-dose (SD; 60 Gy) versus high-dose (HD; 74 Gy) radiation with concurrent chemotherapy and determined the efficacy of cetuximab for stage III non–small-cell lung cancer (NSCLC). METHODS The study used a 2 × 2 factorial design with radiation dose as 1 factor and cetuximab as the other, with a primary end point of overall survival (OS). RESULTS Median follow-up was 5.1 years. There were 3 grade 5 adverse events (AEs) in the SD arm and 9 in the HD arm. Treatment-related grade ≥3 dysphagia and esophagitis occurred in 3.2% and 5.0% of patients in the SD arm v 12.1% and 17.4% in the HD arm, respectively ( P = .0005 and < .0001). There was no difference in pulmonary toxicity, with grade ≥3 AEs in 20.6% and 19.3%. Median OS was 28.7 v 20.3 months ( P = .0072) in the SD and HD arms, respectively, 5-year OS and progression-free survival (PFS) rates were 32.1% and 23% and 18.3% and 13% ( P = .055), respectively. Factors associated with improved OS on multivariable analysis were standard radiation dose, tumor location, institution accrual volume, esophagitis/dysphagia, planning target volume and heart V5. The use of cetuximab conferred no survival benefit at the expense of increased toxicity. The prior signal of benefit in patients with higher H scores was no longer apparent. The progression rate within 1 month of treatment completion in the SD arm was 4.6%. For comparison purposes, the resultant 2-year OS and PFS rates allowing for that dropout rate were 59.6% and 30.7%, respectively, in the SD arms. CONCLUSION A 60-Gy radiation dose with concurrent chemotherapy should remain the standard of care, with the OS rate being among the highest reported in the literature for stage III NSCLC. Cetuximab had no effect on OS. The 2-year OS rates in the control arm are similar to the PACIFIC trial.

The concept of local consolidative therapy (LCT) for oligometastatic non-small cell lung cancer (NSCLC) using radiation therapy and/or surgical resection has been present for approximately two decades (1-3). However, data supporting this approach has evolved from single-institution retrospective series (which can be influenced by selection bias) to multi-institutional randomized studies.

Objective: To identify potentially actionable dosimetric predictors of local control (LC) for non-small cell lung cancer (NSCLC) brain metastases treated with single-fraction stereotactic radiosurgery (SRS). Methods and materials: Patients with NSCLC brain metastases treated with single-fraction SRS were identified. Eligible patients had at least 1 follow-up magnetic resonance imaging scan and were without prior metastasectomy or SRS to the same lesion. LC and overall survival (OS) were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate (UVA) and multivariate analysis (MVA). Receiver operating characteristic (ROC) analysis was used to identify optimal cut points for dose-volume histogram metrics relative to LC. Results: A total of 612 NSCLC brain metastasis were identified in 299 patients with single-fraction SRS between 1999 and 2014. Median follow-up was 10 months. Median OS from time of SRS was 11 months. Overall LC was 75% and 66% at 1 and 2 years, respectively. On UVA, increasing dose by any measure was associated with improved LC. On MVA, volume receiving at least 32 Gy (V32; hazard ratio [HR], 0.069; P

Although adjuvant chemotherapy improves survival in patients with completely resected NSCLC, it is also associated with potentially disabling or lethal adverse events. Because there is limited information on the early mortality among patients undergoing adjuvant chemotherapy, we used the National Cancer Database to calculate the percentage of deaths within the first 6 months of starting chemotherapy.The National Cancer Database was queried for patients age 18 or older in whom stage IB to IIIA NSCLC had been diagnosed between 2004 and 2012 and who had received multiagent adjuvant chemotherapy starting within 120 days from the surgical resection with negative surgical margins. Age groups were divided as follows: younger than 50, 51 to 60, 61 to 70, 71 to 80, and older than 80 years.A total of 19,691 patients met the eligibility criteria, 19,398 of whom had a known 6-month mortality status. The median age was 65 years (range 19-89). The 1-, 2-, 3-, 4-, 5-, and 6-month cumulative mortality rates from initiation of chemotherapy were 0.7%, 1.3%, 1.9%, 2.6%, 3.2%, and 4.1% respectively. The 6-month mortality rates for each age group (≤ 50 years, 51-60, 61-70, 71-80, and80) were 2.6%, 3.1%, 4.1%, 5.3%, and 7.6%, respectively (p0.001). Independent factors associated with increased 6-month mortality included age 71 to 80 versus younger than 50 (OR = 1.72, 95% confidence interval [CI]: 1.16-2.55, p = 0.007), age older than 80 versus younger than 50 (OR = 2.43, 95% CI: 1.40-4.20, p = 0.002), male sex (OR = 1.42; 95% CI: 1.21-1.67, p0.001), Charlson-Deyo comorbidity score of 2 versus 0 (OR = 1.52, 95% CI 1.22-1.89, p0.001), pneumonectomy (OR = 1.38, 95% CI: 1.11-1.73, p = 0.004), length of postopertive stay longer than 6 days after surgery (OR = 1.21, 95% CI: 1.03-1.41, p = 0.02), and readmission within 30 days from surgery (OR = 1.48, 95% CI: 1.15-1.90, p = 0.02).Early mortality with the use of adjuvant chemotherapy after complete resection of NSCLC is a clinical concern. The risk is higher in patients older than 70 years, with higher comorbidity scores and a prolonged length of stay postoperatively.