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Purpose Our purpose was to characterize the radiation doses to organs-at-risk (OAR) in the phase I trial (NCT02608385) that established safety/efficacy of stereotactic body radiation therapy (SBRT) using NRG-BR001 dose constraints combined with programmed cell death protein 1 blockade for metastatic disease. Methods and Materials Between January 2016 and May 2018, 73 patients with advanced solid tumors were treated with SBRT followed by pembrolizumab. Tumor volumes (gross tumor volume/internal tumor volume) were delineated for each metastasis, with planning target volume contraction to limit OAR dose per protocol (n = 54) or when gross tumor volume/internal tumor volume > 65 cm3 (n = 19). For 20 OAR, doses were compared with NRG-BR001 constraints. Protocol constraints were considered challenged when the minimum of the highest dose received by ≥6 patients without dose-limiting toxicities (DLTs) ( D m a x 6 t h ) was ≥70% of the protocol constraint. Results A total of 151 metastases were irradiated including 32 peripheral lung, 23 central lung, 13 mediastinal/cervical, 24 liver, 28 abdominal-pelvic, 16 osseous, and 15 spinal metastases. A median of 2 metastases (range, 2-4) with mean volumes of 33.5 cm3 (range, 0.4-391 cm3) were treated using average planning target volumes of 50.7 cm3 (range, 3.2-161 cm3). At least 1 dose constraint from NRG-BR001 was exceeded in 38 of 73 (52%) patients. OAR constraints were challenged in 10 serial organs (gastrointestinal, cardio-pulmonary, musculoskeletal, and nervous systems) and 1 parallel OAR (lung). Grade 3 DLTs occurred in 6 patients, including pneumonitis (n = 3), colitis (n = 2), and hepatic failure (n = 1). In 4 patients, the toxicity could be directly attributed to the planned dose to OAR (ie, pneumonitis due to high lung dose or colitis due to high bowel dose). Conclusions Multisite SBRT in combination with programmed cell death protein 1 blockade was safely tolerated when treating critical central, abdominal-pelvic, and peripheral OAR nearing NRG-BR001 constraints with clinically acceptable toxicity in the corresponding organ systems. The observed relationship between dose and DLTs in 4 of 6 patients indicates that NRG-BR001 dose constraints should be respected in subsequent trials to maintain clinical safety.

Purpose Inkjet printers can be used to fabricate anthropomorphic phantoms by the use of iodine-doped ink. However, challenges persist in implementing this technique. The calibration from grayscale to ink density is complex and time-consuming. The purpose of this work is to develop a printing methodology that requires a simpler calibration and is less dependent on printer characteristics to produce the desired range of x-ray attenuation values. Methods Conventional grayscale printing was substituted by single-tone printing; that is, the superposition of pure black layers of iodinated ink. Printing was performed with a consumer-grade inkjet printer using ink made of potassium-iodide (KI) dissolved in water at 1 g/ml. A calibration for the attenuation of ink was measured using a commercial x-ray system at 70 kVp. A neonate radiograph obtained at 70 kVp served as an anatomical model. The attenuation map of the neonate radiograph was processed into a series of single-tone images. Single-tone images were printed, stacked, and imaged at 70 kVp. The phantom was evaluated by comparing attenuation values between the printed phantom and the original radiograph; attenuation maps were compared using the structural similarity index measure (SSIM), while attenuation histograms were compared using the Kullback-Leibler (KL) divergence. A region of interest (ROI)-based analysis was also performed, where the attenuation distribution within given ROIs was compared between phantom and patient. The phantom sharpness was evaluated in terms of modulation transfer function (MTF) estimates and signal spread profiles of high spatial resolution features in the image. Results The printed phantom required 36 pages. The printing queue was automated and it took about 2 h to print the phantom. The radiograph of the printed phantom demonstrated a close resemblance to the original neonate radiograph. The SSIM of the phantom with respect to that of the patient was 0.53. Both patient and phantom attenuation histograms followed similar distributions, and the KL divergence between such histograms was 0.20. The ROI-based analysis showed that the largest deviations from patient attenuation values were observed at the higher and lower ends of the attenuation range. The limiting resolution of the proposed methodology was about 1 mm. Conclusion A methodology to generate a neonate phantom for 2D imaging applications, using single-tone printing, was developed. This method only requires a single-value calibration and required less than 2 h to print a complete phantom.

Surface guided radiotherapy (SGRT) is becoming a routine tool for patient positioning for specific clinical sites in many clinics. However, it has not yet gained its full potential in terms of widespread adoption. This vision paper first examines some of the difficulties in transitioning to SGRT before exploring the current and future role of SGRT alongside and in concert with other imaging techniques. Finally, future horizons and innovative ideas that may shape and impact the direction of SGRT going forward are reviewed.

The clinical use of surface imaging has increased dramatically, with demonstrated utility for initial patient positioning, real-time motion monitoring, and beam gating in a variety of anatomical sites. The Therapy Physics Subcommittee and the Imaging for Treatment Verification Working Group of the American Association of Physicists in Medicine commissioned Task Group 302 to review the current clinical uses of surface imaging and emerging clinical applications. The specific charge of this task group was to provide technical guidelines for clinical indications of use for general positioning, breast deep-inspiration breath hold treatment, and frameless stereotactic radiosurgery. Additionally, the task group was charged with providing commissioning and on-going quality assurance (QA) requirements for surface-guided radiation therapy (SGRT) as part of a comprehensive QA program including risk assessment. Workflow considerations for other anatomic sites and for computed tomography simulation, including motion management, are also discussed. Finally, developing clinical applications, such as stereotactic body radiotherapy (SBRT) or proton radiotherapy, are presented. The recommendations made in this report, which are summarized at the end of the report, are applicable to all video-based SGRT systems available at the time of writing.

Radiomics is a fast-growing research area based on converting standard-of-care imaging into quantitative minable data and building subsequent predictive models to personalize treatment. Radiomics has been proposed as a study objective in clinical trial concepts and a potential biomarker for stratifying patients across interventional treatment arms. In recognizing the growing importance of radiomics in oncology, a group of medical physicists and clinicians from NRG Oncology reviewed the current status of the field and identified critical issues, providing a general assessment and early recommendations for incorporation in oncology studies.

Background: Recent studies incorporating dose escalated radiation identified heart dose as a predictor of cardiac toxicity in unresectable lung cancer patients. Whether conventionally dosed radiation impacts cardiac events remains unclear. Methods: Stage III lung cancer patients undergoing definitive chemoradiation to 60–70 Gy were analyzed. Clinical and dosimetric factors (mean heart dose, heart V5-60 in 5 Gy increments) were analyzed against freedom from ≥ grade 3 cardiac events and overall survival (OS) by log-rank test. Multivariable analysis (MVA) for factors significant on univariate analysis was performed by Cox proportional hazards. Results: A total of 108 patients were identified. Median follow-up was 18.0 months. One- and two-year OS were 79% and 61%, respectively. On MVA, gross tumor volume (GTV) ≥98.6 cm 3 [hazard ratio (HR): 2.11, 95% confidence interval (CI): 1.15–3.93, P=0.02] and female gender (HR: 2.01, 95% CI: 1.09–3.73, P=0.03) predicted for worse survival. Twelve patients (11%) developed ≥ grade 3 cardiac events. One- and two-year freedom from cardiac events (FFCE) was 94% and 84% respectively. On MVA, heart V5 ≥49% predicted for cardiac events (HR: 11.44, 95% CI: 1.31–111.60, P=0.03) while female gender was nearly significant (HR: 3.49, 95% CI: 0.97–16.80, P=0.06). Females presented with similar comorbidity scores, GTVs, and relapse rates but experienced higher heart doses than their male counterparts. Conclusions: Heart V5 ≥49% predicted for cardiac events after chemoradiation. However, cardiac dosimetry was not associated with survival. Rather, female gender and GTV ≥98.6 cm 3 led to worse survival. This study corroborates emerging data that low-dose radiation to the heart impacts cardiac toxicity.

Purpose Developing automated methods to identify task-driven quality assurance (QA) procedures is key toward increasing safety, efficacy, and efficiency. We investigate the use of machine learning (ML) methods for possible visualization, automation, and targeting of QA, and assess its performance using multi-institutional data. Methods To enable automated analysis of QA data given its higher dimensional nature, we used nonlinear kernel mapping with support vector data description (SVDD) driven approaches. Instead of using labeled data as in typical support vector machine (SVM) applications, which requires exhaustive annotation, we applied a clustering extension of SVDD, which identifies the minimal enclosing hypersphere in the feature space defined by a kernel function separating normal operations from possible failures (i.e., outliers). In our case, QA test data are mapped by a Gaussian kernel to a higher dimensional feature space and then the minimal enclosing sphere was identified. This sphere, when mapped back to the input data space along the principal components, can separate the data into several components, each enclosing a separate cluster of QA points that could be used to evaluate tolerance boundaries and test reliability. We evaluated this approach for gantry sag, radiation field shift, and [multileaf collimator (MLC)] offset data acquired using electronic portal imaging devices (EPID), as representative examples. Results Data from eight LINACS and seven institutions (n = 119) were collected. A standardized EPID image of a phantom with fiducials provided deviation estimates between the radiation field and phantom center at four cardinal gantry angles. Deviation measurements in the horizontal direction (0°, 180°) were used to determine the gantry sag and deviations in the vertical direction (90°, 270°) were used to determine the field shift. These measurements were fed into the SVDD clustering algorithm with varying hypersphere radii (Gaussian widths). For gantry sag analysis, two clusters were identified one of which contained 2.5% of the outliers and also exceeded the 1 mm tolerance set by TG-142. In the case of field shifts, SVM clustering identified two distinct classes of measurements primarily driven by variations in the second principal component at 270°. Results from MLC analysis identified one outlier cluster (0.34%) along Leaf offset Constancy (LoC) axis that coincided with TG-142 limits. Conclusion Machine learning methods based on SVDD clustering are promising for developing automated QA tools and providing insights into their reliability and reproducibility.

Previous studies have evaluated stereotactic body radiotherapy (SBRT) in oligometastatic patients with NSCLC, including multimodality treatment with anti-programmed cell death protein-1 monotherapy. Questions remain regarding the timing of SBRT and immunotherapy, safety with dual checkpoint blockade, and the utility in widely metastatic patients. This randomized phase 1 trial combined nivolumab and ipilimumab with sequential or concurrent multisite SBRT in patients with stage IV NSCLC to evaluate safety and obtain preliminary activity data.Treatment-naive patients with metastatic NSCLC were randomized to concurrent (SBRT with immunotherapy) or sequential (SBRT followed by immunotherapy) treatment. A maximum of four treatment fields received SBRT. Nivolumab and ipilimumab were continued until clinical progression, development of toxicity, or after 2 years. Dose-limiting toxicity was defined as greater than or equal to grade 3 toxicity to the relevant organ system attributed to SBRT and immunotherapy occuring within 3 months.A total of 37 patients were assessable. No dose-limiting toxicity occurred in the concurrent cohort (n = 18). The sequential cohort required a dose reduction in the central lung group owing to two grade 4 pneumonitis events (2 of 19). Overall best response was as follows: 5.4% (2 of 37) complete response, 40.5% (15 of 37) partial response, 16.2% (6 of 37) stable disease, and 37.8% (14 of 37) progressive disease. Median progression-free survival was 5.8 months (95% confidence interval: 3.6-11.4 mo), with median follow-up of 17.0 months. Median overall survival was not reached.Concurrent nivolumab, ipilimumab, and SBRT were not more toxic than sequential therapy, and multisite SBRT was well tolerated in widely metastatic patients. Multimodality therapy resulted in durable metastasis control and encouraging early overall survival.

Emerging data indicates SGRT could improve safety and quality by preventing errors in its capacity as an independent system in the treatment room. The aim of this work is to investigate the utility of SGRT in the context of safety and quality. Three incident learning systems (ILS) were reviewed to categorize and quantify errors that could have been prevented with SGRT: SAFRON (International Atomic Energy Agency), UW-ILS (University of Washington) and AvIC (Skane University Hospital). A total of 849/9737 events occurred during the pre-treatment review/verification and treatment stages. Of these, 179 (21%) events were predicted to have been preventable with SGRT. The most common preventable events were wrong isocentre (43%) and incorrect accessories (34%), which appeared at comparable rates among SAFRON and UW-ILS. The proportion of events due to wrong accessories was much smaller in the AvIC ILS, which may be attributable to the mandatory use of SGRT in Sweden. Several case scenarios are presented to demonstrate that SGRT operates as a valuable complement to other quality-improvement tools routinely used in radiotherapy. Cases are noted in which SGRT itself caused incidents. These were mostly related to workflow issues and were of low severity. Severity data indicated that events with the potential to be mitigated by SGRT were of higher severity for all categories except wrong accessories. Improved vendor integration of SGRT systems within the overall workflow could further enhance its clinical utility. SGRT is a valuable tool with the potential to increase patient safety and treatment quality in radiotherapy.

Purpose/Objective(s) A data registry was established upon implementation of a program of intra-operative radiation therapy (IORT) using high-dose rate brachytherapy. We evaluated the initial experience of patients with locally recurrent gastrointestinal (GI) cancers to help inform future patient selection and optimal multi-modal treatment management. Materials/Methods All patients treated with surgical resection and IORT at a tertiary referral center were prospectively enrolled in a registry after program implementation in 2015. Candidates for IORT included patients who presented with disease likely to be resected with either close or positive margins based on multi-disciplinary evaluation. Patient, disease, and treatment characteristics including radiation history and acute (within 90 days, Clavien-Dindo grade) were recorded. IORT was administered using a HAM applicator, with field size and location determined intra-operatively, prescribed to 1 cm depth with lead blocking as appropriate. Patterns of failure and toxicity were analyzed. Time to event analysis was conducted using Kaplan Meier method, and contingency tables and chi square statistics evaluated differences in frequency of events. Results Twenty-one patients were identified with locally recurrent GI cancer (rectal 62%, colon 29%, and anal cancer, 9%) who underwent surgical resection and IORT with curative intent. Median age was 58 years. All patients had a history of pelvic external beam radiotherapy (EBRT, median 50.4 Gy); 9 (43%) were treated with pre-operative reirradiation (median dose 43 Gy, median 2 mo prior to surgery). The median IORT dose was 12.5 Gy (range 10-15). Resection was pathologically complete (R0, n = 9), or with microscopic (R1, n = 11) or macroscopic residual (R2, n = 1). Median follow up was 20 months. Twelve (57%) patients had failure at the site of IORT, at a median 7 mo. Freedom from failure (FFF) within the IORT field was associated with resection status (FFF-1y 75% for R0 vs 15% for R1/2, P = 0.0065) but not re-irradiation EBRT or IORT dose (P > 0.05). Pelvic failure beyond the IORT site occurred in 5 (24%) patients at a median 5 mo, and 13 (62%) had eventual distant metastases, at a median 5.5 months. Ultimately, only 3 patients (14%) were disease free at last follow-up. The median hospital stay was 6 days, the 90-day readmission rate was 25%, and acute grade 3 toxicity was observed in 43%, with abscess/sepsis most common (n = 5, 24%). Grade 3 toxicities and 90-day admission were not associated with resection status or EBRT (all P > 0.1). There were no 90-day grade 4/5 toxicities. Conclusion In patients treated with surgical excision and IORT for locally recurrent GI cancer, the ability to achieve a clear resection margin is a critical determinant of in-field local control. Patient selection should consider the chance for R0 resection, as well as the risk of regional or distant progression, when evaluating patients for this aggressive multi-modal treatment.

1007 Background: Prospective and retrospective studies of patients (pts) with oligometastatic (OM) disease have supported that metastases (mets) directed treatment (MDT) with SBRT or SR in addition to standard of care systemic therapy (SOC ST) can improve progression-free (PFS) and overall survival (OS) compared with SOC ST alone. However, randomized evidence in oligometastatic breast cancer (OMBC) are lacking. NRG-BR002, a randomized Phase IIR/III trial, sought to determine the efficacy of SOC ST + MDT (SBRT or SR) as first line treatment of OMBC. Methods: OMBC pts with ≤ 4 extracranial mets on standard imaging with controlled primary disease were eligible if on first line SOC ST for ≤ 12 months without progression. Pts were randomized (1:1) to ARM 1 – SOC ST (mainly chemotherapy, endocrine therapy, anti-HER2) or ARM 2 – SOC ST with MDT of all mets. Stratification included mets number (1 vs > 1), ER/PR and Her2 status, and chemotherapy use. Phase IIR targeted sample size was 128 total/116 eligible pts, for 92% power and 1-sided significance level = 0.15 to determine if adding MDT shows a signal for improved PFS (hazard ratio [HR] = 0.55, corresponding to median PFS (mPFS) from 10.5 to 19 months), in order to continue to the full phase III trial for OS. PFS and OS were estimated by Kaplan-Meier and arms compared with log-rank. Results: 125 of the 129 pts randomized were eligible (ARM 1 = 65, ARM 2 = 60). Key characteristics included median age 54, 79% ER+ or PR+/HER2-, 13% HER2+, 8% triple negative. 60% had 1 metastasis and 20% presented synchronously with primary disease. Following randomization, systemic therapy was delivered to 95% in ARM 1 and 93% in ARM 2; ablation: SBRT 93%, SR 2%, and 5% none. The median follow-up was 30 mo. The mPFS (70% CI) in ARM 1 was 23 mo (18, 29) and 19.5 mo (17, 36) in ARM 2; 24 and 36-mo PFS (70% CI) for ARM 1 were 45.7% (38.9, 52.5) and 32.8% (26.0, 39.5) compared with 46.8 (39.2, 54.3) and 38.1 (29.7, 46.6) in ARM 2; HR (70% CI): 0.92 (0.71, 1.17); and 1-sided log-rank p = 0.36. As PFS did not show signal, OS reporting is included: median OS was not reached in either arm; 36-mo OS (95% CI) in ARM 1 71.8% (58.9, 84.7) and ARM 2 68.9% (55.1, 82.6; 2-sided log-rank p = 0.54). Analysis of first failure showed new mets outside index area (Arm 1) /RT field (Arm 2) developed similarly in both arms at 40%. There were fewer new mets inside treated/index area for Arm 2 6.7% vs ARM 1 29.2%, respectively. There were no grade 5 treatment-related adverse events (AEs), 1 grade 4 AE in ARM 1, and 9.7% and 5.3% grade 3 AEs in ARMS 1 and 2, respectively. Circulating tumor cell counts (0 vs ≥1) at baseline were similar in both arms and were not prognostic HR (95% CI): 1.04 (0.54, 2.02). Conclusions: The addition of MDT to SOC ST did not show signal for improved PFS, nor OS difference in patients with OMBC. The trial will not proceed to the Phase III component. Clinical trial information: NCT02364557.

Studies investigating the effects of computed tomography (CT) image acquisition and reconstruction parameters have mostly been limited to non-human phantoms to limit exposure to patients. This study investigates these variations using a cadaveric liver and determines harmonization methods to mitigate these variations. A reference CT scan of a cadaveric liver was acquired along with 16 modified scans. Modified scans were obtained with altered image acquisition and reconstruction parameters. In each slice, the liver was segmented and used to calculate 142 features. Student's t-tests assessed differences between reference and modified scans for each feature after correcting for multiple comparisons. Features were harmonized between reference and modified scans using histogram normalization, pixel resampling, Butterworth filtering, resampling and filtering combined, and ComBat harmonization. The number of features reflecting significant differences before and after harmonization were compared across imaging parameters. Reducing the field-of-view (FOV) and using coronal instead of axial scans resulted in the greatest number of features reflecting significant differences (67.6%, and 35.9%, respectively) and resulted in the greatest median relative change in feature values (25.4% and 18.2%, respectively). Changes in tube voltage, pitch, and slice interval resulted in the smallest number of features reflecting significance (0.7%) with median relative changes in feature

Studies investigating variations in radiomic features due to changes in image acquisition and reconstruction parameters have focused on non-human phantoms to limit the exposure to human subjects. This study investigated such variations in the computed tomography (CT) scans of a cadaveric human liver. A reference CT scan of a normal cadaveric liver and 16 modified scans were acquired with one parameter changed from the reference for each modified scan: two iterative reconstruction strength levels, one reconstruction kernel, one slice thickness, one coronal view, one sagittal view, one field of view (FOV), two pitch levels, one slice interval, two CTDIvol levels, three kV settings, and one scan acquired using a scanner from another manufacturer. The liver was segmented in each scan, and 142 radiomic features were calculated on each slice across all scans. Unpaired Student’s t-tests assessed significant differences in feature distributions between reference and modified scans for all features after correcting for multiple comparisons (p

Purpose We calculated setup margins for whole breast radiotherapy during voluntary deep‐inspiration breath‐hold (vDIBH) using real‐time surface imaging (SI). Methods and Materials Patients (n = 58) with a 27‐to‐31 split between right‐ and left‐sided cancers were analyzed. Treatment beams were gated using AlignRT by registering the whole breast region‐of‐interest to the surface generated from the simulation CT scan. AlignRT recorded (three‐dimensional) 3D displacements and the beam‐on‐state every 0.3 s. Means and standard deviations of the displacements during vDIBH for each fraction were used to calculate setup margins. Intra‐DIBH stability and the intrafraction reproducibility were estimated from the medians of the 5th to 95th percentile range of the translations in each breath‐hold and fraction, respectively. Results A total of 7269 breath‐holds were detected over 1305 fractions in which a median dose of 200 cGy was delivered. Each fraction was monitored for 5.95 ± 2.44 min. Calculated setup margins were 4.8 mm (A/P), 4.9 mm (S/I), and 6.4 mm (L/R). The intra‐DIBH stability and the intrafraction reproducibility were ≤0.7 mm and ≤2.2 mm, respectively. The isotropic margin according to SI (9.2 mm) was comparable to other institutions’ calculations that relied on x‐ray imaging and/or spirometry for patients with left‐sided cancer (9.8–11.0 mm). Likewise, intra‐DIBH variability and intrafraction reproducibility of breast surface measured with SI agreed with spirometry‐based positioning to within 1.2 and 0.36 mm, respectively. Conclusions We demonstrated that intra‐DIBH variability, intrafraction reproducibility, and setup margins are similar to those reported by peer studies who utilized spirometry‐based positioning.

Purpose Interstitial brachytherapy implemented for locally advanced gynecologic cancer can result in toxicity due to the proximity of organs at risk (OAR). We report our experience using superflab bolus as vaginal packing to displace OAR during interstitial brachytherapy. Material and methods Twelve patients with stage IB-IVA gynecologic cancer were treated with definitive chemoradiation including interstitial brachytherapy. A Syed template was used for a computed tomography (CT)-based pre-plan with magnetic resonance imaging (MRI) fusion. A 1-2 cm superflab bolus was cut and sterilized. The tandem and obturator were placed, and superflab was then inserted into the vagina. Interstitial needles were then placed through the template and superflab as per the pre-plan under transabdominal ultrasound guidance. Prescription doses ranged from 85-90 Gy EQD2 including external beam radiation therapy (EBRT). 5-6 Gy per fraction was delivered biologically effective dose (BID) over 2-3 days in 1-2 implants. Toxicities were evaluated post-treatment, 1 month, and 3 months. Results The rectum, bladder, and sigmoid had significant average displacement from the prescription isodose line. The average reduction in D2cc between pre- and post-implant was 5.19 Gy per fraction (p < 0.0001), 7.19 Gy (p < 0.0004), and 1.78 Gy (p < 0.003) for the rectum, bladder, and sigmoid, respectively. The high-risk target volume (HR-TV) received a median D90 of 104% (range, 58-122%) of the prescription dose, and 92% (range, 71-131%) in the pre-/post-implant plans, respectively (p = 0.4). Conclusions Our initial experience with superflab as vaginal packing demonstrates technical feasibility and dosimetric improvement for OAR.

The purpose of this study was to develop and evaluate a framework to support automated standardized testing and analysis of Cone Beam Computed Tomography (CBCT) image quality QA across multiple institutions. A survey was conducted among the participating institutions to understand the variability of the CBCT QA practices. A commercial, automated software platform was validated by seven institutions participating in a consortium dedicated to automated quality assurance. The CBCT image analysis framework was used to compare periodic QA results among 23 linear accelerators (linacs) from seven institutions. The CBCT image quality metrics (geometric distortion, spatial resolution, contrast, HU constancy, uniformity and noise) data are plotted as a function of means with the upper and lower control limits compared to the linac acceptance criteria and AAPM recommendations. For example, mean geometric distortion and HU constancy metrics were found to be 0.13 mm (TG142 recommendation: ≤2 mm) and 13.4 respectively (manufacturer acceptance specification: ≤±50).Image upload and analysis process was fully automated using a MATLAB-based platform. This analysis enabled a quantitative, longitudinal assessment of the performance of quality metrics which were also compared across 23 linacs. For key CBCT parameters such as uniformity, contrast, and HU constancy, all seven institutions used stricter goals than what would be recommended based on the analysis of the upper and lower control limits. These institutional goals were also found to be stricter than that found in AAPM published guidance. This work provides a reference that could be used to machine-specific optimized tolerance of CBCT image maintenance via control charts to monitor performance we well as the sensitivity of different tests in support of a broader quality assurance program. To ensure the daily image quality needed for patient care, the optimized statistical QA metrics recommended to using along with risk-based QA.

PURPOSE To determine whether the addition of standardized uptake value (SUV) from PET scans to CT lung texture features could improve a radiomics-based model of radiation pneumonitis (RP) diagnosis in patients undergoing radiotherapy. METHODS AND MATERIALS Anonymized data from 96 esophageal cancer patients (18 RP-positive cases of Grade ≥ 2) were collected including pre-therapy PET/CT scans, pre-/post-therapy diagnostic CT scans and RP status. Twenty texture features (first-order, fractal, Laws' filter and gray-level co-occurrence matrix) were calculated from diagnostic CT scans and compared in anatomically matched regions of the lung. Classifier performance (texture, SUV, or combination) was assessed by calculating the area under the receiver operating characteristic curve (AUC). For each texture feature, logistic regression classifiers consisting of the average change in texture feature value and the pre-therapy SUV standard deviation (SUVSD ) were created and compared with the texture feature as a lone classifier using ANOVA with correction for multiple comparisons (P < 0.0025). RESULTS While clinical parameters (mean lung dose, smoking history, tumor location) were not significantly different among patients with and without symptomatic RP, SUV and texture parameters were significantly associated with RP status. AUC for single-texture feature classifiers alone ranged from 0.58 to 0.81 and 0.53 to 0.71 in high-dose (≥ 30 Gy) and low-dose (< 10 Gy) regions of the lungs, respectively. AUC for SUVSD alone was 0.69 (95% confidence interval: 0.54-0.83). Adding SUVSD into a logistic regression model significantly improved model fit for 18, 14 and 11 texture features and increased the mean AUC across features by 0.08, 0.06, and 0.04 in the low-, medium-, and high-dose regions, respectively. CONCLUSIONS Addition of SUVSD to a single-texture feature improves classifier performance on average, but the improvement is smaller in magnitude when SUVSD is added to an already effective classifier using texture alone. These findings demonstrate the potential for more accurate assessment of RP using information from multiple imaging modalities.

Background: The current standard of care for metastatic breast cancer patients (pts) is to deliver palliative chemotherapy, biologic &/or hormonal therapy when appropriate, with radiation &/or surgery reserved for the management of symptomatic or non-responsive (mets). For selected pts with limited metastatic (met) disease, mets-directed ablative therapy, with either surgical resection or high dose conformal radiotherapy (in addition to standard systemic therapies) to lung, liver, CNS adrenal, & multiple organs has been shown to result in long-term disease control numerically superior to systemic therapy alone. NRG-BR002 is a randomized Phase II trial to evaluate stereotactic body radiotherapy (SBRT) &/or surgical resection (SR) of all met sites in newly oligometastatic breast cancer in addition to standard systemic therapy. Trial Design & Eligibility For the Ph IIR, eligible breast cancer pts with biopsy confirmed metastatic disease to < /= 2 sites will be randomized to receive either standard systemic therapy with mets directed therapy as needed ( control arm) versus ablative therapy of all met sites with either body SBRT &/or surgical resection (SR) ( per the treating physician discretion) to determine if there is an improvement median progression free survival (PFS). If this aim is met the trial continues as a Ph III to evaluate if SBRT/SR improves 5 year overall survival. Secondary aims include local control in the met site, new distant met rate, & technical quality. The primary translational endpoint tests whether < 5 CTCs (per 7.5ml of blood) is an independent prognostic (outcome) marker for improved PFS & OS in oligometastatic breast cancer. Women are within 1 year of metastatic diagnosis, on first line systemic therapy without progression & the primary site disease is controlled. CNS mets are ineligible. ER/PR & HER-2 neu are required on either the primary or met site. Site radiation credentialing & a facility questionnaire are required. Randomization is to standard systemic therapy with local radiotherapy/ surgery for palliation when necessary vs ablative therapy of all mets with SBRT &/or SR. Statistics: For the Ph IIR portion to detect a signal for improved median PFS from 10.5 months to 19 months with 95% power & accounting for ineligible/lost pts, 146 pts will be required. For the Ph III, an additional 246, for a total of 402 pts will be required to definitively determine if ablative therapy improves 5-year overall survival from 28% to 42.5% (HR=0.67), with 85% power & a 1-sided type I error of 0.025. For the translational research, the number of pts accrued in the Ph IIR & Ph III portions will provide sufficient power ≥ 91% to detect whether < 5 CTC's is a prognostic marker for improved PFS & OS. Present Accrual & Target Accrual NRG BR002 activated 12/24/2014 with a target accrual of 146 pts for the Ph II component & 256 additional for the Ph III. Contact Information: Protocol: CTSU member web site https://www.ctsu.org. Enrollment: OPEN at https://open.ctsu.org. Support: Supported by NRG Oncology grants U10CA180868 & U10CA180822 from the National Cancer Institute (NCI). Citation Format: Chmura SJ, Winter KA, Salama JK, Woodward WW, Borges VF, Al-Hallaq H, Martuszak M, Jaskowiak NT, Milano MT, Bandos H, White JR. NRG-BR002: A phase IIR/III trial of standard of care therapy with or without stereotactic body radiotherapy (SBRT) &/or surgical ablation for newly oligometastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-04-06.

Introduction To quantify the dosimetric and clinical effects of intrafractional cylinder movement in patients receiving high-dose-rate vaginal cuff brachytherapy (VBT) without a formal immobilization device and the implication of motion on institutional clinical outcomes. Methods From 2013-2018, 119 patients were treated with VBT with no formal immobilization device at a single institution. As a quality assessment study, pre-and post-cylinder brachytherapy kilovoltage (kV) images were acquired for 37 fractions in nine consecutive patients who underwent VBT and clinical care representative of institutional practice standards. The D90 and D90 EqD2 were calculated according to each patient's average intrafractional movement throughout the treatment course. The D2cc for organs-at-risk (OARs) were also re-evaluated following the simulated movements. The survival outcomes and toxicity were recorded from the 119 patients. Toxicity was graded as per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results The measured mean ± standard deviation movement was 5.0 mm ± 3.5, with 62% moving caudad. The D90 from each patient's maximum and average movements were lower than the pre-planned doses: 71%, and 89%, respectively. The doses to the OARs were lower than the pre-planned doses. After a median follow-up of 20 months, there were three local recurrences with a median time of 14.5 months (range: 10-31). There were two acute grade 3+ toxicities and one late grade 3+ toxicity. There was a moderate correlation (r = 0.40) between body mass index (BMI) and intrafraction movement with caudad being more common in smaller BMIs (p = 0.0216). Conclusions Intrafractional vaginal cylinder movement without a table fixation device is about 5.0 mm, with the majority of movements moving caudad. While institutional outcomes suggest that local control may not be compromised, consideration of more formal immobilization devices is warranted, especially for those patients with lower BMIs.

An interstitial brachytherapy approach for gynecologic cancers is typically considered for patients with lesions exceeding 5 mm within tissue or that are not easily accessible for intracavitary applications. Recommendations for treating gynecologic malignancies with this approach are available through the American Brachytherapy Society, but vary based on available resources, staffing, and logistics. The intent of this manuscript is to share the collective experience of 3 academic centers that routinely perform interstitial gynecologic brachytherapy. Discussion points include indications for interstitial implants, procedural preparations, applicator selection, anesthetic options, imaging, treatment planning objectives, clinical workflows, timelines, safety, and potential challenges. Interstitial brachytherapy is a complex, high-skill procedure requiring routine practice to optimize patient safety and treatment efficacy. Clinics planning to implement this approach into their brachytherapy practice may benefit from considering the discussion points shared in this manuscript.

Purpose To evaluate the dosimetric impact of daily positioning variations measured with cone‐beam computed tomography (CBCT) on whole‐breast radiotherapy patients treated in the prone position. Methods Daily CBCT was prospectively acquired for 30 consecutive patients positioned prone. Treatment for early‐stage (≤II) breast cancer was prescribed with standard dose (50 Gy/25 fractions) or hypofractionation (42.56 Gy/16 fractions) for 13 and 17 patients, respectively. Systematic and random errors were calculated from the translational CBCT shifts and used to determine population‐based setup margins. Mean translations (±one standard deviation) for each patient were used to simulate the dosimetric impact on targets (PTV_eval and lumpectomy cavity), heart, and lung. Paired Student’s t tests at α = 0.01 were used to compare dose metrics after correction for multiple testing (P

Importance Stereotactic body radiotherapy (SBRT) for oligometastases is hypothesized to improve survival and is increasingly used. Little evidence supports its safe use to treat patients with multiple metastases. Objective To establish safety of SBRT dose schedules in patients with 3 to 4 metastases or 2 metastases in close proximity to each other. Design, Setting, and Participants This phase 1 trial opened on August 4, 2014, and closed to accrual on March 20, 2018. Metastases to 7 anatomic locations were included: bone/osseous (BO), spinal/paraspinal (SP), peripheral lung (PL), central lung (CL), abdominal-pelvic (AP), mediastinal/cervical lymph node (MC), and liver (L). Six patients could be enrolled per anatomic site. The setting was a consortium of North American academic and community practice cancer centers participating in NRG Oncology trials. Patients with breast, prostate, or non–small cell lung cancer with 3 to 4 metastases or 2 metastases in close proximity (≤5 cm) amenable to SBRT were eligible for this phase 1 study. Statistical analyses were performed from December 31, 2017, to September 19, 2019. Interventions The starting dose was 50 Gy in 5 fractions (CL, MC), 45 Gy in 3 fractions (PL, AP, L), and 30 Gy in 3 fractions (BO, SP). Main Outcomes and Measures The primary end point was dose-limiting toxicity (DLT) defined by the Common Terminology Criteria for Adverse Events, version 4.0, as specific adverse events (AEs) of grades 3 to 5 (definite or probable per the protocol DLT definition) related to SBRT within 180 days of treatment. Dose levels were considered safe if DLTs were observed in no more than 1 of 6 patients per location; otherwise, the dose at that location would be de-escalated. Results A total of 42 patients enrolled, 39 were eligible, and 35 (mean [SD] age, 63.1 [14.2] years; 20 men [57.1%]; 30 White patients [85.7%]) were evaluable for DLT. Twelve patients (34.3%) had breast cancer, 10 (28.6%) had non–small cell lung cancer, and 13 (37.1%) had prostate cancer; there was a median of 3 metastases treated per patient. Median survival was not reached. No protocol-defined DLTs were observed. When examining all AEs, 8 instances of grade 3 AEs, most likely related to protocol therapy, occurred approximately 125 to 556 days from SBRT initiation in 7 patients. Conclusions and Relevance This phase 1 trial demonstrated the safety of SBRT for patients with 3 to 4 metastases or 2 metastases in close proximity. There were no treatment-related deaths. Late grade 3 AEs demonstrate the need for extended follow-up in long-surviving patients with oligometastatic disease. Treatment with SBRT for multiple metastases has been expanded into multiple ongoing randomized phase 2/3 National Cancer Institute–sponsored trials (NRG-BR002, NRG-LU002). Trial Registration ClinicalTrials.gov Identifier:NCT02206334

Purpose: The goal is to develop a stand-alone application, which automatically and consistently computes the coordinates of the dose calculation point recommended by the American Brachytherapy Society (i.e., point A) based solely on the implanted applicator geometry for cervical cancer brachytherapy. Material and methods: The application calculates point A coordinates from the source dwell geometries in the computed tomography (CT) scans, and outputs the 3D coordinates in the left and right directions. The algorithm was tested on 34 CT scans of 7 patients treated with high-dose-rate (HDR) brachytherapy using tandem and ovoid applicators. A single experienced user retrospectively and manually inserted point A into each CT scan, whose coordinates were used as the “gold standard” for all comparisons. The gold standard was subtracted from the automatically calculated points, a second manual placement by the same experienced user, and the clinically used point coordinates inserted by multiple planners. Coordinate differences and corresponding variances were compared using nonparametric tests. Results: Automatically calculated, manually placed, and clinically used points agree with the gold standard to < 1 mm, 1 mm, 2 mm, respectively. When compared to the gold standard, the average and standard deviation of the 3D coordinate differences were 0.35 ± 0.14 mm from automatically calculated points, 0.38 ± 0.21 mm from the second manual placement, and 0.71 ± 0.44 mm from the clinically used point coordinates. Both the mean and standard deviations of the 3D coordinate differences were statistically significantly different from the gold standard, when point A was placed by multiple users (p < 0.05) but not when placed repeatedly by a single user or when calculated automatically. There were no statistical differences in doses, which agree to within 1-2% on average for all three groups. Conclusions: The study demonstrates that the automated algorithm calculates point A coordinates consistently, while reducing inter-user variability. Point placement using the algorithm expedites the planning process and minimizes associated potential human errors.

We performed a dosimetric comparison of sequential IMRT (sIMRT) and simultaneously integrated boost (SIB) IMRT to boost PET‐avid lymph nodes while concurrently treating pelvic targets to determine the potential of SIB IMRT to reduce overall treatment duration in locally advanced cervical cancer. Ten patients receiving definitive radiation therapy were identified retrospectively. RTOG consensus guidelines were followed to delineate the clinical target volume and organs at risk (OAR), which were then expanded per IMRT consortium guidelines to yield the planning target volume (PTV). Dosimetric parameters for PTVs and OAR including conformity (CI95%) were collected and compared using Wilcoxon signed‐rank tests with Bonferroni correction. The median PTV volume was 1843 cc (1088–2225 cc) and the median boost volume was 43 cc (15–129 cc). Comparable target volume coverage was achieved with sIMRT and SIB plans, while hot spots were significantly reduced using SIB. SIB plans improved sparing for all OAR, though only rectum and small bowel doses were statistically significant. Comparing sIMRT and SIB plans averaged over all patients, rectal doses were V45: 70.8% vs. 64.5%(p=0.002) and 0.1 cc: 50.7 Gy vs. 48.7 Gy (p=0.006). For small bowel, sIMRT and SIB IMRT plans yielded V45: 13.4% vs. 11.4%(p=0.006) and 1 cc: 54.4 Gy vs. 52.6 Gy (p=0.006), respectively. Doses to femoral heads and bladder trended towards significance in favor of SIB plans. The mean treatment time was 25 versus 29 days for SIB and sIMRT plans, respectively. When compared to sIMRT, SIB for treatment of nodal targets provides a significant, but small, dose reduction (3.8%–4.4%) to OAR, which leads to comparable biological dose despite higher fractional doses. Furthermore, SIB IMRT reduces overall treatment time and simplifies the planning process, and should be considered for targeting PET‐positive nodal disease in patients with locally advanced cervical cancer. PACS number(s): 87.19.xj cancer

Purpose: While radiomics feature values can differ when extracted using different radiomics software, the effects of these variations when applied to a particular clinical task are currently unknown. The goal of our study was to use various radiomics software packages to classify patients with radiation pneumonitis (RP) and to quantify the variation in classification ability among packages. Approach: A database of serial thoracic computed tomography scans was obtained from 105 patients with esophageal cancer. Patients were treated with radiation therapy (RT), resulting in 20 patients developing RP grade [Formula: see text]. Regions of interest (ROIs) were randomly placed in the lung volume of the pre-RT scan within high-dose regions ([Formula: see text]), and corresponding ROIs were anatomically matched in the post-RT scan. Three radiomics packages were compared: A1 (in-house), IBEX v1.0 beta, and PyRadiomics v.2.0.0. Radiomics features robust to deformable registration and common among radiomics packages were calculated: four first-order and four gray-level co-occurrence matrix features. Differences in feature values between time points were calculated for each feature, and logistic regression was used in conjunction with analysis of variance to classify patients with and without RP ([Formula: see text]). Classification ability for each package was assessed using receiver operating characteristic (ROC) analysis and compared using the area under the ROC curve (AUC). Results: Of the eight radiomics features, five were significantly correlated with RP status for all three packages, whereas one feature was not significantly correlated with RP for all three packages. The remaining two features differed in whether or not they were significantly associated with RP status among the packages. Seven of the eight features agreed among the packages in whether the AUC value was significantly [Formula: see text]. Conclusions: Radiomics features extracted using different software packages can result in differences in classification ability.

Background Some patients cannot be imaged with cone-beam CT for image-guided radiation therapy because their size, pose, or fixation devices cause collisions with the machine. Objective To investigate imaging trajectories that avoid such collisions by using virtual isocenter and variable magnification during acquisition while yielding comparable image quality. Methods The machine components most likely to collide are the gantry and kV detector. A virtual isocenter trajectory continuously moves the patient during gantry rotation to maintain an increased separation between the two. With dynamic magnification, the kV detector is dynamically moved to increase clearance for an angular range around the potential collision point while acquiring sufficient data to maintain the field-of-view. Both strategies were used independently and jointly with the resultant image quality evaluated against the standard circular acquisition. Results Collision avoiding trajectories show comparable contrast and resolution to standard techniques. For an anthropomorphic phantom, the RMSE is 0.97, and visual image fidelity is >0.96 for all trajectories when compared to a standard circular scan. Conclusions The proposed trajectories avoid machine-patient collisions while providing comparable image quality to the current standard thereby enabling CBCT imaging for patients that could not otherwise be scanned.

Given the increased need for consistent quantitative image analysis, variations in radiomics feature calculations due to differences in radiomics software were investigated. Two in-house radiomics packages and two freely available radiomics packages, MaZda and IBEX, were utilized. Forty [Formula: see text] regions of interest (ROIs) from 40 digital mammograms were studied along with 39 manually delineated ROIs from the head and neck (HN) computed tomography (CT) scans of 39 patients. Each package was used to calculate first-order histogram and second-order gray-level co-occurrence matrix (GLCM) features. Friedman tests determined differences in feature values across packages, whereas intraclass-correlation coefficients (ICC) quantified agreement. All first-order features computed from both mammography and HN cases (except skewness in mammography) showed significant differences across all packages due to systematic biases introduced by each package; however, based on ICC values, all but one first-order feature calculated on mammography ROIs and all but two first-order features calculated on HN CT ROIs showed excellent agreement, indicating the observed differences were small relative to the feature values but the bias was systematic. All second-order features computed from the two databases both differed significantly and showed poor agreement among packages, due largely to discrepancies in package-specific default GLCM parameters. Additional differences in radiomics features were traced to variations in image preprocessing, algorithm implementation, and naming conventions. Large variations in features among software packages indicate that increased efforts to standardize radiomics processes must be conducted.

Open-source texture analysis software allows for the advancement of radiomics research. Variations in texture features, however, result from discrepancies in algorithm implementation. Anatomically matched regions of interest (ROIs) that captured normal breast parenchyma were placed in the magnetic resonance images (MRI) of 20 patients at two time points. Six first-order features and six gray-level co-occurrence matrix (GLCM) features were calculated for each ROI using four texture analysis packages. Features were extracted using package-specific default GLCM parameters and using GLCM parameters modified to yield the greatest consistency among packages. Relative change in the value of each feature between time points was calculated for each ROI. Distributions of relative feature value differences were compared across packages. Absolute agreement among feature values was quantified by the intra-class correlation coefficient. Among first-order features, significant differences were found for max, range, and mean, and only kurtosis showed poor agreement. All six second-order features showed significant differences using package-specific default GLCM parameters, and five second-order features showed poor agreement; with modified GLCM parameters, no significant differences among second-order features were found, and all second-order features showed poor agreement. While relative texture change discrepancies existed across packages, these differences were not significant when consistent parameters were used.

Purpose Stereotactic body radiotherapy (SBRT) may stimulate innate and adaptive immunity to augment immunotherapy response. Multisite SBRT is an emerging paradigm for treating metastatic disease. Anti-PD-1–treatment outcomes may be improved with lower disease burden. In this context, we conducted a phase I study to evaluate the safety of pembrolizumab with multisite SBRT in patients with metastatic solid tumors. Patients and Methods Patients progressing on standard treatment received SBRT to two to four metastases. Not all metastases were targeted, and metastases > 65 mL were partially irradiated. SBRT dosing varied by site and ranged from 30 to 50 Gy in three to five fractions with predefined dose de-escalation if excess dose-limiting toxicities were observed. Pembrolizumab was initiated within 7 days after completion of SBRT. Pre- and post-SBRT biopsy specimens were analyzed in a subset of patients to quantify interferon-γ–induced gene expression. Results A total of 79 patients were enrolled; three patients did not receive any treatment and three patients only received SBRT. Patients included in the analysis were treated with SBRT and at least one cycle of pembrolizumab. Most (94.5%) of patients received SBRT to two metastases. Median follow-up for toxicity was 5.5 months (interquartile range, 3.3 to 8.1 months). Six patients experienced dose-limiting toxicities with no radiation dose reductions. In the 68 patients with imaging follow-up, the overall objective response rate was 13.2%. Median overall survival was 9.6 months (95% CI, 6.5 months to undetermined) and median progression-free survival was 3.1 months (95% CI, 2.9 to 3.4 months). Expression of interferon-γ–associated genes from post–SBRT tumor biopsy specimens significantly correlated with nonirradiated tumor response. Conclusion Multisite SBRT followed by pembrolizumab was well tolerated with acceptable toxicity. Additional studies exploring the clinical benefit and predictive biomarkers of combined multisite SBRT and PD-1–directed immunotherapy are warranted.

Purpose: The purpose of this study was 2-fold. One purpose was to develop an automated, streamlined quality assurance (QA) program for use by multiple centers. The second purpose was to evaluate machine performance over time for multiple centers using linear accelerator (Linac) log files and electronic portal images. The authors sought to evaluate variations in Linac performance to establish as a reference for other centers. Methods: The authors developed analytical software tools for a QA program using both log files and electronic portal imaging device (EPID) measurements. The first tool is a general analysis tool which can read and visually represent data in the log file. This tool, which can be used to automatically analyze patient treatment or QA log files, examines the files for Linac deviations which exceed thresholds. The second set of tools consists of a test suite of QA fields, a standard phantom, and software to collect information from the log files on deviations from the expected values. The test suite was designed to focus on the mechanical tests of the Linac to include jaw, MLC, and collimator positions during static, IMRT, and volumetric modulated arc therapy delivery. A consortium of eight institutions delivered the test suitemore » at monthly or weekly intervals on each Linac using a standard phantom. The behavior of various components was analyzed for eight TrueBeam Linacs. Results: For the EPID and trajectory log file analysis, all observed deviations which exceeded established thresholds for Linac behavior resulted in a beam hold off. In the absence of an interlock-triggering event, the maximum observed log file deviations between the expected and actual component positions (such as MLC leaves) varied from less than 1% to 26% of published tolerance thresholds. The maximum and standard deviations of the variations due to gantry sag, collimator angle, jaw position, and MLC positions are presented. Gantry sag among Linacs was 0.336 ± 0.072 mm. The standard deviation in MLC position, as determined by EPID measurements, across the consortium was 0.33 mm for IMRT fields. With respect to the log files, the deviations between expected and actual positions for parameters were small (

We evaluated the image registration accuracy achieved using two deformable registration algorithms when radiation-induced normal tissue changes were present between serial computed tomography (CT) scans. Two thoracic CT scans were collected for each of 24 patients who underwent radiation therapy (RT) treatment for lung cancer, eight of whom experienced radiologically evident normal tissue damage between pre- and post-RT scan acquisition. For each patient, 100 landmark point pairs were manually placed in anatomically corresponding locations between each pre- and post-RT scan. Each post-RT scan was then registered to the pre-RT scan using (1) the Plastimatch demons algorithm and (2) the Fraunhofer MEVIS algorithm. The registration accuracy for each scan pair was evaluated by comparing the distance between landmark points that were manually placed in the post-RT scans and points that were automatically mapped from pre- to post-RT scans using the displacement vector fields output by the two registration algorithms. For both algorithms, the registration accuracy was significantly decreased when normal tissue damage was present in the post-RT scan. Using the Plastimatch algorithm, registration accuracy was 2.4 mm, on average, in the absence of radiation-induced damage and 4.6 mm, on average, in the presence of damage. When the Fraunhofer MEVIS algorithm was instead used, registration errors decreased to 1.3 mm, on average, in the absence of damage and 2.5 mm, on average, when damage was present. This work demonstrated that the presence of lung tissue changes introduced following RT treatment for lung cancer can significantly decrease the registration accuracy achieved using deformable registration.

We investigated the accuracy of surface matching compared to kV positioning of 10 post-mastectomy chestwall patients receiving inverse-planned, non-gated IMRT.During 130 treatment sessions, non-gated 3D surfaces were captured using AlignRT (v4.5) before and after table translations as indicated by kV imaging. Surfaces were compared to a reference generated from CT data. Pearson's correlations between 'indicated' AlignRT and kV shifts were studied for surface registration of user-defined regions-of-interest (ROIs): the entire surface ('all') and the chestwall ('cw'). In 21% of sessions, two consecutive surfaces of patients in identical positions were used to estimate variability. Finally, the 'implemented' shifts detected by AlignRT were calculated and compared to the absolute table translations.Correlations between 'indicated' AlignRT and kV shifts were higher for 'cw' than for 'all': r=0.65 (Anterior-Posterior), r=0.65 (Superior-Inferier), r=0.44 (Left-Right). Correlations exhibited large inter-patient variability; 60% had r0.6 in at least 1 direction thereby resulting in ow correlation between 3D Euclidian shift distances (r=0.48). Correlations between 'cw' and kV increased (r0.8) for 'implemented' table shifts; only 2 patients demonstrated r0.6 in any single direction. Comparison of consecutively-acquired 'cw' surfaces controlled for patient movement demonstrated standard deviations (STDs) of: 1.2mm (A-P), 2.0mm (S-I), 1.6mm (L-R). While STDs between 'implemented' and kV shifts were on the same order, STDs between 'indicated' and kV shifts were twice as large: 2.9mm (A-P), 3.5mm (S-I), 4.1mm (L-R). Rotational differences1degree were calculated more often when registering 'cw' (22%) than 'all' (5%). At the treatment position, residual STDs remained high (3.0-3.6mm).On average, 'cw' shifts correlated with kV shifts but exhibited significant inter-patient variability and larger rotations than 'all'. Differences between AlignRT and kV were ∼3mm for initial patient positioning. The lack of a one-to-one correspondence between surface and kV shifts in any single session must be further investigated before clinical implementation.

The purpose of this study was to quantify the variability of the breast surface position when aligning whole‐breast patients to bony landmarks based on MV portal films or skin marks alone. Surface imaging was used to assess the breast surface position of 11 whole‐breast radiotherapy patients, but was not used for patient positioning. On filmed fractions, AlignRT v5.0 was used to capture the patient's surface after initial positioning based on skin marks (28 “preshifts” surfaces), and after treatment couch shifts based on MV films (41 “postshifts” surfaces). Translations and rotations based on surface captures were recorded, as well as couch shifts based on MV films. For nonfilmed treatments, “daily” surface images were captured following positioning to skin marks alone. Group mean and systematic and random errors were calculated for all datasets. Pearson correlation coefficients, setup margins, and 95% limits of agreement (LOA) were calculated for preshifts translations and MV film shifts. LOA between postshifts surfaces and the filmed treatment positions were also computed. All the surface captures collected were retrospectively compared to both a DICOM reference surface created from the planning CT and to an AlignRT reference surface. All statistical analyses were performed using the DICOM reference surface dataset. AlignRT reference surface data was only used to calculate the LOA with the DICOM reference data. This helped assess any outcome differences between both reference surfaces. Setup margins for preshifts surfaces and MV films range between 8.3–12.0 mm and 5.4–13.4 mm, respectively. The largest margin is along the left–right (LR) direction for preshift surfaces, and along craniocaudal (CC) for films. LOA ranges between the preshifts surfaces and MV film shifts are large (12.6–21.9 mm); these decrease for postshifts surfaces (9.8–18.4 mm), but still show significant disagreements between the two modalities due to their focus on different anatomical landmarks (patient's topography versus bony anatomy). Pearson's correlation coefficients further support this by showing low to moderate correlations in the anterior–posterior (AP) and LR directions (0.47–0.69) and no correlation along CC(

TPS1117 Background: This is a randomized Phase II/III trial to evaluate if stereotactic body radiotherapy (SBRT) and/or surgical resection (SR) of all metastatic sites in newly oligo-metastatic breast cancer who have received up to 12 months of first line systemic therapy without progression will significantly improve median progression free survival (PFS). If this aim is met the trial continues as a phase III to evaluate if SBRT/SR improves 5 year overall survival. Secondary aims include local control in the metastatic site, new distant metastatic rate, and technical quality. Translational primary endpoint is to determine whether < 5 CTCs is an independent prognostic marker for improved PFS and OS. Methods: Women with pathologically confirmed metastatic breast cancer to ≤ 4 sites who have been diagnosed within 365 days with metastatic disease and the primary tumor site disease is controlled. CNS metastases are ineligible. ER/PR and HER-2 neu status is required. Site radiation credentialing with a facility questionnaire and pre-treatment review of first case is required. Randomization is to standard systemic therapy with local radiotherapy/ surgery for palliation when necessary versus ablative therapy of all metastases with SBRT and/or SR. For the phase IIR portion to detect a signal for improved median PFS from 10.5 months to 19 months with 95% power and a 1-sided alpha of 0.15 and accounting for ineligible/lost patients, 128 patients will be required. For the Phase III, an additional 232 patients will be required to definitively determine if ablative therapy improves 5-year overall survival from 28% to 42.5% (HR=0.67), with 85% power and a one-sided type I error of 0.025. For the translational research assuming a two-sided probability of type I error of 0.05, the number of patients accrued in the Phase II-R and Phase III portions will provide sufficient power of at least 91% and 93% to detect whether < 5 CTC’s is prognostic for PFS and OS, respectively. Present accrual (1-31-2019): 105. Contact Information: Protocol: CTSU member web site https://www.ctsu.org . Enrollment: OPEN at https://open.ctsu.org . Support: This project is supported by NRG Oncology grants U10CA180868 and U10CA180822 from the National Cancer Institute (NCI). Translational science is supported by the Ludwig Foundation for Cancer Research. Clinical trial information: NCT02364557.

Purpose Stereotactic body radiotherapy (SBRT) may be appealing in medically inoperable endometrial cancer to avoid procedural risks. We performed a dosimetric comparison to triple-tandem, high-dose-rate (HDR) brachytherapy. Methods and Materials Six consecutive clinical stage I, grade 1–2, medically inoperable endometrial cancer patients were treated with triple-tandem HDR brachytherapy. We report patient factors and acute toxicity. Also, we performed dosimetric comparison to SBRT using both 3D conformal arc (3DArc) and volumetric-modulated arc therapy. D2cc values for normal tissues were calculated and compared to the HDR plans. Results Median age was 57 years. Patient comorbidities included morbid obesity, congestive heart failure, diabetes, and pulmonary emboli. In three patients who received prior external beam radiation (EBRT), median EBRT and HDR doses were 46 Gy and 20 Gy, respectively. The median dose with HDR brachytherapy monotherapy was 35 Gy. Acute toxicities during EBRT included gastrointestinal (3/3 with grade 1–2) and genitourinary (3/3 with grade 1–2). Acute toxicities during HDR brachytherapy were gastrointestinal (2/6 total with grade 1–2) and genitourinary (2/6 total with grade 1). The mean D2cc/Gy of prescription dose for rectum, sigmoid, and bladder were 0.58, 0.40, and 0.47 respectively. Overall, doses to normal tissues were higher for SBRT plans as compared to HDR. Also, the R50 (ratio of the 50% prescription isodose volume to the PTV) was lowest with HDR brachytherapy. Conclusions In medically inoperable, clinical stage I endometrial cancer patients with multiple comorbidities, definitive triple-tandem, HDR brachytherapy results in mild acute toxicity. In addition, HDR brachytherapy achieves relatively lower doses to surrounding normal tissues as compared to SBRT.

Purpose The NRG-BR001 trial is the first National Cancer Institute–sponsored trial to treat multiple (range 2-4) extracranial metastases with stereotactic body radiation therapy. Benchmark credentialing is required to ensure adherence to this complex protocol, in particular, for metastases in close proximity. The present report summarizes the dosimetric results and approval rates. Methods and Materials The benchmark used anonymized data from a patient with bilateral adrenal metastases, separated by Results Of 63 benchmarks submitted through October 2015, 94% were approved, with 51% approved at the first attempt. Most used volumetric arc therapy (VMAT) (78%), a single plan for both PTVs (90%), and prioritized the PTV over the stomach (75%). The median dose to 95% of the volume was 44.8 ± 1.0 Gy and 44.9 ± 1.0 Gy for the right and left PTV, respectively. The median dose to 0.03 cm 3 was 14.2 ± 2.2 Gy to the spinal cord and 46.5 ± 3.1 Gy to the stomach. Plans that spared the stomach significantly reduced the dose to the left PTV and stomach. Conformity metrics were significantly better for single plans that simultaneously treated both PTVs with VMAT, intensity modulated radiation therapy, or 3-dimensional conformal radiation therapy compared with separate plans. No significant differences existed in the dose at 2 cm from the PTVs. Conclusions Although most plans used VMAT, the range of conformity and dose falloff was large. The decision to prioritize either OARs or PTV coverage varied considerably, suggesting that the toxicity outcomes in the trial could be affected. Several benchmarks met the dose-volume histogram metrics but produced unacceptable plans owing to low conformity. Dissemination of a frequently-asked-questions document improved the approval rate at the first attempt. Benchmark credentialing was found to be a valuable tool for educating institutions about the protocol requirements.

Inhomogeneously broadened, non-Lorentzian water resonances have been observed in small image voxels of breast tissue. The non-Lorentzian components of the water resonance are likely produced by bulk magnetic susceptibility shifts caused by dense, deoxygenated tumor blood vessels (the ‘BOLD’ effect), but can also be produced by other characteristics of local anatomy and physiology, including calcifications and interfaces between different types of tissue. Here, we tested the hypothesis that detection of non-Lorentzian components of the water resonance with high spectral and spatial resolution (HiSS) MR imaging allows classification of breast lesions without the need to inject contrast agent. Eighteen malignant lesions and nine benign lesions were imaged with HiSS MRI at 1.5T. A new algorithm was developed to detect non-Lorentzian (or off-peak) components of the water resonance. After a Lorentzian fit was subtracted from the data, the largest peak in the residual spectrum in each voxel was identified as the major off-peak component of the water resonance. The difference in frequency between these off-peak components and the main water peaks, and their amplitudes were measured in malignant lesions, benign lesions, and breast fibroglandular tissue. Off-peak component frequencies were significantly different between malignant and benign lesions (p