Longitudinal brain volumetrics in glioma survivors.

OBJECTIVE: Radiation therapy (RT) is used selectively for patients with low-grade glioma (LGG) given the concerns for potential cognitive effects in survivors, but prior cognitive outcome studies among LGG survivors have had inconsistent findings. Translational studies that characterize changes in brain anatomy and physiology after treatment of LGG may help to both contextualize cognitive findings and improve the overall understanding of radiation effects in normal brain tissue. This study aimed to investigate the hypothesis that patients with LGG who are treated with RT will experience greater brain volume loss than those who do not receive RT. METHODS: This retrospective longitudinal study included all patients with WHO grade 2 glioma who received posttreatment surveillance MRI at the University of Alabama at Birmingham. Volumetric analysis of contralateral cortical white matter (WM), cortical gray matter (GM), and hippocampus was performed on all posttreatment T1-weighted MRI sequences using the SynthSeg script. The effect of clinical and treatment variables on brain volumes was assessed using two-level hierarchical linear models. RESULTS: The final study cohort consisted of 105 patients with 1974 time points analyzed. The median length of imaging follow-up was 4.6 years (range 0.36-18.9 years), and the median number of time points analyzed per patient was 12 (range 2-40). Resection was performed in 79 (75.2%) patients, RT was administered to 61 (58.1%) patients, and chemotherapy was administered to 66 (62.9%) patients. Age at diagnosis (ß = -0.06, p < 0.001) and use of RT (ß = -1.12, p = 0.002) were associated with the slope of the contralateral cortical GM volume model (i.e., change in GM over time). Age at diagnosis (ß = -0.08, p < 0.001), midline involvement (ß = 1.31, p = 0.006), and use of RT (ß = -1.45, p = 0.001) were associated with slope of the contralateral cortical WM volume model. Age (ß = -0.0027, p = 0.001), tumor resection (ß = -0.069, p < 0.001), use of chemotherapy (ß = -0.0597, p = 0.003), and use of RT (ß = -0.0589, p < 0.001) were associated with the slope of the contralateral hippocampus volume model. CONCLUSIONS: This study demonstrated volume loss in contralateral brain structures among LGG survivors, and patients who received RT experienced greater volume loss than those who did not. The results of this study may help to provide context for cognitive outcome research in LGG survivors and inform the design of future strategies to preserve cognition.

Prospective Evaluation of Automated Contouring for CT-Based Brachytherapy for Gynecologic Malignancies.

Purpose: The use of deep learning to auto-contour organs at risk (OARs) in gynecologic radiation treatment is well established. Yet, there is limited data investigating the prospective use of auto-contouring in clinical practice. In this study, we assess the accuracy and efficiency of auto-contouring OARs for computed tomography-based brachytherapy treatment planning of gynecologic malignancies. Methods and Materials: An inhouse contouring tool automatically delineated 5 OARs in gynecologic radiation treatment planning: the bladder, small bowel, sigmoid, rectum, and urethra. Accuracy of each auto-contour was evaluated using a 5-point Likert scale: a score of 5 indicated the contour could be used without edits, while a score of 1 indicated the contour was unusable. During scoring, automated contours were edited and subsequently used for treatment planning. Dice similarity coefficient, mean surface distance, 95% Hausdorff distance, Hausdorff distance, and dosimetric changes between original and edited contours were calculated. Contour approval time and total planning time of a prospective auto-contoured (AC) cohort were compared with times from a retrospective manually contoured (MC) cohort. Results: Thirty AC cases from January 2022 to July 2022 and 31 MC cases from July 2021 to January 2022 were included. The mean (±SD) Likert score for each OAR was the following: bladder 4.77 (±0.58), small bowel 3.96 (±0.91), sigmoid colon 3.92 (±0.81), rectum 4.6 (±0.71), and urethra 4.27 (±0.78). No ACs required major edits. All OARs had a mean Dice similarity coefficient > 0.86, mean surface distance < 0.48 mm, 95% Hausdorff distance < 3.2 mm, and Hausdorff distance < 10.32 mm between original and edited contours. There was no significant difference in dose-volume histogram metrics (D2.0 cc/D0.1 cc) between original and edited contours (P values > .05). The average time to plan approval in the AC cohort was 19% less than the MC cohort. (AC vs MC, 117.0 + 18.0 minutes vs 144.9 ± 64.5 minutes, P = .045). Conclusions: Automated contouring is useful and accurate in clinical practice. Auto-contouring OARs streamlines radiation treatment workflows and decreases time required to design and approve gynecologic brachytherapy plans.

Characterization of Photon Intensity Modulated Radiation Therapy Robustness in Patients With Prostate Cancer as a Proposed Benchmark for Proton Therapy Robustness Evaluation.

PURPOSE: Robustness evaluation is increasingly used in particle therapy planning to assess clinical target volume (CTV) coverage in the setting of setup and range uncertainty. However, no clear standard exists as to an acceptable degree of plan robustness. The aim of this study is to quantify x-ray robustness parameters, as this could inform proton planning when held to a similar standard. METHODS AND MATERIALS: Consecutive patients with prostate adenocarcinoma treated with definitive x-irradiation to the prostate alone at a single institution in 2019 were retrospectively reviewed. CTV to planned target volume (PTV) margins of 7 mm in all directions, except 4 mm posteriorly, were used in the main cohort. Plans were normalized to PTV V100% ≥ 95%. Patient setup errors were simulated by shifting the isocenter relative to the patient in each of the cardinal directions. The magnitude of each shift equaled the magnitude of the CTV to PTV expansion in that direction. Range uncertainty was set to 0%. RESULTS: A total of 27 patients were evaluated. The mean (SD) nominal plan CTV V100% was 99.6% (1.1%). The mean (SD) worst-case shift CTV V100% was 97.2% (2.8%). The mean (SD) nominal and worst-case CTV V95% were 100% (0%) and 99.7% (0.5%), respectively. A worst-case CTV V100% > 90% and a worst-case CTV V95% > 99% were achieved in over 95% of plans. The mean (SD) nominal and worst-case rectal V70 Gy were 2.37 cc (1.00 cc) and 11.60 cc (3.16 cc), respectively. The mean (SD) nominal and worst-case bladder V60 Gy were 7.8% (4.8%) and 14.5% (9.3%), respectively. Paired 2-tailed t tests comparing the nominal to worst-case dose-volume histograms were significant for each dosimetric parameter (P < .01). CONCLUSIONS: X-ray planning uses PTV margins to inherently provide robustness to patient setup errors. Although the prostate remains well covered in various setup uncertainty scenarios, organs at risk routinely exceeded nominal treatment plan institutional constraints in the worst-case scenarios. Robustness metrics obtained from x-ray plans could serve as a benchmark for proton therapy robust optimization and evaluation.

Automated evaluation for rapid implementation of knowledge-based radiotherapy planning models.

PURPOSE: Knowledge-based planning (KBP) offers the ability to predict dose-volume metrics based on information extracted from previous plans, reducing plan variability and improving plan quality. As clinical integration of KBP is increasing there is a growing need for quantitative evaluation of KBP models. A .NET-based application, RapidCompare, was created for automated plan creation and analysis of Varian RapidPlan models. METHODS: RapidCompare was designed to read calculation parameters and a list of reference plans. The tool copies the reference plan field geometry and structure set, applies the RapidPlan model, optimizes the KBP plan, and generates data for quantitative evaluation of dose-volume metrics. A cohort of 85 patients, divided into training (50), testing (10), and validation (25) groups, was used to demonstrate the utility of RapidCompare. After training and tuning, the KBP model was paired with three different optimization templates to compare various planning strategies in the validation cohort. All templates used the same set of constraints for the planning target volume (PTV). For organs-at-risk, the optimization template provided constraints using the whole dose-volume histogram (DVH), fixed-dose/volume points, or generalized equivalent uniform dose (gEUD). The resulting plans from each optimization approach were compared using DVH metrics. RESULTS: RapidCompare allowed for the automated generation of 75 total plans for comparison with limited manual intervention. In comparing optimization techniques, the Dose/Volume and Lines optimization templates generated plans with similar DVH metrics, with a slight preference for the Lines technique with reductions in heart V30Gy and spinal cord max dose. The gEUD model produced high target heterogeneity. CONCLUSION: Automated evaluation allowed for the exploration of multiple optimization templates in a larger validation cohort than would have been feasible using a manual approach. A final KBP model using line optimization objectives produced the highest quality plans without human intervention.

Prostate Stereotactic Body Radiation Therapy With a Focal Simultaneous Integrated Boost: 5-Year Toxicity and Biochemical Recurrence Results From a Prospective Trial.

PURPOSE: Stereotactic body radiation therapy (SBRT) is increasingly used as a definitive treatment option for patients with prostate adenocarcinoma. The aim of this study was to assess the late toxicity, patient-reported quality of life outcomes, and biochemical recurrence rates after prostate SBRT with simultaneous integrated boost (SIB) targeting lesions defined by magnetic resonance imaging (MRI). METHODS AND MATERIALS: Patients were eligible if they had biopsy-proven low- or intermediate-risk prostate adenocarcinoma, one or more focal lesions on MRI, and an MRI-defined total prostate volume of <120 mL. All patients received SBRT delivered to the entire prostate to a dose of 36.25 Gy in 5 fractions with an SIB to the lesions seen on MRI to 40 Gy in 5 fractions. Late toxicity was defined as any possible treatment-related adverse event occurring after 3 months from the completion of SBRT. Patient-reported quality of life was ascertained using standardized patient surveys. RESULTS: A total of 26 patients were enrolled. Six patients (23.1%) had low-risk disease and 20 patients had intermediate-risk disease (76.9%). Seven patients (26.9%) received androgen deprivation therapy. Median follow-up was 59.5 months. No biochemical failures were observed. Three patients (11.5%) experienced late grade 2 genitourinary (GU) toxicity requiring cystoscopy, and 7 patients (26.9%) had late grade 2 GU toxicity requiring oral medications. Three patients (11.5%) had late grade 2 gastrointestinal toxicity characterized by hematochezia requiring colonoscopy and steroids per rectum. There were no grade 3 or higher toxicity events observed. The patient-reported quality-of-life metrics at the time of last follow-up were not significantly different than the pre-treatment baseline. CONCLUSIONS: The results of this study support that SBRT to the entire prostate to a dose of 36.25 Gy in 5 fractions with focal SIB to 40 Gy in 5 fractions has excellent biochemical control and is not associated with undue late gastrointestinal or GU toxicity or long-term quality of life decrement. Focal dose escalation with an SIB planning approach may be an opportunity to improve biochemical control while limiting dose to nearby organs at risk.

Improving Communication of Peer-Review Conference Outcomes: A Practical Experience.

Purpose: The aim of this work was to describe the design and implementation of a more robust workflow for communicating outcomes from a peer-review chart rounds conference. We also provide information regarding cycle times, plan revisions, and other key metrics that we have observed since initial implementation. Methods and Materials: A multidisciplinary team of stakeholders including physicians, physicists, and dosimetrists developed a revised peer-review workflow that addressed key needs to improve the prior process. Consensus terminology was developed to reduce ambiguity regarding the priority of peer-review outcomes and to clarify expectations of the treating physician in response to peer-review outcomes. A custom workflow software tool was developed to facilitate both upstream and downstream processes from the chart rounds conference. The peer-review outcomes of the chart rounds conference and resulting plan changes for the first 18 months of implementation were summarized. Results: In the first 18 months after implementation of the revised processes, 2294 plans were reviewed, and feedback priority levels assigned. Across all cases with feedback, the median time for the treating attending physician to acknowledge conference comments was 1 day and was within 7 calendar days for 89.1% of cases. Conference feedback was acknowledged within 1 day for 74 of 115 (64.3%) cases with level 2 comments and for 18 of 21 (85.7%) cases with level 3 comments (P = .054). Contours were modified in 13 of 116 (11%) cases receiving level 2 feedback and 10 of 21 (48%) cases receiving level 3 feedback (P < .001). The treatment plan was revised in 18 of 116 (16%) cases receiving level 2 feedback and 13 of 21 (61%) cases receiving level 3 feedback (P < .001). Conclusions: We successfully implemented a workflow to improve upstream and downstream processes for a chart rounds conference. Standardizing how peer-review outcomes were communicated and recording physician responses allow for improved ability to monitor conference activities.

Patterns of Failure and Optimal Treatment Paradigm for Large, Inoperable, Node-Negative Non-small Cell Lung Cancer.

OBJECTIVES: The ideal non-operative treatment for patients with large, node-negative non-small cell lung cancer (NSCLC) is poorly defined. To inform optimal treatment paradigms for this cohort, we examined patterns of failure and the impact of radiation therapy (RT) and chemotherapy receipt. MATERIALS AND METHODS: Node-negative NSCLC patients with 5+ cm primary tumors receiving definitive RT at our institution were identified. Sites of initial progression were analyzed. Local progression, regional/distant progression, progression-free survival, and overall survival were analyzed via cumulative incidence function and Kaplan-Meier. Associations between local vs. regional/distant progression with treatment and clinicopathologic variables were assessed via univariable and multivariable competing risks regression. RESULTS AND CONCLUSION: We identified 88 patients for analysis. Among patients with recurrent disease (N = 36), initial patterns of failure analysis showed that isolated distant (27.8%) and isolated regional progression (22.2%) were most common. Distant or regional failure as a component of initial failure was seen in 88.9% of patients who progressed, while isolated local failure was uncommon (11.1%). Univariable and multivariable competing risks regression showed that receipt of SBRT was associated with reduced risk of local progression (HR 0.23, P = .012), and receipt of chemotherapy was associated with reduced risk of regional/distant progression (HR 0.12, P = .040). In conclusion, patients with large, node-negative NSCLC treated with definitive RT are at high risk of regional and distant progression. SBRT correlates with a reduced risk of local failure while chemotherapy is associated with reduced regional/distant progression in this patient population. Ideal treatment may include SBRT when feasible with appropriate systemic therapy.

Stereotactic body radiation therapy with simultaneous integrated boost for prostate cancer: does MRI-targeted biopsy alter the boost field?

INTRODUCTION: We aim to investigate if the addition of MRI-US fusion biopsy (FB) can aid in radiation planning and alter the boost field in cases of stereotactic body radiation therapy (SBRT) for prostate cancer with a simultaneous integrated boost (SIB) to a magnetic resonance imaging (MRI)-defined intraprostatic lesion. MATERIALS AND METHODS: Patients undergoing SBRT with SIB for biopsy-proven prostatic adenocarcinoma and a pre-radiation MRI were retrospectively reviewed. 36.25 Gy in 5 fractions was delivered to entire prostate along with SIB of 40 Gy to an MRI-defined intraprostatic lesion. Demographic, radiation planning details, and post-procedural outcomes were compared between patients undergoing systematic transrectal ultrasound (TRUS) biopsy followed by MRI to those undergoing an MRI followed by a FB prior to radiation planning. RESULTS: Forty-three patients underwent systematic TRUS biopsy followed by MRI and 46 patients underwent FB prior to radiation planning. Patients undergoing systematic TRUS biopsy had a smaller prostate volume when compared to the FB cohort (37.58 ± 13.78 versus 50.28 ± 26.76 cc, p = 0.007). No differences in prostate planning target volume (PTVprostate) and boost volume (PTVboost) were noted, but those undergoing TRUS biopsy prior to MRI had a higher integrated boost volume density (IBVD = PTVboost/total prostate volume) (0.16 ± 0.09 versus 0.13 ± 0.06, p = 0.045). No differences were observed in genitourinary or gastrointestinal toxicity rates. CONCLUSIONS: Compared to systematic TRUS biopsy, implementation of prebiopsy prostate MRI and FB allows for safe and feasible SBRT in patients with significantly larger prostate volumes without increasing SIB cancer-directed treatment volumes, oncologic outcomes, quality of life measures, or treatment-related toxicities.

A Holographic Augmented Reality Guidance System for Patient Alignment: A Feasibility Study.

Purpose To evaluate the accuracy of an augmented reality holographic guidance system for potential use in patient alignment in radiotherapy applications. Methods A cubic phantom was scanned on a CT simulator and a 3D mesh was extracted using the Eclipse Scripting API. An application was created for the Microsoft HoloLens to allow users to see the scanned mesh as a hologram overlaid in the treatment vault. Six therapists were equipped with the HoloLens glasses and instructed to move the real phantom to align with the perceived spatial hologram using only couch controls. The initial couch coordinates were recorded and then recorded at each step as the therapist moved the phantom to each new location. The application varied the position of the virtual phantom to 10 preprogrammed locations within a 40-cm cubic volume in a combination of vertical, longitudinal, and lateral axis shifts. The absolute position difference between the holographic world and real-world phantom was recorded at each step. Also, the relative position from one position to the next was recorded. Results Fifty shifts were collected across the six therapists. The mean difference between the physical position and instructed holographic position was 0.58 ± 0.31 cm for relative shifts and 0.51 ± 0.33 cm for absolute position. The maximum difference between the holographic position and the actual post shift position was 1.53 cm for relative and 1.58 cm for absolute. Conclusion Holographic augmented reality guidance using the Microsoft HoloLens provides adequate accuracy for initial treatment alignment but lacks the fine alignment accuracy of X-ray imaging systems.

Transition From Manual to Automated Planning and Delivery of Volumetric Modulated Arc Therapy Stereotactic Radiosurgery: Clinical, Dosimetric, and Quality Assurance Results.

PURPOSE: Properly planned single isocenter volumetric modulated arc therapy (VMAT) radiosurgery plans exhibit high quality and efficiency. We report here the largest clinical experience to date, to our knowledge, comparing manual planning with a new automated platform designed to standardize and simplify radiosurgery planning and delivery processes. METHODS: We treated 693 patients with single isocenter VMAT radiosurgical plans generated by either our conventional manual (mVMAT) or a recently implemented automated (HyperArcTM) technique. All plans targeted the gross tumor volume without margin. Radiochromic film was used for patient-specific quality assurance (PSQA). We evaluated local control and toxicity data for a subgroup of 107 patients having 377 metastatic tumors that were treated with HyperArc. RESULTS: The median Radiation Therapy Oncology Group (RTOG) conformity index was 1.14 and was not different between the 2 techniques. The median Paddick gradient index was 5.42 for HyperArc versus 7.09 for mVMAT (P < .001). The median mean brain doses were 4.6% and 5.1% for HyperArc and mVMAT, respectively (P = .04). The PSQA for both techniques met clinical criteria, but 97% of the HyperArc plans satisfied the gamma tolerance limit recommended by the American Association of Physicists in Medicine Task Group No. 218, compared with 94% of the mVMAT plans (P = .02). The median treatment-planning times were not significantly different. The median treatment times were 10.5 and 11.4 minutes for HyperArc and mVMAT, respectively (P < .001). The Kaplan-Meier estimate of local control was 90.1% at 1 year. CONCLUSIONS: HyperArc produces high-quality radiosurgical plans that are at least as good as mVMAT plans created by an expert manual planner with easier planning and more efficient delivery workflow. A less experienced planner can produce very high-quality radiosurgical plans even for patients with more than 10 targets. The use of a single-isocenter technique for multiple targets with no PTV margin did not compromise clinical outcomes, and 1-year local control for treated targets remained congruent with historical series.

Accuracy of dose-volume metric calculation for small-volume radiosurgery targets.

PURPOSE: For stereotactic radiosurgery (SRS), accurate evaluation of dose-volume metrics for small structures is necessary. The purpose of this study was to compare the DVH metric capabilities of five commercially available SRS DVH analysis tools (Eclipse, Elements, Raystation, MIM, and Velocity). METHODS: DICOM RTdose and RTstructure set files created using MATLAB were imported and evaluated in each of the tools. Each structure set consisted of 50 randomly placed spherical targets. The dose distributions were created on a 1-mm grid using an analytic model such that the dose-volume metrics of the spheres were known. Structure sets were created for 3, 5, 7, 10, 15, and 20 mm diameter spheres. The reported structure volume, V100% [cc], and V50% [cc], and the RTOG conformity index and Paddick Gradient Index, were compared with the analytical values. RESULTS: The average difference and range across all evaluated target sizes for the reported structure volume was - 4.73%[-33.2,0.2], 0.11%[-10.9, 9.5], -0.39%[-12.1, 7.0], -2.24%[-21.0, 1.3], and 1.15%[-15.1,0.8], for TPS-A through TPS-E, respectively. The average difference and range for the V100%[cc] (V20Gy[cc]) was - 0.4[-24.5,9.8], -2.73[-23.6, 1.1], -3.01[-23.6, 0.6], -3.79[-27.3, 1.3], and 0.26[-6.1,2.6] for TPS-A through TPS-E, respectively. For V50%[cc](V10Gy[cc]) in TPS-A through TPS-E the average and ranger were - 0.05[-0.8,0.4], -0.18[-1.2, 0.5], -0.44[-1.4, 0.3], -0.26[-1.8, 2.6], and 0.09[-1.4,2.7]. CONCLUSION: This study expanded on the previously published literature to quantitatively compare the DVH analysis capabilities of software commonly used for SRS plan evaluation and provides freely available and downloadable analytically derived set of ground truth DICOM dose and structure files for the use of radiotherapy clinics. The differences between systems highlight the need for standardization and/or transparency between systems, especially when evaluating plan quality for multi-institutional clinical trials.

Technical Note: Use of automation to eliminate shift errors.

PURPOSE: To create automated tools within the treatment planning system (TPS) that eliminate the common error pathway of providing incorrect shift instructions to therapists. MATERIALS/METHODS: Two scripts were created within the TPS using the Eclipse API (Varian Medical Systems, Palo Alto, CA). One script detects whether or not the user origin has been placed correctly at the intersection of the simulation markers while the other calculates a shift instruction sheet that can be printed for treatment. RESULTS: Analysis of our RO-ILS database identified eight errors caused by improper setting of the user origin in the treatment planning system. The user origin script flagged all of the treatment plans for markers inconsistent with user origin. Automated calculation of shifts eliminated the error pathway of miscalculating or transcribing shift values. CONCLUSION: Automation can eliminate the common error pathway of providing the wrong shifts to therapists. The scripts have been made available as open-source software for implementation at other radiotherapy clinics.

Using a whiteboard web application for tracking treatment workflow metrics for dosimetrists and physicians.

We present a framework for collecting data which elucidates detailed clinical flow timelines for different treatment sites, modalities, planners, and physicians in radiotherapy treatments. A web based tool, the Whiteboard, was developed which allows communication between the physicians and staff about the current state of the radiotherapy treatment plan and provides detailed time data for each stage of the patient's journey from simulation to treatment. Detailed timestamped data was collected over a period of 6 years which included 22 discrete steps of the treatment planning process. Whiteboard data was combined with data in the treatment planning database Aria (Varian Medical Systems, Palo Alto, CA) using the Eclipse Scripting API to include treatment plan information. Over 6 years, 110,477 patient statuses were time-logged for 9683 courses of treatment using our Whiteboard software, which allowed determination of patient volumes per individual and the time to perform planning tasks. The mean planning volume per dosimetrist was 375.8 ± 142.4 plans and 71.03 ± 27.10 plan revisions per year. The mean planning volume per physician was 218.9 ± 110.8 plan approvals with 41.55 ± 43.73 plan revisions per year. Physician contour time was a mean of 79.59 ± 84.61 hours, but varied greatly by diagnosis category and physician. The longest median modality planning time of 119.6 hours was for the IMRT plans with 8 or more fields. The shortest median times were 48.25, 49.53, and 50.98 hours for plans with 5, 4, and 3 fields, respectively. We demonstrated a framework that could help facilities in staff planning and aid in workload distribution, and could be used to improve understanding of radiotherapy timelines for patients, payers, and other institutions involved in radiotherapy processes.

Technical Note: An open source solution for improving TG-263 compliance.

PURPOSE: Compliance with TG-263 nomenclature standards can be challenging. We introduce an open source solution to this problem and evaluate its impact on compliance within our institution. MATERIALS/METHODS: The TG-236 nomenclature standards were implemented in our clinic in two phases. In phase 1, we deployed TG-263 compliant templates for each disease site. In phase 2, we developed and deployed a script for evaluating compliance which presented errors to the user. After each phase the compliance was recorded. RESULTS: Mean compliance errors prior to phase 1 was 31.8% ± 17.4%. Error rates dropped to 8.1% ± 12.2% across phase 1 and dropped further to 2.2% ± 6.9% during the automation system deployed in phase 2. CONCLUSION: Both structure templates and automation scripts are very useful for increasing compliance with structure naming standards. Our software solution is made available on GitHub for other institutions to implement.

Stereotactic radiosurgery with MLC-defined arcs: Verification of dosimetry, spatial accuracy, and end-to-end tests.

PURPOSE: To measure dosimetric and spatial accuracy of stereotactic radiosurgery (SRS) delivered to targets as small as the trigeminal nerve (TN) using a standard external beam treatment planning system (TPS) and multileaf collimator-(MLC) equipped linear accelerator without cones or other special attachments or modifications. METHODS: Dosimetric performance was assessed by comparing computed dose distributions to film measurements. Comparisons included the γ-index, beam profiles, isodose lines, maximum dose, and spatial accuracy. Initially, single static 360° arcs of MLC-shaped fields ranging from 1.6 × 5 to 30 × 30 mm2 were planned and delivered to an in-house built block phantom having approximate dimensions of a human head. The phantom was equipped with markings that allowed accurate setup using planar kV images. Couch walkout during multiple-arc treatments was investigated by tracking a ball pointer, initially positioned at cone beam computed tomography (CBCT) isocenter, as the couch was rotated. Tracks were mapped with no load and a 90 kg stack of plastic plates simulating patient treatment. The dosimetric effect of walkout was assessed computationally by comparing test plans that corrected for walkout to plans that neglected walkout. The plans involved nine 160° arcs of 2.4 × 5 mm2 fields applied at six different couch angles. For end-to-end tests that included CT simulation, target contouring, planning, and delivery, a cylindrical phantom mimicking a 3 mm lesion was constructed and irradiated with the nine-arc regimen. The phantom, lacking markings as setup aids was positioned under CBCT guidance by registering its surface and internal structures with CTs from simulation. Radiochromic film passing through the target center was inserted parallel to the coronal and the sagittal plane for assessment of spatial and dosimetric accuracy. RESULTS: In the single-arc block phantom tests computed maximum doses of all field sizes agreed with measurements within 2.4 ± 2.0%. Profile widths at 50% maximum agreed within 0.2 mm. The largest targeting error was 0.33 mm. The γ-index (3%, 1 mm) averaged over 10 experiments was >1 in only 1% of pixels for field sizes up to 10 × 10 mm2 and rose to 4.4% as field size increased to 20 × 20 mm2 . Table walkout was not affected by load. Walkout shifted the target up to 0.6 mm from CBCT isocenter but, according to computations shifted the dose cloud of the nine-arc plan by only 0.16 mm. Film measurements verified the small dosimetric effect of walkout, allowing walkout to be neglected during planning and treatment. In the end-to-end tests average and maximum targeting errors were 0.30 ± 0.10 and 0.43 mm, respectively. Gamma analysis of coronal and sagittal dose distributions based on a 3%/0.3 mm agreement remained <1 at all pixels. To date, more than 50 functional SRS treatments using MLC-shaped static field arcs have been delivered. CONCLUSION: Stereotactic radiosurgery (SRS) can be planned and delivered on a standard linac without cones or other modifications with better than 0.5 mm spatial and 5% dosimetric accuracy.

Assessing the feasibility of single target radiosurgery quality assurance with portal dosimetry.

PURPOSE: To assess the feasibility of using portal dosimetry (PD) for pre-treatment quality assurance of single target, flattening filter free (FFF), volumetric arc therapy intracranial radiosurgery plans. METHODS: A PD algorithm was created for a 10X FFF beam on a Varian Edge linear accelerator (Varian Inc, Palo Alto, CA, USA). Treatment plans that were previously evaluated with Gafchromic EBT-XD (Ashland, Bridgewater, NJ, USA) film were measured via PD and analyzed with the ARIA Portal Dosimetry workspace. Absolute dose evaluation for film and PD was done by computing the mean dose in the region receiving greater than or equal to 90% of the max dose and comparing to the mean dose in the same region calculated by the treatment planning system (TPS). Gamma analysis with 10% threshold and 3%/2 mm passing criteria was performed on film and portal images. RESULTS: Thirty-six PD verification plans were delivered and analyzed. The average PD to TPS dose was 0.989 ± 0.01 while film to TPS dose was 1.026 ± 0.01. All PD plans passed the gamma analysis with 100% of points having gamma <1. Overall, PD to TPS dose agreement was found to be target size dependent. As target size decreases, PD to TPS dose ratio decreased from 1.004 for targets with diameters between 15-31 mm and 0.978 for targets with diameters less than 15 mm. CONCLUSION: The agreement of PD to TPS mean dose in the high dose region was found to be dependent on target size. Film measurements did not exhibit size dependence. All PD plans passed the 3%/2 mm gamma analysis, but caution should be used when using PD to assess overall dosimetric accuracy of the treatment plan for small targets.

Prostate Stereotactic Body Radiation Therapy With a Focal Simultaneous Integrated Boost: Acute Toxicity and Dosimetry Results From a Prospective Trial.

PURPOSE: This study aimed to report the early toxicity results of a prospective clinical trial of prostate stereotactic body radiation therapy (SBRT) to the entire prostate with a simultaneous integrated boost (SIB) to magnetic resonance imaging (MRI)-defined focal lesions. METHODS AND MATERIALS: Eligible patients included men with biopsy-proven prostate stage T1c to T2c adenocarcinoma, a Gleason score ≤7, and prostate-specific antigen values of ≤20 ng/mL, who had at least 1 focal lesion visible on MRI and a total prostate volume no greater than 120 cm3. SBRT consisted of a dose of 36.25 Gy to the entire prostate with an SIB of 40 Gy to the MRI-defined lesions, delivered in 5 fractions. The primary purpose of the study was to confirm the feasibility of treatment planning/delivery and to estimate the rate of urinary retention requiring placement of a Foley catheter within 90 days of treatment. This study was to be considered successful if urinary retention occurred in no more than 15% of cases, with a planned enrollment of at least 25 patients. RESULTS: A total of 26 men were enrolled, and all underwent SBRT as planned. Twenty patients (77%) had intermediate-risk features, and the remainder were low risk. A treatment plan that met the protocol-defined goals for all cases was developed. Two patients (7.7%) developed acute urinary symptoms that required the temporary placement of a Foley catheter. No grade 3+ toxicity events were observed. CONCLUSIONS: Planning and delivery of prostate SBRT with a whole prostate dose of 36.25 Gy and a focal 40 Gy SIB is feasible. Early follow-up suggests that this treatment is not associated with undue morbidity.

Model for Estimating Power and Downtime Effects on Teletherapy Units in Low-Resource Settings.

PURPOSE: More than 6,500 megavoltage teletherapy units are needed worldwide, many in low-resource settings. Cobalt-60 units or linear accelerators (linacs) can fill this need. We have evaluated machine performance on the basis of patient throughput to provide insight into machine viability under various conditions in such a way that conclusions can be generalized to a vast array of clinical scenarios. MATERIALS AND METHODS: Data from patient treatment plans, peer-reviewed studies, and international organizations were combined to assess the relative patient throughput of linacs and cobalt-60 units that deliver radiotherapy with standard techniques under various power and maintenance support conditions. Data concerning the frequency and duration of power outages and downtime characteristics of the machines were used to model teletherapy operation in low-resource settings. RESULTS: Modeled average daily throughput was decreased for linacs because of lack of power infrastructure and for cobalt-60 units because of limited and decaying source strength. For conformal radiotherapy delivered with multileaf collimators, average daily patient throughput over 8 years of operation was equal for cobalt-60 units and linacs when an average of 1.83 hours of power outage occurred per 10-hour working day. Relative to conformal treatments delivered with multileaf collimators on the respective machines, the use of advanced techniques on linacs decreased throughput between 20% and 32% and, for cobalt machines, the need to manually place blocks reduced throughput up to 37%. CONCLUSION: Our patient throughput data indicate that cobalt-60 units are generally best suited for implementation when machine operation might be 70% or less of total operable time because of power outages or mechanical repair. However, each implementation scenario is unique and requires consideration of all variables affecting implementation.

Subcutaneous adipose tissue characteristics and the risk of biochemical recurrence in men with high-risk prostate cancer.

PURPOSE/OBJECTIVE(S): To assess subcutaneous adipose tissue characteristics by computed tomography (CT) as potential imaging biomarkers predictive of biochemical recurrence in men with high-risk prostate cancer receiving radiotherapy (RT). MATERIALS AND METHODS: This retrospective study included men with high-risk prostate cancer (PSA>20ng/ml, Gleason score ≥8, or clinical extraprostatic extension) treated between 2001 and 2012. All patients received definitive, dose-escalated external beam RT along with a course of neoadjuvant, concurrent, and adjuvant androgen deprivation therapy (ADT). Each patient also had a treatment planning CT that included the L4-L5 vertebral interface and prostate specific antigen (PSA) measurements for at least 2 years following RT. The subcutaneous adipose tissue was contoured on a single axial CT slice at the level of L4-L5. The average CT attenuation, in Hounsfield units (HU), of the structure was calculated and defined as SATHU. SATAREA was defined as the cross-sectional area of the structure (in cm2) that was then normalized by the square of patient height. Biochemical failure (BF) was defined as a PSA rise of 2ng/ml from the nadir. Freedom from BF (FFBF) was calculated from start time of ADT using the Kaplan-Meier method. Estimates of FFBF were stratified by SATHU and SATAREA quartiles. RESULTS: A total of 171 men met the inclusion criteria with a median follow-up of 5.6 years. The mean SATHU (±standard deviation) was -99.2HU (±6.1HU), and the mean SATAREA was 93.2cm2/m2 (±39.4cm2/m2). The 5- and 8-year rates of FFBF across all patients were 81.5% and 73.5%, respectively. Patients in the lowest quartile of SATHU experienced significantly higher FFBF compared to the other quartiles (Q4 vs. Q1, P = 0.017; Q4 vs. Q2, P = 0.045; Q4 vs. Q3, P = 0.044). No other differences in FFBF were observed between quartiles of SATAREA or other quartiles of SATHU. CONCLUSION: Lower subcutaneous adipose tissue density was associated with a lower rate of BF following RT with ADT for men with high-risk prostate cancer. Further research is needed to elucidate the biological underpinnings of this clinical finding and the role adipose tissue plays in modulating oncologic behavior and outcomes.