Pit excision with fibrin glue closure versus lateralizing flap procedures in the management of pilonidal sinus disease in adolescents: a 14-year cohort study.

INTRODUCTION: Pilonidal sinus disease (PSD) arises in the hair follicles of the gluteal cleft with many cases occurring during adolescence. Early studies of pit excision with fibrin glue closure (PEF), a minimally invasive procedure for the management of chronic PSD, suggest it is safe and effective with similar results to traditional lateralizing flap procedures (LFP), without the need for extensive tissue excision and associated complications. However, these studies lack large sample sizes and prolonged follow-up. METHODOLOGY: All children undergoing primary operative procedures for chronic PSD from May 2009 to February 2022 received either a PEF or a LFP. Recurrence and complications rates alongside their demographic and disease severity data were compared using statistical and Kaplan-Meier analyses. RESULTS: Seventy-eight children had 33 primary PEF and 45 primary LFP procedures with a median follow-up of 2.21 and 2.52 years, respectively. Demographic and disease severity indicators were similar between groups (p > 0.05). The overall recurrence rate in each cohort was 3% for PEF and 11% for LFP, respectively (p = 0.2346). The all-cause repeat intervention rate was 12% and 49% in the PEF and LFP cohorts, respectively (p = 0.0007). Kaplan-Meier analysis showed a reduction in the requirement of re-operation in the PEF cohort (p = 0.0340). Operative time was significantly decreased in the PEF cohort compared to the LFP cohort (p < 0.0001). Wound dehiscence was significantly decreased in the PEF cohort compared to the LFP cohort (3% vs 31%; p = 0.0026). CONCLUSION: This 14-year study is the largest pediatric-focused cohort utilizing PEF to manage PSD and demonstrated clinically relevant decreases in symptom recurrence alongside significantly decreased rates of complications and further surgical intervention compared to traditional LFP techniques. We conclude that PEF is a viable minimally invasive technique in the management of pediatric PSD.

Effects of Ataxia-Telangiectasia Mutated Variants on Radionecrosis and Local Control After Stereotactic Radiation Surgery for Non-Small Cell Lung Cancer Brain Metastases.

Purpose: Genetic variants affecting the radiation response protein ataxia-telangiectasia mutated (ATM) have been associated with increased adverse effects of radiation but also with improved local control after conventional radiation therapy. However, it is unknown whether ATM variants affect rates of radionecrosis (RN) and local intracranial progression (LIP) after stereotactic radiosurgery (SRS) for brain metastases. Methods and Materials: Patients undergoing an initial course of SRS for non-small cell lung cancer (NSCLC) brain metastases at a single institution were retrospectively identified. Kaplan-Meier estimates were calculated and Cox proportional hazards testing was performed based on ATM variant status. Results: A total of 541 patients completed SRS for brain metastasis secondary to NSCLC, of whom 260 completed molecular profiling. Variants of ATM were identified in 36 cases (13.8%). Among patients who completed molecular profiling, RN incidence was 4.9% (95% CI, 1.6%-8.2%) at 6 months and 9.9% (95% CI, 4.8%-15.0%) at 12 months. Incidence of RN was not significantly increased among patients with ATM variants, with an RN incidence of 5.3% (95% CI, 0.0%-15.3%) at both 6 and 12 months (P = .46). For all patients who completed genomic profiling, LIP was 5.4% (95% CI, 2.4%-8.4%) at 6 months and 9.8% (5.5%-14.1%) at 12 months. A significant improvement in LIP was not detected among patients with ATM variants, with an LIP incidence of 3.1% (0.0%-9.1%) at both 6 and 12 months (P = .26). Although differences according to ATM variant type (pathologic variant or variant of unknown significance) did not reach significance, no patients with ATM pathologic variants experienced LIP. Conclusions: We did not detect significant associations between ATM variant status and RN or LIP after SRS for NSCLC brain metastases. The current data set allows estimation of patient cohort sizes needed to power future investigations to identify genetic variants that associate with significant differences in outcomes after SRS.

A structured FMEA approach to optimizing combinations of plan-specific quality assurance techniques for IMRT and VMAT QA.

BACKGROUND: Many commercial tools are available for plan-specific quality assurance (QA) of radiotherapy plans, with their functionality assessed in isolation. However, multiple QA tools are required to review the full range of potential errors. It is important to assess their effectiveness in combination with each other to look for ways to both streamline the QA process and to make certain that errors of high impact and/or high occurrence are caught before reaching patient treatment. PURPOSE: To develop a structured method to assess the effective risk reduction of combinations of QA methods for IMRT/VMAT treatments. METHODS: First, a structured prospective risk assessment was performed to establish the major failure modes (FMs) of IMRT/VMAT QA, and assign occurrence (O), severity (S), and baseline detectability (BD) rankings to them. The baseline assumed that chart checks and linear accelerator QA was performed, but no plan-specific secondary dose calculation or measurement was done. Second, the detectability of each FM for two secondary dose calculation methods and four plan measurement methods (point-based dose calculation, Monte-Carlo-based dose calculation, 2D fluence-based measurement, 2.5D phantom-based measurement, log file analysis with dose recalculation, and log file analysis combined with MLC QA) was determined. Third, we used a minimum detectability approach in addition to each FM's occurrence and severity to determine the optimal combination of QA methods. We analyzed the cumulative risk priority number of eight combinations of QA methods. The analysis was done on (1) all FMs, (2) FMs with high severity, (3) FMs with high-risk priority numbers (RPN) of O*S*BD, and (4) on FMs with both high severity and high RPN. RESULTS: Our analysis resulted in 54 FMs, including commissioning, planning, data transfer, and linear accelerator failures. 1D secondary dose calculation plus measurement provided a 19%-22% risk reduction from baseline. 1D/3D secondary dose calculation plus log files created a 25%-32% reduction. 3D secondary dose calculation plus measurement resulted in a 27%-34% reduction. 3D secondary dose calculation plus log files with additional machine QA provided the greatest reduction of 31%-42%. CONCLUSION: This novel structured approach to comparing combinations of QA methods will allow us to optimize our procedures, with the goal of detecting all clinically significant FMs. Our results show that log-file QA with 3D dose recalculation and supplemental machine QA provides better risk reduction than measurement-based QA. This work builds evidence to justify reducing or eliminating measurement-based PSQA with an independent 3D dose verification, log-file measurement, and appropriate supplementation of machine QA. The process also highlights FMs that cannot be caught by pre-treatment QA, prompting us to consider future directions for on-treatment QA.

A Genome-Wide Association Study Meta-Analysis of Alpha Angle Suggests Cam-Type Morphology May Be a Specific Feature of Hip Osteoarthritis in Older Adults.

OBJECTIVE: To examine the genetic architecture of cam morphology using alpha angle (AA) as a proxy measure and conduct an AA genome-wide association study (GWAS) followed by Mendelian randomization (MR) to evaluate its causal relationship with hip osteoarthritis (OA). METHODS: Observational analyses examined associations between AA measurements derived from hip dual x-ray absorptiometry (DXA) scans from the UK Biobank study and radiographic hip OA outcomes and subsequent total hip replacement. Following these analyses, an AA GWAS meta-analysis was performed (N = 44,214) using AA measurements previously derived in the Rotterdam Study. Linkage disequilibrium score regression assessed the genetic correlation between AA and hip OA. Genetic associations considered significant (P < 5 × 10-8 ) were used as AA genetic instrument for 2-sample MR analysis. RESULTS: DXA-derived AA showed expected associations between AA and radiographic hip OA (adjusted odds ratio [OR] 1.63 [95% confidence interval (95% CI) 1.58, 1.67]) and between AA and total hip replacement (adjusted hazard ratio 1.45 [95% CI 1.33, 1.59]) in the UK Biobank study cohort. The heritability of AA was 10%, and AA had a moderate genetic correlation with hip OA (rg  = 0.26 [95% CI 0.10, 0.43]). Eight independent genetic signals were associated with AA. Two-sample MR provided weak evidence of causal effects of AA on hip OA risk (inverse variance weighted OR 1.84 [95% CI 1.14, 2.96], P = 0.01). In contrast, genetic predisposition for hip OA had stronger evidence of a causal effect on increased AA (inverse variance weighted ß = 0.09 [95% CI 0.04, 0.13], P = 4.58 × 10-5 ). CONCLUSION: Expected observational associations between AA and related clinical outcomes provided face validity for the DXA-derived AA measurements. Evidence of bidirectional associations between AA and hip OA, particularly for risk of hip OA on AA, suggests that hip shape modeling secondary to a genetic predisposition to hip OA contributes to the well-established relationship between hip OA and cam morphology in older adults.

Brain metastasis as the first and only metastatic relapse site portends worse survival in patients with advanced HER2 + breast cancer.

PURPOSE: Current systemic therapy guidelines for patients with HER2 + breast cancer brain metastases (BCBrM) diverge based on the status of extracranial disease (ECD). An in-depth understanding of the impact of ECD on outcomes in HER2 + BCBrM has never been performed. Our study explores the implications of ECD status on intracranial progression-free survival (iPFS) and overall survival (OS) after first incidence of HER2 + BCBrM and radiation. METHODS: A retrospective analysis was performed of 151 patients diagnosed with initial HER2 + BCBrM who received radiation therapy to the central nervous system (CNS) at Duke between 2008 and 2021. The primary endpoint was iPFS defined as the time from first CNS radiation treatment to intracranial progression or death. OS was defined as the time from first CNS radiation or first metastatic disease to death. Systemic staging scans within 30 days of initial BCBrM defined ECD status as progressive, stable/responding or none (isolated brain relapse). RESULTS: In this cohort, > 70% of patients had controlled ECD with either isolated brain relapse (27%) or stable/responding ECD (44%). OS from initial metastatic disease to death was markedly worse for patients with isolated intracranial relapse (median = 28.4 m) compared to those with progressive or stable/responding ECD (48.8 m and 71.5 m, respectively, p = 0.0028). OS from first CNS radiation to death was significantly worse for patients with progressive ECD (16.9 m) versus stable/responding (36.6 m) or isolated intracranial relapse (28.4 m, p = 0.007). iPFS did not differ statistically based on ECD status. Receipt of systemic therapy after first BCBrM significantly improved iPFS (HR 0.45, 95% CI: 0.25-0.81, p = 0.008) and OS (HR: 0.43 (95% CI: 0.23-0.81); p = 0.001). CONCLUSION: OS in patients with HER2 + isolated BCBrM was inferior to those with concurrent progressive or stable/responding ECD. Studies investigating initiation of brain-penetrable HER2-targeted therapies earlier in the disease course of isolated HER2 + intracranial relapse patients are warranted.

Virtual patient-specific QA with DVH-based metrics.

We demonstrate a virtual pretreatment patient-specific QA (PSQA) procedure that is capable of quantifying dosimetric effect on patient anatomy for both intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). A machine learning prediction model was developed to use linear accelerator parameters derived from the DICOM-RT plan to predict delivery discrepancies at treatment delivery (defined as the difference between trajectory log file and DICOM-RT) and was coupled with an independent Monte Carlo dose calculation algorithm for dosimetric analysis. Machine learning models for IMRT and VMAT were trained and validated using 120 IMRT and 206 VMAT fields of prior patients, with 80% assigned for iterative training and testing, and 20% for post-training validation. Various prediction models were trained and validated, with the final models selected for clinical implementation being a boosted tree and bagged tree for IMRT and VMAT, respectively. After validation, these models were then applied clinically to predict the machine parameters at treatment delivery for 7 IMRT plans from various sites (61 fields) and 10 VMAT multi-target intracranial radiosurgery plans (35 arcs) and compared to the dosimetric effect calculated directly from trajectory log files. Dose indices tracked for targets and organs at risk included dose received by 99%, 95%, and 1% of the volume, mean dose, percent of volume receiving 25%-100% of the prescription dose. The average coefficient of determination (r2 ) when comparing intra-field predicted and actual delivery error was 0.987 ± 0.012 for IMRT and 0.895 ± 0.095 for VMAT, whereas r2 when comparing inter-field predicted versus actual delivery error was 0.982 for IMRT and 0.989 for VMAT. Regarding dosimetric analysis, r2 when comparing predicted versus actual dosimetric changes for all dose indices was 0.966 for IMRT and 0.907 for VMAT. Prediction models can be used to anticipate the dosimetric effect calculated from trajectory files and have potential as a "delivery-free" pretreatment analysis to enhance PSQA.

Outcomes in Patients With 4 to 10 Brain Metastases Treated With Dose-Adapted Single-Isocenter Multitarget Stereotactic Radiosurgery: A Prospective Study.

PURPOSE: To examine the effectiveness and safety of single-isocenter multitarget stereotactic radiosurgery using a volume-adapted dosing strategy in patients with 4 to 10 brain metastases. METHODS AND MATERIALS: Adult patients with 4 to 10 brain metastases were eligible for this prospective trial. The primary endpoint was overall survival. Secondary endpoints were local recurrence, distant brain failure, neurologic death, and rate of adverse events. Exploratory objectives were neurocognition, quality of life, dosimetric data, salvage rate, and radionecrosis. Dose was prescribed in a single fraction per RTOG 90-05 or as 5 Gy × 5 fractions for lesions ≥3 cm diameter, lesions involving critical structures, or single-fraction brain V12Gy >20 mL. RESULTS: Forty patients were treated with median age of 61 years, Karnofsky performance status 90, and 6 brain metastases. Twenty-two patients survived longer than expected from the time of protocol SRS, with 1 living patient who has not reached that milestone. Median overall survival was 8.1 months with a 1-year overall survival of 35.7%. The 1-year local recurrence rate was 5% (10 of 204 of evaluable lesions) in 12.5% (4 of 32) of the patients. Distant brain failure was observed in 19 of 32 patients with a 1-year rate of 35.8%. Grade 1-2 headache was the most common complaint, with no grade 3-5 treatment-related adverse events. Radionecrosis was observed in only 5 lesions, with a 1-year rate of 1.5%. Rate of neurologic death was 20%. Neurocognition and quality of life did not significantly change 3 months after SRS compared with pretreatment. CONCLUSIONS: These results suggest that volume-adapted dosing single-isocenter multitarget stereotactic radiosurgery is an effective and safe treatment for patients with 4 to 10 brain metastases.

Hippocampal Avoidance in Multitarget Radiosurgery.

Brain metastases are a common complication for patients diagnosed with cancer. As stereotactic radiosurgery (SRS) becomes a more prevalent treatment option for patients with many brain metastases, further research is required to better characterize the ability of SRS to treat large numbers of metastases (≥4) and the impact on normal brain tissue and, ultimately, neurocognition and quality of life (QOL). This study serves first as an evaluation of the feasibility of hippocampal avoidance for SRS patients, specifically receiving single-isocenter multitarget treatments (SIMT) planned with volumetric modulated arc therapy (VMAT). Second, this study analyzes the effects of standard-definition (SD) multileaf collimators (MLCs) (5 mm width) on plan quality and hippocampal avoidance. The 40 patients enrolled in this Institutional Review Board (IRB)-approved study had between four and 10 brain metastases and were treated with SIMT using VMAT. From the initial 40 patients, eight hippocampi across seven patients had hippocampal doses exceeding the maximum biologically effective dose (BED) constraint given by RTOG 0933. With the addition of upper constraints in the optimization objectives and one arc angle adjustment in one patient plan, four out of seven patient plans were able to meet the maximum hippocampal BED constraint, avoiding five out of eight total hippocampi at risk. High-definition (HD) MLCs allowed for an average decrease of 29% ± 23% (p = 0.007) in the maximum BED delivered to all eight hippocampi at risk. The ability to meet dose constraints depended on the distance between the hippocampus and the nearest planning target volume (PTV). Meeting the maximum hippocampal BED constraint in re-optimized plans was equally likely with the use of SD-MLCs (five out of eight hippocampi at risk were avoided) but resulted in increased dose to normal tissue volumes (23.67% ± 16.3% increase in V50%[cc] of normal brain tissue, i.e., brain volume subtracted by the total PTV) when compared to the HD-MLC re-optimized plans. Comparing the effects of SD-MLCs on plans not optimized for hippocampal avoidance resulted in increases of 48.2% ± 32.2% (p = 0.0056), 31.5% ± 16.3% (p = 0.024), and 16.7% ± 8.5% (p = 0.022) in V20%[cc], V50%[cc], and V75%[cc], respectively, compared to the use of HD-MLCs. The conformity index changed significantly neither when plans were optimized for hippocampal avoidance nor when SD-MLC leaves were used for treatment. In plans not optimized for hippocampal avoidance, mean hippocampal dose increased with the use of SD-MLCs by 38.0% ± 37.5% (p = 0.01). However, the use of SD-MLCs did not result in an increased number of hippocampi at risk.

Single isocenter SRS using CAVMAT offers improved robustness to commissioning and treatment delivery uncertainty compared to VMAT.

PURPOSE: In this study, we evaluate and compare single isocenter multiple target VMAT (SIMT) and Conformal Arc Informed VMAT (CAVMAT) radiosurgery's sensitivity to uncertainties in dosimetric leaf gap (DLG) and treatment delivery. CAVMAT is a novel planning technique that uses multiple target conformal arcs as the starting point for limited inverse VMAT optimization. METHODS: All VMAT and CAVMAT plans were recalculated with DLG values of 0.4, 0.8, and 1.2 mm. DLG effect on V6Gy [cc], V12Gy [cc], and V16Gy [cc], and target dose was evaluated. Plans were delivered to a Delta4 (ScandiDos, Madison, WI) phantom and gamma analysis performed with varying criteria. Log file analysis was performed to evaluate MLC positional error. Sixteen targets were delivered to a SRS MapCHECK (Sun Nuclear Corp., Melbourne, FL) to evaluate VMAT and CAVMAT's dose difference (DD) as a function of DLG. RESULTS: VMAT's average maximum and minimum target dose sensitivity to DLG was 9.08 ±3.50%/mm and 9.50 ± 3.30%/mm, compared to 3.20 ± 1.60%/mm and 4.72 ± 1.60%/mm for CAVMAT. For VMAT, V6Gy [cc], V12Gy [cc], and V16Gy [cc] sensitivity was 35.83 ± 9.50%/mm, 34.12 ± 6.60%/mm, and 39.23 ± 8.40%/mm. In comparison, CAVMAT's sensitivity was 23.19 ± 4.50%/mm, 22.45 ± 4.40%/mm, and 24.88 ± 4.90%/mm, respectively. Upon delivery to the Delta4 , CAVMAT offered superior dose agreement compared to VMAT. For a 1%/1 mm gamma analysis, VMAT and CAVMAT had a passing rate of 94.53 ± 4.40% and 99.28 ± 1.70%, respectively. CAVMAT was more robust to DLG variation, with the SRS MapCHECK plans yielding an absolute average DD sensitivity of 2.99 ± 1.30%/mm compared to 5.07 ± 1.10%/mm for VMAT. Log files demonstrated minimal differences in MLC positional error for both techniques. CONCLUSIONS: CAVMAT remains robust to delivery uncertainties while offering a target dose sensitivity to DLG less than half that of VMAT, and 65% of that of VMAT for V6Gy [cc], V12Gy [cc], and V16Gy [cc]. The superior dose agreement and reduced sensitivity of CAVMAT to DLG uncertainties indicate promise as a robust alternative to VMAT for SIMT SRS.

A tool for patient-specific prediction of delivery discrepancies in machine parameters using trajectory log files.

PURPOSE: Multileaf collimator (MLC) delivery discrepancy between planned and actual (delivered) positions have detrimental effect on the accuracy of dose distributions for both IMRT and VMAT. In this study, we evaluated the consistency of MLC delivery discrepancies over the course of treatment and over time to verify that a predictive machine learning model would be applicable throughout the course of treatment. Next, the MLC and gantry positions recorded in prior trajectory log files were analyzed to build a machine learning algorithm to predict MLC positional discrepancies during delivery for a new treatment plan. An open source tool was developed and released to predict the MLC positional discrepancies at treatment delivery for any given plan. METHODS: Trajectory log files of 142 IMRT plans and 125 VMAT plans from 9 Varian TrueBeam linear accelerators were collected and analyzed. The consistency of delivery discrepancy over patient-specific quality assurance (QA) and patient treatment deliveries was evaluated. Data were binned by treatment site and machine type to determine their relationship with MLC and gantry angle discrepancies. Motion-related parameters including MLC velocity, MLC acceleration, control point, dose rate, and gravity vector, gantry velocity and gantry acceleration, where applicable, were analyzed to evaluate correlations with MLC and gantry discrepancies. Several regression models, such as simple/multiple linear regression, decision tree, and ensemble method (boosted tree and bagged tree model) were used to develop a machine learning algorithm to predict MLC discrepancy based on MLC motion parameters. RESULTS: MLC discrepancies at patient-specific QA differed from those at patient treatment deliveries by a small (mean = 0.0021 ± 0.0036 mm, P = 0.0089 for IMRT; mean = 0.0010 ± 0.0016 mm, P = 0.0003 for VMAT) but statistically significant amount, likely due to setting the gantry angle to zero for QA in IMRT. MLC motion parameters, MLC velocity and gravity vector, showed significant correlation (P < 0.001) with MLC discrepancy, especially MLC velocity, which had an approximately linear relationship (slope = -0.0027, P < 0.001, R2  = 0.79). Incorporating MLC motion parameters, the final generalized model trained by data from all linear accelerators can predict MLC discrepancy to a high degree of accuracy with high correlation (R2  = 0.86) between predicted and actual MLC discrepancies. The same prediction results were found across different treatment sites and linear accelerators. CONCLUSION: We have developed a machine learning model using trajectory log files to predict the MLC discrepancies during delivery. This model has been a released as a research tool in which a DICOM-RT with predicted MLC positions can be generated using the original DICOM-RT file as input. This tool can be used to simulate radiotherapy treatment delivery and may be useful for studies evaluating plan robustness and dosimetric uncertainties from treatment delivery.

Will artificial intelligence eventually replace psychiatrists?

SUMMARY: The dystopian scenario of an 'artificial intelligence takeover' imagines artificial intelligence (AI) becoming the dominant form of intelligence on Earth, rendering humans redundant. As a society we have become increasingly familiar with AI and robots replacing humans in many tasks, certain jobs and even some areas of medicine, but surely this is not the fate of psychiatry?Here a computational neuroscientist (Janaina Mourão-Miranda) and psychiatrist (Justin Taylor Baker) suggest that psychiatry as a profession is relatively safe, whereas psychiatrists Christian Brown and Giles William Story predict that robots will be taking over the asylum.

Radiosurgery treatment planning using conformal arc informed volumetric modulated arc therapy.

Linac based radiosurgery to multiple metastases is commonly planned with volumetric modulated arc therapy (VMAT) as it effectively achieves high conformality to complex target arrangements. However, as the number of targets increases, VMAT can struggle to block between targets, which can lead to highly modulated and/or nonconformal multi-leaf collimator (MLC) trajectories that unnecessarily irradiation of healthy tissue. In this study we introduce, describe, and evaluate a treatment planning technique called Conformal Arc Informed VMAT (CAVMAT), which aims to reduce the dose to healthy tissue while generating highly conformal treatment plans. CAVMAT is a hybrid technique which combines the conformal MLC trajectories of dynamic conformal arcs with the MLC modulation and versatility of inverse optimization. CAVMAT has 3 main steps. First, targets are assigned to subgroups to maximize MLC blocking between targets. Second, arc weights are optimized to achieve the desired target dose, while minimizing MU variation between arcs. Third, the optimized conformal arc plan serves as the starting point for limited inverse optimization to improve dose conformity to each target. Twenty multifocal VMAT cases were replanned with CAVMAT with 20Gy applied to each target. The total volume receiving 2.5Gy[cm3], 6Gy[cm3], 12Gy[cm3], and 16Gy[cm3], conformity index, treatment delivery time, and the total MU were used to compare the VMAT and CAVMAT plans. In addition, CAVMAT was compared to a broad range of planning strategies from various institutions (108 linear accelerator based plans, 14 plans using other modalities) for a 5-target case utilized in a recent plan challenge. For the linear accelerator-based plans, a plan complexity metric based on aperture opening area and perimeter, total monitor units (MU), and MU for a given aperture opening was utilized in the plan challenge scoring algorithm to compare the submitted plans to CAVMAT. After re-planning the 20 VMAT cases, CAVMAT reduced the average V2.5Gy[cm3] by 25.25 ± 19.23%, V6Gy[cm3] by 13.68 ± 18.97%, V12Gy[cm3] by 11.40 ± 19.44%, and V16Gy[cm3] by 6.38 ± 19.11%. CAVMAT improved conformity by 3.81 ± 7.57%, while maintaining comparable target dose. MU for the CAVMAT plans increased by 24.35 ± 24.66%, leading to an increased treatment time of 2 minutes. For the plan challenge case, CAVMAT was 1 of 12 linac based plans that met all plan challenge scoring criteria. Compared to the average submitted VMAT plan, CAVMAT increased the V10%Gy[%] of healthy tissue (Brain-PTV) by roughly 3.42%, but in doing so was able to reduce the V25%Gy[%] by roughly 3.73%, while also reducing V50%Gy[%], V75%Gy[%], and V100%Gy[%]. The CAVMAT technique successfully eliminated insufficient MLC blocking between targets prior to the inverse optimization, leading to less complex treatment plans and improved tissue sparing. Tissue sparing, improved conformity, and decreased plan complexity at the cost of slight increase in treatment delivery time indicates CAVMAT to be a promising method to treat brain metastases.

On the use of trajectory log files for machine & patient specific QA.

Purpose:Trajectory log files are increasingly being utilized clinically for machine and patient specific QA. The process of converting the DICOM-RT plan to a deliverable trajectory by the linac control software introduces some uncertainty that is inherently incorporated into measurement-based patient specific QA but is not necessarily included for trajectory log file-based methods. Roughly half of prior studies have included this uncertainty in the analysis while the remaining studies have ignored it, and it has yet to be quantified in the literature.Methods:We collected DICOM-RT files from the treatment planning system and the trajectory log files from four TrueBeam linear accelerators for 25 IMRT and 10 VMAT plans. We quantified the DICOM-RT Conversion to Trajectory Residual (DCTR, difference between 'planned' MLC position from TPS DICOM-RT file and 'expected' MLC position (the deliverable MLC positions calculated by the linac control software) from trajectory log file) and compared it to the discrepancy between actual and expected machine parameters recorded in trajectory log files.Results:RMS of the DCTR was 0.0845 mm (range of RMS per field/arc: 0.0173-0.1825 mm) for 35 plans (114 fields/arcs) and was independent of treatment technique, with a maximum observed discrepancy at any control point of 0.7255 mm. DCTR was correlated with MLC velocity and was consistent over the course of treatment and over time, with a slight change in magnitude observed after a linac software upgrade. For comparison, the RMS of trajectory log file reported delivery error for moving MLCs was 0.0205 mm, thus DCTR is about four times the recorded delivery error in the trajectory log file.Conclusion:The uncertainty introduced from the conversion process by the linac control software from DICOM-RT plan to a deliverable trajectory is 3-4 times larger than the discrepancy between actual and expected machine parameters recorded in trajectory log files. This uncertainty should be incorporated into the analysis when using trajectory log file-based methods for analyzing MLC performance or patient-specific QA.

The effect of MLC leaf width in single-isocenter multi-target radiosurgery with volumetric modulated arc therapy.

PURPOSE: Single-isocenter multi-target (SIMT) volumetric modulated arc therapy (VMAT) is primarily limited to linear accelerators utilizing 2.5 mm leaf width MLCs. We explore feasibility of applying this technique to linear accelerators utilizing MLCs with leaf width of 5 mm. METHODS: Twenty patients with 3-10 intracranial brain metastases originally treated with 2.5 mm MLCs were re-planned using 5 mm MLCs and relevant dosimetric indices were compared. We also evaluated various strategies of adding VMAT arcs to mitigate degradations of dose quality values. RESULTS: Wider MLCs caused small changes in total MUs (5827 ± 2334 vs 5572 ± 2220, p = 0.006), and conformity index (CI) (2.22% ± 0.05%, p = 0.045), but produced more substantial increases in brain V30%[%] and V50%[%] (27.75% ± 0.16% and 20.04% ± 0.13% respectively, p < 0.001 for both), and V12Gy[cc] (16.91% ± 0.12%, p < 0.001). CONCLUSION: SIMT radiosurgery delivered via VMAT using 5 mm wide MLCs can achieve similar CI compared to that using 2.5 mm leaf width MLCs but with moderately increased isodose spill, which can be only partially mitigated by increasing the number of VMAT arcs.

The effect of setup uncertainty on optimal dosimetric margin in LINAC-based stereotactic radiosurgery with dynamic conformal arc technique.

PURPOSE: To estimate the combined effect of setup uncertainty on optimal dosimetric margin by analyzing the dose distribution and biological effect in LINAC-based stereotactic radiosurgery (SRS) with dynamic conformal arc (DCA) technique. METHODS: SRS treatment plans were generated from CT scans of the Rando head phantom using four non-coplanar DCA's with total 480-degrees of arc. A single spherical planning target volume (PTV) of 4 different diameters was placed at the center of the phantom to simulate brain lesions. For each PTV, 5 treatment plans were created using identical dose calculation parameters, each with 5 different dosimetric margins. To simulate the effect of setup uncertainty, the isocenter for each plan was shifted to 13 different positions. A marginal dose of 20Gy in a single fraction with 6MV photon beam was prescribed to 49 different percentage isodose surfaces (%IDS). The plan quality was evaluated using Conformity Index (CI), Gradient Index (GI), EUD-based Tumor Control Probability (TCP), Normal Tissue Complication Probability (NTCP), and uncomplicated biological objective function (TCP x (1-NTCP) =p+). RESULTS: A +1mm dosimetric margin could result in a much higher p+ compared to 0mm and 1mm dosimetric margins and a smaller GI while achieving an equivalent p+ in a certain range of %IDS compared to +2mm and +3mm dosimetric margins. With 2mm setup error and +1mm dosimetric margin, the %IDS range optimized for each PTV is: around 80%IDS (10mm diameter); 63~70%IDS (20mm diameter); 66~79%IDS (30mm diameter). CONCLUSION: This simulation study identified the preferred prescription %IDS for a given setup error and dosimetric margin to achieve an optimal dose distribution and favorable biological effect.

An interprojection sensor fusion approach to estimate blocked projection signal in synchronized moving grid-based CBCT system.

PURPOSE: A preobject grid can reduce and correct scatter in cone beam computed tomography (CBCT). However, half of the signal in each projection is blocked by the grid. A synchronized moving grid (SMOG) has been proposed to acquire two complimentary projections at each gantry position and merge them into one complete projection. That approach, however, suffers from increased scanning time and the technical difficulty of accurately merging the two projections per gantry angle. Herein, the authors present a new SMOG approach which acquires a single projection per gantry angle, with complimentary grid patterns for any two adjacent projections, and use an interprojection sensor fusion (IPSF) technique to estimate the blocked signal in each projection. The method may have the additional benefit of reduced imaging dose due to the grid blocking half of the incident radiation. METHODS: The IPSF considers multiple paired observations from two adjacent gantry angles as approximations of the blocked signal and uses a weighted least square regression of these observations to finally determine the blocked signal. The method was first tested with a simulated SMOG on a head phantom. The signal to noise ratio (SNR), which represents the difference of the recovered CBCT image to the original image without the SMOG, was used to evaluate the ability of the IPSF in recovering the missing signal. The IPSF approach was then tested using a Catphan phantom on a prototype SMOG assembly installed in a bench top CBCT system. RESULTS: In the simulated SMOG experiment, the SNRs were increased from 15.1 and 12.7 dB to 35.6 and 28.9 dB comparing with a conventional interpolation method (inpainting method) for a projection and the reconstructed 3D image, respectively, suggesting that IPSF successfully recovered most of blocked signal. In the prototype SMOG experiment, the authors have successfully reconstructed a CBCT image using the IPSF-SMOG approach. The detailed geometric features in the Catphan phantom were mostly recovered according to visual evaluation. The scatter related artifacts, such as cupping artifacts, were almost completely removed. CONCLUSIONS: The IPSF-SMOG is promising in reducing scatter artifacts and improving image quality while reducing radiation dose.

Scatter Reduction and Correction for Dual-Source Cone-Beam CT Using Prepatient Grids.

PURPOSE: Scatter significantly limits the application of the dual-source cone-beam computed tomography by inducing scatter artifacts and degrading contrast-to-noise ratio, Hounsfield-unit accuracy, and image uniformity. Although our previously developed interleaved acquisition mode addressed the cross scatter between the 2 X-ray sources, it doubles the scanning time and doesn't address the forward scatter issue. This study aims to develop a prepatient grid system to address both forward scatter and cross scatter in the dual-source cone-beam computed tomography. METHODS: Grids attached to both X-ray sources provide physical scatter reduction during the image acquisition. Image data were measured in the unblocked region, while both forward scatter and cross scatter were measured in the blocked region of the projection for postscan scatter correction. Complementary projections were acquired with grids at complementary locations and were merged to form complete projections for reconstruction. Experiments were conducted with different phantom sizes, grid blocking ratios, image acquisition modes, and reconstruction algorithms to investigate their effects on the scatter reduction and correction. The image quality improvement by the prepatient grids was evaluated both qualitatively through the artifact reduction and quantitatively through contrast-to-noise ratio, Hounsfield-unit accuracy, and uniformity using a CATphan 504 phantom. RESULTS: Scatter artifacts were reduced by scatter reduction and were removed by scatter correction method. Contrast-to-noise ratio, Hounsfield-unit accuracy, and image uniformity were improved substantially. The simultaneous acquisition mode achieved comparable contrast-to-noise ratio as the interleaved and sequential modes after scatter reduction and correction. Higher grid blocking ratio and smaller phantom size led to higher contrast-to-noise ratio for the simultaneous mode. The iterative reconstruction with total variation regularization was more effective than the Feldkamp, Davis, and Kress method in reducing noise caused by the scatter correction to enhance contrast-to-noise ratio. CONCLUSION: The prepatient grid system is effective in removing the scatter effects in the simultaneous acquisition mode of the dual-source cone-beam computed tomography, which is useful for scanning time reduction or dual energy imaging.

Onboard functional and molecular imaging: a design investigation for robotic multipinhole SPECT.

PURPOSE: Onboard imaging-currently performed primarily by x-ray transmission modalities-is essential in modern radiation therapy. As radiation therapy moves toward personalized medicine, molecular imaging, which views individual gene expression, may also be important onboard. Nuclear medicine methods, such as single photon emission computed tomography (SPECT), are premier modalities for molecular imaging. The purpose of this study is to investigate a robotic multipinhole approach to onboard SPECT. METHODS: Computer-aided design (CAD) studies were performed to assess the feasibility of maneuvering a robotic SPECT system about a patient in position for radiation therapy. In order to obtain fast, high-quality SPECT images, a 49-pinhole SPECT camera was designed which provides high sensitivity to photons emitted from an imaging region of interest. This multipinhole system was investigated by computer-simulation studies. Seventeen hot spots 10 and 7 mm in diameter were placed in the breast region of a supine female phantom. Hot spot activity concentration was six times that of background. For the 49-pinhole camera and a reference, more conventional, broad field-of-view (FOV) SPECT system, projection data were computer simulated for 4-min scans and SPECT images were reconstructed. Hot-spot localization was evaluated using a nonprewhitening forced-choice numerical observer. RESULTS: The CAD simulation studies found that robots could maneuver SPECT cameras about patients in position for radiation therapy. In the imaging studies, most hot spots were apparent in the 49-pinhole images. Average localization errors for 10-mm- and 7-mm-diameter hot spots were 0.4 and 1.7 mm, respectively, for the 49-pinhole system, and 3.1 and 5.7 mm, respectively, for the reference broad-FOV system. CONCLUSIONS: A robot could maneuver a multipinhole SPECT system about a patient in position for radiation therapy. The system could provide onboard functional and molecular imaging with 4-min scan times.

A dual cone-beam CT system for image guided radiotherapy: initial performance characterization.

PURPOSE: The purpose of this study is to evaluate the performance of a recently developed benchtop dual cone-beam computed tomography (CBCT) system with two orthogonally placed tube∕detector sets. METHODS: The benchtop dual CBCT system consists of two orthogonally placed 40 × 30 cm flat-panel detectors and two conventional x-ray tubes with two individual high-voltage generators sharing the same rotational axis. The x-ray source to detector distance is 150 cm and x-ray source to rotational axis distance is 100 cm for both subsystems. The objects are scanned through 200° of rotation. The dual CBCT system utilized 110° of projection data from one detector and 90° from the other while the two individual single CBCTs utilized 200° data from each detector. The system performance was characterized in terms of uniformity, contrast, spatial resolution, noise power spectrum, and CT number linearity. The uniformities, within the axial slice and along the longitudinal direction, and noise power spectrum were assessed by scanning a water bucket; the contrast and CT number linearity were measured using the Catphan phantom; and the spatial resolution was evaluated using a tungsten wire phantom. A skull phantom and a ham were also scanned to provide qualitative evaluation of high- and low-contrast resolution. Each measurement was compared between dual and single CBCT systems. RESULTS: Compared to single CBCT, the dual CBCT presented: (1) a decrease in uniformity by 1.9% in axial view and 1.1% in the longitudinal view, as averaged for four energies (80, 100, 125, and 150 kVp); (2) comparable or slightly better contrast (0∼25 HU) for low-contrast objects and comparable contrast for high-contrast objects; (3) comparable spatial resolution; (4) comparable CT number linearity with R(2) ≥ 0.99 for all four tested energies; (5) lower noise power spectrum in magnitude. Dual CBCT images of the skull phantom and the ham demonstrated both high-contrast resolution and good soft-tissue contrast. CONCLUSIONS: The performance of a benchtop dual CBCT imaging system has been characterized and is comparable to that of a single CBCT.

Interleaved acquisition for cross scatter avoidance in dual cone-beam CT.

PURPOSE: Cone-beam x-ray imaging with flat panel detectors is used for target localization in image guided radiation therapy. This imaging includes cone-beam computed tomography (CBCT) and planar imaging. Use of two orthogonal x-ray systems could reduce imaging time for CBCT, provide simultaneous orthogonal views in planar imaging, facilitate dual-energy methods, and be useful in alleviating cone-beam artifacts by providing two axially offset focal-spot trajectories. However, the potential advantages of a second cone-beam system come at the cost of cross scatter, i.e., scatter of photons originating from one tube into the noncorresponding detector. Herein, cross scatter is characterized for dual cone-beam imaging, and a method for avoiding cross scatter is proposed and evaluated. METHODS: A prototype dual-source CBCT system has been developed that models the geometry of a gantry-mounted kV imaging device used in radiation therapy. Cross scatter was characterized from 70 to 145 kVp in projections and reconstructed images using this system and three cylindrical phantoms (15, 20, and 30 cm) with a common Catphan core. A novel strategy for avoiding cross scatter in dual CBCT was developed that utilized interleaved data acquisition on each imaging chain. Interleaving, while maintaining similar angular sampling, can be achieved by either doubling the data acquisition rate or, as presented herein, halving the rotation speed. RESULTS: The ratio of cross scatter to the total detected signal was found to be as high as 0.59 in a 30 cm diameter phantom. The measured scatter-to-primary ratio in some cases exceeded 4. In the 30 cm phantom, reconstructed contrast was reduced across all ROIs by an average of 48.7% when cross scatter was present. These cross-scatter degradations were almost entirely avoided by the method of interleaved exposures. CONCLUSIONS: Cross scatter is substantial in dual cone-beam imaging, but its effects can be largely removed by interleaved acquisition, which can be achieved at the same angular sampling rate either by doubling the data acquisition rate or halving the rotation speed.