Microcanonical treatment of HCl dissociative chemisorption on Au(111): Reactive dampening through inefficient translational energy coupling and an active surface.

Microcanonical unimolecular rate theory is applied to Shirhatti and Wodtke's recent supersonic molecular beam experiments examining the activated dissociative chemisorption of HCl on Au(111). A precursor mediated microcanonical trapping (PMMT) model (where the surface vibrates and HCl rotations, vibration, and translation directed along the surface normal are treated as active degrees of freedom) gave dissociative sticking coefficient predictions that are several orders of magnitude higher than experimental values but in good accord with prior quantum and molecular dynamics simulations. Density functional theory (DFT) electronic structure calculations using the Perdew-Burke-Ernzerhof (PBE) functional served to fix the vibrational frequencies of the reactive transition state and the threshold energy for dissociation, E0 = 72.9 kJ/mol. To explore the possibilities of varying threshold energy, coupling to phonons, and dynamics, a three-parameter [E0, s, ɛn] dynamically biased (d-) PMMT model was fit to the experiments. A dynamical bias was introduced using an efficiency, ɛn, of normal translational energy to contribute to the active exchangeable energy capable of promoting reactivity. To achieve the low sticking probabilities observed in experiment, severe normal translational energy dampening (ɛn → 0.26) was imposed, leading to a large vibrational efficacy of ηv = εv/εn = 3.85. The optimal threshold energy for dissociation was E0 = 30.88 kJ/mol, some 40 kJ/mol below the PBE-DFT prediction, and the optimal number of Au surface oscillators was s = 1. The d-PMMT modeling indicates that HCl/Au(111) reactivity can be consistent with electronically adiabatic passage across a relatively low and late transition state that dynamically disfavors normal translational energy.

Contour subregion error detection methodology using deep learning auto-segmentation.

BACKGROUND: Inaccurate manual organ delineation is one of the high-risk failure modes in radiation treatment. Numerous automated contour quality assurance (QA) systems have been developed to assess contour acceptability; however, manual inspection of flagged cases is a time-consuming and challenging process, and can lead to users overlooking the exact error location. PURPOSE: Our aim is to develop and validate a contour QA system that can effectively detect and visualize subregional contour errors, both qualitatively and quantitatively. METHODS/MATERIALS: A novel contour subregion error detection (CSED) system was developed using subregional surface distance discrepancies between manual and deep learning auto-segmentation (DLAS) contours. A validation study was conducted using a head and neck public dataset containing 339 cases and evaluated according to knowledge-based pass criteria derived from a clinical training dataset of 60 cases. A blind qualitative evaluation was conducted, comparing the results from the CSED system with manual labels. Subsequently, the CSED-flagged cases were re-examined by a radiation oncologist. RESULTS: The CSED system could visualize the diverse types of subregional contour errors qualitatively and quantitatively. In the validation dataset, the CSED system resulted in true positive rates (TPR) of 0.814, 0.800, and 0.771; false positive rates (FPR) of 0.310, 0.267, and 0.298; and accuracies of 0.735, 0.759, and 0.730, for brainstem and left and right parotid contours, respectively. The CSED-assisted manual review caught 13 brainstem, 19 left parotid, and 21 right parotid contour errors missed by conventional human review. The TPR/FPR/accuracy of the CSED-assisted manual review improved to 0.836/0.253/0.784, 0.831/0.171/0.830, and 0.808/0.193/0.807 for each structure, respectively. Further, the time savings achieved through CSED-assisted review improved by 75%, with the time for review taking 24.81 ± 12.84, 26.75 ± 10.41, and 28.71 ± 13.72 s for each structure, respectively. CONCLUSIONS: The CSED system enables qualitative and quantitative detection, localization, and visualization of manual segmentation subregional errors utilizing DLAS contours as references. The use of this system has been shown to help reduce the risk of high-risk failure modes resulting from inaccurate organ segmentation.

How much rotational error is clinically acceptable for single-isocenter/two-lesion lung SBRT treatment on halcyon ring delivery system (RDS)?

PURPOSE: SBRT treatment of two separate lung lesions via single-isocenter/multi-target (SIMT) plan on Halcyon RDS could improve patient comfort, compliance, patient throughput, and clinic efficiency. However, aligning two separate lung lesions synchronously via a single pre-treatment CBCT scan on Halcyon can be difficult due to rotational patient setup errors. Thus, to quantify the dosimetric impact, we simulated loss of target(s) coverage due to small, yet clinically observable rotational patient setup errors on Halcyon for SIMT treatments. METHODS: Seventeen previously treated 4D-CT based SIMT lung SBRT patients with two separate lesions (total 34 lesions, 50 Gy in five fractions to each lesion) on TrueBeam (6MV-FFF) were re-planned on Halcyon (6MV-FFF) using a similar arc geometry (except couch rotation), dose engine (AcurosXB algorithm), and treatment planning objectives. Rotational patient setup errors of [± 0.5° to ± 3.0°] on Halcyon were simulated via Velocity registration software in all three rotation axes and recalculated dose distributions in Eclipse treatment planning system. Dosimetric impact of rotational errors was evaluated for target coverage and organs at risk (OAR). RESULTS: Average PTV volume and distance to isocenter were 23.7 cc and 6.1 cm. Average change in Paddick's conformity indexes were less than -5%, -10%, and -15% for 1°, 2°, and 3°, respectively for yaw, roll, and pitch rotation directions. Maximum drop off of PTV(D100%) coverage for 2° rotation was -2.0% (yaw), -2.2% (roll), and -2.5% (pitch). With ±1° rotational error, no PTV(D100%) loss was found. Due to anatomical complexity: irregular and highly variable tumor sizes and locations, highly heterogenous dose distribution, and steep dose gradient, no trend for loss of target(s) coverage as a function of distance to isocenter and PTV size was found. Change in maximum dose to OAR were acceptable per NRG-BR001 within ±1.0° rotation, but were up to 5 Gy higher to heart with 2° in the pitch rotation axis. CONCLUSION: Our clinically realistic simulation results show that rotational patient setup errors up to 1.0° in any rotation axis could be acceptable for selected two separate lung lesions SBRT patients on Halcyon. Multivariable data analysis in large cohort is ongoing to fully characterize Halcyon RDS for synchronous SIMT lung SBRT.

Benchmarking halcyon ring delivery system for hypofractionated breast radiotherapy: Validation and clinical implementation of the fast-forward trial.

PURPOSE: The aim of this study was to demonstrate the feasibility and efficacy of an iterative CBCT-guided breast radiotherapy with Fast-Forward trial of 26 Gy in five fractions on a Halcyon Linac. This study quantifies Halcyon plan quality, treatment delivery accuracy and efficacy by comparison with those of clinical TrueBeam plans. MATERIALS AND METHODS: Ten accelerated partial breast irradiation (APBI) patients (four right, six left) who underwent Fast-Forward trial at our institute on TrueBeam (6MV beam) were re-planned on Halcyon (6MV-FFF). Three site-specific partial coplanar VMAT arcs and an Acuros-based dose engine were used. For benchmarking, PTV coverage, organs-at-risk (OAR) doses, beam-on time, and quality assurance (QA) results were compared for both plans. RESULTS: The average PTV was 806 cc. Compared to TrueBeam plans, Halcyon provided highly conformal and homogeneous plans with similar mean PTVD95 (25.72  vs. 25.73 Gy), both global maximum hotspot < 110% (p = 0.954) and similar mean GTV dose (27.04  vs. 26.80 Gy, p = 0.093). Halcyon provided lower volume of ipsilateral lung receiving 8 Gy (6.34% vs. 8.18%, p = 0.021), similar heart V1.5 Gy (16.75% vs. 16.92%, p = 0.872), V7Gy (0% vs. 0%), mean heart dose (0.96  vs. 0.9 Gy, p = 0.228), lower maximum dose to contralateral breast (3.2  vs. 3.6 Gy, p = 0.174), and nipple (19.6  vs. 20.1 Gy, p = 0.363). Compared to TrueBeam, Halcyon plans provided similar patient-specific QA pass rates and independent in-house Monte Carlo second check results of 99.6% vs. 97.9% (3%/2 mm gamma criteria) and 98.6% versus 99.2%, respectively, suggesting similar treatment delivery accuracy. Halcyon provided shorter beam-on time (1.49  vs. 1.68 min, p = 0.036). CONCLUSION: Compared to the SBRT-dedicated TrueBeam, Halcyon VMAT plans provided similar plan quality and treatment delivery accuracy, yet potentially faster treatment via one-step patient setup and verification with no patient collision issues. Rapid delivery of daily APBI on Fast-Forward trial on Halcyon with door-to-door patient time < 10 min, could reduce intrafraction motion errors, and improve patient comfort and compliance. We have started treating APBI on Halcyon. Clinical follow-up results are warranted. We recommend Halcyon users consider implementing the protocol to remote and underserved APBI patients in Halcyon-only clinics.

The spatial accuracy of ring-mounted halcyon linac versus C-arm TrueBeam linac for single-isocenter/multi-target SBRT treatment.

Stereotactic body radiotherapy (SBRT) treatment of oligometastatic lesions via single-isocenter/multi-target (SIMT) plan is more efficient than using multi-isocenter/multitarget SBRT. This study quantifies the spatial positioning accuracy of 2 commercially available LINAC systems for SIMT treatment pertaining to the potential amplification of error as a function of the target's distance-to-isocenter. We compare the Ring-Gantry Halcyon LINAC equipped with the fast iterative conebeam-CT (iCBCT) for image-guided SIMT treatment, and the SBRT-dedicated C-Arm TrueBeam with standard pretreatment CBCT imaging. For both systems, Sun Nuclear's MultiMet Winston-Lutz Cube phantom with 6 metallic BBs distributed at different planes up to 7 cm away from the isocenter was used. The phantom was aligned and imaged via CBCT, and then couch corrections were applied. To treat all 6 BBs, an Eclipse 10-field 3D-conformal Field-in-Field (2×2 cm2 MLC field to each BB) plan for varying gantry, collimator, and couch (TrueBeam only) positions was developed for both machines with 6MV-FFF beam. The plan was delivered through ARIA once a week. The EPID images were analyzed via Sun Nuclear's software for spatial positioning accuracy. On TrueBeam, the treatment plan was delivered twice: once with 3DoF translational corrections and once with PerfectPitch 6DoF couch corrections. The average 3D spatial positioning accuracy was 0.55 ± 0.30 mm, 0.54 ± 0.24 mm, and 0.56 ± 0.28 mm at isocenter, and 0.59 ± 0.30 mm, 0.69 ± 0.30 mm, and 0.70 ± 0.35 mm at 7 cm distance-to-isocenter for Halcyon, TrueBeam 3DoF, and TrueBeam 6DoF, respectively. This suggests there are no clinically significant deviations of spatial uncertainty between the platforms with the distance-to-isocenter. On both platforms, our weekly independent measurements demonstrated the reproducibility for less than 1.0 mm positional accuracy of off-axis targets up to 7 cm from the isocenter. Due to this, no additional PTV-margin is suggested for lesions within 7 cm of isocenter. This study confirms that Halcyon can deliver similar positional accuracy to SBRT-dedicated TrueBeam to off-axis targets up to 7 cm from isocenter. These results further benchmark the spatial uncertainty of our extensively used SBRT-dedicated TrueBeam LINAC for SIMT SBRT treatments.

Contouring quality assurance methodology based on multiple geometric features against deep learning auto-segmentation.

BACKGROUND: Contouring error is one of the top failure modes in radiation treatment. Multiple efforts have been made to develop tools to automatically detect segmentation errors. Deep learning-based auto-segmentation (DLAS) has been used as a baseline for flagging manual segmentation errors, but those efforts are limited to using only one or two contour comparison metrics. PURPOSE: The purpose of this research is to develop an improved contouring quality assurance system to identify and flag manual contouring errors. METHODS AND MATERIALS: DLAS contours were used as a reference to compare with manually segmented contours. A total of 27 geometric agreement metrics were determined from the comparisons between the two segmentation approaches. Feature selection was performed to optimize the training of a machine learning classification model to identify potential contouring errors. A public dataset with 339 cases was used to train and test the classifier. Four independent classifiers were trained using five-fold cross validation, and the predictions from each classifier were ensembled using soft voting. The trained model was validated on a held-out testing dataset. An additional independent clinical dataset with 60 cases was used to test the generalizability of the model. Model predictions were reviewed by an expert to confirm or reject the findings. RESULTS: The proposed machine learning multiple features (ML-MF) approach outperformed traditional nonmachine-learning-based approaches that are based on only one or two geometric agreement metrics. The machine learning model achieved recall (precision) values of 0.842 (0.899), 0.762 (0.762), 0.727 (0.842), and 0.773 (0.773) for Brainstem, Parotid_L, Parotid_R, and mandible contours, respectively compared to 0.526 (0.909), 0.619 (0.765), 0.682 (0.882), 0.773 (0.568) for an approach based solely on Dice similarity coefficient values. In the external validation dataset, 66.7, 93.3, 94.1, and 58.8% of flagged cases were confirmed to have contouring errors by an expert for Brainstem, Parotid_L, Parotid_R, and mandible contours, respectively. CONCLUSIONS: The proposed ML-MF approach, which includes multiple geometric agreement metrics to flag manual contouring errors, demonstrated superior performance in comparison to traditional methods. This method is easy to implement in clinical practice and can help to reduce the significant time and labor costs associated with manual segmentation and review.

Clinical validation of novel lightning dose optimizer for gamma knife radiosurgery of irregular-shaped arteriovenous malformations and pituitary adenomas.

PURPOSE: To demonstrate the clinical feasibility of a novel treatment planning algorithm via lightning dose optimizer (LDO) on Leksell Gamma Knife (LGK) GammaPlan with significantly faster planning times for stereotactic radiosurgery (SRS) of the complex and difficult arteriovenous malformations (AVMs) and pituitary adenomas. METHODS AND MATERIALS: After completing the in-house end-to-end phantom testing and independent dose verification of the recently upgraded LDO algorithm on GammaPlan using the MD Anderson's IROC anthropomorphic SRS head phantom irradiation credentialing, 20 previously treated GK-SRS patients (10 AVM, average volume 3.61 cm3 and 10 pituitary adenomas, average volume 0.86 cm3 ) who underwent manual forward planning on GammaPlan were retrospectively replanned via LDO. These pathologies were included because of the need for adequate dose delivery with organs at risk in very close proximity. LDO finds the target curvature boundary by well-formulated linear programing objectives and inversely optimizes the GK-SRS plan by isocenter placement, optimization, and sequencing. For identical target coverage, the LDO and original manual plans were compared for target conformity, gradient index, dose to critical organs, and surrounding normal brain. Additionally, various treatment delivery parameters, including beam-on time were recorded. RESULTS: For both patient cohorts, LDO provided similar target coverage with better dose conformity, tighter radiosurgical dose distribution with a lower value of gradient indices (all p < 0.001), and lower dose to critical organs. For AVMs, there was a significant reduction of normal brain V10Gy , V12Gy , and V14Gy by 4.74, 3.67, and 2.67 cm3 (all p < 0.001). LDO had twice the number of shots (p < 0.001), and longer beam-on time (p = 0.012) by a factor of 1.44. For pituitary adenomas, LDO provided systematically lower values of V10Gy , V12Gy , and V14Gy by 1.08, 0.86, and 0.68 cm3 (all p < 0.001), and lower maximum dose to optic pathway by 0.7 Gy (p = 0.005), but had almost twice the numbers of shots (p < 0.001) and increased beam-on time (p = 0.005) by a factor of 1.2. However, for both patient groups, the average planning time for the LDO was <5 min, compared to the estimated 30-90 min of manual planning times. CONCLUSION: GK-SRS treatment on Leksell Perfexion GammaPlan using the LDO provided highly conformal target coverage with a steep dose gradient, spared critical organs, and significantly reduced normal brain dose for complex targets at the cost of slightly higher treatment times. LDO generated high-quality treatment plans and could significantly reduce planning time. If available, the LDO algorithm is suggested for validation and clinical use for complex and difficult GK cases.

Feasibility Study of Stereotactic Radiosurgery Treatment of Glomus Jugulare Tumors via HyperArc VMAT.

This study aims to report on the clinical validation and feasibility of utilizing a novel fully automated treatment planning and delivery system, HyperArc VMAT stereotactic radiosurgery (SRS) for glomus jugulare tumors (GJT). Independent dose verification of the HyperArc module via the MD Anderson's SRS head phantom irradiation and credentialing results showed compliance with the SRS treatment requirements per IROC MD Anderson's standard. Following the Alliance clinical trial, AAPM, RTOG protocols, and QUANTEC requirements, utilizing selected three-partial arc geometry of HyperArc module on TrueBeam Linac with 6MV-FFF beam, GJT SRS plans were generated for nine previously treated Gamma Knife (GK) radiosurgery patients using advanced Acuros-based algorithm to account for tissue inhomogeneity corrections and frameless immobilization with Q-fix mask and Encompass device insert. HyperArc VMAT produced highly conformal SRS dose distributions to GJT, a steep dose gradient around the GJT, and spared adjacent critical organs including the spinal cord (< 3.0 Gy). Due to faster patient setup and less MLC modulation through the target (average beam-on time, 6.2 minutes), the HyperArc VMAT plan can deliver a single high-dose of 18 Gy to the GJT in less than 15 minutes overall treatment time, significantly improving patient comfort and clinic workflow. Pretreatment portal dosimetry quality assurance results and independent dose verification via Monte Carlo-based physics second check met our clinical SRS protocol's requirements for treatment. Due to the highly conformal dose distribution, rapid dose fall-off, excellent sparing of adjacent critical organs, and highly precise and accurate treatment, clinical implementation of frameless HyperArc VMAT for GJT patients who may not have access to nor tolerate frame-based GK SRS treatment are underway.

Conebeam CT-guided 3D MLC-based spatially fractionated radiation therapy for bulky masses.

For fast, safe, and effective management of large and bulky (≥8 cm) non-resectable tumors, we have developed a conebeam CT-guided three-dimensional (3D)-conformal MLC-based spatially fractionated radiation therapy (SFRT) treatment. Using an in-house MLC-fitting algorithm, Millennium 120 leaves were fitted to the gross tumor volume (GTV) generating 1-cm diameter holes at 2-cm center-to-center distance at isocenter. SFRT plans of 15 Gy were generated using four to six coplanar crossfire gantry angles 60° apart with a 90° collimator, differentially weighted with 6- or 10-MV beams. A dose was calculated using AcurosXB algorithm, generating sieve-like dose channels without post-processing the physician-drawn GTV contour within an hour of CT simulation allowing for the same day treatment. In total, 50 extracranial patients have been planned and treated using this method, comprising multiple treatment sites. This novel MLC-fitting algorithm provided excellent dose parameters with mean GTV (V7.5 Gy) and mean GTV doses of 53.2% and 7.9 Gy, respectively, for 15 Gy plans. Average peak-to-valley dose ratio was 3.2. Mean beam-on time was 3.32 min, and treatment time, including patient setup and CBCT to beam-off, was within 15 min. Average 3D couch correction from original skin-markers was <1.0 cm. 3D MLC-based SFRT plans enhanced target dose for bulky masses, including deep-seated large tumors while protecting skin and adjacent critical organs. Additionally, it provides the same day, safe, effective, and convenient treatment by eliminating the risk to therapists and patients from heavy gantry-mounted physical GRID-block-we recommend other centers to use this simple and clinically useful method. This rapid SFRT planning technique is easily adoptable in any radiation oncology clinic by eliminating the need for plan optimization and patient-specific quality assurance times while providing dosimetry information in the treatment planning system. This potentially allows for dose-escalation to deep-seated masses to debulk unresectable large tumors providing an option for neoadjuvant treatment. An outcome study of clinical trial is underway.

HyperArc VMAT stereotactic radiotherapy for locally recurrent previously-irradiated head and neck cancers: Plan quality, treatment delivery accuracy, and efficiency.

PURPOSE: This paper demonstrates the clinical feasibility and efficacy of HyperArc VMAT treatments for locally recurrent, locally advanced, or previously irradiated head and neck cancers treated with stereotactic radiotherapy (SRT). MATERIALS/METHODS: First, an anthropomorphic SRS head phantom from the MD Anderson's IROC credentialing laboratory containing a 1.9 cm diameter spherical target, including in vivo dosimetry system, was imaged, planned, and irradiated (25 Gy in 1 fraction) using HyperArc VMAT with a 6 MV flattening filter free (FFF) beam. Second, RANDO phantom was imaged, planned, and irradiated (35 Gy in 5 fractions) by generating eight HyperArc VMAT plans (4 right, 4 left neck tumors) at different anatomical locations (C1-C4). Average tumor volume was 21.7 cm3 up to 32.3 cm3 . Distance to isocenter from the central marker of the Encompass device down to neck was 25.8 cm up to 28.0 cm and 24.3 cm up to 27.1 cm for left- and right-sided neck tumors, respectively, and 9 cm from both lateral markers defined by the patient protection zone. Third, seven recurrent head and neck cancer patients with 80.3 cm3 tumors on average, and up to 159 cm3 , were imaged, planned, and treated with 30-40 Gy in 5 fractions with HyperArc SRT. Plan quality, treatment delivery accuracy, and efficiency are reported herein. RESULTS: Phantom irradiation results met all the compliance requirements set forth by the IROC for HyperArc SRS treatment. For end-to-end RANDO phantom tests, a highly conformal target dose distribution with 50% isodose fall-off within 5 mm from the surface of the target was obtained. Average beam modulation factor, beam-on-time, and overall treatment time were 2.9, 2.56 min, and 13.96 min with 99.1% pre-treatment quality assurance pass rate for the 2%/2 mm gamma criteria, respectively. Immediately adjacent critical structures, such as the spinal cord (maximum, 3.9 Gy and 0.35 cm3 of cord, 3.7 Gy) and skin (maximum, 10.3 Gy and 10 cm3 of skin, 5.7 Gy), were spared. Similar results were found on the patient's HyperArc VMAT plans including highly conformal target coverage, sharp dose fall-off, and low doses to the adjacent critical organs such as the spinal cord (< 5 Gy). Average perfect pitch couch correction was <1.5 mm and 2° in each direction. Average beam-on-time was approximately 3.21 min and treatments were completed within 15 min. CONCLUSION: For recurrent head and neck SRT treatments, HyperArc VMAT provided highly conformal dose distributions, rapid dose fall-off, excellent sparing of adjacent critical organs, and highly accurate treatments that could be delivered down to the C4 vertebral level. This could potentially allow for delivery of HyperArc SRT to patients with glomus tumors as well to those who may not tolerate frame-based SRS treatment. Clinical follow up of these patients is ongoing to confirm the therapeutic benefits of this novel treatment option.

Feasibility of using ring-mounted Halcyon Linac for single-isocenter/two-lesion lung stereotactic body radiation therapy.

PURPOSE: To demonstrate the plan quality and delivery efficiency of volumetric-modulated arc therapy (VMAT) with the Halcyon Linac ring delivery system (RDS) in the treatment of single-isocenter/two-lesion lung stereotactic body radiation therapy (SBRT). MATERIALS/METHODS: Sixteen previously treated non-coplanar VMAT single-isocenter/two-lesion lung SBRT plans delivered with SBRT-dedicated C-arm TrueBeam Linac were selected. Prescribed dose was 50 Gy to each lesion over five fractions with treatment delivery every other day and AcurosXB algorithm as the final dose calculation algorithm. TrueBeam single-isocenter plans were reoptimized for Halcyon Linac with coplanar geometry. Both TrueBeam and Halcyon plans were normalized for identical combined target coverage and evaluated. Conformity indices (CIs), heterogeneity index (HI), gradient index (GI), gradient distance (GD), and D2cm were compared. The normal lung V5Gy, V10Gy, V20Gy, mean lung dose (MLD), and dose to organs at risk (OAR) were evaluated. Treatment delivery parameters, including beam-on time, were recorded. RESULTS: Halcyon plans were statistically similar to clinically delivered TrueBeam plans. No statistical differences in target conformity, dose heterogeneity, or intermediate-dose spillage were observed (all, p > 0.05). Halcyon plans, on average, demonstrated statistically insignificant reduced maximum dose to most adjacent OAR and normal lung. However, Halcyon yielded statistically significant lower maximal dose to the ribs (p = 0.041) and heart (p = 0.026), dose to 1 cc of ribs (p = 0.035) and dose to 5 cc of esophagus (p = 0.043). Plan complexity slightly increased as seen in the average increase of total monitor units, modulation factor, and beam-on time by 480, 0.48, and 2.78 min, respectively. However, the estimated overall treatment time was reduced by 2.22 min, on average. Mean dose delivery accuracy of clinical TrueBeam plans and the corresponding Halcyon plans was 98.9 ± 0.85% (range: 98.1%-100%) and 98.45 ± 0.99% (range: 97.9%-100%), respectively, demonstrating similar treatment delivery accuracy. CONCLUSION: SBRT treatment of synchronous lung lesions via single-isocenter VMAT on Halcyon RDS is feasible and dosimetrically equivalent to clinically delivered TrueBeam plans. Halcyon provides excellent plan quality and shorter overall treatment time that may improve patient compliance, reduce intrafraction movement, improve clinic efficiency, and potentially offering lung SBRT treatments for underserved patients on a Halcyon only clinic.

Double-vertebral segment SBRT via novel ring-mounted Halcyon Linac: Plan quality, delivery efficiency and accuracy.

To evaluate the plan quality, treatment delivery efficiency, and accuracy of single-isocenter/multi-target (SIMT) volumetric modulated arc therapy (VMAT) of double-vertebral segments stereotactic body radiation therapy (SBRT) on Halcyon ring delivery system (RDS). In-house multi-target end-to-end phantom testing and independent dose verification using the MD Anderson's single-isocenter/multi-target (lung/spine targets) thorax phantom were completed. Six previously treated patients with 2-vertebral segments on thoracic and/or lumber spine were replanned on Halcyon RDS with 6MV-FFF beam using a single-isocenter placed between the vertebral segments. Three full VMAT arcs with 0° and ±10° collimator angles and advanced Acuros-based dose engine for heterogeneity corrections were used. Prescription was 35 Gy in 5 fractions to each vertebral-segment, simultaneously. For comparison, Halcyon VMAT-SBRT plans were retrospectively created on SBRT-dedicated Truebeam with a 6MV-FFF beam using identical planning geometry and optimization objectives. Target coverage, conformity index (CI), heterogeneity index (HI), gradient index (GI), dose to 2-cm away from each target (D2-cm), and dose to adjacent organs-at-risk (OAR) were evaluated per NRG-BR002 protocol. Treatment delivery parameters were evaluated for both plans. In-house phantom measurements showed acceptable spatial accuracy (< 1mm within 5-cm from the isocenter) of conebeam CT-guided Halcyon SBRT treatments. The MD Anderson phantom irradiation credentialing results met IROC requirements for protocol patients. Mean isocenter-to-tumor center distance was 3.3 ± 0.6-cm (range 2.4 to 4.3-cm). Mean combined PTV was 57.3 ± 31.3 cc (range 20.1 to 99.9 cc). Both Halcyon and Truebeam SIMT-VMAT plans met NRG-BR002 compliance criteria and show similar CI, HI, GI, D2-cm. Maximal and volumetric doses to adjacent OAR including dose to partial spinal cord were lower with Halcyon RDS. Average total monitor units, modulation, and overall treatment time were lower with Halcyon plans by 130 MU, 0.2, 3.8 min, respectively, with similar beam-on time. Average pre-treatment patient-specific portal-dosimetry QA results on Halcyon showed a high pass rate of 99.6%, compared to SBRT-dedicated Truebeam pass rate of 96.8%, for 2%/2 mm clinical gamma passing criteria, suggesting more accurate treatment delivery on Halcyon RDS. SBRT treatment of double-vertebral segments via SIMT-VMAT plans on Halcyon for selected patients is feasible and dosimetrically superior to Truebeam Linac. Faster treatment delivery (<10 min) of double-vertebral segment SBRT on Halcyon could reduce patient intolerance due to severe back pain, potentially reduce intra-fraction motion errors, and improve patient throughput, and clinic workflow.

Fast generation of lung SBRT plans with a knowledge-based planning model on ring-mounted Halcyon Linac.

PURPOSE: To demonstrate fast treatment planning feasibility of stereotactic body radiation therapy (SBRT) for centrally located lung tumors on Halcyon Linac via a previously validated knowledge-based planning (KBP) model to support offline adaptive radiotherapy. MATERIALS/METHODS: Twenty previously treated non-coplanar volumetric-modulated arc therapy (VMAT) lung SBRT plans (c-Truebeam) on SBRT-dedicated C-arm Truebeam Linac were selected. Patients received 50 Gy in five fractions. c-Truebeam plans were re-optimized for Halcyon manually (m-Halcyon) and with KBP model (k-Halcyon). Both m-Halcyon and k-Halcyon plans were normalized for identical or better target coverage than clinical c-Truebeam plans and compared for target conformity, dose heterogeneity, dose fall-off, and dose tolerances to the organs-at-risk (OAR). Treatment delivery parameters and planning times were evaluated. RESULTS: k-Halcyon plans were dosimetrically similar or better than m-Halcyon and c-Truebeam plans. k-Halcyon and m-Halcyon plan comparisons are presented with respect to c-Truebeam. Differences in conformity index were statistically insignificant in k-Halcyon and on average 0.02 higher (p = 0.04) in m-Halcyon plans. Gradient index was on average 0.43 (p = 0.006) lower and 0.27 (p = 0.02) higher for k-Halcyon and m-Halcyon, respectively. Maximal dose 2 cm away in any direction from target was statistically insignificant. k-Halcyon increased maximal target dose on average by 2.9 Gy (p < 0.001). Mean lung dose was on average reduced by 0.10 Gy (p = 0.004) in k-Halcyon and increased by 0.14 Gy (p < 0.001) in m-Halcyon plans. k-Halcyon plans lowered bronchial tree dose on average by 1.2 Gy. Beam-on-time (BOT) was increased by 2.85 and 1.67 min, on average for k-Halcyon and m-Halcyon, respectively. k-Halcyon plans were generated in under 30 min compared to estimated dedicated 180 ± 30 min for m-Halcyon or c-Truebeam plan. CONCLUSION: k-Halcyon plans were generated in under 30 min with excellent plan quality. This adaptable KBP model supports high-volume clinics in the expansion or transfer of lung SBRT patients to Halcyon.

Gamma Knife Radiosurgery to Four Brainstem Lesions After Whole Brain Radiation Therapy.

Our patient was a 58-year-old female with a history of extensive stage small cell lung cancer initially diagnosed in November 2018. She received palliative radiation to the right hip and whole brain in December of 2018 and then received chemotherapy. Unfortunately, in October 2019, the repeat brain magnetic resonance imaging (MRI) showed recurrent lesions and she was referred for Gamma Knife Radiosurgery (GKRS). At the time of the treatment, she was found to have four brainstem lesions as well as a left frontal lobe and a right frontal lobe lesion. She completed GKRS to all six lesions without any neurological complications seen in her short-term follow-up. This case report adds to the growing body of literature showing safety of GKRS for multiple brainstem lesions.

Dose Summation Strategies for External Beam Radiation Therapy and Brachytherapy in Gynecologic Malignancy: A Review from the NRG Oncology and NCTN Medical Physics Subcommittees.

Definitive, nonsurgical management of gynecologic malignancies involves external beam radiation therapy (EBRT) and/or brachytherapy (BT). Summation of the cumulative dose is critical to assess the total biologic effective dose to targets and organs at risk. Cumulative dose calculation from EBRT and BT can be performed with or without image registration (IR) and biologic dose summation. Among these dose summation strategies, linear addition of dose-volume histogram (DVH) parameters without IR is the global standard for composite dose reporting. This approach stems from an era without image guidance and simple external beam and brachytherapy treatment approaches. With technological advances, EBRT and high-dose-rate BT have evolved to allow for volume-based treatment planning and delivery. Modern conformal therapeutic radiation involves volumetric or intensity modulated EBRT, capable of simultaneously treating multiple targets at different specified dose levels. Therefore, given the complexity of modern radiation treatment, the linear addition of DVH parameters from EBRT and high-dose-rate BT is challenging to represent the combined dose distribution. Deformable image registration (DIR) between EBRT and image guided brachytherapy (IGBT) data sets may provide a more nuanced calculation of multimodal dose accumulation. However, DIR is still nascent in this regard, and needs further development for accuracy and efficiency for clinical use. Biologic dose summation can combine physical dose maps from EBRT and each IGBT fraction, thereby generating a composite DVH from the biologic effective dose. However, accurate radiobiologic parameters are tissue-dependent and not well characterized. A combination of voxel-based DIR and biologic weighted dose maps may be the best approximation of dose accumulation but remains invalidated. The purpose of this report is to review dose summation strategies for EBRT and BT, including conventional equivalent dose in 2-Gy fractions dose summation without image registration, physical dose summation using 3-dimensional rigid IR and DIR, and biologic dose summation. We also provide general clinical workflows for IGBT with a focus on cervical cancer.

A novel restricted single-isocenter stereotactic body radiotherapy (RESIST) method for synchronous multiple lung lesions to minimize setup uncertainties.

Treating multiple lung lesions synchronously using a single-isocenter volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) plan can improve treatment efficiency and patient compliance. However, due to set up uncertainty, aligning multiple lung tumors on a single daily cone beam CT (CBCT) image has shown clinically unacceptable loss of target(s) coverage. Herein, we propose a Restricted Single-Isocenter Stereotactic Body Radiotherapy (RESIST), an alternative treatment that mitigates patient setup uncertainties. Twenty-one patients with two lung lesions were treated with single-isocenter VMAT-SBRT using a 6MV-FFF beam to 54 Gy in 3 fractions (n = 7) or 50 Gy in 5 fractions (n = 14) prescribed to 70-80% isodose line. To minimize setup uncertainties, each plan was re-planned using the RESIST method, utilizing a single-isocenter placed at the patient's mediastinum. It allows for an individual plan to be created for each tumor, using the first plan as the base-dose for the second plan, while still allowing both tumors to be treated in the same session. The technique uses novel features in Eclipse, including dynamic conformal arc (DCA)-based dose and aperture shape controller before each VMAT optimization. RESIST plans provided better target dose conformity (p < 0.001) and gradient indices (p < 0.001) and lower dose to adjacent critical organs. Using RESIST to treat synchronous lung lesions with VMAT-SBRT significantly reduces plan complexity as demonstrated by smaller beam modulation factors (p < 0.001), without unreasonably increasing treatment time. RESIST reduces the chance of a geometric miss due by allowing CBCT matching of one tumor at a time. Placement of isocenter at the mediastinum avoids potential patient/gantry collisions, provides greater flexibility of noncoplanar arcs and eliminates the need for multiple couch movements during CBCT imaging. Efficacy of RESIST has been demonstrated for two lesions and can potentially be used for more lesions. Clinical implementation of this technique is ongoing.

Automation and integration of a novel restricted single-isocenter stereotactic body radiotherapy (a-RESIST) method for synchronous two lung lesions.

Synchronous treatment of two lung lesions using a single-isocenter volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) plan can decrease treatment time and reduce the impact of intrafraction motion. However, alignment of both lesions on a single cone beam CT (CBCT) can prove difficult and may lead to setup errors and unacceptable target coverage loss. A Restricted Single-Isocenter Stereotactic Body Radiotherapy (RESIST) method was created to minimize setup uncertainties and provide treatment delivery flexibility. RESIST utilizes a single-isocenter placed at patient's midline and allows both lesions to be planned separately but treated in the same session. Herein is described a process of automation of this novel RESIST method. Automation of RESIST significantly reduced treatment planning time while maintaining the benefits of RESIST. To demonstrate feasibility, ten patients with two lung lesions previously treated with a single-isocenter clinical VMAT plan were replanned manually with RESIST (m-RESIST) and with automated RESIST (a-RESIST). a-RESIST method automatically sets isocenter, creates beam geometry, chooses appropriate dose calculation algorithms, and performs VMAT optimization using an in-house trained knowledge-based planning model for lung SBRT. Both m-RESIST and a-RESIST showed lower dose to normal tissues compared to manually planned clinical VMAT although a-RESIST provided slightly inferior, but still clinically acceptable, dose conformity and gradient indices. However, a-RESIST significantly reduced the treatment planning time to less than 20 min and provided a higher dose to the lung tumors. The a-RESIST method provides guidance for inexperienced planners by standardizing beam geometry and plan optimization using DVH estimates. It produces clinically acceptable two lesions VMAT lung SBRT plans efficiently. We have further validated a-RESIST on phantom measurement and independent pretreatment dose verification of another four selected 2-lesions lung SBRT patients and implemented clinically. Further development of a-RESIST for more than two lung lesions and refining this approach for extracranial oligometastastic abdominal/pelvic SBRT, including development of automated simulated collision detection algorithm, merits future investigation.

Radiopharmaceutical Validation for Clinical Use.

Radiopharmaceuticals are reemerging as attractive anticancer agents, but there are no universally adopted guidelines or standardized procedures for evaluating agent validity before early-phase trial implementation. To validate a radiopharmaceutical, it is desirous for the radiopharmaceutical to be specific, selective, and deliverable against tumors of a given, molecularly defined cancer for which it is intended to treat. In this article, we discuss four levels of evidence-target antigen immunohistochemistry, in vitro and in vivo preclinical experiments, animal biodistribution and dosimetry studies, and first-in-human microdose biodistribution studies-that might be used to justify oncology therapeutic radiopharmaceuticals in a drug-development sequence involving early-phase trials. We discuss common practices for validating radiopharmaceuticals for clinical use, everyday pitfalls, and commonplace operationalizing steps for radiopharmaceutical early-phase trials. We anticipate in the near-term that radiopharmaceutical trials will become a larger proportion of the National Cancer Institute Cancer Therapy Evaluation Program (CTEP) portfolio.

Risk of target coverage loss for stereotactic body radiotherapy treatment of synchronous lung lesions via single-isocenter volumetric modulated arc therapy.

Treating multiple lung lesions synchronously via single-isocenter volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) improves treatment efficiency and patient compliance. However, aligning multiple lung tumors accurately on single pretreatment cone beam CTs (CBCTs) can be problematic. Tumors misaligned could lead to target coverage loss. To quantify this potential target coverage loss due to small, clinically realistic setup errors, a novel simulation method was developed. This method was used on 26 previously treated patients with two metastatic lung lesions. Patients were treated with 4D CT-based, highly conformal noncoplanar VMAT plans (clinical VMAT) with 6MV-flattening filter free (FFF) beam using AcurosXB dose calculation algorithm with heterogeneity corrections. A single isocenter was placed approximately between the lesions to improve patient convenience and clinic workflow. Average isocenter to tumor distance was 5.9 cm. Prescription dose was 54 Gy/50 Gy in 3/5 fractions. For comparison, a plan summation (simulated VMAT) was executed utilizing randomly simulated, clinically relevant setup errors, obtained from pretreatment setup, per treatment fraction, in Eclipse treatment planning system for each of the six degrees of freedom within ± 5.0 mm and ± 2°. Simulations yielded average deviations of 27.4% (up to 72% loss) (P < 0.001) from planned target coverage when treating multiple lung lesions using a single-isocenter plan. The largest deviations from planned coverage and desired biological effective dose (BED10, with α/ß = 10 Gy) were seen for the smallest targets (<10 cc), some of which received < 100 Gy BED10. Patient misalignment resulted in substantial decrease in conformity and increase in the gradient index, violating major characteristics of SBRT. Statistically insignificant differences were seen for normal tissue dose. Although, clinical follow-up of these patients is ongoing, the authors recommend an alternative treatment planning strategy to minimize the probability of a geometric miss when treating small lung lesions synchronously with single-isocenter VMAT SBRT plans.