Dosimetric impact of intrafraction patient motion on MLC-based 3D-conformal spatially fractionated radiation therapy treatment of large and bulky tumors.

PURPOSE: To evaluate the dosimetric impact on spatially fractionated radiation therapy (SFRT) plan quality due to intrafraction patient motion via multi-field MLC-based method for treating large and bulky (≥8 cm) unresectable tumors. METHODS: For large tumors, a cone beam CT-guided 3D conformal MLC-based SFRT method was utilized with 15 Gy prescription. An MLC GTV-fitting algorithm provided 1 cm diameter apertures with a 2 cm center-to-center distance at the isocenter. This generated a highly heterogeneous sieve-like dose distribution within an hour, enabling same-day SFRT treatment. Fifteen previously treated SFRT patients were analyzed (5 head & neck [H&N], 5 chest and lungs, and 5 abdominal and pelvis masses). For each plan, intrafraction motion errors were simulated by incrementally shifting original isocenters of each field in different x-, y-, and z-directions from 1 to 5 mm. The dosimetric metrics analyzed were: peak-to-valley-dose-ratio (PVDR), percentage of GTV receiving 7.5 Gy, GTV mean dose, and maximum dose to organs-at-risk (OARs). RESULTS: For ±1, ±2, ±3, ±4, and ±5 mm isocenter shifts: PVDR dropped by 3.9%, 3.8%, 4.0%, 4.1%, and 5.5% on average respectively. The GTV(V7.5) remained within 0.2%, and the GTV mean dose remained within 3.3% on average, compared to the original plans. The average PVDR drop for 5 mm shifts was 4.2% for H&N cases, 10% for chest and lung, and 2.2% for abdominal and pelvis cases. OAR doses also increased. The maximum dose to the spinal cord increased by up to 17 cGy in H&N plans, mean lung dose (MLD) changed was small for chest/lung, but the bowel dose varied up to 100 cGy for abdominal and pelvis cases. CONCLUSION: Due to tumor size, location, and characteristics of MLC-based SFRT, isocenter shifts of up to ±5 mm in different directions had moderate effects on PVDR for H&N and pelvic tumors and a larger effect on chest tumors. The dosimetric impact on OAR doses depended on the treatment site. Site-specific patient masks, Vac-Lok bags, and proper immobilization devices similar to SBRT/SRT setups should be used to minimize these effects.

Feasibility of a Single-Fraction Stereotactic Dose of 30 Gy to Solitary Lung Lesions on Halcyon.

Purpose We sought to explore the feasibility of using the current co-planar Halcyon ring delivery system (RDS) with a novel multileaf collimator (MLC) aperture shape controller in delivering a single high dose of 30 Gy to solitary lung lesions via stereotactic body radiotherapy (SBRT). Materials and methods Thirteen non-small-cell lung cancer (NSCLC) patients previously treated with a single dose of 30 Gy to lung lesions via SBRT on the TrueBeam (6MV-FFF) using non-coplanar volumetric modulated arc therapy (VMAT) arcs were anonymized and replanned onto the Halcyon RDS (6MV-FFF) following RTOG-0915 single-fraction criteria. The Halcyon plans utilized a novel dynamic conformal arc (DCA)-based MLC-fitting approach before VMAT optimization with a user-defined aperture shape controller option. The clinical TrueBeam and Halcyon plans were compared via their protocol compliance, target conformity, gradient index, and dose to organs-at-risk (OAR). Treatment delivery efficacy and accuracy were assessed through end-to-end quality assurance (QA) tests on Halcyon and independent dose verification via in-house Monte Carlo (MC) second-check validation. Results All Halcyon lung SBRT plans met RTOG-0915 protocol's requirements for target coverage, conformity, and gradient indices, and maximum dose 2 cm away from the target (D2cm) while being statistically insignificant (p > 0.05) when compared to clinical TrueBeam plans. Additionally, Halcyon provided a similar dose to OAR except for the ribs, where Halcyon demonstrated a lower maximum dose (15.22 Gy vs 17.01 Gy, p < 0.001). However, Halcyon plans required a higher total monitor unit (8892 MU vs 7413 MU, p < 0.001), resulting in a higher beam modulation factor (2.96 MU/cGy vs 2.47 MU/cGy, p < 0.001) and an increase in beam-on time by a factor of 2.1 (11.11 min vs 5.3 min, p < 0.005). End-to-end QA measurements demonstrate that Halcyon plans were clinically acceptable with an average gamma passing rate of 99.8% for 2%/2mm criteria and independent MC 2nd checks within ±2.86%. Conclusion Our end-to-end testing and validation study demonstrates that by utilizing a DCA-based MLC aperture shape controller before VMAT optimization, Halcyon can be used for delivering a single dose of lung SBRT treatment. However, future improvements of Halcyon RDS are recommended to allow higher output rates, rotational couch corrections, and an integrated intrafraction motion management system that will further enhance Halcyon's capability for site-specific single dosage of SBRT.

Stereotactic radiotherapy of intracranial tumor beds on a ring-mounted Halcyon LINAC.

PURPOSE: This study sought to evaluate the feasibility and efficacy of the Halcyon Ring Delivery System (RDS) for delivering stereotactic radiotherapy (SRT) treatments for intracranial tumors beds. METHODS: Ten previously treated brain SRT patients for 30 Gy in five fractions with non-coplanar HyperArc plans on TrueBeam (6MV-FFF) were replanned on Halcyon (6MV-FFF) using the same number of arcs and Eclipse's AcurosXB dose engine. Plan quality evaluation metrics per SRT protocol included: PTV coverage, GTV dose (minimum and mean), target conformity indices (CI), heterogeneity index (HI), gradient index (GI), maximum dose 2 cm away from the PTV (D2cm), and doses to organs-at-risk (OAR). Additionally, patient-specific quality assurance (QA) results and beam-on-time (BOT) were analyzed. RESULTS: The Halcyon RDS provided highly conformal SRT plans for intracranial tumor beds with similar dose to target. When benchmarked against clinically delivered HyperArc plans, target coverage, CI(s) and HI were statistically similar. The Halcyon plans saw no statistical difference in maximum OAR doses to the brainstem, spinal cord, and cochlea. Due to the machine's coplanar geometry, the Halcyon plans showed a decrease in optic pathway dose (0.75 Gy vs. 2.08 Gy, p = 0.029). Overall, Halcyon's coplanar geometry resulted in a larger GI (3.33 vs. 2.72, p = 0.008) and a larger D2cm (39.59% vs. 29.07%, p < 0.001). In this cohort, multiple cases had the PTV and the optic pathway in the same axial plane. In one such instance, the PTV was <2 cm away from the optic pathway but even at this close proximity OAR, Halcyon still adequately spared the optic pathway. Additionally, the Halcyon's geometry provided slightly larger amount of normal brain dose receiving 24.4 Gy (8.99 cc vs. 7.36 cc) and 28.8 Gy (2.9 cc vs. 2.5 cc), although statistically insignificant. The Halcyon plans achieved similar delivery accuracy, quantified by patient-specific QA results evaluated with a 2%/2 mm gamma criteria (99.42% vs. 99.70%). For both plans, independent Monte Carlo second checks calculation agreed within 1%. Average Halcyon BOT was slightly higher by 0.35 min (p = 0.045), however, due to the one-step patient set-up and verification overall estimated treatment times on Halcyon were lower compared to HyperArc treatments (7.61 min vs. 10.26 min, p < 0.001). CONCLUSIONS: When benchmarked against clinically delivered HyperArc treatments, the Halcyon brain SRT plans provided similar plan quality and delivery accuracy but achieved faster overall treatment times. We have started treating select brain SRT patients on the Halcyon RDS for patients having tumor beds greater than 1 cm in diameter with the closest OAR distance of greater than 2 cm away from the target. We recommend other clinics to consider commissioning SRT treatments on their Halcyon systems-allowing including remote Halcyon-only clinics to provide exceptionally high-quality therapeutic brain SRT treatments to an otherwise underserved patient cohort.

Overview and Recommendations for Prospective Multi-institutional Spatially Fractionated Radiation Therapy Clinical Trials.

PURPOSE: The highly heterogeneous dose delivery of spatially fractionated radiation therapy (SFRT) is a profound departure from standard radiation planning and reporting approaches. Early SFRT studies have shown excellent clinical outcomes. However, prospective multi-institutional clinical trials of SFRT are still lacking. This NRG Oncology/American Association of Physicists in Medicine working group consensus aimed to develop recommendations on dosimetric planning, delivery, and SFRT dose reporting to address this current obstacle toward the design of SFRT clinical trials. METHODS AND MATERIALS: Working groups consisting of radiation oncologists, radiobiologists, and medical physicists with expertise in SFRT were formed in NRG Oncology and the American Association of Physicists in Medicine to investigate the needs and barriers in SFRT clinical trials. RESULTS: Upon reviewing the SFRT technologies and methods, this group identified challenges in several areas, including the availability of SFRT, the lack of treatment planning system support for SFRT, the lack of guidance in the physics and dosimetry of SFRT, the approximated radiobiological modeling of SFRT, and the prescription and combination of SFRT with conventional radiation therapy. CONCLUSIONS: Recognizing these challenges, the group further recommended several areas of improvement for the application of SFRT in cancer treatment, including the creation of clinical practice guidance documents, the improvement of treatment planning system support, the generation of treatment planning and dosimetric index reporting templates, and the development of better radiobiological models through preclinical studies and through conducting multi-institution clinical trials.

Effects of Interfraction Dose Variations of Target and Organs at Risk on Clinical Outcomes in High Dose Rate Brachytherapy for Cervical Cancer.

Meeting dose prescription is critical to control tumors in radiation therapy. Interfraction dose variations (IDVs) from the prescribed dose in high dose rate brachytherapy (HDR) would cause the target dose to deviate from the prescription but their clinical effect has not been widely discussed in the literature. Our previous study found that IDVs followed a left-skewed distribution. The clinical effect of the IDVs in 100 cervical cancer HDR patients will be addressed in this paper. An in-house Monte Carlo (MC) program was used to simulate clinical outcomes by convolving published tumor dose response curves with IDV distributions. The optimal dose and probability of risk-free local control (RFLC) were calculated using the utility model. The IDVs were well-fitted by the left-skewed Beta distribution, which caused a 3.99% decrease in local control probability and a 1.80% increase in treatment failure. Utility with respect to IDV uncertainty increased the RFLC probability by 6.70% and predicted an optimal dose range of 83 Gy-91 Gy EQD2. It was also found that a 10 Gy dose escalation would not affect toxicity. In conclusion, HRCTV IDV uncertainty reduced LC probabilities and increased treatment failure rates. A dose escalation may help mitigate such effects.

Two novel stereotactic radiotherapy methods for locally advanced, previously irradiated head and neck cancers patients.

To determine the feasibility and utility of conebeam CT-guided stereotactic radiotherapy for locally recurrent, previously irradiated head and neck cancer (HNC) patients on the Halcyon, a ring delivery system (RDS). This research aims to quantify plan quality, treatment delivery accuracy, and overall efficacy by comparing against novel clinical TrueBeam HyperArc method. Ten recurrent HNC patients who were treated at our institution on TrueBeam (6MV-FFF) for 3 to 40 Gy in 3 to 5 fractions with noncoplanar HyperArc plans were re-planned on Halcyon (6MV-FFF). These plans were re-planned with the same Acuros-based dose engine. Additionally, we used site-specific full/partial coplanar VMAT arcs. PTV coverage, mean dose to GTV, maximum dose to organs-at-risk (OAR), beam-on time (BOT), and quality assurance (QA) results were investigated and compared. Halcyon provided highly conformal HNC SRT plans with slightly superior mean PTVD99 coverage (96.7% vs 95.5%, p = 0.071), and slightly lower mean GTV dose (37.8 Gy vs 38.2 Gy, p = 0.241) when compared to the HyperArc plans. Differences in plan conformality and maximum dose to OARs were statistically insignificant. Due to Halcyon's coplanar geometry, D2cm was significantly higher (p = 0.001) but Halcyon did result in a reduced normal brain dose by 1 Gy on average and up to 5.2 Gy in some cases. Halcyon provided similar patient-specific QA pass rates with a 2%/2mm gamma criteria (98.2% vs 98.5%) and independent in-house Monte Carlo second check results (97.7% vs 98.2%), suggesting identical treatment delivery accuracy. Halcyon plans resulted in slightly longer beam-on time (3.16 vs 2.30 minutes, p = 0.010), however door-to-door patient time is expected to be <10 minutes. Compared to clinical TrueBeam HyperArc, Halcyon SRT plans provided similar plan quality and treatment delivery accuracy with a potentially faster overall treatment using fully automated patient setup and verification. Rapid delivery of recurrent HNC SRT may reduce intrafraction motion errors while also improving patient compliance and comfort. To provide high-quality of HNC SRT similar to HyperArc, we recommend Halcyon users consider commissioning this novel method. This method will be useful for remote and underserved patient cohorts including Halcyon-only clinics as well.

Development and Quality Assurance of Multileaf Collimator (MLC) Auto-Feathering Junctions for Multi-Isocenter Supine Volumetric Modulated Arc Therapy (VMAT) Craniospinal Axis Irradiation on Halcyon.

Currently, there is a lack of methods and tools that efficiently evaluate the auto-feathering junctions created by multileaf collimator (MLCs) for supine volumetric modulated arc therapy (VMAT) craniospinal irradiation (CSI) plans. We have investigated the feasibility of stitching together multi-isocenter fluence maps to then analyze the feathered junctions for patient-specific quality assurance (QA). Furthermore, we investigated the capability of Halcyon for the treatment of CSI patients. Three patients, who previously underwent VMAT CSI treatment on TrueBeam (6-MV flattening filter-free (FFF)) for 36 Gy in 20 fractions were replanned for Halcyon. A multi-isocenter approach with only translational superior-inferior shifts was used for both platforms. Each isocenter consists of two full arcs with anterior avoidance sectors, ±5° collimator rotations between arcs, and 5-8 cm of overlapping MLC auto-feathering junctions. All plans were QA'd via electronic portal imaging device (EPID) portal dosimetry and analyzed with a gamma criteria of 3%/3 mm. A variety of plan quality metrics were analyzed to evaluate dose distributions to the target, doses to organs at risk (OARs), and integral dose to the patient. A MATLAB script was developed to stitch the calculated and measured fluence maps in order to perform patient-specific QA for the composite fluence. The Halcyon plans provided highly conformal and homogenous dose distributions to the entire CSI target, superior to the clinical TrueBeam plans, while sparing critical organs with significantly lower values of V10Gy and V18Gy by up to 2% and 2.5%, respectively. Qualitative depictions of vertical dose profiles from the stitched DICOM of the entire CSI target for both planned and delivered fluence maps demonstrated equivalency, with slightly lower average pass rates with Halcyon (97%) compared to TrueBeam (99.9%). This approach to stitch multiple measured versus calculated EPID fluence maps has shown to be a feasible and accurate method and will be helpful for comprehensive VMAT CSI QA on both platforms. Further implementation of this script will be used in examining dosimetric impacts of daily patient positioning errors at MLC auto-feathering junctions.

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.

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.

Predicting the effect of indirect cell kill in the treatment of multiple brain metastases via single-isocenter/multitarget volumetric modulated arc therapy stereotactic radiosurgery.

PURPOSE: Due to spatial uncertainty, patient setup errors are of major concern for radiosurgery of multiple brain metastases (m-bm) when using single-isocenter/multitarget (SIMT) volumetric modulated arc therapy (VMAT) techniques. However, recent clinical outcome studies show high rates of tumor local control for SIMT-VMAT. In addition to direct cell kill (DCK), another possible explanation includes the effects of indirect cell kill (ICK) via devascularization for a single dose of 15 Gy or more and by inducing a radiation immune intratumor response. This study quantifies the role of indirect cell death in dosimetric errors as a function of spatial patient setup uncertainty for stereotactic treatments of multiple lesions. MATERIAL AND METHODS: Nine complex patients with 61 total tumors (2-16 tumors/patient) were planned using SIMT-VMAT with geometry similar to HyperArc with a 10MV-FFF beam (2400 MU/min). Isocenter was placed at the geometric center of all tumors. Average gross tumor volume (GTV) and planning target volume (PTV) were 1.1 cc (0.02-11.5) and 1.9 cc (0.11-18.8) with an average distance to isocenter of 5.4 cm (2.2-8.9). The prescription was 20 Gy to each PTV. Plans were recalculated with induced clinically observable patient setup errors [±2 mm, ±2o ] in all six directions. Boolean structures were generated to calculate the effect of DCK via 20 Gy isodose volume (IDV) and ICK via 15 Gy IDV minus the 20 Gy IDV. Contributions of each IDV to the PTV coverage were analyzed along with normal brain toxicity due to the patient setup uncertainty. Induced uncertainty and minimum dose covering the entire PTV were analyzed to determine the maximum tolerable patient setup errors to utilize the ICK effect for radiosurgery of m-bm via SIMT-VMAT. RESULTS: Patient setup errors of 1.3 mm /1.3° in all six directions must be maintained to achieve PTV coverage of the 15 Gy IDV for ICK. Setup errors of ±2 mm/2° showed clinically unacceptable loss of PTV coverage of 29.4 ± 14.6% even accounting the ICK effect. However, no clinically significant effect on normal brain dosimetry was observed. CONCLUSIONS: Radiosurgery of m-bm using SIMT-VMAT treatments have shown positive clinical outcomes even with small residual patient setup errors. These clinical outcomes, while largely due to DCK, may also potentially be due to the ICK. Potential mechanisms, such as devascularization and/or radiation-induced intratumor immune enhancement, should be explored to provide a better understanding of the radiobiological response of stereotactic radiosurgery of m-bm using a SIMT-VMAT plan.

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.