Pencil Beam Scanning Proton Bragg Peak Conformal FLASH in Prostate Cancer Stereotactic Body Radiotherapy.

Bragg peak FLASH radiotherapy (RT) uses a distal tracking method to eliminate exit doses and can achieve superior OAR sparing. This study explores the application of this novel method in stereotactic body radiotherapy prostate FLASH-RT. An in-house platform was developed to enable intensity-modulated proton therapy (IMPT) planning using a single-energy Bragg peak distal tracking method. The patients involved in the study were previously treated with proton stereotactic body radiotherapy (SBRT) using the pencil beam scanning (PBS) technique to 40 Gy in five fractions. FLASH plans were optimized using a four-beam arrangement to generate a dose distribution similar to the conventional opposing beams. All of the beams had a small angle of two degrees from the lateral direction to increase the dosimetry quality. Dose metrics were compared between the conventional PBS and the Bragg peak FLASH plans. The dose rate histogram (DRVH) and FLASH metrics of 40 Gy/s coverage (V40Gy/s) were investigated for the Bragg peak plans. There was no significant difference between the clinical and Bragg peak plans in rectum, bladder, femur heads, large bowel, and penile bulb dose metrics, except for Dmax. For the CTV, the FLASH plans resulted in a higher Dmax than the clinical plans (116.9% vs. 103.3%). For the rectum, the V40Gy/s reached 94% and 93% for 1 Gy dose thresholds in composite and single-field evaluations, respectively. Additionally, the FLASH ratio reached close to 100% after the application of the 5 Gy threshold in composite dose rate assessment. In conclusion, the Bragg peak distal tracking method can yield comparable plan quality in most OARs while preserving sufficient FLASH dose rate coverage, demonstrating that the ultra-high dose technique can be applied in prostate FLASH SBRT.

Setup Uncertainty of Pediatric Brain Tumor Patients Receiving Proton Therapy: A Prospective Study.

This study quantifies setup uncertainty in brain tumor patients who received image-guided proton therapy. Patients analyzed include 165 children, adolescents, and young adults (median age at radiotherapy: 9 years (range: 10 months to 24 years); 80 anesthetized and 85 awake) enrolled in a single-institution prospective study from 2020 to 2023. Cone-beam computed tomography (CBCT) was performed daily to calculate and correct manual setup errors, once per course after setup correction to measure residual errors, and weekly after treatments to assess intrafractional motion. Orthogonal radiographs were acquired consecutively with CBCT for paired comparisons of 40 patients. Translational and rotational errors were converted from 6 degrees of freedom to a scalar by a statistical approach that considers the distance from the target to the isocenter. The 95th percentile of setup uncertainty was reduced by daily CBCT from 10 mm (manual positioning) to 1-1.5 mm (after correction) and increased to 2 mm by the end of fractional treatment. A larger variation existed between the roll corrections reported by radiographs vs. CBCT than for pitch and yaw, while there was no statistically significant difference in translational variation. A quantile mixed regression model showed that the 95th percentile of intrafractional motion was 0.40 mm lower for anesthetized patients (p=0.0016). Considering additional uncertainty in radiation-imaging isocentricity, the commonly used total plan robustness of 3 mm against positional uncertainty would be appropriate for our study cohort.

Pencil Beam Scanning Bragg Peak FLASH Technique for Ultra-High Dose Rate Intensity-Modulated Proton Therapy in Early-Stage Breast Cancer Treatment.

Bragg peak FLASH-RT can deliver highly conformal treatment and potentially offer improved normal tissue protection for radiotherapy patients. This study focused on developing ultra-high dose rate (≥40 Gy × RBE/s) intensity-modulated proton therapy (IMPT) for hypofractionated treatment of early-stage breast cancer. A novel tracking technique was developed to enable pencil beaming scanning (PBS) of single-energy protons to adapt the Bragg peak (BP) to the target distally. Standard-of-care PBS treatment plans of consecutively treated early-stage breast cancer patients using multiple energy layers were reoptimized using this technique, and dose metrics were compared between single-energy layer BP FLASH and conventional IMPT plans. FLASH dose rate coverage by volume (V40Gy/s) was also evaluated for the FLASH sparing effect. Distal tracking can precisely stop BP at the target distal edge. All plans (n = 10) achieved conformal IMPT-like dose distributions under clinical machine parameters. No statistically significant differences were observed in any dose metrics for heart, ipsilateral lung, most ipsilateral breast, and CTV metrics (p > 0.05 for all). Conventional plans yielded slightly superior target and skin dose uniformities with 4.5% and 12.9% lower dose maxes, respectively. FLASH-RT plans reached 46.7% and 61.9% average-dose rate FLASH coverage for tissues receiving more than 1 and 5 Gy plan dose total under the 250 minimum MU condition. Bragg peak FLASH-RT techniques achieved comparable plan quality to conventional IMPT while reaching adequate dose rate ratios, demonstrating the feasibility of early-stage breast cancer clinical applications.

Monte Carlo dosimetry of a novel Yttrium-90 disc source for episcleral brachytherapy.

PURPOSE: To calculate the dose distribution using Monte Carlo simulations for a novel high-dose-rate Yttrium-90 (Y-90) disc source recently developed for episcleral brachytherapy and provide a lookup table for treatment planning. METHODS: Monte Carlo simulations were performed to calculate the in-water dose distribution of the Y-90 disc source using the "GATE", a software based on the "Geant4" Monte Carlo simulation toolkit developed by the international OpenGATE collaboration. The geometry of this novel beta source, its capsule, and the surrounding water medium were accurately modeled in the simulation input files. The standard Y-90 element beta spectrum from ICRU 72 was used, and the physics processes for beta and photon interactions with matters were all included. The dose distribution of this Y-90 disc source was measured in a separate study using Gafchromic EBT-3 films and the results were reported elsewhere. To match the setup of the experiment, a Gafchromic EBT-3 film was also included in the simulation geometry. The simulated dose profiles were exported from the 3D dose distribution results and compared with the measured dose profiles. Transverse dose profiles at different distances from the seed surface were also obtained to study the lateral coverage of the source. RESULTS: The measured percent depth dose (PDD) curves along the central axis perpendicular to the surface of the Y-90 disc were constructed from the experimental and simulated data, and normalized to the reference point at 1 mm from the source capsule. Both PDD curves agreed well up to 4 mm from the source surface (maximum difference ± 10%) but deviated from each other beyond 4 mm. The deviation might be caused by the increased measurement uncertainty in the low-dose region. The dose rate at the reference point calculated from the Monte Carlo simulation was 1.09 cGy/mCi-s and agreed very well with the measured dose rate of 1.05 cGy/mCi-s. If the 80% isodose line is selected as the lateral coverage, the lateral dose coverage is maximal (∼4.5 mm) at the plane next to the source surface, and gradually decreases with the increasing distance, approaching 3.5 mm when the plane is 5 mm from the 6-mm diameter source surface. CONCLUSION: Monte Carlo simulations were successfully performed to confirm the measured PDD curve of the novel Y-90 disc source. This simulation work laid a solid foundation for characterizing the full dosimetry parameters of this source for episcleral brachytherapy applications.

Does Size Matter? On the Role of Stereotactic Radiosurgery for Large Vestibular Schwannomas as Seen in an Institutional Experience of Gamma Knife Radiosurgery for High-Grade Tumors.

OBJECTIVE: Management of large vestibular schwannoma (VS) is controversial. Surgery has historically been the treatment of choice, but emerging literature suggests that definitive stereotactic radiosurgery is feasible. We report our institutional experience of control and morbidity outcomes treating Koos grade 3-4 VS with Gamma Knife radiosurgery (GKRS). METHODS: An institutional review board-approved database compiled outcomes of Koos grade 3-4 VS treated by GKRS from March 2014 to January 2021 with >6 months' follow-up. Baseline symptoms per Common Terminology Criteria for Adverse Events definitions were recorded. Control rates, toxicities, and post-treatment volumetric changes were analyzed. Aggregate impairment scores (AIs) were defined by the sum of relevant Common Terminology Criteria for Adverse Events grades to categorize symptomatic burdens. Baseline and post-treatment AIs were tested for association with definitive versus adjuvant strategies. RESULTS: In total, 34 patients with Koos grade 3-4 VS were identified, 19 treated with definitive GKRS (GKRS-D) and 15 with adjuvant GKRS (GKRS-A). Median follow-up was 34.2 months for GKRS-D and 48.8 months for GKRS-A. Patients who received GKRS-A had greater AIs at presentation (3.73 vs. 2.11, P = 0.017). Irrespective of treatment approach, tumor control rates were 100% without instances of brainstem necrosis or shunt placement. Six of 19 patients who received GKRS-D had improved post-treatment AI, and 63% of patients who received GKRS-D and 66% of patients who received GKRS-A had tumor shrinkage >20%. CONCLUSIONS: In well-selected patients with Koos grade 3-4 VS, definitive stereotactic radiosurgery may be an appropriate strategy with excellent control and minimal toxicity. Our data suggest that the need for surgical decompression should be considered based on pretreatment symptom burden rather than tumor size.

Direct dosimetric comparison of linear accelerator vs. Gamma Knife fractionated stereotactic radiotherapy (fSRT) of large brain tumors.

The purpose of this study was to directly compare the plan quality of Gamma Knife (GK) (Elekta, Stockholm, Sweden)- vs linear accelerator (LINAC)-based delivery techniques for fractionated stereotactic radiotherapy (fSRT) of large brain metastases. Eighteen patients with clinical target volumes (CTVs) larger than 9.5 cc were selected to generate comparative plans for the prescription dose of 9 Gy × 3 fractions, utilizing the Eclipse (Varian, Palo Alto, US) vs Leksell GammaPlan (LGP) (Elekta, Stockholm, Sweden) treatment planning systems (TPS). Each GK plan was first developed using LGP's automatic planning, followed by manual adjustments/refinements. The same MRI and structures, including CTVs and organs at risk, were then DICOM-transferred to the Eclipse TPS. Volumetric Modulated Arc Therapy (VMAT) and Dynamic Conformal Arc (DCA) plans for a Truebeam, with high-definition multi-leaf collimators (MLCs), were developed on these MR images and structures using a single isocenter and 3 non-coplanar arcs. No planning target volume (PTV) margins were added, and no heterogeneity correction was used for either TPS. GK plans were prescribed to the 50% isodose line, and Eclipse VMAT and DCA plans allowed a maximum dose up to 170% and ∼125%, respectively. Gradient index (GI), Paddick Conformity Index (PCI), V20GyRind, and V4GyRind of all 3 techniques were calculated and compared. One-way analysis of variance (ANOVA) was performed to determine the statistical significance of the differences of these planning indices for the 3 planning techniques. A total of eighteen treatment targets were analyzed. Median CTV volume was 14.4 cc (range 9.5 cc - 55.9 cc). Mean ± standard deviation of PCI were 0.85 ± 0.03, 0.90 ± 0.03, and 0.72 ± 0.11 for GK, VMAT and DCA plans, respectively. They were respectively 2.64 ± 0.17, 2.46 ± 0.18, and 2.83 ± 0.48 for GI; 15.33 ± 8.45 cc, 10.47 ± 4.32 cc and 23.51 ± 16 cc for V20GyRind; and 316.28 ± 138.35 cc, 317.81 ± 108.21 cc, and 394.85 ± 142.16 cc for V4GyRind. The differences were statistically significant with p < 0.01 for all indices, except for V4GyRind (p > 0.129). In conclusion, a direct dosimetric comparison using the same MRI scan and contours was performed to evaluate the plan quality of various fSRT delivery techniques for CTV > 9.5 cc. LINAC VMAT plans provided the best dosimetric outcome in regard to PCI, GI, and V20GyRind. GK outcomes were similar to LINAC VMAT plans while LINAC DCA outcomes were significantly worse. Even though GK has a smaller physical penumbra, LINAC VMAT outperformed GK in this study due to enhanced penumbra sharpening and better beam optimization.

Retrospective Analysis of Treatment Workflow in Frame-Based and Frameless Gamma Knife Radiosurgery.

Objective To improve the efficiency of frame-based and frameless Gamma Knife® Icon™ (GKI) treatments by analyzing the workflows of both treatment approaches and identifying steps that lead to prolonged patient in-clinic or treatment time. Methods The treatment processes of 57 GKI patients, 16 frame-based and 41 frameless cases were recorded and analyzed. For frame-based treatments, time points were recorded for various steps in the process, including check-in, magnetic resonance imaging (MRI) completion, plan approval, and treatment start/end times. The time required for completing each step was calculated and investigated. For frameless treatments, the actual and planned treatment times were compared to evaluate the patient tolerance of the treatment. In addition, the time spent on room cleaning and preparation between treatments was also recorded and analyzed. Results For frame-based cases, the average in-clinic time was 6.3 hours (ranging from 4 to 8.7 hours). The average time from patient check-in to plan approval was 4.2 hours (ranging from 2.8 to 5.5 hours), during which the frame was placed, stereotactic reference MRI images were taken, target volumes were contoured, and the treatment plan was developed and second-checked. For patients immobilized with a mask, treatment pauses triggered by the intra-fractional motion monitoring system resulted in a significantly longer actual treatment time than the planned time. In 50 (or 55%) of the 91 frameless treatments, the patient on-table time was longer than the planned treatment time by more than 10 minutes, and in 19 (or 21%) of the treatments the time difference was larger than 20 minutes. Major treatment interruptions, defined as pauses leading to a longer than 10-minute delay, were more commonly encountered in patients with a planned treatment time longer than 40 minutes, which accounted for 64% of the recorded major interruptions. Conclusion For frame-based cases, the multiple pretreatment steps (from patient check-in to plan approval) in the workflow were time-consuming and resulted in prolonged patient in-clinic time. These pretreatment steps may be shortened by performing some of these steps before the treatment day, e.g., pre-planning the treatment using diagnostic MRI scans acquired a few days earlier. For frameless patients, we found that a longer planned treatment time is associated with a higher chance of treatment interruption. For patients with a long treatment time, a planned break or consideration of fractionated treatments (i.e., 3 to 5 fractionated stereotactic radiosurgery) may optimize the workflow and improve patient satisfaction.

Assessing initial plan check efficacy using TG 275 failure modes and incident reporting.

Plan checks are important components of a robust quality assurance (QA) program. Recently, the American Association of Physicists in Medicine (AAPM) published two reports concerning plan and chart checking, Task Group (TG) 275 and Medical Physics Practice Guideline (MPPG) 11.A. The purpose of the current study was to crosswalk initial plan check failure modes revealed in TG 275 against our institutional QA program and local incident reporting data. Ten physicists reviewed 46 high-risk failure modes reported in Table S1.A.i of the TG 275 report. The committee identified steps in our planning process which sufficiently checked each failure mode. Failure modes that were not covered were noted for follow-up. A multidisciplinary committee reviewed the narratives of 1599 locally-reported incidents in our Radiation Oncology Incident Learning System (ROILS) database and categorized each into the high-risk TG 275 failure modes. We found that over half of the 46 high-risk failure modes, six of which were top-ten failure modes, were covered in part by daily contouring peer-review rounds, upstream of the traditional initial plan check. Five failure modes were not adequately covered, three of which concerned pregnancy, pacemakers, and prior dose. Of the 1599 incidents analyzed, 710 were germane to the initial plan check, 23.4% of which concerned missing pregnancy attestations. Most, however, were caught prior to CT simulation (98.8%). Physics review and initial plan check were the least efficacious checks, with error detection rates of 31.8% and 31.3%, respectively, for some failure modes. Our QA process that includes daily contouring rounds resulted in increased upstream error detection. This work has led to several initiatives in the department, including increased automation and enhancement of several policies and procedures. With TG 275 and MPPG 11.A as a guide, we strongly recommend that departments consider an internal chart checking policy and procedure review.

Evaluating dosimetric accuracy of the 6 MV calibration on EBT3 film in the use of Ir-192 high dose rate brachytherapy.

PURPOSE: To evaluate the dosimetric accuracy of EBT3 film calibrated with a 6 MV beam for high dose rate brachytherapy and propose a novel method for direct film calibration with an Ir-192 source. METHODS: The 6 MV calibration was performed in water on a linear accelerator (linac). The Ir-192 calibration was accomplished by irradiating the film wrapped around a cylinder applicator with an Ir-192 source. All films were scanned 1-day post-irradiation to acquire calibration curves for all three (red, blue, and green) channels. The Ir-192 calibration films were also used for single-dose comparison. Moreover, an independent test film under a H.A.M. applicator was irradiated and the 2D dose distribution was obtained separately for each calibration using the red channel data. Gamma analysis and point-by-point profile comparison were performed to evaluate the performance of both calibrations. The uncertainty budget for each calibration system was analyzed. RESULTS: The red channel had the best performance for both calibration systems in the single-dose comparison. We found a significant 4.89% difference from the reference for doses <250 cGy using the 6 MV calibration, while the difference was only 0.87% for doses >600 cGy. Gamma analysis of the 2D dose distribution showed the Ir-192 calibration had a higher passing rate of 91.9% for the 1 mm/2% criterion, compared to 83.5% for the 6 MV calibration. Most failing points were in the low-dose region (<200 cGy). The point-by-point profile comparison reported a discrepancy of 2%-3.6% between the Ir-192 and 6 MV calibrations in this low-dose region. The linac- and Ir-192-based dosimetry systems had an uncertainty of 4.1% (k = 2) and 5.66% (k = 2), respectively. CONCLUSIONS: Direct calibration of EBT3 films with an Ir-192 source is feasible and reliable, while the dosimetric accuracy of 6 MV calibration depends on the dose range. The Ir-192 calibration should be used when the measurement dose range is below 250 cGy.

A novel and effective method for validation and measurement of output factors for Leksell Gamma Knife® Icon™ using TRS 483 protocol.

The objective of this work was to identify the exact location of the effective point of measurement (EPM) of four different active detectors to compare the relative collimator output factors (ROF) of Leksell Gamma Knife (LGK) according to IAEA TRS-483 recommendations. ROF was measured at the center of the spherical LGK-Solid Water (LGK-SW) Phantom for three (4-, 8-, and 16-mm in diameter) collimators using four (PTW-TN60008, PTW-TN60016, PTW-TN60017, and PTW-60019 diode/diamond) detectors. Since diode detectors have a much smaller sensitive volume than the PTW-31010 ion chamber used for reference dosimetry, its EPM might not be at the center of the phantom, or (100, 100, 100) of the Leksell Coordinate System, particularly in the z-direction. Hence for each diode detector, a CBCT image was acquired after it was inserted into the phantom, from which the z-Leksell coordinate of EPM was determined. Relative collimator output factors was then measured by focusing GK beams on the determined EPM of each diode. Measured ROFs were compared with the vendor-provided values in GK treatment planning system. For validation, a plan was generated to measure the output of 4-mm collimator for PTW-TN60017 at various couch locations along the z-axis. For PTW-TN60008, the percentage variations were 0.6 ± 0.4%, and -0.8 ± 0.2% for 4 and 8-mm collimators, respectively. For PTW-TN60016, the percentage variations were 0.8 ± 0.0%, and 0.2 ± 0.1%, respectively. The percentage variations were -3.3 ± 0.0% and -0.9 ± 0.1%, respectively, for PTW-TN60017, and -0.5 ± 0.0% and -0.8 ± 0.2%, respectively, for PTW-TN60019. Center of the measured profile for PTW-TN60017 was only 0.1 mm different from that identified using the CBCT. In conclusion, we have developed a simple and effective method to determine the EPMs of diode detectors when inserted into the existing LGK-SW phantom. With the acquired positional information and using TRS-483 protocol, good agreements were obtained between the measured ROFs and manufacturer recommended values.

Dosimetric benefits of gantry-static couch-motion (GsCM) technique for breast boost radiation therapy: Reduced dose to organs-at-risk and improved dosimetric indices.

To evaluate the clinical feasibility and dosimetric benefits of a novel gantry-static couch-motion (GsCM) technique for external beam photon boost treatment of lumpectomy cavity in patients with early-stage breast cancer in comparison to three-dimensional conformal radiotherapy (3D-CRT), wedge pair in supine position (WPS), and wedge pair in decubitus position (WPD) techniques. A retrospective review was conducted on breast patients (right breast, n = 10 and left breast, n = 10) who received 10 Gy boost after 50 Gy to whole breast. The treatment plans were generated using an isocentric-based GsCM technique (a VMAT type planning approach) integrating couch rotational motion at static gantry positions. Static fields for each tangential side were merged using a Matlab® script and delivered automatically within the Varian TruebeamTM STx in Developer Mode application as a VMAT arc (wide-angular medial and short-angular lateral arcs). The dosimetric accuracy of the plan delivery was evaluated by ion chamber array measurements in phantom. For both right and left breast boost GsCM, 3D-CRT, WPS, and WPD all provided an adequate coverage to PTV. GsCM significantly reduced the ipsilateral lung V30% for right side (mean, 80%) and left side (mean, 70%). Heart V5% reduced by 90% (mean) for right and 80% (mean) for left side. Ipsilateral breast V50% and mean dose were comparable for all techniques but for GsCM, V100% reduced by 50% (mean) for right and left side. The automated delivery of both arcs was under 2 min as compared to delivering individual fields (30 ± 5 min). The gamma analysis using 2 mm distance to agreement (DTA) and 2% dose difference (DD) was 98 ± 1.5% for all 20 plans. The GsCM technique facilitates coronal plane dose delivery appropriate for deep-seated breast boost cavities, with sufficient dose conformity of target volume paired with sparing of the OARs.

Tumor control and survival in patients with ten or more brain metastases treated with stereotactic radiosurgery: a retrospective analysis.

INTRODUCTION: To assess tumor control and survival in patients treated with stereotactic radiosurgery (SRS) for 10 or more metastatic brain tumors. METHODS: Patients were retrospectively identified. Clinical records were reviewed for follow-up data, and post-treatment MRI studies were used to assess tumor control. For tumor control studies, patients were separated based on synchronous or metachronous treatment, and control was assessed at 3-month intervals. The Kaplan-Meier method was employed to create survival curves, and regression analyses were employed to study the effects of several variables. RESULTS: Fifty-five patients were treated for an average of 17 total metastases. Forty patients received synchronous treatment, while 15 received metachronous treatment. Univariate analysis revealed an association between larger brain volumes irradiated with 12 Gy and decreased overall survival (p = 0.0406); however, significance was lost on multivariate analysis. Among patients who received synchronous treatment, the median percentage of tumors controlled was 100%, 91%, and 82% at 3, 6, and 9 months, respectively. Among patients who received metachronous treatment, the median percentage of tumors controlled after each SRS encounter was 100% at all three time points. CONCLUSIONS: SRS can be used to treat patients with 10 or more total brain metastases with an expectation of tumor control and overall survival that is equivalent to that reported for patients with four or fewer tumors. Development of new metastases leading to repeat SRS is not associated with worsened tumor control or survival. Survival may be adversely affected in patients having a higher volume of normal brain irradiated.

Incorporating the rotational setup uncertainty into the planning target volume margin expansion for the single isocenter for multiple targets technique.

PURPOSE: The single isocenter for multiple targets (SIMT) technique has become a popular treatment approach for multiple brain metastases. However, the rotational error that is introduced is usually not considered in planning target volume (PTV) expansion. We have developed a statistical model that takes into account both translational and rotational uncertainties. In this study, we incorporated the rotational error into PTV margin expansion for the clinical use of the SIMT technique. METHODS AND MATERIALS: In the statistical model, both translational and rotational errors are assumed to follow the 3-dimensional, independent, normal distribution with a zero mean and standard deviations of σS and σR, where σR = 0.01424σD (rotational uncertainty in degree)×dI ⇔ T (distance in mm from isocenter to target). Based on this model, we derived in this study the additional PTV margin, ∆M, that is required to maintain the same coverage probability when the rotational uncertainty is present as a function of MS (initial PTV margin), σD, and dI ⇔ T. The maximum allowable dI ⇔ T, C and σD, C were also calculated as a function of user-specified ∆Mc/MS, the fraction of MS below which the extra PTV margins can be ignored. RESULTS: Combined PTV margin, ME, and additional PTV margin, ∆M, were plotted for commonly encountered clinical parameters including dI ⇔ T, MS, or σD. Unlike other reported margin recipes, ∆M is not a linear function of any of these 3 parameters. In addition, the rate of increase for ∆M is quite slow for small dI ⇔ T and becomes more significant for larger dI ⇔ T. Cutoff values dI ⇔ T, C and σD, C were also plotted for various ∆Mc/MS, which can be used to determine if an additional PTV margin is needed for the SIMT technique. CONCLUSIONS: The presented data provide a convenient way for clinics to determine the appropriate PTV margin for the SIMT technique.

Restricted single isocenter for multiple targets dynamic conformal arc (RSIMT DCA) technique for brain stereotactic radiosurgery (SRS) planning.

PURPOSE/OBJECTIVES: In stereotactic radiosurgery (SRS), the multiple isocenters for multiple targets dynamic conformal arc (MIMT DCA) technique is traditionally used to treat multiple brain metastases, with one isocenter for each target. The single isocenter for multiple targets (SIMT) technique has recently been adopted to reduce the treatment time at the cost of plan quality. The objective of this study was to develop a restricted single isocenter for multiple targets DCA (RSIMT DCA) technique that can significantly reduce the treatment time but still maintain similar plan quality as the MIMT DCA technique. MATERIALS AND METHODS: Treating multiple brain metastases with a single isocenter poses a challenge to SRS planning using DCA beams that are intrinsically 3D and do not modulate the beam intensity to spare the normal tissue between targets. To address this obstacle, we have developed a RSIMT DCA technique and used it to treat SRS patients with multiple brain metastases since February 2015. This planning approach is similar to the SIMT technique except that the number of targets for each isocenter is restricted and the distance between the isocenter and target is limited. In this technique, the targets are first split into batches so that all targets in a batch are within a chosen distance (e.g., 7 cm) of each other. All targets in a batch are combined into one target and the geometric center of the combined target is the isocenter for the group of DCA beams associated with that batch. Each DCA group typically consists of 3-4 DCA beams to irradiate 1-3 targets. For each DCA beam, the collimator angle is adjusted to minimize the exposure of normal tissue between targets. The dose of each treatment group is normalized so that the maximal point dose to the combined target is 125% of the prescription dose, which is equivalent to normalize the prescription dose to 80% isodose line. If the maximal point dose of a target is <123%, an additional beam is used to boost the maximal point dose of that target to 125%. To evaluate the plan quality, we randomly selected 10 cases planned with the RSIMT DCA technique, and re-planned them using the MIMT DCA technique. There were in total 38 PTVs, and 22 isocenters were used to treat all of these targets. The prescription for each target was 20 Gy with a maximal point dose of 25 Gy. Plan quality indexes were calculated and compared. Paired sample t-test was performed to determine if the mean normalized difference, (RSIMT-MIMT)/MIMT of each plan index was statistically significantly (p-value < 5%) larger than 0. RESULTS: Satisfactory PTV coverage (V20Gy>95% and V19Gy=100%) was achieved for all plans using either technique. Most PTVs have a maximal point dose between 24.9 and 25.1 Gy, with 2 PTVs between 24.5 and 24.9 Gy. Overall, the plan quality was slightly better for the MIMT DCA technique and the normalized difference was statistically significantly larger than 0 for all investigated dose quality indexes. The normalized difference of body mean dose and conformity index (CI) between the RSIMT and MIMT techniques was respectively 4.2% (p=0.002) and 9.4% (p=0.001), indicating similar plan quality globally and in the high dose area. The difference was more pronounced for the mid-to-low dose spillage with the ratios of V12Gy and V10Gy/VPTV being 13.9% (p=3.8×10-6) and 14.9% (p=1.3×10-5), respectively. The treatment time was reduced by 30%-50% with the RSIMT DCA technique. CONCLUSION: The RSIMT DCA technique can produce satisfactory SRS plans for treating multiple targets and can significantly reduce the treatment time.

A statistical model for analyzing the rotational error of single isocenter for multiple targets technique.

PURPOSE: To develop a statistical model that incorporates the treatment uncertainty from the rotational error of the single isocenter for multiple targets technique, and calculates the extra PTV (planning target volume) margin required to compensate for this error. METHODS: The random vector for modeling the setup (S) error in the three-dimensional (3D) patient coordinate system was assumed to follow a 3D normal distribution with a zero mean, and standard deviations of σx , σy , σz . It was further assumed that the rotation of clinical target volume (CTV) about the isocenter happens randomly and follows a three-dimensional (3D) independent normal distribution with a zero mean and a uniform standard deviation of σδ . This rotation leads to a rotational random error (R), which also has a 3D independent normal distribution with a zero mean and a uniform standard deviation of σR equal to the product of σδπ180 and dI⇔T, the distance between the isocenter and CTV. Both (S and R) random vectors were summed, normalized, and transformed to the spherical coordinates to derive the Chi distribution with three degrees of freedom for the radial coordinate of S+R. PTV margin was determined using the critical value of this distribution for a 0.05 significance level so that 95% of the time the treatment target would be covered by the prescription dose. The additional PTV margin required to compensate for the rotational error was calculated as a function of σR and dI⇔T. RESULTS: The effect of the rotational error is more pronounced for treatments that require high accuracy/precision like stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT). With a uniform 2-mm PTV margin (or σx = σy = σz = 0.715 mm), a σR = 0.328 mm will decrease the CTV coverage probability from 95.0% to 90.9%, or an additional 0.2-mm PTV margin is needed to prevent this loss of coverage. If we choose 0.2 mm as the threshold, any σR > 0.328 mm will lead to an extra PTV margin that cannot be ignored, and the maximal σδ that can be ignored is 0.45° (or 0.0079rad ) for dI⇔T = 50 mm or 0.23° (or 0.004rad ) for dI⇔T = 100 mm. CONCLUSIONS: The rotational error cannot be ignored for high-accuracy/-precision treatments like SRS/SBRT, particularly when the distance between the isocenter and target is large.

Innovative Hypofractionated Stereotactic Regimen Achieves Excellent Local Control with No Radiation Necrosis: Promising Results in the Management of Patients with Small Recurrent Inoperable GBM.

Management of recurrent glioblastoma multiforme (GBM) remains a challenge. Several institutions reported that a single fraction of ≥ 20 Gy for small tumor burden results in excellent local control; however, this is at the expense of a high incidence of radiation necrosis (RN). Therefore, we developed a hypofractionation pattern of 33 Gy/3 fractions, which is a radiobiological equivalent of 20 Gy, with the aim to lower the incidence of RN. We reviewed records of 21 patients with recurrent GBM treated with hypofractionated stereotactic radiation therapy (HFSRT) to their 22 respective lesions. Sixty Gy fractioned external beam radiotherapy was performed as first-line treatment. Median time from primary irradiation to HFSRT was 9.6 months (range: 3.1 - 68.1 months). In HFSRT, a median dose of 33 Gy in 11 Gy fractions was delivered to the 80% isodose line that encompassed the target volume. The median tumor volume was 1.07 cm3 (range: 0.11 - 16.64 cm3). The median follow-up time after HFSRT was 9.3 months (range: 1.7 - 33.6 months). Twenty-one of 23 lesions treated (91.3%) achieved local control while 2/23 (8.7%) progressed. Median time to progression outside of the treated site was 5.2 months (range: 2.2 - 9.6 months). Progression was treated with salvage chemotherapy. Five of 21 patients (23.8%) were alive at the end of this follow-up; two patients remain disease-free. The remaining 16/21 patients (76.2%) died of disease. Treatment was well tolerated by all patients with no acute CTC/RTOG > Grade 2. There was 0% incidence of RN. A prospective trial will be underway to validate these promising results.

Calibration of a detector array through beam profile reconstruction with error-locking.

An iterative method is proposed to calibrate radiation sensitivities of an arbitrary two-dimensional (2D) array of detectors. The array is irradiated with a wide open- field beam at the central position, as well as at laterally and longitudinal shifted positions; the 2D beam profile of the wide field is reconstructed iteratively from the ratios of shifted images to the central image. The propagation errors due to output variation and inaccurate array positioning are estimated and removed from the reconstructed beam profile by an error-locking scheme with narrow open-field irradiations. The beam profile is interpolated when necessary and then compared to raw detector responses to determine sensitivities. Two additional methods were implemented for comparison: 1) the commercial iterative calibration method for MapCHECK2 with translation and rotation operations; 2) a labor-intensive noniterative method without the issue of error propagation. A MapCHECK2 2D detector array was used to validate the proposed method with the 6 MV photon beam from a Varian iX linear accelerator. All calibration methods were repeated three times. A total of 5, 9, and 29 irradiations were required to implement the commercial method, the proposed method and the noniterative method respec- tively. Moreover, a 5 mm positioning error was intentionally introduced into the calibration procedures of the commercial and the proposed method to test their robustness. Under the normal operation condition of the linear accelerator and with careful alignment of the MapCHECK2, the deviations of the calibrated sensitivities of the proposed method and commercial method with respect to the noniterative method were 0.30% ± 0.29% and 0.92% ± 0.63% respectively; when the 5 mm positioning error was presented, these two methods resulted in deviations of 0.40% ± 0.36% and 3.58% ± 1.94%, respectively. A patient study suggested that, due to this 5 mm positioning error, the mean DTA (dose to agreement) passing rate by the commercial method was 2.7% lower than that by the noniterative method, whereas the proposed method led to a comparable passing rate. It is evident from this study that the proposed iterative method leads to within 1% mean calibration results to established methods. It requires much fewer number of measurements than noniterative method and is more robust against the positioning error than the commercial iterative method. The method also eliminates the need of rotation operations and, therefore, is applicable to inline detector arrays without rotation function, such as electronic portal imager device (EPID). 

Is there a tradeoff in using modified high tangent field radiation for treating an undissected node-positive axilla?

INTRODUCTION: Recent data are changing axillary management in patients with 1 to 2 positive sentinel nodes. The proposed omission of completion axillary node dissection calls into question the need for axillary nodal irradiation. This study evaluates the difference in dose to the lung and heart and risk of radiation pneumonitis (RP) for patients treated with standard tangent fields (STF) compared with modified high tangent fields (MHTF). MATERIALS AND METHODS: Plans of 30 patients treated with STF were evaluated. A second plan (MHTF) was developed to include axillary levels I (Ax1) and II (Ax2). Ax1 and Ax2 volumes were contoured based on the RTOG (Radiation Therapy Oncology Group) Atlas guidelines. Dose-volume histograms of the 2 plans were used to compare doses received by Ax1, Ax2, lung, and heart volumes. The risk of RP was calculated using normal tissue complication probability (NTCP) modeling. RESULTS: The D95 (dose to 95% of volume) received by Ax1 and Ax2 volumes increased from 16.38 Gy and 5.71 Gy for STF to 49.38 Gy and 48.08 Gy for MHTF, respectively. Mean lung dose increased from 5.40 Gy for STF to 9.47 Gy for MHTF. Mean ipsilateral lung V5, V10, and V20 values increased from 19%, 14%, and 10%, respectively, for STF, to 32%, 24%, and 18%, respectively, for MHTF. Mean heart dose increased from 1.98 Gy for STF to 3.93 Gy for MHTF. Mean heart V25 and V30 values increased from 2% and 1%, respectively, for STF, to 4% and 3%, respectively, for MHTF. NTCP for RP increased from near 0% for STF to 1% for MHTF. CONCLUSION: Modified high tangent fields are necessary for definitive coverage of Ax1 and Ax2. This technique increases mean ipsilateral lung and heart doses as well as the V5, V10, and V20 of ipsilateral lung and the V25 and V30 of the heart. Risk of RP remains low by use of MHTF.