A study on inter-planner plan quality variability using a manual planning- or Lightning dose optimizer-approach for single brain lesions treated with the Gamma Knife® Icon™.

PURPOSE: The purpose of this study is to investigate inter-planner plan quality variability using a manual forward planning (MFP)- or fast inverse planning (FIP, Lightning)-approach for single brain lesions treated with the Gamma Knife® (GK) Icon™. METHODS: Thirty patients who were previously treated with GK stereotactic radiosurgery or radiotherapy were selected and divided into three groups (post-operative resection cavity, intact brain metastasis, and vestibular schwannoma [10 patients per group]). Clinical plans for the 30 patients were generated by multiple planners using FIP only (1), a combination of FIP and MFP (12), and MFP only (17). Three planners (Senior, Junior, and Novice) with varying experience levels re-planned the 30 patients using MFP and FIP (two plans per patient) with planning time limit of 60 min. Statistical analysis was performed to compare plan quality metrics (Paddick conformity index, gradient index, number of shots, prescription isodose line, target coverage, beam-on-time (BOT), and organs-at-risk doses) of MFP or FIP plans among three planners and to compare plan quality metrics between each planner's MFP/FIP plans and clinical plans. Variability in FIP parameter settings (BOT, low dose, and target max dose) and in planning time among the planners was also evaluated. RESULTS: Variations in plan quality metrics of FIP plans among three planners were smaller than those of MFP plans for all three groups. Junior's MFP plans were the most comparable to the clinical plans, whereas Senior's and Novice's MFP plans were superior and inferior, respectively. All three planners' FIP plans were comparable or superior to the clinical plans. Differences in FIP parameter settings among the planners were observed. Planning time was shorter and variations in planning time among the planners were smaller for FIP plans in all three groups. CONCLUSIONS: The FIP approach is less planner dependent and more time-honored than the MFP approach.

OptImal Gamma kNife lIghTnIng sOlutioN (IGNITION) score to characterize the solution space of the Gamma Knife FIP optimizer for stereotactic radiosurgery.

OBJECTIVES: The objective of this study is to evaluate the user-defined optimization settings in the Fast Inverse Planning (FIP) optimizer in Leksell GammaPlan® and determine the parameters that result in the best stereotactic radiosurgery (SRS) plan quality for brain metastases, benign tumors, and arteriovenous malformations (AVMs). METHODS: Thirty patients with metastases and 30 with benign lesions-vestibular schwannoma, AVMs, pituitary adenoma, and meningioma-treated with SRS were evaluated. Each target was planned by varying the low dose (LD) and beam-on-time (BOT) penalties in increments of 0.1, from 0 to 1. The following plan quality metrics were recorded for each plan: Paddick conformity index (PCI), gradient index (GI), BOT, and maximum organ-at-risk (OAR) doses. A novel objective score matrix was calculated for each target using a linearly weighted combination of the aforementioned metrics. A histogram of optimal solutions containing the five best scores was extracted. RESULTS: A total of 7260 plans were analyzed with 121 plans per patient for the range of LD/BOT penalties. The ranges of PCI, GI, and BOT across all metastatic lesions were 0.58-0.97, 2.1-3.8, and 8.8-238 min, respectively, and were 0.13-0.97, 2.1-3.8, and 8.8-238 min, respectively, for benign lesions. The objective score matrix showed unique optimal solutions for metastatic lesions and benign lesions. Additionally, the plan metrics of the optimal solutions were significantly improved compared to the clinical plans for metastatic lesions with equivalent metrics for all other cases. CONCLUSION: In this study, FIP optimizer was evaluated to determine the optimal solution space to maximize PCI and minimize GI, BOT and OAR doses simultaneously for single metastatic/benign/non-neoplastic targets. The optimal solution chart was determined using a novel objective score which provides novice and expert planners a roadmap to generate the most optimal plans efficiently using FIP.

Surgically targeted radiation therapy versus stereotactic radiation therapy: A dosimetric comparison for brain metastasis resection cavities.

PURPOSE: Surgically targeted radiation therapy (STaRT) with Cesium-131 seeds embedded in a collagen tile is a promising treatment for recurrent brain metastasis. In this study, the biological effective doses (BED) for normal and target tissues from STaRT plans were compared with those of external beam radiotherapy (EBRT) modalities. METHODS: Nine patients (n = 9) with 12 resection cavities (RCs) who underwent STaRT (cumulative physical dose of 60 Gy to a depth of 5 mm from the RC edge) were replanned with CyberKnifeⓇ (CK), Gamma KnifeⓇ (GK), and intensity modulated proton therapy (IMPT) using an SRT approach (30 Gy in 5 fractions). Statistical significance comparing D95% and D90% in BED10Gy (BED10Gy95% and BED10Gy90%) and to RC + 0 to + 5 mm expansion margins, and parameters associated with radiation necrosis risk (V83Gy, V103Gy, V123Gy and V243Gy) to the normal brain were evaluated by a Wilcoxon-signed rank test. RESULTS: For RC + 0 mm, median BED10Gy 90% for STaRT (90.1 Gy10, range: 64.1-140.9 Gy10) was significantly higher than CK (74.3 Gy10, range:59.3-80.4 Gy10, p = 0.04), GK (69.4 Gy10, range: 59.8-77.1 Gy10, p = 0.005), and IMPT (49.3 Gy10, range: 49.0-49.7 Gy10, p = 0.003), respectively. However, for the RC + 5 mm, the median BED10Gy 90% for STaRT (34.1 Gy10, range: 22.2-59.7 Gy10) was significantly lower than CK (44.3 Gy10, range: 37.8-52.4 Gy10), and IMPT (46.6 Gy10, range: 45.1-48.5 Gy10), respectively, but not significantly different from GK (34.1 Gy10, range: 22.8-47.0 Gy10). The median V243Gy was significantly higher in CK (11.7 cc, range: 4.7-20.1 cc), GK(6.2 cc, range: 2.3-11.9 cc) and IMPT (19.9 cc, range: 11.1-36.6 cc) compared to STaRT (1.1 cc, range: 0.0-7.8 cc) (p < 0.01). CONCLUSIONS: This comparative analysis suggests a STaRT approach may treat recurrent brain tumors effectively via delivery of higher radiation doses with equivalent or greater BED up to at least 3 mm from the RC edge as compared to EBRT approaches.

Clinical application of an institutional fractionated stereotactic radiosurgery (FSRS) program for brain metastases delivered with MRIdianⓇ BrainTx™.

Single-fraction stereotactic radiosurgery (SRS) or fractionated SRS (FSRS) are well established strategies for patients with limited brain metastases. A broad spectrum of modern dedicated platforms are currently available for delivering intracranial SRS/FSRS; however, SRS/FSRS delivered using traditional CT-based platforms relies on the need for diagnostic MR images to be coregistered to planning CT scans for target volume delineation. Additionally, the on-board image guidance on traditional platforms yields limited inter-fraction and intra-fraction real-time visualization of the tumor at the time of treatment delivery. MR Linacs are capable of obtaining treatment planning MR and on-table MR sequences to enable visualization of the targets and organs-at-risk and may subsequently help identify anatomical changes prior to treatment that may invoke the need for on table treatment adaptation. Recently, an MR-guided intracranial package (MRIdian A3i BrainTxTM) was released for intracranial treatment with the ability to perform high-resolution MR sequences using a dedicated brain coil and cranial immobilization system. The objective of this report is to provide, through the experience of our first patient treated, a comprehensive overview of the clinical application of our institutional program for FSRS adaptive delivery using MRIdian's A3i BrainTx system-highlights include reviewing the imaging sequence selection, workflow demonstration, and details in its delivery feasibility in clinical practice, and dosimetric outcomes.

Dosimetric Impact of Lesion Number, Size, and Volume on Mean Brain Dose with Stereotactic Radiosurgery for Multiple Brain Metastases.

We evaluated the effect of lesion number and volume for brain metastasis treated with SRS using GammaKnife® ICON™ (GK) and CyberKnife® M6™ (CK). Four sets of lesion sizes (<5 mm, 5-10 mm, >10-15 mm, and >15 mm) were contoured and prescribed a dose of 20 Gy/1 fraction. The number of lesions was increased until a threshold mean brain dose of 8 Gy was reached; then individually optimized to achieve maximum conformity. Across GK plans, mean brain dose was linearly proportional to the number of lesions and total GTV for all sizes. The numbers of lesions needed to reach this threshold for GK were 177, 57, 29, and 10 for each size group, respectively; corresponding total GTVs were 3.62 cc, 20.37 cc, 30.25 cc, and 57.96 cc, respectively. For CK, the threshold numbers of lesions were 135, 35, 18, and 8, with corresponding total GTVs of 2.32 cc, 12.09 cc, 18.24 cc, and 41.52 cc respectively. Mean brain dose increased linearly with number of lesions and total GTV while V8 Gy, V10 Gy, and V12 Gy showed quadratic correlations to the number of lesions and total GTV. Modern dedicated intracranial SRS systems allow for treatment of numerous brain metastases especially for ≤10 mm; clinical evidence to support this practice is critical to expansion in the clinic.

Surgically targeted radiation therapy (STaRT) for recurrent brain metastases: Initial clinical experience.

PURPOSE: This study evaluates the outcomes of recurrent brain metastasis treated with resection and brachytherapy using a novel Cesium-131 carrier, termed surgically targeted radiation therapy (STaRT), and compares them to the first course of external beam radiotherapy (EBRT). METHODS: Consecutive patients who underwent STaRT between August 2020 and June 2022 were included. All patients underwent maximal safe resection with pathologic confirmation of viable disease prior to STaRT to 60 Gy to a 5-mm depth from the surface of the resection cavity. Complications were assessed using CTCAE version 5.0. RESULTS: Ten patients with 12 recurrent brain metastases after EBRT (median 15.5 months, range: 4.9-44.7) met the inclusion criteria. The median BED10Gy90% and 95% were 132.2 Gy (113.9-265.1 Gy) and 116.0 Gy (96.8-250.6 Gy), respectively. The median maximum point dose BED10Gy for the target was 1076.0 Gy (range: 120.7-1478.3 Gy). The 6-month and 1-year local control rates were 66.7% and 33.3% for the prior EBRT course; these rates were 100% and 100% for STaRT, respectively (p < 0.001). At a median follow-up of 14.5 months, there was one instance of grade two radiation necrosis. Surgery-attributed complications were observed in two patients including pseudomeningocele and minor headache. CONCLUSIONS: STaRT with Cs-131 presents an alternative approach for operable recurrent brain metastases and was associated with superior local control than the first course of EBRT in this series. Our initial clinical experience shows that STaRT is associated with a high local control rate, modest surgical complication rate, and low radiation necrosis risk in the reirradiation setting.

Analysis of potential time saving in brain arteriovenous malformation stereotactic radiosurgery planning using a new software platform.

To evaluate the utility of integrating a 3D vessel tree co-registration software platform into the stereotactic radiosurgery (SRS) workflow and its time saving for brain arteriovenous malformation (bAVM) treatment in adults compared to the conventional stereotactic head frame workflow. Eight consecutive adult bAVM cases were selected and retrospectively reviewed. Total number of angiograms and SRS procedures were 8. The electronic medical records were analyzed by time stamps to determine the length of time for each component of the set-up, transport, and frame removal. Times were averaged and the start of sedation by anesthesia used as a surrogate for the start of the frame application process. Reductions in workflow times were then modeled assuming cerebral angiography as a separate procedure. There were 8 adult bAVM cases included. Six were female. All patients had a single treatment session. Average age was 51.5 years (Range: 36-71). All patients were treated under monitored anesthesia care. In 6 patients, the AVM was deeply located (basal ganglia, midbrain, brainstem); in 2 cases, the lesion was frontal. Spetzler-Martin grades were 4 (50%) Grade 2 and 4 (50%) Grade 3. The average prescription isodose volume (PIV) and 12 Gy volumes (V12Gy) were 0.85 cc and 1.74 cc, respectively. The mean time from frame application to arrival in the angiography room was 111.5 minutes (range 40 to 171 min; median 107 min; SD 35.3 min); transport from angiography room to SRS was 47.5 minutes (range 15 to 107 min; median 36 min; SD 31.1 min), and frame removal after SRS was 20.5 minutes (range 10 to 47 min; median 16 min; SD 11.6 min). The average total additional time for the entire process of frame application, patient transportation, and frame removal was 132 minutes (range 87 to 181 min; median 127.5 min; SD 28.4 min). Therefore, assuming a non-frame based workflow and with angiography performed ahead of the actual radiosurgical treatment, the total time savings on the day of treatment was estimated at 132 minutes (range 87 to 181 min; median 127.5 min; SD 28.4 min). The ability to perform angiography, image fusion, and treatment planning for the actual day-of-delivery using 3-dimensional vessel tree co-registration could result in significant time savings over traditional workflow practices. Further experience with this system will evaluate its accuracy, reproducibility, and potential broader use in SRS workflow paradigms for the treatment of vascular pathologies. For bAVMs, the benefits of this time savings might allow for streamlined workflows on the day of SRS.

Zero Setup Margin Mask versus Frame Immobilization during Gamma Knife® Icon™ Stereotactic Radiosurgery for Brain Metastases.

We compared the clinical outcomes of BM treated with mask immobilization with zero-SM (i.e., zero-PTV) to standard zero-SM frame immobilization SRS. Consecutive patients with BM, 0.5−2.0 cm in maximal diameter, treated with single-fraction SRS (22−24 Gy) during March 2019−February 2021 were included. Univariable and multivariable analysis were performed using the Kaplan−Meier method and Cox proportional hazards regression. A total of 150 patients with 453 BM met inclusion criteria. A total of 129 (28.5%) lesions were treated with a zero-SM mask immobilization and 324 (71.5%) with zero-SM frame immobilization. Frame immobilization treatments were associated with a higher proportion of gastrointestinal and fewer breast-cancer metastases (p = 0.024), and a higher number of treated lesions per SRS course (median 7 vs. 3; p < 0.001). With a median follow up of 15 months, there was no difference in FFLF between the mask and frame immobilization groups on univariable (p = 0.29) or multivariable analysis (p = 0.518). Actuarial FFLF at 1 year was 90.5% for mask and 92% for frame immobilization (p = 0.272). Radiation necrosis rates at 1 year were 12.5% for mask and 4.1% for frame immobilization (p = 0.502). For BM 0.5−2.0 cm in maximal diameter treated with single-fraction SRS using 22−24 Gy, mask immobilization with zero SM produces comparable clinical outcomes to frame immobilization. The initial findings support omitting a SM when using mask immobilization with this treatment approach on a Gamma Knife® Icon™.

Systematic evaluation and plan quality assessment of the Leksell® gamma knife® lightning dose optimizer.

To compare stereotactic radiosurgery (SRS) plan quality metrics of manual forward planning (MFP) and Elekta Fast Inverse Planning™ (FIP)-based inversely optimized plans for patients treated with Gamma Knife®. Clinically treated, MFP SRS plans for 100 consecutive patients (115 lesions; 67 metastatic and 48 benign) were replanned with the FIP dose optimizer based on a convex linear programming formulation. Comparative plans were generated to match or exceed the following metrics in order of importance: Target Coverage (TC), Paddick Conformity Index (PCI), beam-on time (BOT), and Gradient Index (GI). Plan quality metrics and delivery parameters between MFP and FIP were compared for all lesions and stratified into subgroups for further analysis. Additionally, performance of FIP for multiple punctate (<4 mm) metastatic lesions on a subset of cases was investigated. A Wilcoxon signed-rank test for non-normal distributions was used to assess the statistical differences between the MFP and FIP treatment plans. Overall, 76% (87/115) of FIP plans showed a statistically significant improvement in plan quality compared to MFP plans. As compared to MFP, FIP plans demonstrated an increase in the median PCI by 1.1% (p<0.01), a decrease in GI by 3.7% (p< 0.01), and an increase in median number of shots by 74% (p< 0.01). TC and BOT were not statistically significantly different between MFP and FIP plans (p>0.05). FIP plans showed a statistically significant increase in use of 16 mm (p< 0.01) and blocked shots (p< 0.01), with a corresponding decrease in 4 mm shots (p< 0.01). Use of multiple shots per coordinate was significantly higher in FIP plans (p<0.01). The FIP optimizer failed to generate a clinically acceptable plan in 4/115 (3.5%) lesions despite optimization parameter changes. The mean optimization time for FIP plans was 5.0 min (Range: 1.0 - 10.0 min). In the setting of multiple punctate lesions, PCI for FIP was significantly improved (p<0.01) by changing the default low-dose/BOT penalty optimization setting from a default of 50/50 to 75-85/40. FIP offers a significant reduction in manual effort for SRS treatment planning while achieving comparable plan quality to an expert planner-substantially improving overall planning efficiency. FIP plans employ a non-intuitive increased use of blocked sectors and shot-in-shot technique to achieve high quality plans. Several FIP plans failed to achieve clinically acceptable treatments and warrant further investigation.

Dedicated isotropic 3-D T1 SPACE sequence imaging for radiosurgery planning improves brain metastases detection and reduces the risk of intracranial relapse.

BACKGROUND: Stereotactic radiosurgery (SRS) is increasingly used for brain metastases (BM) patients, but distant intracranial failure (DIF) remains the principal disadvantage of this focal therapeutic approach. The objective of this study was to determine if dedicated SRS imaging would improve lesion detection and reduce DIF. METHODS: Between 02/2020 and 01/2021, SRS patients at a tertiary care institution underwent dedicated treatment planning MRIs of the brain including MPRAGE and SPACE post-contrast sequences. DIF was calculated using the Kaplan-Meier method; comparisons were made to a historical consecutive cohort treated using MPRAGE alone (02/2019-01/2020). RESULTS: 134 patients underwent 171 SRS courses for 821 BM imaged with both MPRAGE and SPACE (primary cohort). MPRAGE sequence evaluation alone detected 679 lesions. With neuroradiologists evaluating SPACE and MPRAGE, an additional 108 lesions were identified (p < 0.001). Upon multidisciplinary review, 34 additional lesions were identified. Compared to the historical cohort (103 patients, 135 SRS courses, 479 BM), the primary cohort had improved median time to DIF (13.5 vs. 5.1 months, p = 0.004). The benefit was even more pronounced for patients treated for their first SRS course (18.4 vs. 6.3 months, p = 0.001). SRS using MPRAGE and SPACE was associated with a 60% reduction in risk of DIF compared to the historical cohort (HR: 0.40; 95% CI: 0.28-0.57, p < 0.001). CONCLUSIONS: Among BM patients treated with SRS, a treatment planning SPACE sequence in addition to MPRAGE substantially improved lesion detection and was associated with a statistically significant and clinically meaningful prolongation in time to DIF, especially for patients undergoing their first SRS course.

Impact of MRI timing on tumor volume and anatomic displacement for brain metastases undergoing stereotactic radiosurgery.

BACKGROUND: The objective of this study was to evaluate the impact of the time interval between planning imaging and stereotactic radiosurgery (SRS) delivery on tumor volumes and spatial anatomic displacements of brain metastases (BM). METHODS: Consecutive patients diagnosed with BM treated with SRS over a 3-year period were evaluated. Only patients who underwent an institutionally standardized diagnostic MRI (MRI-1) and a treatment planning MRI (MRI-2) were included. The impact of histology, inter-scan time interval, lesion location, tumor volume, and diameter were evaluated on final lesion diameter, volume, anatomic displacement, and ultimate need for change in management (ie, expanding margins, rescanning). RESULTS: 101 patients (531 lesions) with a median inter-scan time interval of 8 days (range: 1-42 days) met the inclusion criteria. The median percentage increase in BM diameter and volume were 9.5% (IQR: 2.25%-24.0%) and 20% (IQR: 0.7%-66.7%). Overall, 147 lesions (27.7%) in 57 patients (56.4%) required a change in management. There was a statistically significant relationship between initial tumor diameter (cm) and change in management (OR: 2.69, 95% CI: 1.93-3.75; P < .001). Each day between MRI-1 and MRI-2 was associated with a change in management with an OR of 1.05 (95% CI: 1.03-1.07; P < .001). CONCLUSIONS: Changes in tumor diameter, volume, and spatial position occur as a function of time. Planning imaging for SRS is recommended to occur in close temporal proximity to treatment; for those with delays, a larger setup margin may need to be used to ensure tumor coverage and account for positional changes.

Accelerated partial breast irradiation is safe and effective using intensity-modulated radiation therapy in selected early-stage breast cancer.

PURPOSE: To report the feasibility, toxicity, cosmesis, and efficacy of using intensity-modulated radiation therapy (IMRT) with respiratory gating to deliver accelerated partial breast irradiation (APBI) in selected Stage I/II breast cancer after breast-conserving surgery. METHODS AND MATERIALS: Eligible patients with node-negative Stage I/II breast cancer were prospectively enrolled in an institutional review board approved protocol to receive APBI using IMRT after breast-conserving surgery. The target volume was treated at 3.8 Gy/fraction twice daily for 5 days, to a total dose of 38 Gy. RESULTS: Thirty-six patients were enrolled for a median follow-up time of 44.8 months. The median tumor size was 0.98 cm (range, 0.08-3 cm). The median clinical target volume (CTV) treated was 71.4 cc (range, 19-231 cc), with the mean dose to the CTV being 38.96 Gy. Acute toxicities included Grade 1 erythema in 44% of patients and Grade 2 in 6%, Grade 1 hyperpigmentation in 31% of patients and Grade 2 in 3%, and Grade 1 breast/chest wall tenderness in 14% of patients. No Grade 3/4 acute toxicities were observed. Grade 1 and 2 late toxicities as edema, fibrosis, and residual hyperpigmentation occurred in 14% and 11% of patients, respectively; Grade 3 telangiectasis was observed in 3% of patients. The overall cosmetic outcome was considered "excellent" or "good" by 94% of patients and 97% when rated by the physician, respectively. The local control rate was 97%; 1 patient died of a non-cancer-related cause. CONCLUSIONS: APBI can be safely and effectively administered using IMRT. In retrospective analysis, IMRT enabled the achievement of normal tissue dose constraints as outlined by Radiation Therapy Oncology Group 04-13/NSABP B-13 while providing excellent conformality for the CTV. Local control and cosmesis have remained excellent at current follow-up, with acceptable rates of acute/late toxicities. Our data suggest that cosmesis is dependent on target volume size. Further prospective multi-institutional trials should be performed to evaluate IMRT to deliver APBI.