Brain Stereotactic Radiotherapy Research Articles

Clinical and radiological effects of Bevacizumab for the treatment of radionecrosis after stereotactic brain radiotherapy

PurposeThe purpose of this multicenter retrospective study was to analyze the clinical and radiological effects of bevacizumab (BV) on radionecrosis (RN) that developed after stereotactic radiotherapy (SRT) for brain metastasis.MethodsForty patients with SRT related symptomatic brain RN treated in 10 radiation oncology centers were analyzed. The clinical response to BV treatment was categorized as follows: complete (no additional treatment required), partial (requiring either steroids or repeat BV), and unresponsive (requiring surgery). The radiological features of brain RN were analyzed in 10 patients whose serial MRI scans were available after corticosteroid and BV treatments.ResultsBV was used as a first line treatment in 11 (27.5%) and as a second line treatment in 29 (72.5%) of patients. The neurological symptoms regressed in 77.5% of patients after treatment with BV (45% complete response, 32.5% partial response). The median edema volume increased from 75.9 cc (range: 5.9-125.8 cc) at RN to 113.65 cc (range: 1.5-382.1 cc) after use of corticosteroids, representing a rate of 39.8% increase (p = 0.074). However, after BV treatment the median volume of edema decreased to 19.5 cc (range: 0-163.3 cc) which represents a difference of 62.2% (p = 0.041) from RN.ConclusionThe use of BV caused clinical response rate of 77.5% and a good radiological response in corticosteroid unresponsive patients. The role of BV should be further investigated in prospective studies.

“Positioning of tucatinib in the new clinical scenario of HER2-positive metastatic breast cancer: An Italian and Spanish consensus paper”

IntroductionAdvancements in monoclonal antibodies, tyrosine kinase inhibitors, and antibody drug conjugates (ADCs) have notably enhanced outcomes for metastatic HER2-positive breast cancer patients. Despite the expanding treatment options and clinical complexities, determining the optimal sequence of HER2-targeted therapies remains partly uncertain, influenced by various factors. MethodsTo refine HER2-positive metastatic breast cancer management, particularly regarding tucatinib's position, a Steering Committee of leading oncologists in breast cancer care devised a panel of statements via a Delphi approach, focusing on five key topics: general clinical management, therapeutic approaches for patients with HER2-positive breast cancer and brain metastases, treatment sequence, and tucatinib's safety and efficacy. ResultsA total of 29 statements were deliberated, with strong consensus achieved for most. However, no consensus emerged regarding the management of brain progression alongside stable extracranial disease: 48 % advocated for switching to tucatinib, while 53 % favored a stereotactic brain radiotherapy (SBRT) approach if feasible. ConclusionThe unanimous consensus attained in this Delphi panel, particularly regarding tucatinib's efficacy and safety, underscores oncologists' recognition of its clinical significance based on existing trial data. These findings align closely with current literature, shedding light on areas necessitating further investigation, not thoroughly explored in prior studies. Moreover, the results underscore the scarcity of data on managing brain progression alongside stable extracranial disease, emphasizing the imperative for dedicated research to address these gaps and yield definitive insights.

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

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. Ten previously treated brain SRT patients for 30Gy 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 2cm 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. 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 (0.75Gy vs. 2.08Gy, p=0.029). Overall, Halcyon's coplanar geometry resulted in a larger GI (3.33vs. 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<2cm 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 24.4Gy (8.99 cc vs. 7.36 cc) and 28.8Gy (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%/2mm 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 0.35min (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 (7.61min vs. 10.26min, p<0.001). 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 1cm in diameter with the closest OAR distance of greater than 2cm 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.

CNN-based multi-modal radiomics analysis of pseudo-CT utilization in MRI-only brain stereotactic radiotherapy: a feasibility study

BackgroundPseudo-computed tomography (pCT) quality is a crucial issue in magnetic resonance image (MRI)-only brain stereotactic radiotherapy (SRT), so this study systematically evaluated it from the multi-modal radiomics perspective.Methods34 cases (< 30 cm³) were retrospectively included (2021.9-2022.10). For each case, both CT and MRI scans were performed at simulation, and pCT was generated by a convolutional neural network (CNN) from planning MRI. Conformal arc or volumetric modulated arc technique was used to optimize the dose distribution. The SRT dose was compared between pCT and planning CT with dose volume histogram (DVH) metrics and gamma index. Wilcoxon test and Spearman analysis were used to identify key factors associated with dose deviations. Additionally, original image features were extracted for radiomic analysis. Tumor control probability (TCP) and normal tissue complication probability (NTCP) were employed for efficacy evaluation.ResultsThere was no significant difference between pCT and planning CT except for radiomics. The mean value of Hounsfield unit of the planning CT was slightly higher than that of pCT. The Gadolinium-based agents in planning MRI could increase DVH metrics deviation slightly. The median local gamma passing rates (1%/1 mm) between planning CTs and pCTs (non-contrast) was 92.6% (range 63.5–99.6%). Also, differences were observed in more than 85% of original radiomic features. The mean absolute deviation in TCP was 0.03%, and the NTCP difference was below 0.02%, except for the normal brain, which had a 0.16% difference. In addition, the number of SRT fractions and lesions, and lesion morphology could influence dose deviation.ConclusionsThis is the first multi-modal radiomics analysis of CNN-based pCT from planning MRI for SRT of small brain lesions, covering dosiomics and radiomics. The findings suggest the potential of pCT in SRT plan design and efficacy prediction, but caution needs to be taken for radiomic analysis.

Changing trends in gamma knife surgery to linear accelerator brain stereotactic radiotherapy in Japan: a survey based on the nationwide claims database

PurposeThis study evaluated the trends in the platform for stereotactic radiotherapy to the brain (SRT), utilizing the open data of the National Database published by the Ministry of Health, Labour, and Welfare.Materials and methodsThis study analyzed data from FY2014 to FY2021. The practices included in the study were gamma knife surgery (GKS) and SRT with a linear accelerator (LINAC). The total number of outpatient and inpatient cases in each SRT system was evaluated annually.ResultsFrom April 2014 to March 2022, the study included 212,016 cases (102,691 GKS and 109,325 LINAC) of the registered 1,996,540 radiotherapy cases. In the first year, 13,117 (54.1%) cases were GKS, and 11,128 (45.9%) were LINAC; after that, GKS decreased, and LINAC increased, reaching the same rate in FY2017. Compared to the first year, the final year showed 11,702 GKS (− 1415 or − 10.8%) and 17,169 LINAC (+ 6041 or + 54.3%), with an increase of 4626 total SRT cases to 28,871 (+ 19.1%). The percentage of outpatient treatment also increased from 4.6 to 11.8% for GKS and from 44.7 to 57.9% for LINAC.ConclusionThe study found a gradual decrease in the selection of GKS, an increasing trend in the selection of LINAC, and an increase in the overall number of stereotactic irradiations. In particular, the proportion of outpatient treatment increased, indicating that more than half of LINAC was selected for outpatient treatment.

Feasibility of Using Pseudo-CT for Dosimetry, Radiomics, and Efficacy Assessment in IMRT/VMAT of Brain Tumors: A Multi-Omics Analysis

Pseudo-CT generated by convolutional neural networks (CNN) and planning MRI has facilitated the promotion of MRI-Only. The technology not only reduces the time and money spent on CT scans, but also eliminates the cumbersome CT-MR registration. The feasibility in Stereotactic Brain Radiotherapy has been analyzed in previous studies by our team. However, when the prescribed requirements are not met, IMRT/VMAT are still selected. The study aims to evaluate the feasibility of pseudo-CT in IMRT/VMAT for brain cancer via the following 5 aspects: (1) image difference, (2) dose accuracy, (3) radiomics feature, (4) efficacy assessment, and (5) correlation analysis. Brain tumor patients who had received radiotherapy at our institution and had planning MRI and CT were included in the study. Redesign of IMRT and VMAT radiotherapy plans according to 3 × 15Gy for each patient. Hounsfield unit (HU) values for PTV and OARs were used to assess image differences. And dose accuracy analysis contained a 2D dose volume histogram (DVH) metrics (Dmax, Dmean, D2%, D50%, D98%, HI, CI) and 3D gamma metrics (criteria: 1-3%/2mm, 1%/1mm, 10% threshold). Then 107 original image features of PTV and OARs were extracted for radiometry analysis. And tumor control probability (TCP) of PTV (Poisson model) and normal tissue complication probability (NTCP) of OARs (Lyman-Kutcher-Burman model) were used for the variance analysis of efficacy assessment. Wilcox-test was used for significance of differences test (0.05), and spearman correlation analysis was used to explore the key features of the dose bias. A total of 42 patients were included, with 42 planning CTs and pseudo-CTs (mDixon-T1), and 38 pseudo-CTs (mDixon-T1-CE). The median volume of PTV was 4.1 cc (range 0.5-27.3), with no significant differences in HU, DVH, 3D gamma, and NTCP/TCP metrics. The median local gamma passing rates (1%/1mm) between planning CTs and pseudo-CTs (mDixon-T1) were 93.1% (range 65.5%-99.7%, IMRT) and 93.3% (range 63.9%-99.6%, VMAT). And more than 85% original radiomics features have significant difference. Further, the feature HU-Min was found to be more correlated with dose metrics in the correlation analysis. We speculate that it may be caused by the smoothing of the low frequency signal before outputting image. And since Shape_MeshVolume, Shape_VoxelVolume and PTV volume difference are highly correlated with dose deviation, it indicates that dose deviation affected by CT-MR registration. This study has the potential to provide guidance for the clinical application of pseudo-CT in the MRI-Only workflow with IMRT/VMAT for brain tumors. These quantitative results strongly indicate pseudo-CT can be used as a substitute for the initial CT in IMRT/VMAT for small brain lesions (size <5 cm, numbers <5), but not for radiomics analysis. Additionally, the impact of inter-image differences on dose accuracy is less significant compared to the deviation caused by image registration.

Effect of Different Timing of Local Brain Radiotherapy on Survival of EGFR-Mutated NSCLC Patients with Limited Brain Metastases.

(1) Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been the first line therapy for EGFR-mutant lung adenocarcinoma (LAC) patients with brain metastases (BMs). However, the role and the optimal time of brain radiotherapy remains controversial. We aimed to investigate the role of upfront brain stereotactic radiotherapy (SRS) and the impact of deferral radiotherapy on patients' clinical outcomes. (2) Methods: We retrospectively studied 53 EGFR-mutant LAC patients with limited synchronous BMs between 2014 and 2020 at our institute. The limited BMs was defined with one to four BM lesions, with a maximal size of ≤4 cm. Patients were categorized into two groups: upfront brain SRS (upfront RT) and upfront TKIs. The intracranial progression-free survival (iPFS), progression-free survival (PFS), and overall survival (OS) between groups were analyzed. (3) Results: The median iPFS (21.0 vs. 12.0 months, p = 0.002) and PFS (20.0 vs. 11.0 months, p = 0.004) of the upfront RT group was longer than that of the upfront TKI group. There were no significant differences in median OS (30.0 vs. 26.0 months, p = 0.552) between the two groups. The upfront RT group is less likely to suffer from intracranial progression of the original sites than that of upfront TKIs during the disease course (36.1% vs. 0.0%, p = 0.025). Multivariate analysis showed that the Karnofsky Performance Scale and the presence of synchronous meningeal metastases were associated with overall survival. (4) Conclusions: Compared with upfront TKI, the combination of upfront SRS with TKIs can improve the iPFS and PFS in EGFR-mutant LAC with synchronous BMs. The addition of upfront brain SRS was useful for the original intracranial metastatic lesions.

Surface guided radiation therapy with an innovative open-face mask and mouth bite: patient motion management in brain stereotactic radiotherapy.

To guarantee treatment reproducibility and stability, immobilization devices are essential. Additionally, surface-guided radiation therapy (SGRT) serves as an accurate complement to frameless stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) by aiding patient positioning and real-time monitoring, especially when non-coplanar fields are in use. At our institute, we have developed a surface-guided SRS (SG-SRS) workflow that incorporates our innovative open-face mask (OM) and mouth bite (MB) to guarantee a precise and accurate dose delivery. This study included 40 patients, and all patients were divided into closed mask (CM) and open-face mask (OM) groups according to different positioning flow. Cone beam computed tomography (CBCT) scans were performed, and the registration results were recorded before and after the treatment. Then Bland-Altman method was used to analyze the consistency of AlignRT-guided positioning errors and CBCT scanning results in the OM group. The error changes between 31 fractions in one patient were recorded to evaluate the feasibility of monitoring during treatment. The median of translation error between stages of the AlignRT positioning process was (0.03-0.07) cm, and the median of rotation error was (0.20-0.40)°, which were significantly better than those of the Fraxion positioning process (0.09-0.11) cm and (0.60-0.75)°. The mean bias values between the AlignRT guided positioning errors and CBCT were 0.01cm, -0.07cm, 0.03cm, -0.30°, -0.08° and 0.00°. The 31 inter-fractional errors of a single patient monitored by SGRT were within 0.10cm and 0.50°. The application of the SGRT with an innovative open-face mask and mouth bite device could achieve precision positioning accuracy and stability, and the accuracy of the AlignRT system exhibits excellent constancy with the CBCT gold standard. The non-coplanar radiation field monitoring can provide reliable support for motion management in fractional treatment.

Effective clinical applications of Monte Carlo-based independent secondary dose verification software for helical tomotherapy

PurposeTo investigate the scope of the effective clinical application of Monte Carlo (MC)-based independent dose verification software for helical tomotherapy. MethodsDoseCHECK was selected as the MC-based dose calculation software. First, the dose calculation accuracy of DoseCHECK was evaluated with film and chamber measurements in a water-equivalent phantom. Second, the dose calculation accuracy was examined in several heterogeneous materials. Finally, dosimetric comparisons between DoseCHECK and the treatment planning system (TPS) were performed for clinical patient plans. Prostate IMRT, head and neck IMRT (HN), total body irradiation (TBI), and brain stereotactic radiotherapy (SRT) were evaluated. ResultThe DoseCHECK calculations agreed with the chamber and film measurements in the homogenous phantom. For heterogeneous phantom cases, the dose differences between DoseCHECK and TPS were within 3 %, except in air, in which large dose differences of 20 % were observed. In clinical patient plans, the median dose differences between the lung Dmean in TBI cases and the normal brain Dmean in brain SRT cases were significantly >3 %. For HN and brain SRT cases, the median target dose differences were >3 %. ConclusionOur results show that independent dose verification with the MC algorithm can detect systematic errors caused by the lack of heterogeneity correction in the TPS. In particular, MC-based independent dose verification is required for HN, TBI, and brain SRT cases in helical tomotherapy.

Leveraging Serial MRI Radiomics and Machine Learning to Predict Risk of Radiation Necrosis in Patients with Brain Metastases Managed with Stereotactic Radiation and Immunotherapy

<h3>Purpose/Objective(s)</h3> Radiation necrosis (RN) is the primary dose-limiting toxicity of stereotactic radiotherapy (SRT) for brain metastases (BMs), especially in patients also receiving immunotherapy (IO). We investigated the utility of serial magnetic resonance imaging (MRI) radiomic features to develop predictive quantitative imaging biomarkers of brain metastases response to SRT and IO. <h3>Materials/Methods</h3> Using an IRB-approved single-institution database, we retrospectively identified adult patients with brain metastases managed with SRT and IO between 2006 and 2021. We collected per-lesion outcomes measures of RN (radiographic and/or symptomatic), progressive disease (PD), or neither (NA). Routine pre- and post-SRT contrast-enhanced T1-weighted MRIs were pushed to MIM Software (Beachwood, OH), where individual BMs were manually contoured. A total of 1061 radiomics features were extracted per lesion using a digital gene expression panel. They were selected from the following categories: shape, intensity, neighborhood intensity difference (NID), grey-level co-occurrence matrix (GLCM), and grey-level run-length matrix (GLRLM). Feature reduction followed using Spearman's correlation coefficient (0.3 cut-off). Features with non-significantly different mean ranks pre- and post-SRT (p<0.01) per Wilcoxon signed-rank test were also excluded. Simple then multiple nominal logistic regressions (SLR and MLR) with Bonferroni correction were used to model the risk of RN, PD, or NA based on pre- and post-SRT, and delta-radiomic ([post-pre]/pre) features. 95% CI of ROC AUC was obtained by 10,000 bootstrapping. Statistical analysis was performed using software. <h3>Results</h3> Our dataset encompassed 301 BMs from 92 patients with NSCLC, melanoma, and renal cell carcinoma, all treated with brain SRT and IO. 74 (24.6%), 75 (24.9%), and 152 developed RN, PD, or NA, respectively. The final radiomic feature set included 39 features that significantly changed post-SRT (p<0.01). MLR resulted in a 3-radiomic feature model that predicted risk of RN (ROC AUC 0.71). The model included post-SRT BM surface area and texture (GLCM 3D Homogeneity) and pre-RT BM roundness. Interestingly, another 5-radiomic feature MLR model predicted RN and PD (ROC AUC 0.71) based on pre-SRT GLCM 3D texture feature, 3 post-SRT shape features (surface area, mean breadth, and roundness), in addition to delta-volume. <h3>Conclusion</h3> Our analysis showed that static and serial MR radiomic features could potentially predict BMs response to SRT and IO. Model external validation, combination with clinical variables, and integration of other MRI sequences are warranted before the large-scale adoption of this novel diagnostic approach.

Efficacy and Safety of Combined Brain Stereotactic Radiotherapy and Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer with Brain Metastases.

Background: To analyze the outcomes of patients with brain metastases (BM) from non-small cell lung cancer (NSCLC) treated with immunotherapy (IT) and stereotactic radiotherapy (SRT) and to study the impact of the sequence between the two modalities. Methods: The authors reviewed the records of 51 patients with 84 BM from NSCLC treated at Institut Curie with IT and SRT. BM were categorized into three groups: ‘SRT before IT’, ‘concurrent SRT and IT’, and ‘SRT after IT.’ Regional progression-free interval (R-PFI) and overall survival (OS) were estimated using the Kaplan–Meier method. Results: After a median follow-up from SRT of 22.5 months (2.7–47.3), the 1-year and 2-year OS were 69.7% (95%CI [58.0–83.8]) and 44.0% [30.6–63.2], respectively. Concerning distant intracranial control, the 1-year and 2-year R-PFI were 40.1% [30.1–53.3] and 35.2% [25.1–49.4], respectively. Moreover, one-year R-PFI in ‘SRT before IT’, ‘concurrent SRT and IT’, and ‘SRT after IT’ groups were 24.1%, 49.6%, and 34.2%, respectively (p = 0.094). The type of therapeutic sequence did not appear to impact the risk of brain necrosis. Conclusions: The concurrent administration of SRT and IT appeared to offer the best locoregional control, without increasing the risk of toxicity, compared to patients treated with SRT before or after IT.

Radiosurgery and Stereotactic Brain Radiotherapy with Systemic Therapy in Recurrent High-Grade Gliomas: Is It Feasible? Therapeutic Strategies in Recurrent High-Grade Gliomas.

Purpose. For recurrent high-grade gliomas (HGG), no standard therapeutic approach has been reported; thus, surgery, chemotherapy, and re-irradiation (re-RT) may all be proposed. The aim of the study was to evaluate safety and efficacy of re-RT by radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) in association to chemotherapy in patients with recurrent HGG. Material/Methods: All patients with histological diagnosis of HGG that suffered by recurrent disease diagnosed by magnetic resonance imaging (MRI), according to Response Assessment in Neuro-Oncology (RANO) criteria, after primary/adjuvant chemo-radiotherapy treatment and underwent to re-RT by SRS/FSRT were included in the analysis. Second-line chemotherapy was administered. Outcomes were evaluated by neurological examination and brain MRI performed 1 month after re-RT and then every 2–3 months. Results: From November 2019 to September 2021, 30 patients presenting recurrent HGG underwent re-RT. Median dose was 24 Gy (range 15–36 Gy), and median fractions was 5 (range 1–6). Twenty-one patients (70%) had RPA class ≤ IV. One patient had a histological diagnosis of anaplastic oligodendroglioma, 24 patients (80%) were affected by glioblastoma (GBM) including 3 cases of multifocal form, and 5 patients (17%) by anaplastic astrocytoma. Median time between primary/adjuvant RT and disease recurrence was 8 months. In six cases (20%) re-operation was performed, and in most cases (87%), a second line of systemic therapy was administrated. At a median follow-up time from recurrence of 13 months (range 6–56 months), 10 patients (33%) were alive: 2 patients with partial response disease, 7 patients with stable disease, and 1 patient with out-field progression disease. Of the 20 patients who died (67%), 15 (75%) died for progression disease and 5 (25%) for other causes (3 due to septic event, 1 due to thrombo-embolic event, and 1 due to car accident). Median OS and PFS after recurrence were 12.1 and 11.2 months. Six-month and one-year OS were, respectively, 81% and 51%. No acute or late neurological side effects grade ≥ 2 and no case of radio-necrosis were reported. One patient experienced, after reintervention and during Regorafenib treatment (administered 40 days after surgery), dehiscence of the surgical wound. In three cases, grade 2 distal paresthesia was reported. Grade 3–4 hematologic toxicity occurred in seven cases. Three case of grade 5 toxicities during chemotherapy were reported: three septic events and one thrombo-embolic event. Conclusion. Re-RT with SRT/FSRT in association with second-line systemic therapy is a safe and feasible treatment for patients with HGG recurrence. Validation of these results by prospective studies is needed.

Delayed [ 18 F]-FDG PET Imaging Increases Diagnostic Performance and Reproducibility to Differentiate Recurrence of Brain Metastases From Radionecrosis.

Differentiating brain metastasis recurrence from radiation necrosis can be challenging during MRI follow-up after stereotactic radiotherapy. [ 18 F]-FDG is the most available PET tracer, but standard images performed 30 to 60 minutes postinjection provide insufficient accuracy. We compared the diagnostic performance and interobserver agreement of [ 18 F]-FDG PET with delayed images (4-5 hours postinjection) with the ones provided by standard and dual-time-point imaging. Consecutive patients referred for brain [ 18 F]-FDG PET after inconclusive MRI were retrospectively included between 2015 and 2020 in 3 centers. Two independent nuclear medicine physicians interpreted standard (visually), delayed (visually), and dual-time-point (semiquantitatively) images, respectively. Adjudication was applied in case of discrepancy. The final diagnosis was confirmed histologically or after 6 months of MRI follow-up. Areas under the receiver operating characteristic curves were pairwise compared. Forty-eight lesions from 46 patients were analyzed. Primary tumors were mostly located in the lungs (57%) and breast (23%). The median delay between radiotherapy and PET was 15.7 months. The final diagnosis was tumor recurrence in 24 of 48 lesions (50%), with histological confirmation in 19 of 48 lesions (40%). Delayed images provided a larger area under the receiver operating characteristic curve (0.88; 95% confidence interval [CI], 0.75-0.95) than both standard (0.69; 95% CI, 0.54-0.81; P = 0.0014) and dual-time-point imaging (0.77; 95% CI, 0.63-0.88; P = 0.045), respectively. Interobserver agreement was almost perfect with delayed images ( κ = 0.83), whereas it was moderate with both standard ( κ = 0.48) and dual-time-point images ( κ = 0.61). [ 18 F]-FDG PET with delayed images is an accurate and reliable alternative to differentiate metastasis recurrence from radiation necrosis in case of inconclusive MRI after brain stereotactic radiotherapy.

Accuracy of MRI-CT registration in brain stereotactic radiotherapy: Impact of MRI acquisition setup and registration method

BackgroundIn MR-based radiotherapy (RT), MRI images are co-registered to the planning CT to leverage MR image information for RT planning. Especially in brain stereotactic RT, where typical CTV-PTV margins are 1-2 mm, high registration accuracy is critical. Several factors influence the registration accuracy, including the acquisition setup during MR simulation and the registration methods. PurposeIn this work, the impact of the MRI acquisition setup and registration method was evaluated in the context of brain RT, both geometrically and dosimetrically. Methods and MaterialsMRI of 20 brain radiotherapy patients was acquired in two MRI acquisition setups (RT and diagnostic). Three different automatic registration tools provided by three treatment planning systems were used to rigidly register both MRIs and CT in addition to the clinical registration. Segmentation-based evaluation using Hausdorff Distance (HD)/Dice Similarity Coefficient and landmark-based evaluation were used as evaluation metrics. Dose-volume-histograms were evaluated for target volumes and various organs at risks. ResultsMRI acquisition in the RT setup provided a similar head extension as compared to the planning CT. The registration method had a more significant influence than the acquisition setup (Wilcoxon signed-rank test, p<0.05). When registering using a less optimal registration method, the RT setup improved the registration accuracy compared to the diagnostic setup (Difference: ΔMHD = 0.16 mm, ΔHDP95 = 0.64 mm, mean Euclidean distance (ΔmEuD) = 2.65 mm). Different registration methods and acquisition setups lead to the variation of the clinical DVH. Acquiring MRI in the RT setup can improve PTV and GTV coverage compared to the diagnostic setup. ConclusionsBoth MRI acquisition setup and registration method influence the MRI-CT registration accuracy in brain RT patients geometrically and dosimetrically. MR-simulation in the RT setup assures optimal registration accuracy if automatic registration is impaired, and therefore recommended for brain RT.

Clinical implementation of HyperArc.

The aim of this study was to present our experience on clinical implementation of HyperArc including dosimetric comparison between VMAT and HyperArc plans and dosimetric verification of HyperArc. In this study, eleven previously treated cases of brain metastasis were selected from our brain stereotactic radiotherapy program. The cases were retrospectively planned using HyperArc technique and the plan quality was evaluated. In addition, dosimetric effects of HyperArc plan with different energies and using jaw tracking technique were evaluated. Furthermore, dosimetric verification of HyperArc plans was performed using ion chamber and radiochromic film. Our results of dosimetric comparison shows that HyperArc technique improved both conformity index and gradient index compared to VMAT plans. We also found that using 6MV flattening filter free (6MV-FFF) beam improves gradient index in HyperArc plans compared to using 6MV flattening filter beam. Furthermore, our results show that jaw tracking technique reduces the size of low dose volume while maintaining similar target coverage, conformity index, and gradient index. In our dosimetric verification study, results of ion chamber and film measurement indicate no significant difference between VMAT and HyperArc plans. In conclusion, HyperArc simplifies planning of stereotactic treatment for brain and improves the dosimetry in treatment plans. Additionally, HyperArc provides for a safe and efficient treatment delivery system for stereotactic treatments to brain.

Comparison with Conventional Arc and Split-Partial Arc Techniques of Volumetric Modulated Arc Therapy (VMAT) in Terms of Planning Efficiency for Stereotactic Radiotherapy (SRT) Treatment of Multiple Brain Metastases

Purpose: In stereotactic radiotherapy of multiple brain metastases (BM), Conventional Arc (CA) of the volumetric modulated arc therapy (VMAT) technique with on a single isocentric is a frequently used technique with Linac (Linear Accelerator) treatment devices. Reducing the dose of healthy brain tissue as well as improved delivery efficiency in SRT treatment of BM is important to reduce possible treatment toxicity. Therefore, multileaf collimator (MLC) movements in wide arcs of CA technique may result in non-optimal dose distribution and increasing low-dose volume in the brain. To evaluate improve the protection in brain of SPA technique having reduced field sizes which minimizes physical limitations of MLC moves. Methods: 28 patients with 3≤, ≥6 of multiple BM included in this retrospective planning study. All plans were generated 27 Gy in 3 fractions using conventional arcs with automated wide of fields and split partial arcs with the manual arrangement of fields according to tumors localization in brain. Dosimetric parameters included tumor coverage, conformity index (CI), gradient index (GI), V4Gy, V10Gy and V12Gy volumes of brain from both techniques were compared by Wilcoxon signed-ranked tests. Results: Both techniques satisfied clinical requirements in coverages of PTV and CI. CA technique had a significantly higher GI than SPA of VMAT (GI; 4.19 vs. 3.58; p &lt; 0.001). SPA technique was found significantly lower V4Gy (18.50 vs. 21.30 cm3, p &lt; 0.001), V10Gy (30.71 vs. 40.76 cm3, p &lt; 0.05) and V12Gy (213.32 vs. 305.71 cm3, p&lt;0.05) volumes. Conclusions: Due to rapid MLC modulation and less tongue-and-groove effect in arcs with smaller field widths, SPA technique can reduce OAR and brain dose radiation exposure in brain stereotactic radiotherapy for different tumor localizations in the brain. This technique may be the first choice compared to the CA technique for SRT of BM having distant and scattered targets.

OD04 - An assessment of the accuracy of the different delivery methods of stereotactic brain radiotherapy

OD04 - An assessment of the accuracy of the different delivery methods of stereotactic brain radiotherapy

Combined effect of dose gradient and rotational error on prescribed dose coverage for single isocenter multiple brain metastases in frameless stereotactic radiotherapy

BackgroundTo evaluate the combined effect of rotational error and dose gradient on target dose coverage in frameless stereotactic radiotherapy.MethodsThree spherical targets of different diameters (1, 1.5, and 2 cm) were drawn and placed equidistantly on the same axial brain computed tomography (CT) images. To test the different isocenter-target distances, 2.5- and 5-cm configurations were prepared. Volumetric modulated arc therapy plans were created for different dose gradients from the target, in which the dose gradients were modified using the maximum dose inside the target. To simulate the rotational error, CT images and targets were rotated in two ways by 0.5°, 1°, and 2°, in which one rotation was in the axial plane and the other was in three dimensions. The initial optimized plan parameters were copied to the rotated CT sets, and the doses were recalculated. The coverage degradation after rotation was analyzed according to the target dislocation and 12-Gy volume.ResultsA shallower dose gradient reduced the loss of target coverage under target dislocation, and the effect was clearer for small targets. For example, the coverage of the 1-cm target under 1-mm dislocation increased from 93 to 95% by increasing the Paddick gradient index from 5.0 to 7.9. At the same time, the widely accepted necrosis indicator, the 12-Gy volume, increased from 1.2 to 3.5 cm3, which remained in the tolerable range. From the differential dose volume histogram (DVH) analysis, the shallower dose gradient ensured that the dose-deficient under-covered target volume received a higher dose similar to that in the prescription.ConclusionsFor frameless stereotactic brain radiotherapy, the gradient, alongside the margin addition, can be adjusted as an ancillary parameter for small targets to increase target coverage or at least limit coverage reduction in conditions with probable positioning error.

Intrafraction stability using full head mask for brain stereotactic radiotherapy.

PurposeWe investigated the immobilization accuracy of a new type of thermoplastic mask—the Double Shell Positioning System (DSPS)—in terms of geometry and dose delivery.MethodsThirty‐one consecutive patients with 1–5 brain metastases treated with stereotactic radiotherapy (SRT) were selected and divided into two groups. Patients were divided into two groups. One group of patients was immobilized by the DSPS (n = 9). Another group of patients was immobilized by a combination of the DSPS and a mouthpiece (n = 22). Patient repositioning was performed with cone beam computed tomography (CBCT) and six‐degree of freedom couch. Additionally, CBCT images were acquired before and after treatment. Registration errors were analyzed with off‐line review. The inter‐ and intrafractional setup errors, and planning target volume (PTV) margin were also calculated. Delivered doses were calculated by shifting the isocenter according to inter‐ and intrafractional setup errors. Dose differences of GTV D99% were compared between planned and delivered doses against the modified PTV margin of 1 mm.ResultsInterfractional setup errors associated with the mouthpiece group were significantly smaller than the translation errors in another group (p = 0.03). Intrafractional setup errors for the two groups were almost the same in all directions. PTV margins were 0.89 mm, 0.75 mm, and 0.90 mm for the DSPS combined with the mouthpiece in lateral, vertical, and longitudinal directions, respectively. Similarly, PTV margins were 1.20 mm, 0.72 mm, and 1.37 mm for the DSPS in the lateral, vertical, and longitudinal directions, respectively. Dose differences between planned and delivered doses were small enough to be within 1% for both groups.ConclusionsThe geometric and dosimetric assessments revealed that the DSPS provides sufficient immobilization accuracy. Higher accuracy can be expected when the immobilization is combined with the use of a mouthpiece.

Dosimetric Validation of a GAN-Based Pseudo-CT Generation for MRI-Only Stereotactic Brain Radiotherapy.

Simple SummaryStereotactic radiotherapy (SRT) has become widely accepted as a treatment of choice for patients with a small number of brain metastases that are of an acceptable size. A magnetic resonance imaging (MRI)-only workflow could shorten the planning time and reduce the risk of misalignment in this treatment. Given the absence of a calibrated electronic density in MRI, we successfully compared generative adversarial network (GAN)-generated computed tomography (CT) scans from diagnostic brain MRIs with initial CT scans for the planning of brain stereotactic radiotherapy, finding a high similarity between the planning CT and the synthetic CT for both the organs at risk and the target volumes.Purpose: Stereotactic radiotherapy (SRT) has become widely accepted as a treatment of choice for patients with a small number of brain metastases that are of an acceptable size, allowing for better target dose conformity, resulting in high local control rates and better sparing of organs at risk. An MRI-only workflow could reduce the risk of misalignment between magnetic resonance imaging (MRI) brain studies and computed tomography (CT) scanning for SRT planning, while shortening delays in planning. Given the absence of a calibrated electronic density in MRI, we aimed to assess the equivalence of synthetic CTs generated by a generative adversarial network (GAN) for planning in the brain SRT setting. Methods: All patients with available MRIs and treated with intra-cranial SRT for brain metastases from 2014 to 2018 in our institution were included. After co-registration between the diagnostic MRI and the planning CT, a synthetic CT was generated using a 2D-GAN (2D U-Net). Using the initial treatment plan (Pinnacle v9.10, Philips Healthcare), dosimetric comparison was performed using main dose-volume histogram (DVH) endpoints in respect to ICRU 91 guidelines (Dmax, Dmean, D2%, D50%, D98%) as well as local and global gamma analysis with 1%/1 mm, 2%/1 mm and 2%/2 mm criteria and a 10% threshold to the maximum dose. t-test analysis was used for comparison between the two cohorts (initial and synthetic dose maps). Results: 184 patients were included, with 290 treated brain metastases. The mean number of treated lesions per patient was 1 (range 1–6) and the median planning target volume (PTV) was 6.44 cc (range 0.12–45.41). Local and global gamma passing rates (2%/2 mm) were 99.1 CI95% (98.1–99.4) and 99.7 CI95% (99.6–99.7) respectively (CI: confidence interval). DVHs were comparable, with no significant statistical differences regarding ICRU 91′s endpoints. Conclusions: Our study is the first to compare GAN-generated CT scans from diagnostic brain MRIs with initial CT scans for the planning of brain stereotactic radiotherapy. We found high similarity between the planning CT and the synthetic CT for both the organs at risk and the target volumes. Prospective validation is under investigation at our institution.