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Background: Fractionated stereotactic radiosurgery (fSRS) is an important treatment strategy for unresected brain metastases. We previously reported that a good volumetric response 6 months after fSRS can be the first step for local control. Few studies have reported the association between gross tumor volume (GTV) dose, volumetric response, and local control in patients treated with the same number of fractions. Therefore, in this study, we aimed to investigate the GTV dose and volumetric response 6 months after fSRS in five daily fractions and identify the predictive GTV dose for local failure (LF) for unresected brain metastasis., Methods: This retrospective study included 115 patients with 241 unresected brain metastases treated using fSRS in five daily fractions at our hospital between January 2013 and April 2022. The median prescription dose was 35 Gy (range, 30-35 Gy) in five fractions. The median follow-up time after fSRS was 16 months (range, 7-66 months)., Results: GTV D80 > 42 Gy and GTV D98 > 39 Gy were prognostic factors for over 65% volume reduction (odds ratio, 3.68, p < 0.01; odds ratio, 4.68, p < 0.01, respectively). GTV D80 > 42 Gy was also a prognostic factor for LF (hazard ratio, 0.37; p = 0.01)., Conclusions: GTV D80 > 42 Gy in five fractions led to better volume reduction and local control. The goal of planning an inhomogeneous dose distribution for fSRS in brain metastases may be to increase the GTV D80 and GTV D98. Further studies on inhomogeneous dose distributions are required., (© 2024. The Author(s).)

In linear accelerator-based stereotactic irradiation (STI) for brain metastasis, cone-beam computed tomography (CBCT) image quality is essential for ensuring precise patient setup and tumor localization. However, CBCT images may be degraded by the deviation of the CBCT isocenter from the brain center. This study aims to investigate the effects of the distance from the brain center to the CBCT isocenter (DBI) on the image quality in STI. An anthropomorphic phantom was scanned with varying DBI in right, anterior, superior, and inferior directions. Thirty patients undergoing STI were prospectively recruited. Objective metrics, utilizing regions of interest included contrast-to-noise ratio (CNR) at the centrum semiovale, lateral ventricle, and basal ganglia levels, gray and white matter noise at the basal ganglia level, artifact index (AI), and nonuniformity (NU). Two radiation oncologists assessed subjective metrics. In this phantom study, objective measures indicated a degradation in image quality for non-zero DBI. In this patient study, there were significant correlations between the CNR at the centrum semiovale and lateral ventricle levels (r s = - 0.79 and - 0.77, respectively), gray matter noise (r s = 0.52), AI (r s = 0.72), and NU (r s = 0.91) and DBI. However, no significant correlations were observed between the CNR at the basal ganglia level, white matter noise, and subjective metrics and DBI (r s  < ± 0.3). Our results demonstrate the effects of DBI on contrast, noise, artifacts in the posterior fossa, and uniformity of CBCT images in STI. Aligning the CBCT isocenter with the brain center can aid in improving image quality., (© 2024. Australasian College of Physical Scientists and Engineers in Medicine.)

Purpose: The geometric distortion related to magnetic resonance (MR) imaging in a diagnostic radiology (MR DR ) and radiotherapy (MR RT ) setup is evaluated, and the dosimetric impact of MR distortion on fractionated stereotactic radiotherapy (FSRT) in patients with brain metastases is simulated., Materials and Methods: An anthropomorphic skull phantom was scanned using a 1.5‑T MR scanner, and the magnitude of MR distortion was calculated with (MR DR -DC and MR RT -DC) and without (MR DR -nDC and MR RT -nDC) distortion-correction algorithms. Automated noncoplanar volumetric modulated arc therapy (HyperArc, HA; Varian Medical Systems, Palo Alto, CA, USA) plans were generated for 53 patients with 186 brain metastases. The MR distortion at each gross tumor volume (GTV) was calculated using the distance between the center of the GTV and the MR image isocenter (MIC) and the quadratic regression curve derived from the phantom study (MR RT -DC and MR RT -nDC). Subsequently, the radiation isocenter of the HA plans was shifted according to the MR distortion at each GTV (HA DC and HA nDC )., Results: The median MR distortions were approximately 0.1 mm when the distance from the MIC was < 30 mm, whereas the median distortion varied widely when the distance was > 60 mm (0.23, 0.47, 0.37, and 0.57 mm in MR DR -DC, MR DR -nDC, MR RT -DC, and MR RT -nDC, respectively). The dose to the 98% of the GTV volume (D 98% ) decreased as the distance from the MIC increased. In the HA DC plans, the relative dose difference of D 98% was less than 5% when the GTV was located within 70 mm from the MIC, whereas the underdose of GTV exceeded 5% when it was 48 mm (-26.5% at maximum) away from the MIC in the HA nDC plans., Conclusion: Use of a distortion-correction algorithm in the studied MR diagnoses is essential, and the dosimetric impact of MR distortion is not negligible, particularly for tumors located far away from the MIC., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

To compare the dosimetric parameters of automated noncoplanar volumetric modulated arc therapy plans using single-isocentric (SIC) and multi-isocentric (MIC) techniques for patients with two brain metastases (BMs) in stereotactic irradiation and to evaluate the robustness of rotational errors. The SIC and MIC plans were retrospectively generated (35 Gy/five fractions) for 58 patients. Subsequently, a receiver operating characteristic curve analysis between the tumor surface distance (TSD) and V 25Gy was performed to determine the thresholds for the brain tissue. The SIC and MIC plans were recalculated based on the rotational images to evaluate the dosimetric impact of rotational error. The MIC plans showed better brain tissue sparing for TSD > 6.6 cm. The SIC plans provided a significantly better conformity index for TSD ≤ 6.6 cm, while significantly lower gradient index was obtained (3.22 ± 0.56vs. 3.30 ± 0.57, p < 0.05) in the MIC plans with TSD > 6.6 cm. For organs at risk (OARs) (brainstem, chiasm, lens, optic nerves, and retinas), D 0.1 cc was significantly lower (p < 0.05) in the MIC plans than in the SIC plans. The prescription dose could be delivered (D 99% ) to the gross tumor volume (GTV) for patients with TSD ≤ 6.6 cm when the rotational error was < 1°, whereas 31% of the D 99% of GTV fell below the prescription dose with TSD > 6.6 cm. MIC plans can be an optimal approach for reducing doses to OARs and providing robustness against rotational errors in BMs with TSD > 6.6 cm., (© 2023. The Author(s), under exclusive licence to Japanese Society of Radiological Technology and Japan Society of Medical Physics.)

Background: Data on acute toxicities after stereotactic radiotherapy (SRT) for brain metastases, including multiple and large lesions, are lacking. We aimed to evaluate the incidence and nature of toxicities immediately after SRT using a linear accelerator., Methods: This retrospective study reviewed the medical records of 315 patients with brain metastases treated with SRT at our institution between May 2019 and February 2022. In total, 439 SRT sessions were performed for 2161 brain metastases. The outcome of interest was immediate side effects (ISEs), defined as new or worsening symptoms occurring during SRT or within 14 days after the end of SRT., Results: Grade ≥ 2 and ≥ 3 ISEs occurred in 16 (3.6%) and 7 (1.6%) cases, respectively. Among 63 treatments for 10 or more lesions (range: 10-40), 1 (1.6%) ISE occurred. Among 22 treatments for lesions with a maximum tumor volume of > 10 cc, 2 (9.1%) ISEs occurred. Grade ≥ 3 ISEs included 1, 4, 1, and 1 cases of grade 3 nausea, grade 3 new-onset partial and generalized seizures, grade 3 obstructive hydrocephalus, and grade 5 intracranial hemorrhage, respectively. ISEs were more common in patients with a larger maximum tumor volume, primary sites other than lung and breast cancer, and pre-treatment neurological symptoms., Conclusion: SRT using a linear accelerator for brain metastases, including multiple and large lesions, is safe, with a low incidence of ISEs. Serious complications immediately after SRT are rare but possible; therefore, careful follow-up is necessary after treatment initiation., (© 2023. The Author(s).)

Background and Purpose: Few reports include volumetric measurements as endpoints after stereotactic radiotherapy (SRT) despite the importance of such measurements. This study aimed to (1) investigate the impact of the volumetric response (specifically, an over 65% and over 90% volume reduction in brain metastases) at 6 months post-SRT on local control and (2) identify the predictive factors for a volumetric response of over 65% and over 90%., Materials and Methods: This study included 250 unresected brain metastases (>0.3 cc) treated with SRT. Doses were stratified according to the biological effective dose (BED). The BED was calculated using four models: linear-quadratic (LQ): α/β = 10; LQ: α/β = 20; LQ cubic: α/β = 12; and LQ linear: α/β = 10. The median prescription dose was 30 Gy/3 fractions (BED20, 45). The median follow-up time after SRT was 18.6 months (range, 6.4-81.8 months)., Results: In the multivariate analysis, over 65% volume reduction and over 90% volume reduction were prognostic factors for local control (hazard ratio: 2.370, p = 0.011 and hazard ratio: 3.161, p = 0.014, respectively). A dose of 80% of the gross tumor volume (GTV) D80 > BED20 58 was a predictive factor for over 65% and over 90% volume reductions (odds ratio: 1.975, p = 0.023; odds ratio: 3.204, p < 0.001, respectively)., Conclusion: Robust volume reduction of brain metastases at 6 months post-SRT can predict local control. GTV D80 in the LQ model: α/β = 20 may be warranted for good volume reduction., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: To compare the intrafractional motion error (IME) during stereotactic irradiation (STI) in patients with brain metastases immobilized using open- (Encompass) and full-face (DSPS) clamshell-style immobilization devices., Methods: Encompass (38 patients) and DSPS (38 patients) were used for patient immobilization, and HyperArc plans with three to four non-coplanar beams were generated to deliver 25 to 35 Gy in three to five fractions. Cone-beam computed tomography (CBCT) was performed on patients before and after the treatment. Moreover, the difference in patient position between the two CBCT images was considered as the IME. The margins to compensate for IME were calculated using the van Herk margin formula., Results: For Encompass, the mean values of IME in the translational setup were 0.1, 0.2, and 0.0 mm in the anterior-posterior, superior-inferior, and left-right directions, respectively, and the mean values of IME about rotational axes were -0.1, 0.0, and 0.0° for the Pitch, Roll, and Yaw rotations, respectively. For DSPS, the mean values of IME in the translational setup were 0.2, 0.2, and 0.0 mm in the anterior-posterior, superior-inferior, and left-right directions, respectively, and the mean values of IME about rotational axes were -0.1, -0.1, and 0.0° for the Pitch, Roll, and Yaw rotations, respectively. No statistically significant difference was observed between the IME of the two immobilization systems except in the anterior-posterior direction (p = 0.02). Moreover, no statistically significant correlation was observed between three-dimensional IME and treatment time. The margin compensation for IME was less than 1 mm for both immobilization devices., Conclusions: The IME during STI using open- and full-face clamshell-style immobilization devices is approximately equal considering the adequate accuracy in patient positioning., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

Background/aim: To assess the impact of the width of multileaf collimator (MLC) on dose distributions on HyperArc fractionated stereotactic irradiation for multiple (5-10) brain metastases., Patients and Methods: Twenty-one HyperArc (HA) plans were generated using the high definition (HD) MLC (2.5 mm) to deliver 30-35 Gy in 3-5 fractions (HA-HD). The HyperArc plans using Millennium (ML) MLC (5 mm) were retrospectively generated (HA-ML) using the same planning parameters with HA-HD. Dosimetric parameters between the planning target volume (PTV) and organs at risk (OARs) were compared., Results: The conformity index was significantly higher (p<0.0001) in the HA-HD plans (0.95±0.04) than that in the HA-ML plans (0.92±0.06). The HA-HD provided significantly lower (p<0.0001) gradient index (5.6±2.5) than HA-ML (6.2±3.5). For the brainstem and retina (right), a statistically significant difference (p<0.05) was observed between the HA-HD (12.8±10.9 and 2.8±1.7 Gy, for brainstem and retina, respectively) and HA-ML (13.6±11.1 and 3.0±1.8 Gy) plans. For the brain tissue, the HA-HD plans statistically significantly reduced dosimetric parameters (p<0.0001) in all evaluated dose range (V 6Gy -V 28Gy )., Conclusion: The narrower MLC provided significantly higher conformity, steeper dose gradient, and better normal tissue sparing., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: This study investigated the intra-fractional motion (IM) of patients immobilized using the QFix Encompass Immobilization System during HyperArc (HA) treatment., Method: HA treatment was performed on 89 patients immobilized using the Encompass. The IM during treatment (including megavoltage (MV) registration) was analyzed for six degrees of freedom including three axes of translation (anterior-posterior, superior-inferior (SI) and left-right (LR)) and three axes of rotation (pitch, roll, and yaw). Then, the no corrected IM (IM NC ) was retrospectively simulated (excluding MV registration) in three directions (SI, LR, and yaw). Finally, the correlation between the treatment time and the IM of the 3D vector was assessed., Results: The average IM in terms of the absolute displacement were 0.3 mm (SI), 0.3 mm (LR) and 0.2° (yaw) for Stereotactic radiosurgery (SRS), and 0.3 mm (SI), 0.2 mm (LR), and 0.2° (yaw) for stereotactic radiotherapy (SRT). The absolute maximum values of IM were <1 mm along the SI and LR axes and <1° along the yaw axis. The absolute maximum displacements for IM NC were >1 mm along the SI and LR axes and >1° along the yaw axis. In the correlation between the treatment time and the IM, the r-values were -0.025 and 0.027 for SRS and SRT respectively, along the axes of translation. For the axes of rotation, the r-values were 0.012 and 0.206 for SRS and SRT, respectively., Conclusion: Encompass provided patient immobilization with adequate accuracy during HA treatment. The absolute maximum displacement IM was less than IM NC along the translational/rotational axes, and no statistically significant relationship between the treatment time and the IM was observed., (© 2021 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of American Association of Physicists in Medicine.)

The immobilization of patients with a bite block (BB) carries the risk of interpersonal infection, particularly in the context of pandemics such as COVID-19. Here, we compared the intra-fractional patient setup error (intra-SE) with and without a BB during fractionated intracranial stereotactic irradiation (STI). Fifteen patients with brain metastases were immobilized using a BB without a medical mask, while 15 patients were immobilized without using a BB and with a medical mask. The intra-SEs in six directions (anterior-posterior (AP), superior-inferior (SI), left-right (LR), pitch, roll, and yaw) were calculated by using cone-beam computed tomography images acquired before and after the treatments. We analyzed a total of 53 and 67 treatment sessions for the with- and without-BB groups, respectively. A comparable absolute mean translational and rotational intra-SE was observed (P > 0.05) in the AP (0.19 vs 0.23 mm with- and without-BB, respectively), SI (0.30 vs 0.29 mm), LR (0.20 vs 0.29 mm), pitch (0.18 vs 0.27°), roll (0.23 vs 0.23°) and yaw (0.27 vs 22°) directions. The resultant planning target volume (PTV) margin to compensate for intra-SE was <1 mm. No statistically significant correlation was observed between the intra-SE and treatment times. A PTV margin of <1 mm was achieved even when patients were immobilized without a BB during STI dose delivery., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Purpose: This study aimed to generate a functional image of the liver using dual-energy computed tomography (DECT) and a functional-image-based stereotactic body radiation therapy plan to minimize the dose to the volume of the functional liver (V fl )., Material and Methods: A normalized iodine density (NID) map was generated for fifteen patients with liver tumors. The volume of liver with an NID < 0.46 was defined as V fl , and the ratio between V fl and the total volume of the liver (FLR) was calculated. The relationship between the FLR and Fibrosis-4 (FIB-4) was assessed. For patients with 15% < FLR < 85%, functional volumetric modulated-arc therapy plans (F-VMAT) were retrospectively generated to preserve V fl , and compared to the clinical plans (C-VMAT)., Results: FLR showed a significantly strong correlation with FIB-4 (r = -0.71, p < 0.01). For ten generated F-VMAT plans, the dosimetric parameters of D 99% , D 50% , D 1% and the conformity index were comparable to those of the C-VMAT (p > 0.05). For V fl , F-VMAT plans achieved lower V 5Gy (122.4 ± 31.7 vs 181.1 ± 57.3 cc), V 10Gy (44.4 ± 22.2 vs 98.2 ± 33.3 cc), V 15Gy (22.6 ± 20.3 vs 49.8 ± 33.7 cc), V 20Gy (11.6 ± 14.1 vs 24.9 ± 25.1 cc), and D mean (3.9 ± 2.3 vs 5.8 ± 3.0 Gy) values than the C-VMAT plans (p < 0.01)., Conclusions: The functional image derived from DECT was successfully used, allowing for a reduction in the dose to the V fl without compromising target coverage., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The prognosis of hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT) is poor. We conducted a prospective study to evaluate the efficacy and safety of tri-modality therapy, including preoperative stereotactic body radiotherapy (SBRT) and surgery, followed by hepatic arterial infusion chemotherapy (HAIC) in HCC patients with PVTT. In this report, we investigated the pathology of the irradiated PVTT specimen in resected cases and SBRT-related acute toxicity. A total of 8 HCC patients with PVTT received preoperative SBRT targeting the PVTT at a dose of 48 Gy in 4 fractions at our institute from 2012 to 2016. Of the eight patients, six underwent surgery, while the remaining two did not because of disease progression. At the pathological examination, all patients' irradiated PVTT specimens showed necrotic tissue, and three of six patients showed complete pathological response. Two patients showed 30% necrosis with high degeneration and one patient, with 30% necrosis without degeneration, was the only recurrent case found during the follow-up period (median: 22.5, range: 5.9-49.6 months). No SBRT-related acute toxicity worse than grade 2 was observed from SBRT to surgery. In conclusion, the preoperative SBRT for HCC was pathologically effective and the acute toxicities were tolerable.

Objective: Determination of the optimal energy level of virtual monochromatic image (VMI) for brain metastases in contrast-enhanced dual-energy CT (DECT) for radiosurgery and assessment of the subjective and objective image quality of VMI at the optimal energy level., Methods: 20 patients (total of 42 metastases) underwent contrast-enhanced DECT. Spectral image analysis of VMIs at energy levels ranging from 40 to 140 keV in 1 keV increments was performed to determine the optimal VMI (VMI opt ) as the one corresponding to the highest contrast-to-noise ratio (CNR) between brain parenchyma and the metastases. The objective and subjective values of VMI opt were compared to those of the VMI with 120 kVp equivalent, defined as reference VMI (VMI ref , 77 keV). The objective measurement parameters included mean HU value and SD of tumor and brain parenchyma, absolute lesion contrast (LC), and CNR. The subjective measurements included five-point scale assessment of "overall image quality" and "tumor delineation" by three radiation oncologists., Results: The VMI at 63 keV was defined as VMI opt . The LC and CNR of VMI opt were significantly ( p < 0.01) higher than those of VMI ref (LC: 37.4 HU vs 24.7 HU; CNR: 1.1 vs 0.8, respectively). Subjective analysis rated VMI opt significantly ( p < 0.01) superior to VMI ref with respect to the overall image quality (3.2 vs 2.9, respectively) and tumor delineation (3.5 vs 2.9, respectively)., Conclusion: The VMI at 63 keV derived from contrast-enhanced DECT yielded the highest CNR and improved the objective and subjective image quality for radiosurgery, compared to VMI ref ., Advances in Knowledge: This paper investigated for the first time the optimal energy level of VMI in DECT for brain metastases. The findings will lead to improvement in tumor visibility with optimal VMI and consequently supplement accuracy delineation of brain metastases.