Long-Term Outcome of Unilateral Acoustic Neuromas With or Without Hearing Loss: Over 10 Years and Beyond After Gamma Knife Radiosurgery.

BACKGROUND: Since the long-term outcomes of 162 patients who underwent gamma knife radiosurgery (GKS) as an initial or adjuvant treatment for acoustic neuromas (ANs) with unilateral hearing loss were first reported in 1998, there has been no report of a comprehensive analysis of what has changed in GKS practice. METHODS: We performed a retrospective study of the long-term outcomes of 106 patients with unilateral sporadic ANs who underwent GKS as an initial treatment. The mean patient age was 50 years, and the mean initial tumor volume was 3.68 cm3 (range, 0.10-23.30 cm3). The median marginal tumor dose was 12.5 Gy (range, 8.0-15.0 Gy) and the median follow-up duration was 153 months (range, 120-216 months). RESULTS: The tumor volume increased in 11 patients (10.4%), remained stationary in 27 (25.5%), and decreased in 68 patients (64.2%). The actuarial 3, 5, 10, and 15-year tumor control rates were 95.3 ± 2.1%, 94.3 ± 2.2%, 87.7 ± 3.2%, and 86.6 ± 3.3%, respectively. The 10-year actuarial tumor control rate was significantly lower in the patients with tumor volumes of ≥ 8 cm3 (P = 0.010). The rate of maintaining the same Gardner-Robertson scale grade was 28.6%, and that of serviceable hearing was 46.4%. The rates of newly developed facial and trigeminal neuropathy were 2.8% and 4.7%, respectively. The patients who received marginal doses of less than 12 Gy revealed higher tumor control failure rates (P = 0.129) and newly occurred facial or trigeminal neuropathy rates (P = 0.040 and 0.313, respectively). CONCLUSION: GKS as an initial treatment for ANs could be helpful in terms of tumor control, the preservation of serviceable hearing, and the prevention of cranial neuropathy. It is recommended to perform GKS as soon as possible not only for tumor control in unilateral ANs with hearing loss but also for hearing preservation in those without hearing loss.

A 3-month survival model after Gamma Knife surgery in patients with brain metastasis from lung cancer with Karnofsky performance status ≤ 70.

Gamma Knife surgery (GKS) for brain metastasis (BM) has been generally advocated for patients with a Karnofsky performance status (KPS) scale of ≥ 70. However, some patients with a poor KPS scale of < 70 are recoverable after GKS and show durable survival. A purpose of this study is to devise a 3-month survival prediction model to screen patients with BM with a KPS of ≤ 70 in whom GKS is needed. A retrospective analysis of 67 patients with a KPS scale of 60-70 undergoing GKS for BM of non-small cell lung cancer (NSCLC) from 2016 to 2020 in our institute was performed. Univariate and multivariate logistic regression analyses were performed to investigate factors related to survival for more than 3 months after GKS. The probability (P) prediction model was designed by giving a weight corresponding to the odds ratio of the variables. The overall survival was 9.9 ± 12.7 months (range 0.2-53.2), with a 3-month survival rate of 59.7% (n = 40). In multivariate logistic regression analysis, extracranial disease (ECD) control (p = .033), focal neurological deficit (FND) (p = .014), and cumulative tumor volume (∑ TV) (p = .005) were associated with 3-month survival. The prediction model of 3-month survival (Harrell's C index = 0.767) was devised based on associated factors. In conclusion, GKS for BMs is recommended in selected patients, even if the KPS scale is ≤ 70.

Optimal mask fixation method for frameless radiosurgery with Leksell Gamma Knife IconTM.

The Leksell Gamma Knife (LGK) IconTM is used for mask-based and frame-based fixation. The mask fixation provides a noninvasive method. However, an optimal mask fixation method is yet to be established. We evaluated the characteristics of three mask fixation methods (Plain, Folded, and Wide) for the LGK IconTM . Force-sensitive resistor sensors were attached to the forehead, supraorbital, zygoma, mandible, and occipital bone of the phantom, and digital humidity and temperature sensors were attached to both temporal lobes. Cone-beam computed tomography (CBCT) and high-definition motion management (HDMM) for each mask fixation method were used to evaluate the phantom motion during the initial application. Subsequently, the mask was removed and reapplied on the second (1st reapplication) and third days (2nd reapplication). In the initial application, forces acting on most portions of the phantom were stabilized within 1.5 h. The largest force acted on the occipital bone for the Plain and Wide methods and on the mandible for the Folded method. The temperature rapidly approaches the initial temperature, whereas the humidity gradually approached the initial humidity in all fixation methods. The Folded method exhibited a significantly lower translation along the Y-axis of the Leksell coordinate system, and rotations along all axes were under 0.5°. The HDMM values remained at 0.1 mm for all fixation methods. In the reapplications, the force acting on the occipital bone was significantly greater than that during the initial application for all mask fixation methods; the temperature and humidity remained unchanged. All mask fixation methods in the 1st reapplication were not significantly different from those in the 2nd reapplication. The Folded method is recommended as an optimal mask fixation for patients who require tight fixation; the Wide method can be considered if patient comfort is a priority.

Consistency of dose rates after applying machine-specific reference correction factors for the gamma knife 16 mm collimator field.

BACKGROUND: The machine-specific reference (msr) correction factors ( k Q msr , Q 0 f msr , f ref $k_{{Q_{{\rm{msr}}}},\;{Q_0}}^{{f_{{\rm{msr}}}},{f_{{\rm{ref}}}}}$ ) were introduced in International Atomic Energy Agency (IAEA) Technical Report Series 483 (TRS-483) for reference dosimetry of small fields. Several correction factor sets exist for a Leksell Gamma Knife (GK) Perfexion or Icon. Nevertheless, experiments have not rigorously validated the correction factors from different studies. PURPOSE: This study aimed to assess the role and accuracy of k Q msr , Q 0 f msr , f ref $k_{{Q_{{\rm{msr}}}},\;{Q_0}}^{{f_{{\rm{msr}}}},{f_{{\rm{ref}}}}}$ values in determining the absorbed dose rates to water in the reference dosimetry of Gamma Knife. METHODS: The dose rates in the 16 mm collimator field of a GK were determined following the international code of practices with three ionization chambers: PTW T31010, PTW T31016 (PTW Freiberg GmbH, New York, NY), and Exradin A16 (Standard Imaging, Inc., Middleton, WI). A chamber was placed at the center of a solid water phantom (Elekta AB, Stockholm, Sweden) using a detector-specific insert. The reference point of the ionization chamber was confirmed using cone-beam CT images. Consistency checks were repeated five times at a GK site and performed once at seven GK sites. Correction factors from six simulations reported in previous studies were employed. Variations in the dose rates and relative dose rates before and after applying the k Q m s r , Q 0 f m s r , f r e f $k_{{Q_{msr}},\;{Q_0}}^{{f_{msr}},{f_{ref}}}$ were statistically compared. RESULTS: The standard deviation of the dose rates measured by the three chambers decreased significantly after any correction method was applied (p = 0.000). When the correction factors of all studies were averaged, the standard deviation was reduced significantly more than when any single correction method was applied (p ≤ 0.030), except for the IAEA TRS-483 correction factors (p = 0.148). Before any correction was applied, there were statistically significant differences among the relative dose rates measured by the three chambers (p = 0.000). None of the single correction methods could remove the differences among the ionization chambers (p ≤ 0.038). After TRS-483 correction, the dose rate of Exradin A16 differed from those of the other two chambers (p ≤ 0.025). After the averaged factors were applied, there were no statistically significant differences between any pairs of chambers according to Scheffe's post hoc analyses (p ≥ 0.051); however, PTW T31010 differed from PTW 31016 according to Tukey's HSD analyses (p = 0.040). CONCLUSION: The k Q msr , Q 0 f msr , f ref $k_{{Q_{{\rm{msr}}}},\;{Q_0}}^{{f_{{\rm{msr}}}},{f_{{\rm{ref}}}}}$ significantly reduced variations in the dose rates measured by the three ionization chambers. The mean correction factors of the six simulations produced the most consistent results, but this finding was not explicitly proven in the statistical analyses.

Preliminary Study on Natural Killer Cell Activity for Interferon-Gamma Production after Gamma Knife Radiosurgery for Brain Tumors.

OBJECTIVE: High-dose radiation is well known to induce and modulate the immune system. This study was performed to evaluate the correlation between clinical outcomes and changes in natural killer cell activity (NKA) after Gamma Knife Radiosurgery (GKS) in patients with brain cancer. METHODS: We performed an open-label, prospective, cross-sectional study of 38 patients who were treated with GKS for brain tumors, including metastatic and benign brain tumors. All of the patients underwent GKS, and blood samples were collected before and after GKS. NKA was measured using an enzyme-linked immunosorbent assay kit, to measure interferon-gamma (IFNγ) secreted by ex vivo-stimulated NK cells from whole blood. We explored the correlations between NK cell-produced IFNγ (NKA-IFNγ) levels and clinical parameters of patients who were treated with GKS for brain tumors. RESULTS: NKA-IFNγ levels were decreased in metastatic brain tumor patients compared to those with benign brain tumors (p<0.0001). All the patients who used steroid treatment to reduce brain swelling after GKS had an NKA-IFNγ level of zero except one patient. High NKA-IFNγ levels were not associated with a rapid decrease in brain metastasis and did not increase after GKS. CONCLUSION: The activity of NK cells in metastatic brain tumors decreased more than that in benign brain tumors after GKS.

Factors associated with radiation toxicity and long-term tumor control more than 10 years after Gamma Knife surgery for non-skull base, nonperioptic benign supratentorial meningiomas.

OBJECTIVE: Gamma Knife surgery (GKS) is a well-established treatment for benign intracranial meningiomas; however, the dosimetric factors associated with long-term GKS efficacy and safety remain to be elucidated. Using data obtained with at least 10 years of follow-up, the authors aimed 1) to analyze GKS efficacy and safety for the treatment of benign meningiomas confined to non-skull base, nonperioptic supratentorial locations and 2) to determine the radiation dose window that allows for long-term efficacy and safety, namely the minimum dose to achieve long-term local control (LC) and the maximum safe dose to avoid adverse radiation effects (AREs). METHODS: A retrospective analysis was performed on patients who underwent GKS for benign meningiomas in the abovementioned location at the authors' institution between 1998 and 2010 and who received follow-up for more than 10 years. The authors meticulously extracted the values of various dosimetric factors by using a dose-volume histogram. Cox proportional hazard regression analyses were performed to investigate the dosimetric factors associated with LC and ARE. RESULTS: Fifty-five patients (male/female ratio 1:4.2) with 68 tumors were enrolled. The median (range) gross target volume and marginal dose were 4.2 (0.2-31.7) cm3 and 14.3 (9-20) Gy, respectively. In total, 23.5% of tumors progressed at an average of 72 months, with 10- and 15-year progression-free survival rates of 80.9% and 73.5%, respectively. In univariate analysis, higher marginal dose, coverage (%), Dmin, D98%, Dmean, D2%, Dmax, and Paddick conformity index were significantly associated with LC. In multivariate analysis, D98% was the significant factor, with a cutoff value of 11 Gy (HR 0.754, p < 0.001). Symptomatic AREs occurred in 7 patients at an average of 7 months after GKS. AREs were significantly associated with the volume of normal tissue irradiated with more than 14 Gy (nV14Gy), with a cutoff value of 0.66 cm3 (HR 2.459, p = 0.002). CONCLUSIONS: D98% was a barometer of the minimum required dose associated with long-term LC, and nV14Gy was related to symptomatic AREs. The authors recommend a marginal dose ranging from 11 to 14 Gy to achieve long-term efficacy and safety in patients with non-skull base, nonperioptic benign supratentorial meningiomas, with the assumption of thorough tumor coverage.

Feasibility of isodose-shaped scintillation detectors for the measurement of gamma knife output factors.

PURPOSE: Scintillation detectors were 3D printed based on a gamma knife (GK) dose distribution to calculate the volume averaging effect. The collimator output factors were measured using isodose-shaped scintillators (ISSs) and compared with those of a micro-diamond detector and previous reports. METHODS: An absorbed dose distribution in a spherical dosimetry phantom with a radius of 8 cm was obtained from GK treatment planning software (Leksell GammaPlan [LGP], Elekta AB, Stockholm, Sweden). Two types of ISSs were fabricated to fit the 97.2% (ISS-1) and 95.6% (ISS-2) isodose surfaces. The volume averaging correction factors were obtained by dividing the absorbed dose to water in the central voxel (CV) by that in the ISS. The correction effect due to the difference between the ISS and water was calculated by Monte Carlo simulations. Ten ISS detectors, five of each type, were used to measure the output factors of the 4- and 8-mm collimators of a GK Icon to assess system consistency. The output factors of seven GKs were measured using two ISS detectors, one of each type, and a PTW T60019 (PTW, Freiburg, Germany) micro-diamond detector. RESULTS: The detector output ratios (DORs) measured using the five ISSs of each type were consistent, with standard uncertainties less than 0.2%. In the 4-mm field, the volume averaging correction factor ratios were 1.018 and 1.026, and the output factors after all corrections were 0.827 (0.006) and 0.825 (0.006) for ISS-1 and ISS-2, respectively. In the 8-mm field, the volume averaging correction factor ratios were 1.000 for both ISS types, and the output factors were 0.898 (0.003) and 0.900 (0.003) for ISS-1 and ISS-2, respectively. The ISS detectors could measure the output factors of a GK with uncertainties comparable to that of the PTW 60019 detector. The output factors of all detectors decreased with the dose rate. CONCLUSION: The volume averaging effect of an ISS developed in-house could be calculated using known dose distributions. The collimator output factors of the GK Perfexion/Icon models measured using ISS detectors were consistent with those of a commercial synthetic micro-diamond detector and recent studies.

Dosimetric parameters associated with the long-term oncological outcomes of Gamma Knife surgery for sellar and parasellar tumors in pediatric patients.

OBJECTIVE: The authors aimed to investigate the dosimetric parameter and the minimally required dose associated with long-term control of sellar and parasellar tumors after Gamma Knife surgery (GKS) in children. METHODS: A retrospective analysis was performed on pediatric patients younger than 19 years of age who were diagnosed with sellar and parasellar tumors and received GKS at the authors' institution from 1998 to 2019. Cox proportional hazards regression analyses were used to investigate the dosimetric parameters associated with treatment outcome. The Kaplan-Meier method was used to analyze tumor control rates after GKS. RESULTS: Overall, 37 patients with 40 sellar and parasellar tumors, including 22 craniopharyngiomas and 12 pituitary adenomas, had a mean follow-up of 85.8 months. The gross target volume was 0.05 cm3 to 15.28 cm3, and the mean marginal dose was 15.8 Gy (range 9.6-30.0 Gy). Ten patients experienced treatment failure at a mean of 28.0 ± 26.7 months. The actuarial 5- and 10-year tumor control rates were 79.0% and 69.8%, respectively. D98% was an independent predictive factor of tumor control (HR 0.846 [95% CI 0.749-0.956], p = 0.007), with a cutoff value of 11.5 Gy for the entire cohort and 10 Gy for the craniopharyngioma group. Visual deterioration occurred in 2 patients with the maximum point dose of 10.1 Gy and 10.6 Gy to the optic apparatus. CONCLUSIONS: In pediatric patients, D98% was a reliable index of the minimum required dose for long-term control of sellar and parasellar tumors after GKS. The optimal D98% value for each tumor diagnosis needs to be elucidated in the future.

A multivariate approach to determine electron beam parameters for a Monte Carlo 6 MV Linac model: Statistical and machine learning methods.

PURPOSE: This study aimed to determine the optimal initial electron beam parameters of a Linac for radiotherapy with a multivariate approach using statistical and machine-learning tools. METHODS: For MC beam commissioning, a 6 MV Varian Clinac was simulated using the Geant4 toolkit. The authors investigated the relations between simulated dose distribution and initial electron beam parameters, namely, mean energy (E), energy spread (ES), and radial beam size (RS). The goodness of simulation was evaluated by the slope of differences between the simulated and the golden beam data. The best-fit combination of the electron beam parameters that minimized the slope of dose difference was searched through multivariate methods using conventional statistical methods and machine-learning tools of the scikit-learn library. RESULTS: Simulation results with 87 combinations of the electron beam parameters were analyzed. Regardless of being univariate or multivariate, traditional statistical models did not recommend a single parameter set simultaneously minimizing slope of dose differences for percent depth dose (PDD) and lateral dose profile (LDP). Two machine learning classification modules, RandomForestClassifier and BaggingClassifier, agreed in recommending (E = 6.3 MeV, ES = ±5.0%, RS = 1.0 mm) for predicting simultaneous acceptance of PDD and LDP. CONCLUSIONS: The machine learning with random-forest and bagging classifier modules recommended a consistent result. It was possible to draw an optimal electron beam parameter set using multivariate methods for MC simulation of a radiotherapy 6 MV Linac.

Treatment Planning Factors Associated with Long-Term Outcomes of Gamma Knife Surgery in Patients with Trigeminal Neuralgia.

OBJECTIVE: Gamma Knife surgery (GKS) is an established treatment option for trigeminal neuralgia (TN). However, the long-term efficacy of GKS for patients with TN has not been well studied. The aim of the study is to evaluate the sequential course of pain control after GKS and analyze the factors associated with the long-term analgesic effect, focusing on radiation dosimetry and neurovascular conflict (NVC) factors. METHODS: We analyzed 83 patients undergoing GKS for TN in our institution between 2005 and 2013 with a follow-up duration >7 years. Tolerable pain with increased medication, persistent-intractable pain, and recurrence were classified as poor outcomes, and any other outcome was classified as a favorable outcome. The dosimetry factors and locational relationship between NVC and the target were analyzed in terms of their correlation with a favorable outcome. RESULTS: Adequate pain relief was achieved in 93% of patients a month and a half after GKS, but the pain recurred in 41.5% of patients on average 36 months after treatment. A larger V40Gy (P = 0.002) and higher homogeneity index (P = 0.027) were significantly associated with the long-term favorable outcomes. About 40% of patients had multiple NVC sites, and insufficient inclusion of the NVC in the target was significantly correlated with long-term poor outcomes (P = 0.002). CONCLUSIONS: Targeting the center of the trigeminal nerve in the area of NVC with GKS is associated with favorable long-term pain control.

Development of an IAEA phase-space dataset for the Leksell Gamma Knife® Perfexion™ using multi-threaded Geant4 simulations.

This study was conducted to develop a phase-space dataset in the International Atomic Energy Agency (IAEA) format for Monte Carlo (MC) simulations of the Leksell Gamma Knife® (LGK, Elekta Instrument AB, Stockholm, Sweden) Perfexion™ (PFX). An open-source MC code, namely, the Geant4 toolkit with a recently updated multi-threaded mode, was used to maximize the efficiency of the developed IAEA phase-space dataset. The absorbed dose profiles for single shots of the LGK PFX were calculated using the developed dataset and compared with those from radiochromic film measurements and Leksell GammaPlan® version 11.0.3 (LGP, Elekta Instruments) for verification. The mean relative absorbed dose differences in all single shots were less than 3.6% compared with the films and less than 4.0% compared with LGP. The collimator output factors were also calculated for all single shots and compared with the LGP results. The simulated collimator output factor was 0.816 ±â€¯0.003 for a 4-mm shot and 0.903 ±â€¯0.001 for an 8-mm shot in a spherical water phantom. The efficiency of the developed dataset was evaluated by comparing the times required for various simulations. Simulations with the phase-space dataset ran 25, 8.2 and 3.2 times faster than simulations without the phase-space dataset for 4-, 8-, and 16-mm shots, respectively. Using the dataset developed in this study, MC simulations of the LGK PFX can be performed more efficiently for various purposes, such as treatment plan verification and beam quality factor calculations.

Single-Session versus Multisession Gamma Knife Radiosurgery for Large Brain Metastases from Non-Small Cell Lung Cancer: A Retrospective Analysis.

PURPOSE: To evaluate the efficacy of Gamma Knife radiosurgery (GKS) in patients with large brain metastases by comparing single-session radiosurgery (S-GKS) and multisession radiosurgery (M-GKS), we retrospectively analyzed the clinical outcomes of patients who underwent GKS for brain metastases from non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Between January 2010 and December 2016, 66 patients with 74 lesions ≥10 cm3 from large brain metastases from only NSCLC were included. Fifty-five patients with 60 lesions were treated with S-GKS; 11 patients with 14 lesions were treated with M-GKS. Median doses were 16 Gy (range, 11-18 Gy) for the S-GKS group and 8 Gy (range, 7-10 Gy) in three fractions for the M-GKS group. RESULTS: With a mean follow-up period of 13.1 months (range, 1.3-76.4 months), the median survival duration was 21.1 months for all patients. Median tumor volume was 14.3 cm3 (range, 10.0-58.3 cm3). The local control rate was 77.0% and the progression-free survival rate was 73.6% at the last follow-up. There were no significant between-group differences in terms of local control rate (p = 0.10). Compared with S-GKS, M-GKS did not differ significantly in radiation-induced complications (38.1 vs. 45.4%, p =0.83). While 8 patients who underwent S-GKS experienced major complications of grade ≥3, no toxicity was observed in patients treated with M-GKS. CONCLUSIONS: M-GKS may be an effective alternative for large brain metastases from NSCLC. Specifically, severe radiation-induced toxicity (≥grade 3) did not occur in M-GKS for large-volume metastases. Although the long-term effects and results from larger samples remain unclear, M-GKS may be a suitable palliative treatment for preserving neurological function.

Petroclival meningiomas: long-term outcomes of multimodal treatments and management strategies based on 30 years of experience at a single institution.

OBJECTIVE: A thorough investigation of the long-term outcomes and chronological changes of multimodal treatments for petroclival meningiomas is required to establish optimal management strategies. The authors retrospectively reviewed the long-term clinical outcomes of patients with petroclival meningioma according to various treatments, including various surgical approaches, and they suggest treatment strategies based on 30 years of experience at a single institution. METHODS: Ninety-two patients with petroclival meningiomas were treated surgically at the authors' institution from 1986 to 2015. Patient demographics, overall survival, local tumor control rates, and functional outcomes according to multimodal treatments, as well as chronological change in management strategies, were evaluated. The mean clinical and radiological follow-up periods were 121 months (range 1-368 months) and 105 months (range 1-348 months), respectively. RESULTS: A posterior transpetrosal approach was most frequently selected and was followed in 44 patients (48%); a simple retrosigmoid approach, undertaken in 30 patients, was the second most common. The initial extent of resection and following adjuvant treatment modality were classified into 3 subgroups: gross-total resection (GTR) only in 13 patients; non-GTR treatment followed by adjuvant radiosurgery or radiation therapy (non-GTR+RS/RT) in 56 patients; and non-GTR without adjuvant treatment (non-GTR only) in 23 patients. The overall progression-free survival rate was 85.8% at 5 years and 81.2% at 10 years. Progression or recurrence rates according to each subgroup were 7.7%, 12.5%, and 30.4%, respectively. CONCLUSIONS: The authors' preferred multimodal treatment strategy, that of planned incomplete resection and subsequent adjuvant radiosurgery, is a feasible option for the management of patients with large petroclival meningiomas, considering both local tumor control and postoperative quality of life.

Frameless Fractionated Gamma Knife Radiosurgery with ICON™ for Large Metastatic Brain Tumors.

BACKGROUND: Recently, a new generation of gamma knife radiosurgery (GKRS) equipped with a frameless immobilization system has encouraged the use of fractionated GKRS as an increasingly favorable treatment option. We investigated the preliminary outcome of efficacy and toxicity associated with frameless fractionated gamma knife radiosurgery (FF GKRS) for the treatment of large metastatic brain tumors. METHODS: Fifteen patients with 17 lesions were treated using FF GKRS and included in this study, because of the large tumor size of more than 10 cm3. FF GKRS was performed based on a thermoplastic mask system for 3 to 5 consecutive days. RESULTS: The mean duration of clinical follow-up was 12 months (range, 4-24), and the local control rate was 100%. Tumor volume decreased in 13 lesions (76.5%), and remained stable in 4 lesions (23.5%). One patient was classified as new lesion development because of the occurrence of leptomeningeal seeding regardless of the tumor volume change. Compared with the initial volume at the time of FF GKRS, tumor volume change at the last follow-up was 62.32% ± 29.80%. Cumulative survival rate at 12 months was 93.3% ± 6.4%. One patient died during the follow-up period because of the progression of the primary disease. No patient showed radiation necrosis on the follow-up images. CONCLUSION: Daily FF GKRS by gamma knife ICON™ revealed satisfactory tumor control rate and low morbidity, despite the short follow-up period. Further prospective studies and a longer follow-up of a large cohort of patients diagnosed with brain metastases are required to elucidate the effect of FF GKRS in brain metastases.

Development of a PMMA phantom as a practical alternative for quality control of gamma knife® dosimetry.

BACKGROUND: To measure the absorbed dose rate to water and penumbra of a Gamma Knife® (GK) using a polymethyl metacrylate (PMMA) phantom. METHODS: A multi-purpose PMMA phantom was developed to measure the absorbed dose rate to water and the dose distribution of a GK. The phantom consists of a hemispherical outer phantom, one exchangeable cylindrical chamber-hosting inner phantom, and two film-hosting inner phantoms. The radius of the phantom was determined considering the electron density of the PMMA such that it corresponds to 8 g/cm2 water depth, which is the reference depth of the absorbed dose measurement of GK. The absorbed dose rate to water was measured with a PTW TN31010 chamber, and the dose distributions were measured with radiochromic films at the calibration center of a patient positioning system of a GK Perfexion. A spherical water-filled phantom with the same water equivalent depth was constructed as a reference phantom. The dose rate to water and dose distributions at the center of a circular field delimited by a 16-mm collimator were measured with the PMMA phantom at six GK Perfexion sites. RESULTS: The radius of the PMMA phantom was determined to be 6.93 cm, corresponding to equivalent water depth of 8 g/cm2. The absorbed dose rate to water was measured with the PMMA phantom, the spherical water-filled phantom and a commercial solid water phantom. The measured dose rate with the PMMA phantom was 1.2% and 1.8% higher than those measured with the spherical water-filled phantom and the solid water phantom, respectively. These differences can be explained by the scattered photon contribution of PMMA off incoming 60Co gamma-rays to the dose rate. The average full width half maximum and penumbra values measured with the PMMA phantom showed reasonable agreement with two calculated values, one at the center of the PMMA phantom (LGP6.93) and other at the center of a water sphere with a radius of 8 cm (LGP8.0) given by Leksell Gamma Plan using the TMR10 algorithm. CONCLUSIONS: A PMMA phantom constructed in this study to measure the absorbed dose rates to water and dose distributions of a GK represents an acceptable and practical alternative for GK dosimetry considering its cost-effectiveness and ease of handling.

Fractionated Gamma Knife Radiosurgery as Initial Treatment for Large Skull Base Meningioma.

We present our experience on the hypofractionated Gamma Knife radiosurgery (FGKS) for large skull base meningioma as an initial treatment. We retrospectively reviewed 23 patients with large skull base meningioma ≥10 cm3 who underwent FGKS as the initial treatment option. The mean volume of tumors prior to radiosurgery was 21.2±15.63 cm3 (range, 10.09~71.42). The median total margin dose and marginal dose per fraction were 18 Gy (range, 15~20) and 6 Gy (range, 5~6), respectively. Patients underwent three or four fractionations in consecutive days with the same Leksell® frame. The mean follow-up duration was 38 months (range, 17~78). There was no mortality. At the last follow-up, the tumor volume was stationary in 15 patients (65.2%) and had decreased in 8 patients (34.8%). Six patients who had cranial neuropathy at the time of FGKS showed improvement at the last clinical follow-up. Following FGKS, 4 patients (17%) had new cranial neuropathy. The trigeminal neuropathy was the most common and all were transient. The mean Karnofsky Performance Status score at pre-FGKS and the last clinical follow-up was 97.0±10.4 points (median, 100) and 98.6±6.9 (median, 100) points, respectively. FGKS has showed satisfactory tumor control with functional preservation for large skull base meningiomas. Further prospective studies of large cohorts with long term follow-up are required to clarify the efficacy in the tumor control and functional outcome as well as radiation toxicity.

Optimal strategy of gamma knife radiosurgery for craniopharyngiomas.

OBJECT: To analyze the outcomes of gamma knife radiosurgery (GKS) for craniopharyngiomas and elucidate the optimal strategy. METHODS: Between 1998 and 2016, 35 patients underwent GKS for the treatment of 40 recurrent or residual craniopharyngiomas. Among 40 GKSs, 22 procedures were single-session GKSs and 18 procedures were fractionated GKSs. In cases of single-session GKS, the median marginal dose was 15 Gy (range 10-20 Gy). In cases of fractionated GKS, the median marginal dose was 6 Gy (range 5-7.5 Gy) of three fractions. The radiation dose was calculated to the biologic equivalent dose (BED) using α/ß ratios of 10 and 2. RESULT: The location of the tumor, the distance between the optic nerve and tumor (> 10 mm), BED 10 (> 35 Gy), and BED2 (> 80 Gy) were statistically significant with overall response rate (P = 0.008, 0.02, 0.03, and 0.002, respectively). There was a statistically significant difference in progression-free survival according to the distance between the optic nerve and tumor (> 10 mm) and the location of tumor (P = 0.03 and 0.03, respectively). Multivariate logistic regression analysis showed the hypothalamus group had an odds ratio of 0.04 compared with the suprasellar group for tumor progression. The group with BED2 > 80 Gy had an odds ratio of 0.049 compared with the group with BED2 < 80 Gy. CONCLUSION: A sufficient dose is required for treating craniopharyngiomas using single-session and fractionated GKS. The outcomes of GKS can be predicted according to the location of tumor, the distance between the optic nerve and tumor and BED value.

Independent dose validation system for Gamma Knife radiosurgery, using a DICOM-RT interface and Geant4.

Leksell GammaPlan was specifically designed for Gamma Knife (GK) radiosurgery planning, but it has limited accuracy for estimating the dose distribution in inhomogeneous areas, such as the embolization of arteriovenous malformations. We aimed to develop an independent patient dose validation system based on a patient-specific model, constructed using a DICOM-RT interface and the Geant4 toolkit. Leksell Gamma Knife Perfexion was designed in Geant4.10.00 and includes a DICOM-RT interface. Output factors for each collimator in a sector and dose distributions in a spherical water phantom calculated using a Monte Carlo (MC) algorithm were compared with the output factors calculated by the tissue maximum ratio (TMR) 10 algorithm and dose distributions measured using film, respectively. Studies using two types of water phantom and two patient simulation cases were evaluated by comparing the dose distributions calculated by the MC, the TMR and the convolution algorithms. The water phantom studies showed that if the beam size is small and the target is located in heterogeneous media, the dose difference could be up to 11%. In the two patient simulations, the TMR algorithm overestimated the dose by about 4% of the maximum dose if a complex and large bony structure was located on the beam path, whereas the convolution algorithm showed similar results to those of the MC algorithm. This study demonstrated that the in-house system could accurately verify the patient dose based on full MC simulation and so would be useful for patient cases where the dose differences are suspected.

Long-Term Outcome of Gamma Knife Radiosurgery for Symptomatic Brainstem Cavernous Malformation.

OBJECTIVE: We sought to analyze the long-term outcome of Gamma Knife radiosurgery (GKS) for symptomatic brainstem cavernous malformation (s-BSCM). METHODS: Forty-five patients (14 males, 31 females) were treated with GKS for s-BSCM from January 1998 to December 2011. All patients were followed up for >5 years, and their clinical data were analyzed retrospectively. All patients had a history of symptomatic bleeding once or more before GKS. These hemorrhages caused neurologic deficits including cranial nerve deficits, hemiparesis, hemisensory deficits, spasticity, or chorea. The mean target volume of s-BSCM was 1.82 cm3, and the median prescribed marginal dose of radiation was 13 Gy. The mean clinical and imaging follow-up period was 9.31 years (range 5.1-19.4 years). RESULTS: The 45 patients had 69 hemorrhagic events before GKS. During the follow-up period after GKS, 35 patients had no hemorrhagic event, 6 patients had 1 episode of symptomatic hemorrhage, and 4 patients had 2 episodes. The calculated annual hemorrhage rate was 40.06% at pre-GKS, 3.3% at 2 years after GKS, 1.48% at 5 years after GKS, and 4.64% at >5 years after GKS. In this study of 45 patients, symptomatic radiation-induced complications developed in only 1 patient (2.2%). No patients had died at the last follow-up. CONCLUSIONS: GKS for s-BSCM is a safe and effective alternative to surgical resection for reducing the rate of recurrent hemorrhage. Because the annual hemorrhage rate increases >5 years after GKS, clinicians should monitor patients closely to determine their subsequent treatment.

Assessment of the accuracy and stability of frameless gamma knife radiosurgery.

The aim of this study was to assess the accuracy and stability of frameless gamma knife radiosurgery (GKRS). The accuracies of the radiation isocenter and patient couch movement were evaluated by film dosimetry with a half-year cycle. Radiation isocenter assessment with a diode detector and cone-beam computed tomography (CBCT) image accuracy tests were performed daily with a vendor-provided tool for one and a half years after installation. CBCT image quality was examined twice a month with a phantom. The accuracy of image coregistration using CBCT images was studied using magnetic resonance (MR) and computed tomography (CT) images of another phantom. The overall positional accuracy was measured in whole procedure tests using film dosimetry with an anthropomorphic phantom. The positional errors of the radiation isocenter at the center and at an extreme position were both less than 0.1 mm. The three-dimensional deviation of the CBCT coordinate system was stable for one and a half years (mean 0.04 ± 0.02 mm). Image coregistration revealed a difference of 0.2 ± 0.1 mm between CT and CBCT images and a deviation of 0.4 ± 0.2 mm between MR and CBCT images. The whole procedure test of the positional accuracy of the mask-based irradiation revealed an accuracy of 0.5 ± 0.6 mm. The radiation isocenter accuracy, patient couch movement accuracy, and Gamma Knife Icon CBCT accuracy were all approximately 0.1 mm and were stable for one and a half years. The coordinate system assigned to MR images through coregistration was more accurate than the system defined by fiducial markers. Possible patient motion during irradiation should be considered when evaluating the overall accuracy of frameless GKRS.