Is it advisable to perform radiosurgery for EGFR-TKI-controlled brain metastases? A retrospective study of the role of radiosurgery in lung cancer treatment.

PURPOSE: Given the availability of TKIs with high central nervous system efficacy, the question arises as to whether upfront SRS provides additional clinical benefits. The goal of this study was to characterize the clinical outcomes of SRS as salvage therapy for TKI-uncontrolled BMs. METHODS: This retrospective study included EGFR-mutant NSCLC patients presenting BMs at the time of primary tumor diagnosis. BMs were categorized into three subgroups, referred to as "Nature of TKI-treated BMs", "TKI-controlled brain metastases ± SRS", and "SRS salvage therapy". The first subgroup analysis characterized the effects of TKIs on tumor behavior. In the second subgroup, we compared outcomes of TKI-controlled BMs treated with TKI alone versus those treated with combined TKI-SRS therapy. The third subgroup characterized the outcomes of TKI-uncontrolled BMs treated with SRS as salvage therapy Clinical outcomes include local and distant tumor control. RESULTS: This study included 106 patients with a total of 683 BMs. TKI treatment achieved control in 63% of local tumors at 24 months. Among the TKI-controlled BMs, local tumor control was significantly higher in the combined TKI-SRS group (93%) than in the TKI-alone group (65%) at 24 months (p < 0.001). No differences were observed between the two groups in terms of distant tumor control (p = 0.832). In dealing with TKI-uncontrolled BMs, salvage SRS achieved local tumor control in 58% of BMs at 24 months. CONCLUSIONS: While upfront TKI alone proved highly effective in BM control, this study also demonstrated the outcomes of SRS when implemented concurrently with TKI or as salvage therapy for TKI-uncontrolled BMs. This study also presents a strategy of the precise timing and targeting of SRS to lesions in progression.

Magnetic resonance imaging signal characteristics associated with prognosis of skull base chordoma after gamma knife radiosurgery.

OBJECTIVE: To investigate the association between the magnetic resonance imaging (MRI) signal characteristics of skull base chordoma and radiosurgical outcomes. METHODS: Twenty-four patients with skull base chordomas treated with Gamma Knife radiosurgery (GKRS) after previous surgical resection were retrospectively (2001-2021) examined. Pre-GKRS MRIs were analyzed for RT2 (tumor-to-brainstem signal intensity ratio on T2-weighted imaging), RCE (tumor-to-brainstem signal intensity ratio on contrast-enhanced T1-weighted imaging), and mean apparent diffusion coefficient (ADC). Correlations of the parameters with patient survival and local tumor progression were made by using Cox regression and Kaplan-Meier analyses. RESULTS: During a median follow-up of 46 months after GKRS, 9 patients died with significantly more local tumor progression events (median number: 2 vs 0, P = .012) than did 15 alive patients. On multivariable analysis, higher mean ADC was associated with longer patient survival (P = .016) after GKRS. The actuarial 5-year overall survival rates were 88.9% versus 54.7% for chordomas with an ADC of ≥ 1270 × 10-6 mm2/s versus < 1270 × 10-6 mm2/s. RT2 < 1.5 (P = .038) and RCE > 1.57 (P = .022) were associated with a lower probability of local tumor control. CONCLUSION: Lower mean ADC values are associated with shorter patient survival in skull base chordomas after GKRS. Diffusion-weighted imaging may help in GKRS planning and outcome prediction for these patients.

Outflow Patency Correlates with Radiosurgical Outcomes of Lateral Sinus Dural Arteriovenous Fistula.

OBJECTIVE: To explore the impact of outflow patency on radiosurgical outcomes of lateral sinus dural arteriovenous fistulas (DAVFs). METHODS: We retrospectively examined 83 lateral sinus DAVFs treated with Gamma Knife radiosurgery (GKRS) between 1995 and 2020. Two neuroradiologists blinded to the therapeutic outcomes served as imaging evaluators on pre-GKRS digital subtraction angiography and magnetic resonance images. The sinovenous outflow of lateral sinus DAVF was scored using combined conduit score (CCS), ranging from 0 (total occlusion) to 8 (full patency). The patients' follow-up magnetic resonance and digital subtraction angiography images were used to validate the radiosurgical outcomes (obliteration or non-obliteration) of lateral sinus DAVF. Cox regression and Kaplan-Meier analyses were performed to determine the correlations between the variables and outcomes. RESULTS: Among the 83 cases, 60 (72%) lateral sinus DAVFs achieved obliteration after a GKRS at a median latency period of 24.5 months. After adjustment for aggressive presentation, cortical venous reflux, straight sinus reflux, and optic nerve sheath enlargement, a CCS of >6 was independently associated with lateral sinus DAVF obliteration (hazard ratio: 2.335, P = 0.007). The estimated 36-month probabilities of obliteration were 80% versus 53.6% for lateral sinus DAVFs with a CCS of >6 versus ≤6. CONCLUSIONS: Lateral sinus DAVFs with a CCS of >6, indicating a nearly patent sinovenous outflow, were more likely to be obliterated after GKRS. Sinovenous outflow patency is a factor associated with therapeutic outcomes in radiosurgery for lateral sinus DAVFs.

Sinovenous outflow in lateral sinus dural arteriovenous fistulas after stereotactic radiosurgery: a retrospective longitudinal imaging study.

PURPOSE: To investigate sinovenous outflow restriction (SOR) in lateral sinus dural arteriovenous fistulas (LSDAVFs) after Gamma Knife radiosurgery (GKRS) and its association with complete obliteration. METHODS: We retrospectively (1995-2019) enrolled 39 patients with LSDAVFs who had undergone GKRS alone and evaluated their angiography and magnetic resonance imaging (MRI) before and after GKRS. The LS conduits ipsilateral and contralateral to the DAVFs were scored using a 5-point scoring system, with scores ranging from 0 (total occlusion) to 4 (fully patent). SOR was defined by a conduit score < 2. Demographics, imaging features, and outcomes were compared between patients with and without ipsilateral SOR after GKRS. Logistic regression analysis was performed to estimate the odds ratio (OR) for obliteration with the imaging findings. RESULTS: After a median angiographic follow-up of 28 months for the 39 patients, the ipsilateral LS became more restrictive (median conduit score before and after GKRS: 2 vs. 1, p = .011). Twenty-one patients with ipsilateral SOR after GKRS had a significantly lower obliteration rate (52.4% vs. 94.4%, p = .005) than those without SOR. Follow-up SOR was independently associated with a lower obliteration rate (OR 0.05, p = .017) after adjustment for age, cortical venous reflux, and absent sinus flow void on MRI. CONCLUSION: This study demonstrates a restrictive change of outflow in LSDAVFs after GKRS and a lower obliteration rate in patients with SOR. Follow-up imaging for SOR may help predict outcomes of these patients.

Imaging Markers Associated With Radiation-Induced Changes in Brain Arteriovenous Malformations After Radiosurgery.

BACKGROUND: Radiation-induced changes (RICs) in brain tissue, seen as increased perinidal T2-weighted hyperintensity on MRI, are commonly observed in patients with brain arteriovenous malformations (BAVMs) within 2 years after Gamma Knife (Elekta) radiosurgery (GKRS). OBJECTIVE: To explore the imaging markers associated with RICs in patients with BAVMs. METHODS: We retrospectively included 106 treatment-naïve patients with BAVMs who received GKRS alone between 2011 and 2018 and had ≥24 months of clinical and MRI follow-up. Pre-GKRS angiography and MRIs were analyzed for morphological characteristics and quantitative digital subtraction angiography parameters. RIC severity was categorized as mild (grade I), moderate (grade II), or severe (grade III). Firth logistic regression analysis was conducted to determine the associations between the parameters and RICs. RESULTS: Among the 106 patients, 83 (78.3%) developed RICs, with 16 categorized as grade I, 62 as grade II, and 5 as grade III. RICs were symptomatic in 19 patients (17.9%). In multivariable models, BAVMs with a volume of >5 cm3 (odds ratio [OR]: 4.322, P = .024) and neoangiogenesis on angiography before treatment (OR: 3.846, P = .029), and thrombus within nidus or drainage vein on follow-up MRI (OR: 3.679, P = .001) were independently associated with grade II or III RICs. Symptomatic RICs were more likely to develop in basal ganglia or brainstem. CONCLUSION: Large BAVMs and neoangiogenesis were associated with moderate to severe RICs in treatment-naïve patients with BAVMs. Our findings may assist with the complication risk assessment for these patients.

The Irradiated Brain Volume Within 12 Gy Is a Predictor for Radiation-Induced Changes After Stereotactic Radiosurgery in Patients With Unruptured Cerebral Arteriovenous Malformations.

PURPOSE: Our purpose was to determine whether the coverage of brain parenchyma within the 12 Gy radiosurgical volume (V12) correlates with the development of radiation-induced changes (RICs) in patients with unruptured cerebral arteriovenous malformations (AVM) after undergoing stereotactic radiosurgery (SRS). METHODS AND MATERIALS: This study conducted regular follow-up examinations of 165 patients with unruptured AVMs who had previously undergone SRS. The RICs identified in T2-weighted magnetic resonance imaging (MRI) scans at any time point in the first 3 years after SRS were labeled "early RICs." The RICs identified in T2-weighted MRI scans at 5-year follow-up brain images were labeled "late RICs." Fully automated segmentation was used to analyze the MRI scans from these patients, whereupon the volume and proportion of brain parenchyma within the V12 was calculated. Logistic regression analysis was used to characterize the factors affecting the incidence of early and late RICs of any grade after SRS. RESULTS: The median duration of follow-up was 70 months (range, 36-222). Early RICs were identified in 124 of the 165 patients with the highest grades as followed: grade 1 (103 patients), grade 2 (19 patients), and grade 3 (2 patients). Only 103 patients had more than 5 years follow-up, and late RICs were identified in 70 of 103 patients. Seventeen of 70 patients with late RICs were symptomatic. The median volume and proportion of brain parenchyma within the V12 was 22.4 cm3 (range, 0.6-63.9) and 58.7% (range, 18.4-76.8). Univariate analysis revealed that AVM volume and the brain volume within the V12 were correlated with the incidence of both early and late RICs after SRS. Multivariable analysis revealed that only the brain volume within the V12 was significantly associated with the incidence of early and late RICs after SRS. CONCLUSIONS: In patients with unruptured AVM, the volume of brain parenchyma within the V12 was an important factor associated with the incidence of early and late RICs after SRS. Before SRS, meticulous radiosurgical planning to reduce brain parenchyma coverage within the V12 could reduce the risk of complications.

Stem cell transplantation and/or adenoviral glial cell line-derived neurotrophic factor promote functional recovery in hemiparkinsonian rats.

BACKGROUND: Parkinson's disease (PD) is a neurological disorder characterized by the progressive loss of midbrain dopamine (DA) neurons. Bone marrow mesenchymal stem cells (BMSCs) can differentiate into multiple cell types including neurons and glia. Transplantation of BMSCs is regarded as a potential approach for promoting neural regeneration. Glial cell line-derived neurotrophic factor (GDNF) can induce BMSC differentiation into neuron-like cells. This work evaluated the efficacy of nigral grafts of human BMSCs (hMSCs) and/or adenoviral (Ad) GDNF gene transfer in 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats. AIM: To evaluate the efficacy of nigral grafts of hMSCs and/or Ad-GDNF gene transfer in 6-OHDA-lesioned hemiparkinsonian rats. METHODS: We used immortalized hMSCs, which retain their potential for neuronal differentiation. hMSCs, preinduced hMSCs, or Ad-GDNF effectively enhanced neuronal connections in cultured neurons. In vivo, preinduced hMSCs and/or Ad-GDNF were injected into the substantia nigra (SN) after induction of a unilateral 6-OHDA lesion in the nigrostriatal pathway. RESULTS: Hemiparkinsonian rats that received preinduced hMSC graft and/or Ad-GDNF showed significant recovery of apomorphine-induced rotational behavior and the number of nigral DA neurons. However, DA levels in the striatum were not restored by these therapeutic treatments. Grafted hMSCs might reconstitute a niche to support tissue repair rather than contribute to the generation of new neurons in the injured SN. CONCLUSION: The results suggest that preinduced hMSC grafts exert a regenerative effect and may have the potential to improve clinical outcome.

Does the Diffuseness of the Nidus Affect the Outcome of Stereotactic Radiosurgery in Patients with Unruptured Cerebral Arteriovenous Malformations?

BACKGROUND: We proposed an algorithm to automate the components within the identification of components within the nidus of cerebral arteriovenous malformations (AVMs) which may be used to analyze the relationship between its diffuseness and treatment outcomes following stereotactic radiosurgery (SRS). OBJECTIVES: to determine the impact of the diffuseness of the AVM nidus on SRS outcomes. METHODS: This study conducted regular follow-ups of 209 patients with unruptured AVMs who underwent SRS. The diffuseness of the AVM nidus was estimated by quantifying the proportions of vascular nidal component, brain parenchyma, and cerebrospinal fluid in T2-weighted MRIs. We used Cox regression analysis to characterize the association between nidal diffuseness and treatment outcomes in terms of obliteration rate and radiation-induced change (RICs) rate following SRS. RESULTS: The median AVM volume was 20.7 cm3. The median duration of imaging follow-up was 51 months after SRS. The overall AVM obliteration rate was 68.4%. RICs were identified in 156 of the 209 patients (74.6%). The median proportions of the nidus of AVM and brain parenchyma components within the prescription isodose range were 30.2 and 52.2%, respectively. Cox regression multivariate analysis revealed that the only factor associated with AVM obliteration rate after SRS was AVM volume. However, a larger AVM volume (>20 mL) and a larger proportion of brain parenchyma (>50%) within the prescription isodose range were both correlated with a higher RIC rate following SRS. CONCLUSIONS: The diffuseness of the nidus indeed appears to affect the RIC rate following SRS in patients with unruptured AVMs.

Magnetic resonance imaging as a single diagnostic tool for verifying radiosurgery outcomes of cavernous sinus dural arteriovenous fistula.

PURPOSE: MRI and MR angiography (MRA) are noninvasive methods for examining cavernous sinus dural arteriovenous fistulas (CSDAVFs) after radiosurgery. In this study, we investigated the accuracy of unenhanced MRI/3-dimensional time-of-flight (3D TOF) MRA in evaluating CSDAVF obliteration as compared with digital subtraction angiography (DSA). METHODS: From 1995-2012, 48 cases of CSDAVFs received Gamma Knife surgery (GKS) and had undergone both unenhanced MRI/3D TOF MRA and DSA for posttreatment evaluation. Two blinded observers independently interpreted the results of MRI/MRA. The results of MRI/MRA were compared with those of DSA. The sensitivity (the probability of MRI/MRA showing obliteration when DSA showed complete obliteration), specificity, positive predictive value, and negative predictive value for CSDAVF obliteration were reported. RESULTS: The median interval between the final MRI/MRA and the subsequent DSA was 2 months. Follow-up DSA revealed that 38 of 48 (79.2 %) CSDAVFs were completely obliterated. The results of interobserver agreement assessment showed almost perfect agreement between the 2 observers. For unenhanced MRI/3D TOF MRA, the observed sensitivity was 84.2 %, specificity was 100 %, positive predictive value was 100 %, and negative predictive value was 62.5 %. CONCLUSIONS: Unenhanced MRI/3D TOF MRA alone may be adequate to document the complete obliteration of CSDAVFs after GKS. Time-resolved MRA or DSA can be reserved for a suspected residual CSDAVF after a sufficient latency period after GKS.

Inhibitory concentration of propofol in combination with dexmedetomidine during microelectrode recording for deep brain stimulator insertion surgeries under general anesthesia.

BACKGROUND: Microelectrode recording (MER) for target refinement is widely used in deep brain stimulator insertion for Parkinson disease. Signals may be influenced by anesthetics when patients receive general anesthesia (GA). This study determined the inhibitory concentration (IC) of propofol on MER signals when it was coadministered with dexmedetomidine. METHODS: Patients were anesthetized with dexmedetomidine (0.5 µg·kg loading, followed by infusion at 0.4 µg·kgh) and propofol through target-controlled infusion for GA with tracheal intubation. The surgeon conducted the online scoring of the background signals, spiking frequency, amplitude, and pattern of single-unit activities by using a 0-10 verbal numerical rating scale (NRS; 0, maximal suppression; 10, minimal suppression), and responses were grouped into suppression (NRS ≤ 6) and nonsuppression (NRS > 6). The median inhibitory concentration (IC50) of propofol (as target effect-site concentrations: Ceprop) was determined using modified Dixon's up-and-down method. Probit regression analysis was further used to obtain the dose-response relationship, and IC05 and IC95 were calculated. RESULTS: Twenty-three adult patients participated in this study. Under the concomitant infusion of dexmedetomidine, the predicted IC50 value (95% CI) of Ceprop for neuronal suppression during MER was 1.29 (1.24-1.34) µg·mL as calculated using modified Dixon's up-and-down method. Using probit analysis, the estimated IC05, IC50, and IC95 values (95% CIs) were 1.17 (0.87-1.23), 1.28 (1.21-1.34), and 1.40 (1.33-1.85) µg·mL, respectively. CONCLUSION: Our data provided reference values of propofol for dosage adjustment to avoid interference on MER under GA when anesthetics have to be continuously infused during recording.

Treatment Outcomes of Cavernous Sinus Dural Arteriovenous Fistulas: Comparison of Radiosurgery and Endovascular Embolisation.

BACKGROUND AND PURPOSE: Endovascular treatment (EVT) and stereotaxic gamma-knife radiosurgery (GKRS) can both effectively treat cavernous sinus dural arteriovenous fistulas (CSDAVF). This study compared the prognostic factors and treatment effectiveness of GKRS and EVT for different CSDAVF types. METHODS: The charts of 200 patients undergoing GKRS and 105 patients undergoing EVT were reviewed for data on symptoms (e.g. orbital, cavernous, ocular, and cerebral). The CSDAVFs were classified into proliferative, restrictive, and late restrictive types. The prognostic factors for complete obliteration (CO) were evaluated in both the GKRS and EVT groups and the latent period to CO was measured. For statistical analysis χ2-tests were used to compare final CO rates for EVT and GKRS across the three CSDAVF types. RESULTS: The EVT and cavernous symptoms were significant independent predictors of CO. The CO rate after EVT (97.9%) was significantly higher than that after GKRS (63.5%) for restrictive CSDAVFs (P < 0.001) but not for proliferative or late restrictive types. In the GKRS group, cavernous symptoms (hazard ratio, HR: 0.557) and target volume (HR: 0.853) predicted CO, but only target volume remained significant in multivariate analysis. In the EVT group, the latent period to CO was shortest for restrictive CSDAVFs (3.2 ± 1.6 months, P = 0.05). CONCLUSION: Angioarchitecture did not affect treatment outcomes. Cavernous symptoms were strongly associated with lower complete obliteration rates in the GKRS but not the EVT group. The EVT method remains the treatment of choice, especially for restrictive CSDAVFs; however, compared to EVT, GKRS had lower complication rates and similar therapeutic effects for proliferative type fistulas.

Venous outflow restriction as a predictor of cavernous sinus dural arteriovenous fistula obliteration after Gamma Knife surgery.

OBJECTIVE: Gamma Knife surgery (GKS) obliterates 65%-87% of cavernous sinus dural arteriovenous fistulas (CSDAVFs). However, the hemodynamic effect on GKS outcomes is relatively unknown. The authors thus used the classification scheme developed by Suh et al. to explore this effect. METHODS: The authors retrospectively (1993-2016) included 123 patients with CSDAVFs who received GKS alone at the institute and classified them as proliferative type (PT; n = 23), restrictive type (RT; n = 61), or late restrictive type (LRT; n = 39) after analyzing their pre-GKS angiography images. Treatment parameters, the presence of numerous arterial feeders, and venous drainage numbers were compared across the CSDAVF types. Patients' follow-up MR images were evaluated for the presence of complete obliteration. A Kaplan-Meier analysis was conducted to determine the correlation between CSDAVF types and outcomes. RESULTS: The 36-month probability of complete obliteration was 74.3% for all patients, with no significant differences across types (p = 0.56). PT had the largest radiation volume (6.5 cm3, p < 0.001), the most isocenters (5, p = 0.015) and venous drainage routes (3, p < 0.001), and the lowest peripheral dose (16.6 Gy, p = 0.011) and isodose level coverage (64.3%, p = 0.006). CSDAVFs presenting with ocular patterns were less likely to be completely obliterated (hazard ratio 0.531, p = 0.009). After adjustment for age, CSDAVFs with more venous drainage routes were less likely to be completely obliterated (hazard ratio 0.784, p = 0.039). CONCLUSIONS: GKS is an equally effective treatment option for all 3 CSDAVF types. Furthermore, the number of venous drainage routes may help in predicting treatment outcomes and making therapeutic decisions.

Intervening Nidal Brain Parenchyma and Risk of Radiation-Induced Changes After Radiosurgery for Brain Arteriovenous Malformation: A Study Using an Unsupervised Machine Learning Algorithm.

OBJECTIVE: To assess the sensitivity and specificity of arteriovenous malformation (AVM) nidal component identification and quantification using an unsupervised machine learning algorithm and to evaluate the association between intervening nidal brain parenchyma and radiation-induced changes (RICs) after stereotactic radiosurgery. METHODS: Fully automated segmentation via unsupervised classification with fuzzy c-means clustering was used to analyze the AVM nidus on T2-weighted magnetic resonance imaging studies. The proportions of vasculature, brain parenchyma, and cerebrospinal fluid were quantified. These were compared with the results from manual segmentation. The association between the brain parenchyma component and RIC development was assessed. RESULTS: The proposed algorithm was applied to 39 unruptured AVMs in 39 patients (17 female and 22 male patients), with a median age of 27 years. The median proportion of the constituents was as follows: vasculature, 31.3%; brain parenchyma, 48.4%; and cerebrospinal fluid, 16.8%. RICs were identified in 17 of the 39 patients (43.6%). Compared with manual segmentation, the automated algorithm was able to achieve a Dice similarity index of 79.5% (sensitivity, 73.5%; specificity, 85.5%). RICs were associated with a greater proportion of intervening nidal brain parenchyma (52.0% vs. 45.3%; P = 0.015). Obliteration was not associated with greater proportions of nidal vasculature (36.0% vs. 31.2%; P = 0.152). CONCLUSIONS: The automated segmentation algorithm was able to achieve classification of the AVM nidus components with relative accuracy. Greater proportions of intervening nidal brain parenchyma were associated with RICs.

Fully automated tissue segmentation of the prescription isodose region delineated through the Gamma knife plan for cerebral arteriovenous malformation (AVM) using fuzzy C-means (FCM) clustering.

BACKGROUND: Gamma knife radiosurgery (GKRS) is a common treatment for cerebral arterio-venous malformations (AVMs), particularly in cases where the malformation is deep-seated, large, or in eloquent areas of the brain. Unfortunately, these procedures can result in radiation injury to brain parenchyma. The fact that every AVM is unique in its vascular morphology makes it nearly impossible to exclude brain parenchyma from isodose radiation exposure during the formulation of a GKRS plan. Calculating the percentages of the various forms of tissue exposed to specific doses of radiation is crucial to understanding the clinical responses and causes of brain parenchyma injury following GKRS for AVM. METHODS: In this study, we developed a fully automated algorithm using unsupervised classification via fuzzy c-means clustering for the analysis of T2 weighted images used in a Gamma knife plan. This algorithm is able to calculate the percentages of nidus, brain tissue, and cerebrospinal fluid (CSF) within the prescription isodose radiation exposure region. RESULTS: The proposed algorithm was used to assess the treatment plan of 25 patients with AVM who had undergone GKRS. The Dice similarity index (SI) was used to determine the degree of agreement between the results obtained using the algorithm and a visually guided manual method (the gold standard) performed by an experienced neurosurgeon. In the nidus, the SI was (74.86 ±â€¯1.30%) (mean ±â€¯standard deviation), the sensitivity was (83.05 ±â€¯11.91)%, and the specificity was (86.73 ±â€¯10.31)%. In brain tissue, the SI was (79.50 ±â€¯6.01)%, the sensitivity was (73.05 ±â€¯9.77)%, and the specificity was (85.53 ±â€¯7.13)%. In the CSF, the SI was (69.57 ±â€¯15.26)%, the sensitivity was (89.86 ±â€¯5.87)%, and the specificity was (92.36 ±â€¯4.35)%. CONCLUSIONS: The proposed clustering algorithm provides precise percentages of the various types of tissue within the prescription isodose region in the T2 weighted images used in the GKRS plan for AVM. Our results shed light on the causes of brain radiation injury after GKRS for AVM. In the future, this system could be used to improve outcomes and avoid complications associated with GKRS treatment.

Trigeminal Nerve Atrophy Predicts Pain Recurrence After Gamma Knife Stereotactic Radiosurgery for Classical Trigeminal Neuralgia.

BACKGROUND: Trigeminal nerve atrophy and neurovascular compression (NVC) are frequently observed in classical trigeminal neuralgia (CTN). OBJECTIVE: To determine whether nerve characteristics contribute to Gamma Knife (Elekta AB, Stockholm, Sweden) surgery (GKS) outcomes in unilateral CTN without previous surgery. METHODS: From 2006 to 2012, 67 patients with unilateral CTN without previous surgery received GKS with a maximal dose of 90 Gy delivered to the trigeminal nerve juxta brainstem. Two evaluators, blinded to the side of pain, analyzed the magnetic resonance images before GKS to obtain the parameters, including nerve cross-sectional area (CSA), vessel type of NVC, and site of NVC along the nerve. Correlations of the parameters with pain relief (Barrow Neurological Institute [BNI] grades I-IIIb) and recurrence (BNI grades VI-V) were made by using Cox regression and Kaplan-Meier analyses. RESULTS: The median CSA of the symptomatic nerves was significantly smaller than that of the asymptomatic nerves (4.95 vs 5.9 mm2, P < .001). After adjustment for age and sex, larger nerve CSA was associated with lower initial pain relief (hazard ratio 0.81, P = .03) and lower pain recurrence after initial response (hazard ratio 0.58, P = .02). Patients with nerve atrophy (CSA of ≤ 4.4 mm2 after receiver operating characteristic curve analysis) had a lower 5-yr probability of maintaining pain relief after initial response than those without nerve atrophy (65% vs 86%, P = .04). CONCLUSION: Trigeminal nerve atrophy may predict pain recurrence in patients with initial post-GKS relief of CTN. Arterial and proximal NVC are not predictive of GKS outcomes. Future studies are required to determine optimal treatments for long-term pain relief in patients with CTN and trigeminal nerve atrophy.

Lateral Sinus Dural Arteriovenous Fistulas: Sinovenous Outflow Restriction Outweighs Cortical Venous Reflux as a Parameter Associated with Hemorrhage.

Purpose To investigate whether sinovenous outflow restriction (SOR) is more strongly associated with hemorrhage than cortical venous reflux (CVR) in patients with lateral sinus dural arteriovenous fistulas (DAVFs). Materials and Methods An institutional review board approved this retrospective study and waiver of informed consent was obtained. From 1995 to 2016, 163 cases of lateral sinus DAVFs were included and divided into hemorrhagic and nonhemorrhagic groups based on initial presentation. Their angiograms and magnetic resonance images were evaluated, with two evaluators independently grading CVR and SOR. The SOR was scored as the combined conduit score (CCS), ranging from zero (total occlusion) to 8 (fully patent). The CVR and CCS of the hemorrhagic and nonhemorrhagic groups were compared. Logistic regression models were established for both the CVR and CCS to compare their performances in discriminating DAVF hemorrhage. Results Sinovenous outflow was significantly more restrictive (lower median CCS) in the hemorrhagic group than in the nonhemorrhagic group (1 vs 6.5; P < .001). A CCS of less than or equal to 2 best discriminated between the groups with a sensitivity of 90.0% and a specificity of 88.1%. The CCS model had a higher discriminative performance than did the CVR model (area under the curve, 0.933 vs 0.843; P = .018). Conclusion The CCS grading system semiquantifies SOR. SOR may represent a stronger risk factor associated with hemorrhage in patients with lateral sinus DAVFs than does CVR, and thus may offer guidance in therapeutic decision making. © RSNA, 2017.

Magnetic resonance imaging characteristics and the prediction of outcome of vestibular schwannomas following Gamma Knife radiosurgery.

OBJECTIVE Gamma Knife surgery (GKS) is a promising treatment modality for patients with vestibular schwannomas (VSs), but a small percentage of patients have persistent postradiosurgical tumor growth. The aim of this study was to determine the clinical and quantitative MRI features of VS as predictors of long-term tumor control after GKS. METHODS The authors performed a retrospective study of all patients with VS treated with GKS using the Leksell Gamma Knife Unit between 2005 and 2013 at their institution. A total of 187 patients who had a minimum of 24 months of clinical and radiological assessment after radiosurgery were included in this study. Those who underwent a craniotomy with tumor removal before and after GKS were excluded. Study patients comprised 85 (45.5%) males and 102 (54.5%) females, with a median age of 52.2 years (range 20.4-82.3 years). Tumor volumes, enhancing patterns, and apparent diffusion coefficient (ADC) values were measured by region of interest (ROI) analysis of the whole tumor by serial MRI before and after GKS. RESULTS The median follow-up period was 60.8 months (range 24-128.9 months), and the median treated tumor volume was 3.54 cm3 (0.1-16.2 cm3). At last follow-up, imaging studies indicated that 150 tumors (80.2%) showed decreased tumor volume, 20 (10.7%) had stabilized, and 17 (9.1%) continued to grow following radiosurgery. The postradiosurgical outcome was not significantly correlated with pretreatment volumes or postradiosurgical enhancing patterns. Tumors that showed regression within the initial 12 months following radiosurgery were more likely to have a larger volume reduction ratio at last follow-up than those that did not (volume reduction ratio 55% vs 23.6%, respectively; p < 0.001). Compared with solid VSs, cystic VSs were more likely to regress or stabilize in the initial postradiosurgical 6-12-month period and during extended follow-up. Cystic VSs exhibited a greater volume reduction ratio at last follow-up (cystic vs solid: 67.6% ± 24.1% vs 31.8% ± 51.9%; p < 0.001). The mean preradiosurgical maximum ADC (ADCmax) values of all VSs were significantly higher for those with tumor regression or stabilization at last follow-up compared with those with progression (2.391 vs 1.826 × 10-3 mm2/sec; p = 0.010). CONCLUSIONS Loss of central enhancement after radiosurgery was a common phenomenon, but it did not correlate with tumor volume outcome. Preradiosurgical MRI features including cystic components and ADCmax values can be helpful as predictors of treatment outcome.

Gamma Knife radiosurgery for hemangioma of the cavernous sinus.

OBJECTIVE Cavernous sinus hemangiomas (CSHs) are rare vascular tumors. A direct microsurgical approach usually results in massive hemorrhage and incomplete tumor resection. Although stereotactic radiosurgery (SRS) has emerged as a therapeutic alternative to microsurgery, outcome studies are few. Authors of the present study evaluated the role of SRS for CSH. METHODS An international multicenter study was conducted to review outcome data in 31 patients with CSH. Eleven patients had initial microsurgery before SRS, and the other 20 patients (64.5%) underwent Gamma Knife SRS as the primary management for their CSH. Median age at the time of radiosurgery was 47 years, and 77.4% of patients had cranial nerve dysfunction before SRS. Patients received a median tumor margin dose of 12.6 Gy (range 12-19 Gy) at a median isodose of 55%. RESULTS Tumor regression was confirmed by imaging in all 31 patients, and all patients had greater than 50% reduction in tumor volume at 6 months post-SRS. No patient had delayed tumor growth, new cranial neuropathy, visual function deterioration, adverse radiation effects, or hypopituitarism after SRS. Twenty-four patients had presented with cranial nerve disorders before SRS, and 6 (25%) of them had gradual improvement. Four (66.7%) of the 6 patients with orbital symptoms had symptomatic relief at the last follow-up. CONCLUSIONS Stereotactic radiosurgery was effective in reducing the volume of CSH and attaining long-term tumor control in all patients at a median of 40 months. The authors' experience suggests that SRS is a reasonable primary and adjuvant treatment modality for patients in whom a CSH is diagnosed.

Stereotactic Radiosurgery for Brainstem Metastases: An International Cooperative Study to Define Response and Toxicity.

PURPOSE: To pool data across multiple institutions internationally and report on the cumulative experience of brainstem stereotactic radiosurgery (SRS). METHODS AND MATERIALS: Data on patients with brainstem metastases treated with SRS were collected through the International Gamma Knife Research Foundation. Clinical, radiographic, and dosimetric characteristics were compared for factors prognostic for local control (LC) and overall survival (OS) using univariate and multivariate analyses. RESULTS: Of 547 patients with 596 brainstem metastases treated with SRS, treatment of 7.4% of tumors resulted in severe SRS-induced toxicity (grade ≥3, increased odds with increasing tumor volume, margin dose, and whole-brain irradiation). Local control at 12 months after SRS was 81.8% and was improved with increasing margin dose and maximum dose. Overall survival at 12 months after SRS was 32.7% and impacted by age, gender, number of metastases, tumor histology, and performance score. CONCLUSIONS: Our study provides additional evidence that SRS has become an option for patients with brainstem metastases, with an excellent benefit-to-risk ratio in the hands of experienced clinicians. Prior whole-brain irradiation increases the risk of severe toxicity in brainstem metastasis patients undergoing SRS.

Gamma Knife Radiosurgery for Atypical and Anaplastic Meningiomas.

BACKGROUND: Atypical and anaplastic meningiomas have much higher recurrence rates after surgical resection compared with benign meningiomas, but the role of adjuvant radiosurgery remains unclear. This study was undertaken to evaluate the outcomes of gamma knife radiosurgery for patients with atypical and anaplastic meningiomas. METHODS: In this retrospective analysis of a prospectively maintained database, 46 patients with histologically proven atypical or anaplastic meningiomas by current World Health Organization (WHO) criteria underwent postoperative Gamma Knife radiosurgery between 1993 and 2013. The median follow-up period was 32.6 months. The median tumor volume and margin dose were 11.7 mL (range, 2-53 mL) and 13.1 Gy (range, 12.0-16.5 Gy), respectively. RESULTS: Local control at 3 and 5 years was 50.6% and 32.1%, respectively. Gender (P = 0.013) and marginal dose less than or equal to 13 Gy (P = 0.049) were associated with the local control. The 3- and 5-year overall survival for patients with WHO grade II was 97.1% and 88.3%, respectively, compared with 66.7% and 66.7% for patients with WHO grade III meningiomas. Radiation therapy before Gamma Knife radiosurgery (GKRS; P = 0.018) and tumor grade (P = 0.019) were the factors associated with a worse overall survival rate. Fourteen patients (30.4%) developed adverse radiation effects after GKRS treatment, and all were Radiation Therapy Oncology Group grade I. CONCLUSIONS: Postoperative GKRS treatment for patients with atypical and anaplastic meningioma is challenging. More aggressive treatment, including of safely maximizing the extent of surgical resection and using a higher margin dose (>13Gy), should be applied to achieve better local control.