Publications by authors named "Huai-Che Yang"

84 Publications

An International Multicenter Matched Cohort Analysis of Incidental Meningioma Progression During Active Surveillance or After Stereotactic Radiosurgery: The IMPASSE Study.

Neuro Oncol 2021 Jun 9. Epub 2021 Jun 9.

Department of Neurosurgery, University of Liverpool & The Walton Centre NHS Trust, Lower Lane, Liverpool, UK.

Background: The optimal management of patients with an incidental meningiomas remains unclear. The aim of this study was to characterize the radiologic and neurological outcomes of expectant and SRS management of asymptomatic meningioma patients.

Methods: Using data from 14 centers across 10 countries, the study compares SRS outcomes to active surveillance of asymptomatic meningiomas. Local tumor control of asymptomatic meningiomas and development of new neurological deficits attributable to the tumor were evaluated in the SRS and conservatively managed groups.

Results: In unmatched cohorts, 727 meningioma patients underwent SRS and were followed for a mean of 57.2 months. In the conservatively managed cohort, 388 patients were followed for a mean of 43.5 months. Tumor control was 99.0% of SRS and 64.2% of conservatively managed patients (p<0.001; OR 56.860 (95%CI 26.253-123.150))). New neurological deficits were 2.5% in the SRS and 2.8% of conservatively managed patients (p=0.764; OR 0.890 (95% CI 0.416-1.904)). After 1:1 propensity matching for patient age, tumor volume, location, and imaging follow-up, tumor control in the SRS and conservatively managed cohorts was 99.4% and 62.1%, respectively (p<0.001; OR 94.461 (95% CI 23.082-386.568)). In matched cohorts, new neurological deficits were noted in 2.3% of SRS treated and 3.2% of conservatively managed patients (p=0.475; OR 0.700 (95% CI 0.263-1.863)).

Conclusions: SRS affords superior radiologic tumor control compared to active surveillance without increasing the risk of neurological deficits in asymptomatic meningioma patients. While SRS and active surveillance are reasonable options, SRS appears to alter the natural history of asymptomatic meningiomas including tumor progression in the majority of patients treated.
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http://dx.doi.org/10.1093/neuonc/noab132DOI Listing
June 2021

Effects of stereotactic radiosurgery versus conventional radiotherapy on body mass index in patients with craniopharyngioma.

J Neurosurg Pediatr 2021 May 14:1-7. Epub 2021 May 14.

1Department of Neurosurgery, Neurological Institute.

Objective: Hypothalamic obesity is common among patients with craniopharyngioma. This study examined whether precise stereotactic radiosurgery reduces the risk of hypothalamic obesity in cases of craniopharyngioma with expected long-term survival.

Methods: This cohort study included 40 patients who had undergone Gamma Knife radiosurgery (GKRS; n = 22) or fractionated radiotherapy (FRT; n = 18) for residual or recurrent craniopharyngioma. Neurological presentations, tumor volume changes, and BMI values were meticulously reviewed. The median clinical follow-up durations were 9.7 years in the GKRS group and 10.8 years in the FRT group.

Results: The median ages at the time of GKRS and FRT were 9.0 years and 10.0 years, respectively. The median margin dose of GKRS was 12.0 Gy (range 10.0-16.0 Gy), whereas the median dose of FRT was 50.40 Gy (range 44.1-56.3 Gy). Prior to GKRS or FRT, the median BMI values were 20.5 kg/m2 in the GKRS cohort and 20.0 kg/m2 in the FRT cohort. The median BMIs after radiation therapy at final follow-up were 21.0 kg/m2 and 24.0 kg/m2 for the GKRS and FRT cohorts, respectively. In the FRT cohort, BMI curves rapidly increased beyond the 85th percentile of the upper limit of the general population. BMI curves in the GKRS cohort increased more gradually, and many of the patients merged into the normal growth curve after adolescence. However, the observed difference was not statistically significant (p = 0.409).

Conclusions: The study compared the two adjuvant radiation modalities most commonly used for recurrent and residual craniopharyngioma. The authors' results revealed that precise radiosurgery dose planning can mediate the subsequent increase in BMI. There is every indication that meticulous GKRS treatment is an effective approach to treating craniopharyngioma while also reducing the risk of hypothalamic obesity.
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http://dx.doi.org/10.3171/2020.12.PEDS20165DOI Listing
May 2021

Stereotactic Radiosurgery for Differentiated Thyroid Cancer Brain Metastases: An International, Multicenter Study.

Thyroid 2021 May 11. Epub 2021 May 11.

Department of Neurosurgery, University of Virginia, Charlottesville, Virginia, USA.

Brain metastases (BM) from differentiated thyroid cancer are rare. Stereotactic radiosurgery (SRS) is commonly used for the treatment of BMs; however, the experience with SRS for thyroid cancer BMs remains limited. The goal of this international, multi-centered study was to evaluate the efficacy and safety of SRS for thyroid cancer BMs. From 10 institutions participating in the International Radiosurgery Research Foundation, we pooled patients with established papillary or follicular thyroid cancer diagnosis who underwent SRS for histologically confirmed or radiologically suspected BMs. We investigated patient overall survival (OS), local tumor control, and adverse radiation events (AREs). We studied 42 (52% men) patients who underwent SRS for 122 papillary (83%) or follicular (17%) thyroid cancer BMs. The mean age at SRS was 59.86 ± 12.69 years. The mean latency from thyroid cancer diagnosis to SRS for BMs was 89.05 ± 105.49 months. The median number of BMs per patient was 2 (range: 1-10 BMs). The median SRS treatment volume was 0.79 cm (range: 0.003-38.18 cm), and the median SRS prescription dose was 20 Gy (range: 8-24 Gy). The median survival after SRS for BMs was 14 months (range: 3-58 months). The OS was significantly shorter in patients harboring ≥2 BMs, when compared with patients with one BM (Log-rank = 5.452,  = 0.02). Two or more BMs (odds ratio [OR] = 3.688; confidence interval [CI]: 1.143-11.904;  = 0.03) and lower Karnofsky performance score at the time of SRS (OR = 0.807; CI: 0.689-0.945;  = 0.008) were associated with shorter OS. During post-SRS imaging follow-up of 25.21 ± 30.49 months, local failure (progression and/or radiation necrosis) of BMs treated with SRS was documented in five (4%) BMs at 7.2 ± 7.3 months after the SRS. At the last imaging follow-up, the majority of patients with available imaging data had stable intracranial disease (33%) or achieved complete (26%) or partial (24%) response. There were no clinical AREs. Post-SRS peritumoral T2/fluid attenuated inversion recovery signal hyperintensity was noted in 7% BMs. The SRS allows durable local control of papillary and follicular thyroid cancer BMs in the vast majority of patients. Higher number of BMs and worse functional status at the time of SRS are associated with shorter OS in patients with thyroid cancer BMs. The SRS is safe and is associated with a low risk of AREs.
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http://dx.doi.org/10.1089/thy.2020.0947DOI Listing
May 2021

Cerebrospinal fluid diversion and outcomes for lung cancer patients with leptomeningeal carcinomatosis.

Acta Neurochir (Wien) 2021 Mar 1. Epub 2021 Mar 1.

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

Objective: To investigate the outcomes of cerebrospinal fluid (CSF) diversion in lung cancer patients with leptomeningeal carcinomatosis (LMC).

Methods: A retrospective review of consecutive lung cancer patients with LMC suffering from increased intracranial pressure (IICP) and hydrocephalus between February 2017 and February 2020. We evaluated the survival benefit of CSF diversion surgery and assessed the outcomes of treatments administered post-LMC in terms of overall survival and shunt-related complications.

Results: The study cohort included 50 patients (median age: 59 years). Ventricular peritoneal (VP) shunts were placed in 33 patients, and lumbar peritoneal (LP) shunts were placed in 7 patients. Programmable shunts were placed in 36 patients. Shunt adjustment was performed in 19 patients. Kaplan-Meier analysis revealed that shunt placement increased overall survival from 1.95 months to 6.21 months (p = 0.0012) and increased Karnofsky Performance Scores (KPS) from 60 to 70. Univariate analysis revealed no difference between VP or LP shunts in terms of survival. No differences in post-shunt systemic treatments (tyrosine kinase inhibitors (TKIs) or systemic treatments) were observed in overall survival. Shunt-related complications were noted in 7 patients, including shunt obstruction (n = 4), infection (n = 1), and over-drainage (n = 2).

Conclusion: CSF diversion (VP or LP shunt) appears to be an effective and safe treatment for lung cancer patients with LMC and hydrocephalus. Programmable shunts should be considered for complex cases, which commonly require pressure adjustments as the disease progresses.
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http://dx.doi.org/10.1007/s00701-021-04763-wDOI Listing
March 2021

Applying artificial intelligence to longitudinal imaging analysis of vestibular schwannoma following radiosurgery.

Sci Rep 2021 Feb 4;11(1):3106. Epub 2021 Feb 4.

Department of Radiology, Taipei Veteran General Hospital, Taipei, Taiwan.

Artificial intelligence (AI) has been applied with considerable success in the fields of radiology, pathology, and neurosurgery. It is expected that AI will soon be used to optimize strategies for the clinical management of patients based on intensive imaging follow-up. Our objective in this study was to establish an algorithm by which to automate the volumetric measurement of vestibular schwannoma (VS) using a series of parametric MR images following radiosurgery. Based on a sample of 861 consecutive patients who underwent Gamma Knife radiosurgery (GKRS) between 1993 and 2008, the proposed end-to-end deep-learning scheme with automated pre-processing pipeline was applied to a series of 1290 MR examinations (T1W+C, and T2W parametric MR images). All of which were performed under consistent imaging acquisition protocols. The relative volume difference (RVD) between AI-based volumetric measurements and clinical measurements performed by expert radiologists were + 1.74%, - 0.31%, - 0.44%, - 0.19%, - 0.01%, and + 0.26% at each follow-up time point, regardless of the state of the tumor (progressed, pseudo-progressed, or regressed). This study outlines an approach to the evaluation of treatment responses via novel volumetric measurement algorithm, and can be used longitudinally following GKRS for VS. The proposed deep learning AI scheme is applicable to longitudinal follow-up assessments following a variety of therapeutic interventions.
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http://dx.doi.org/10.1038/s41598-021-82665-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862268PMC
February 2021

Outcomes after stereotactic radiosurgery for schwannomas of the oculomotor, trochlear, and abducens nerves.

J Neurosurg 2021 Jan 22:1-7. Epub 2021 Jan 22.

1Division of Neurosurgery, Department of Surgery, Université de Sherbrooke, Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Québec, Canada.

Objective: Cranial nerve (CN) schwannomas are intracranial tumors that are commonly managed by stereotactic radiosurgery (SRS). There is a large body of literature supporting the use of SRS for vestibular schwannomas. Schwannomas of the oculomotor nerves (CNs III, IV, and VI) are rare skull base tumors, occurring close to the brainstem and often involving the cavernous sinus. Resection can cause significant morbidity, including loss of nerve function. As for other schwannomas, SRS can be used to manage these tumors, but only a handful of cases have been published so far, often among reports of other uncommon schwannoma locations.

Methods: The goal of this study was to collect retrospective multicenter data on tumor control, clinical evolution, and morbidity after SRS. This study was performed through the International Radiosurgery Research Foundation. Patients managed with single-session SRS for an oculomotor cranial nerve schwannoma (CN III, IV, or VI) were included. The diagnosis was based on diplopia or ptosis as the main presenting symptom and anatomical location on the trajectory of the presumed cranial nerve of origin, or prior resection confirming diagnosis. Demographic, SRS dose planning, clinical, and imaging data were collected from chart review of the treated patients. Chi-square and Kaplan-Meier analyses were performed.

Results: Seven institutions submitted data for a total of 25 patients. The median follow-up time was 41 months. The median age at the time of treatment was 52 years. There were 11 CN III schwannomas, 11 CN IV schwannomas, and 3 CN VI schwannomas. The median target volume was 0.74 cm3, and the median marginal dose delivered was 12.5 Gy. After SRS, only 2 patients (including the only patient with neurofibromatosis type 2) had continued tumor growth. Crude local control was 92% (23/25), and the 10-year actuarial control was 86%. Diplopia improved in the majority of patients (11/21), and only 3 had worsening following SRS, 2 of whom also had worsened ptosis, both in the context of tumor progression.

Conclusions: SRS for schwannomas of the oculomotor, trochlear, and abducens nerves is effective and provides tumor control rates similar to those for other cranial nerve schwannomas. SRS allows improvement of diplopia in the majority of patients. SRS should therefore be considered as a first-line treatment option for oculomotor nerve schwannomas.
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http://dx.doi.org/10.3171/2020.8.JNS20887DOI Listing
January 2021

Stereotactic Radiosurgery for Perioptic Meningiomas: An International, Multicenter Study.

Neurosurgery 2021 03;88(4):828-837

Department of Radiation Oncology, University of Colorado, Denver, Colorado.

Background: Stereotactic radiosurgery (SRS) is increasingly used for management of perioptic meningiomas.

Objective: To study the safety and effectiveness of SRS for perioptic meningiomas.

Methods: From 12 institutions participating in the International Radiosurgery Research Foundation (IRRF), we retrospectively assessed treatment parameters and outcomes following SRS for meningiomas located within 3 mm of the optic apparatus.

Results: A total of 438 patients (median age 51 yr) underwent SRS for histologically confirmed (29%) or radiologically suspected (71%) perioptic meningiomas. Median treatment volume was 8.01 cm3. Median prescription dose was 12 Gy, and median dose to the optic apparatus was 8.50 Gy. A total of 405 patients (93%) underwent single-fraction SRS and 33 patients (7%) underwent hypofractionated SRS. During median imaging follow-up of 55.6 mo (range: 3.15-239 mo), 33 (8%) patients experienced tumor progression. Actuarial 5-yr and 10-yr progression-free survival was 96% and 89%, respectively. Prescription dose of ≥12 Gy (HR: 0.310; 95% CI [0.141-0.679], P = .003) and single-fraction SRS (HR: 0.078; 95% CI [0.016-0.395], P = .002) were associated with improved tumor control. A total of 31 (10%) patients experienced visual decline, with actuarial 5-yr and 10-yr post-SRS visual decline rates of 9% and 21%, respectively. Maximum dose to the optic apparatus ≥10 Gy (HR = 2.370; 95% CI [1.086-5.172], P = .03) and tumor progression (HR = 4.340; 95% CI [2.070-9.097], P < .001) were independent predictors of post-SRS visual decline.

Conclusion: SRS provides durable tumor control and quite acceptable rates of vision preservation in perioptic meningiomas. Margin dose of ≥12 Gy is associated with improved tumor control, while a dose to the optic apparatus of ≥10 Gy and tumor progression are associated with post-SRS visual decline.
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http://dx.doi.org/10.1093/neuros/nyaa544DOI Listing
March 2021

Stereotactic radiosurgery for treatment of radiation-induced meningiomas: a multiinstitutional study.

J Neurosurg 2021 Jan 1:1-9. Epub 2021 Jan 1.

1Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia.

Objective: Radiation-induced meningiomas (RIMs) are associated with aggressive clinical behavior. Stereotactic radiosurgery (SRS) is sometimes considered for selected RIMs. The authors investigated the effectiveness and safety of SRS for the management of RIMs.

Methods: From 12 institutions participating in the International Radiosurgery Research Foundation, the authors pooled patients who had prior cranial irradiation and were subsequently clinically diagnosed with WHO grade I meningiomas that were managed with SRS.

Results: Fifty-two patients underwent 60 SRS procedures for histologically confirmed or radiologically suspected WHO grade I RIMs. The median ages at initial cranial radiation therapy and SRS for RIM were 5.5 years and 39 years, respectively. The most common reasons for cranial radiation therapy were leukemia (21%) and medulloblastoma (17%). There were 39 multiple RIMs (35%), the mean target volume was 8.61 ± 7.80 cm3, and the median prescription dose was 14 Gy. The median imaging follow-up duration was 48 months (range 4-195 months). RIM progressed in 9 patients (17%) at a median duration of 30 months (range 3-45 months) after SRS. Progression-free survival at 5 years post-SRS was 83%. Treatment volume ≥ 5 cm3 predicted progression (HR 8.226, 95% CI 1.028-65.857, p = 0.047). Seven patients (14%) developed new neurological symptoms or experienced SRS-related complications or T2 signal change from 1 to 72 months after SRS.

Conclusions: SRS is associated with durable local control of RIMs in the majority of patients and has an acceptable safety profile. SRS can be considered for patients and tumors that are deemed suboptimal, poor surgical candidates, and those whose tumor again progresses after removal.
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http://dx.doi.org/10.3171/2020.7.JNS202064DOI Listing
January 2021

Stereotactic Radiosurgery for Choroid Plexus Tumors: A Report of the International Radiosurgery Research Foundation.

Neurosurgery 2021 03;88(4):791-796

Department of Neurological Surgery and Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Background: Choroid plexus tumors (CPT) are rare epithelial tumors of the choroid plexus. Gross total resection (GTR) may be curative, but it is not always possible.

Objective: To evaluate the role of Gamma Knife stereotactic radiosurgery (GKSRS) as either a primary or adjuvant management option for WHO grade I-III CPT through a multicenter project.

Methods: A total of 32 patients (20 females) with a total of 43 treated tumors were included in the analysis. A total of 25 patients (78%) had undergone initial surgical resection. The median total tumor volume was 2.2 cc, and the median margin and maximum doses were 13 and 25.5 Gy, respectively.

Results: Local tumor control was achieved in 69% of cases. Local tumor progression-free survival (PFS) rate for low-grade tumors at 1, 3, and 5 yr was 90%, 77%, 58%, respectively. The actuarial local tumor PFS rate for high-grade tumors at 1, 3, and 5 yr was 77%, 62%, and 62%, respectively. There was no significant difference in local tumor control rates between low- and high-grade CPT (P = .3). Gender, age, and degree of resection were not associated with treated tumor PFS. Distant intracranial spread developed in 6 patients at a median of 22 mo after initial SRS. Actuarial distant brain tumor PFS rate at 1, 2, 5, and 10 yr was 93%, 88%, 78%, and 65%, respectively. Three patients (9%) developed persistent symptomatic adverse radiation effects at a median of 11 mo after the procedure.

Conclusion: GKSRS represents a minimally invasive alternative management strategy for imaging defined or surgically recurrent low- and high-grade CPT.
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http://dx.doi.org/10.1093/neuros/nyaa538DOI Listing
March 2021

Stagnant venous outflow in ruptured arteriovenous malformations revealed by delayed quantitative digital subtraction angiography.

Eur J Radiol 2021 Jan 1;134:109455. Epub 2020 Dec 1.

School of Medicine, National Yang Ming University, Taipei, Taiwan; Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address:

Purpose: To investigate the reproducibility of quantitative digital subtraction angiography (QDSA) measurements and their associations with brain arteriovenous malformation (BAVM) hemorrhage.

Methods: From 2011-2019, 37 patients with BAVMs who had undergone both diagnostic and stereotactic DSA were divided into hemorrhagic and nonhemorrhagic groups. QDSA analysis was performed on the 2 DSA exams. The inter-exam reliabilities of QDSA measurements across the diagnostic and stereotactic DSA were tested using intraclass correlation coefficients (ICCs). Demographics, BAVM characteristics, and QDSA results for the hemorrhagic and nonhemorrhagic groups were compared.

Results: Fifteen of 37 (40.5 %) patients presented with hemorrhage were associated with smaller BAVM volume and the presence of intranidal aneurysm and exclusive deep venous drainage. The median interval between the diagnostic and stereotactic DSA was 49 days and did not differ between the groups. In both groups, the inter-exam QDSA measurements were more reliable for drainage veins and transnidal time (ICCs ranged from 0.38-0.93) than for feeding arteries (ICCs ranged from 0.01-0.74). Among the venous parameters, the hemorrhagic group had lower peak density, area under the curve, inflow gradient, and outflow gradient on both DSA exams and larger full width at half maximum and stasis index on the stereotactic DSA exam than the nonhemorrhagic group.

Conclusions: In BAVMs, the QDSA measurements for veins are more reliable than those for arteries. QDSA analysis reflecting stagnant venous drainage is associated with BAVM hemorrhage, but may be confounded by the acute hemodynamic change after hemorrhage.
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http://dx.doi.org/10.1016/j.ejrad.2020.109455DOI Listing
January 2021

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

Stereotact Funct Neurosurg 2021 2;99(2):113-122. Epub 2020 Dec 2.

Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan,

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.
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http://dx.doi.org/10.1159/000510683DOI Listing
December 2020

Prediction of pseudoprogression and long-term outcome of vestibular schwannoma after Gamma Knife radiosurgery based on preradiosurgical MR radiomics.

Radiother Oncol 2021 02 5;155:123-130. Epub 2020 Nov 5.

Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan. Electronic address:

Background And Purpose: Gamma Knife radiosurgery (GKRS) is a safe and effective treatment modality with a long-term tumor control rate over 90% for vestibular schwannoma (VS). However, numerous tumors may undergo a transient pseudoprogression during 6-18 months after GKRS followed by a long-term volume reduction. The aim of this study is to determine whether the radiomics analysis based on preradiosurgical MRI data could predict the pseudoprogression and long-term outcome of VS after GKRS.

Materials And Methods: A longitudinal dataset of patients with VS treated by single GKRS were retrospectively collected. Overall 336 patients with no previous craniotomy for tumor removal and a median of 65-month follow-up period after radiosurgery were finally included in this study. In total 1763 radiomic features were extracted from the multiparameteric MRI data before GKRS followed by the machine-learning classification.

Results: We constructed a two-level machine-learning model to predict the long-term outcome and the occurrence of transient pseudoprogression after GKRS separately. The prediction of long-term outcome achieved an accuracy of 88.4% based on five radiomic features describing the variation of T2-weighted intensity and inhomogeneity of contrast enhancement in tumor. The prediction of transient pseudoprogression achieved an accuracy of 85.0% based on another five radiomic features associated with the inhomogeneous hypointensity pattern of contrast enhancement and the variation of T2-weighted intensity.

Conclusion: The proposed machine-learning model based on the preradiosurgical MR radiomics provides a potential to predict the pseudoprogression and long-term outcome of VS after GKRS, which can benefit the treatment strategy in clinical practice.
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http://dx.doi.org/10.1016/j.radonc.2020.10.041DOI Listing
February 2021

Combining analysis of multi-parametric MR images into a convolutional neural network: Precise target delineation for vestibular schwannoma treatment planning.

Artif Intell Med 2020 07 20;107:101911. Epub 2020 Jun 20.

National Yang-Ming University, Department of Biomedical Imaging and Radiological Sciences, Taipei, Taiwan; National Yang-Ming University, Institute of Biophotonics, Taipei, Taiwan; Brain Research Center, National Yang-Ming University, Taipei, Taiwan. Electronic address:

Manual delineation of vestibular schwannoma (VS) by magnetic resonance (MR) imaging is required for diagnosis, radiosurgery dose planning, and follow-up tumor volume measurement. A rapid and objective automatic segmentation method is required, but problems have been encountered due to the low through-plane resolution of standard VS MR scan protocols and because some patients have non-homogeneous cystic areas within their tumors. In this study, we retrospectively collected multi-parametric MR images from 516 patients with VS; these were extracted from the Gamma Knife radiosurgery planning system and consisted of T1-weighted (T1W), T2-weighted (T2W), and T1W with contrast (T1W + C) images. We developed an end-to-end deep-learning-based method via an automatic preprocessing pipeline. A two-pathway U-Net model involving two sizes of convolution kernel (i.e., 3 × 3 × 1 and 1 × 1 × 3) was used to extract the in-plane and through-plane features of the anisotropic MR images. A single-pathway model that adopted the same architecture as the two-pathway model, but used a kernel size of 3 × 3 × 3, was also developed for comparison purposes. In addition, we used multi-parametric MR images with different image contrasts as the model training input in order to effectively segment tumors with solid as well as cystic parts. The results of the automatic segmentation demonstrated that (1) the two-pathway model outperformed single-pathway model in terms of dice scores (0.90 ± 0.05 versus 0.87 ± 0.07); both of them having been trained using the T1W, T1W + C and T2W anisotropic MR images, (2) the optimal single-parametric two-pathway model (dice score: 0.88 ± 0.06) was then trained using the T1W + C images, and (3) the two-pathway models trained using bi-parametric (T1W + C and T2W) and tri-parametric (T1W, T2W, and T1W + C) images outperformed the model trained using the single-parametric (T1W + C) images (dice scores: 0.89 ± 0.05 and 0.90 ± 0.05, respectively, larger than 0.88 ± 0.06) because it showed improved segmentation of the non-homogeneous parts of the tumors. The proposed two-pathway U-Net model outperformed the single-pathway U-Net model when segmenting VS using anisotropic MR images. The multi-parametric models effectively improved on the defective segmentation obtained using the single-parametric models by separating the non-homogeneous tumors into their solid and cystic parts.
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http://dx.doi.org/10.1016/j.artmed.2020.101911DOI Listing
July 2020

Effect of Anatomic Segment Involvement on Stereotactic Radiosurgery for Facial Nerve Schwannomas: An International Multicenter Cohort Study.

Neurosurgery 2020 12;88(1):E91-E98

Department of Neurosurgery, University of Virginia Medical Center, Charlottesville, Virginia.

Background: Facial nerve schwannomas are rare, challenging tumors to manage due to their nerve of origin. Functional outcomes after stereotactic radiosurgery (SRS) are incompletely defined.

Objective: To analyze the effect of facial nerve segment involvement on functional outcome for these tumors.

Methods: Patients who underwent single-session SRS for facial nerve schwannomas with at least 3 mo follow-up at 11 participating centers were included. Preoperative and treatment variables were recorded. Outcome measures included radiological tumor response and neurological function.

Results: A total of 63 patients (34 females) were included in the present study. In total, 75% had preoperative facial weakness. Mean tumor volume and margin dose were 2.0 ± 2.4 cm3 and 12.2 ± 0.54 Gy, respectively. Mean radiological follow-up was 45.5 ± 38.9 mo. Progression-free survival at 2, 5, and 10 yr was 98.1%, 87.2%, and 87.2%, respectively. The cumulative proportion of patients with regressing tumors at 2, 5, and 10 yr was 43.1%, 63.6%, and 63.6%, respectively. The number of involved facial nerve segments significantly predicted tumor progression (P = .04). Facial nerve function was stable or improved in 57 patients (90%). Patients with involvement of the labyrinthine segment of the facial nerve were significantly more likely to have an improvement in facial nerve function after SRS (P = .03). Hearing worsened in at least 6% of patients. Otherwise, adverse radiation effects included facial twitching (3 patients), facial numbness (2 patients), and dizziness (2 patients).

Conclusion: SRS for facial nerve schwannomas is effective and spares facial nerve function in most patients. Some patients may have functional improvement after treatment, particularly if the labyrinthine segment is involved.
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http://dx.doi.org/10.1093/neuros/nyaa313DOI Listing
December 2020

Early obliteration of pediatric brain arteriovenous malformations after stereotactic radiosurgery: an international multicenter study.

J Neurosurg Pediatr 2020 Jun 26:1-8. Epub 2020 Jun 26.

1Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia.

Objective: Stereotactic radiosurgery (SRS) is a treatment option for pediatric brain arteriovenous malformations (AVMs), and early obliteration could encourage SRS utilization for a subset of particularly radiosensitive lesions. The objective of this study was to determine predictors of early obliteration after SRS for pediatric AVMs.

Methods: The authors performed a retrospective review of the International Radiosurgery Research Foundation AVM database. Obliterated pediatric AVMs were sorted into early (obliteration ≤ 24 months after SRS) and late (obliteration > 24 months after SRS) responders. Predictors of early obliteration were identified, and the outcomes of each group were compared.

Results: The overall study cohort was composed of 345 pediatric patients with obliterated AVMs. The early and late obliteration cohorts were made up of 95 (28%) and 250 (72%) patients, respectively. Independent predictors of early obliteration were female sex, a single SRS treatment, a higher margin dose, a higher isodose line, a deep AVM location, and a smaller AVM volume. The crude rate of post-SRS hemorrhage was 50% lower in the early (3.2%) than in the late (6.4%) obliteration cohorts, but this difference was not statistically significant (p = 0.248). The other outcomes of the early versus late obliteration cohorts were similar, with respect to symptomatic radiation-induced changes (RICs), cyst formation, and tumor formation.

Conclusions: Approximately one-quarter of pediatric AVMs that become obliterated after SRS will achieve this radiological endpoint within 24 months of initial SRS. The authors identified multiple factors associated with early obliteration, which may aid in prognostication and management. The overall risks of delayed hemorrhage, RICs, cyst formation, and tumor formation were not statistically different in patients with early versus late obliteration.
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http://dx.doi.org/10.3171/2020.4.PEDS19738DOI Listing
June 2020

Evaluation of First-line Radiosurgery vs Whole-Brain Radiotherapy for Small Cell Lung Cancer Brain Metastases: The FIRE-SCLC Cohort Study.

JAMA Oncol 2020 07;6(7):1028-1037

Department of Neurosurgery, New York University Langone Medical Center, New York.

Importance: Although stereotactic radiosurgery (SRS) is preferred for limited brain metastases from most histologies, whole-brain radiotherapy (WBRT) has remained the standard of care for patients with small cell lung cancer. Data on SRS are limited.

Objective: To characterize and compare first-line SRS outcomes (without prior WBRT or prophylactic cranial irradiation) with those of first-line WBRT.

Design, Setting, And Participants: FIRE-SCLC (First-line Radiosurgery for Small-Cell Lung Cancer) was a multicenter cohort study that analyzed SRS outcomes from 28 centers and a single-arm trial and compared these data with outcomes from a first-line WBRT cohort. Data were collected from October 26, 2017, to August 15, 2019, and analyzed from August 16, 2019, to November 6, 2019.

Interventions: SRS and WBRT for small cell lung cancer brain metastases.

Main Outcomes And Measures: Overall survival, time to central nervous system progression (TTCP), and central nervous system (CNS) progression-free survival (PFS) after SRS were evaluated and compared with WBRT outcomes, with adjustment for performance status, number of brain metastases, synchronicity, age, sex, and treatment year in multivariable and propensity score-matched analyses.

Results: In total, 710 patients (median [interquartile range] age, 68.5 [62-74] years; 531 men [74.8%]) who received SRS between 1994 and 2018 were analyzed. The median overall survival was 8.5 months, the median TTCP was 8.1 months, and the median CNS PFS was 5.0 months. When stratified by the number of brain metastases treated, the median overall survival was 11.0 months (95% CI, 8.9-13.4) for 1 lesion, 8.7 months (95% CI, 7.7-10.4) for 2 to 4 lesions, 8.0 months (95% CI, 6.4-9.6) for 5 to 10 lesions, and 5.5 months (95% CI, 4.3-7.6) for 11 or more lesions. Competing risk estimates were 7.0% (95% CI, 4.9%-9.2%) for local failures at 12 months and 41.6% (95% CI, 37.6%-45.7%) for distant CNS failures at 12 months. Leptomeningeal progression (46 of 425 patients [10.8%] with available data) and neurological mortality (80 of 647 patients [12.4%] with available data) were uncommon. On propensity score-matched analyses comparing SRS with WBRT, WBRT was associated with improved TTCP (hazard ratio, 0.38; 95% CI, 0.26-0.55; P < .001), without an improvement in overall survival (median, 6.5 months [95% CI, 5.5-8.0] for SRS vs 5.2 months [95% CI, 4.4-6.7] for WBRT; P = .003) or CNS PFS (median, 4.0 months for SRS vs 3.8 months for WBRT; P = .79). Multivariable analyses comparing SRS and WBRT, including subset analyses controlling for extracranial metastases and extracranial disease control status, demonstrated similar results.

Conclusions And Relevance: Results of this study suggest that the primary trade-offs associated with SRS without WBRT, including a shorter TTCP without a decrease in overall survival, are similar to those observed in settings in which SRS is already established.
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http://dx.doi.org/10.1001/jamaoncol.2020.1271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273318PMC
July 2020

Repeated gamma knife radiosurgery enables longer tumor control in cases of highly-recurrent intracranial ependymoma.

J Neurooncol 2020 Jun 13;148(2):363-372. Epub 2020 May 13.

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

Purpose: Stereotactic radiosurgery (SRS) is a potential re-irradiation treatment for recurrent intracranial ependymoma after prior radiation therapy. The purpose of this study was to examine the efficacy and safety of repeated SRS in the treatment of recurrent intracranial ependymomas.

Methods: This is a retrospective study of consecutive patients with residual or recurrent intracranial ependymomas who were treated with SRS between 1993 and 2018. Tumor progression was defined as a ≥ 10% increase in tumor volume. Tumor regression was defined as a ≥ 10% reduction in tumor volume. A tumor that remained within 10% of its original volume was defined as stable. Tumor control comprised tumor regression and stability. Time-dependent analyses were performed using two treatment failure endpoint definitions: (1) evidence of local tumor progression or distant metastasis (single SRS analysis), and (2) lack of tumor response to SRS (repeated SRS analysis). These analyses were adjusted for the competing risk of death.

Results: The study comprised 37 patients (65 intracranial ependymomas) who underwent multiple SRS sessions (range: 1-7). Median age was 10.2 years (range: 0.8-53.8 years), and median tumor volume was 1.5 mL (range: 0.01-22.5 mL). The median radiation dose was 13.3 Gy (range: 7.9-22.0 Gy) at a median isodose line of 57% (range: 50-90%). Overall tumor control rates in the single SRS analysis adjusting for the competing risk of death were 53.6%, 30.5%, and 23.6% at 1, 3, and 5 years, respectively. Overall tumor control rates in the repeated SRS analysis adjusting for the competing risk of death were 70.6%, 50.4%, and 43.1% at 1, 3, and 5 years, respectively. Prior gross total resection was the only independent predictor of overall tumor control after SRS (aHR = 25.62 (1.55-422.1), p = 0.02).

Conclusions: Repeated GKRS appeared to be an effective treatment strategy for recurrent or residual intracranial ependymomas, with acceptable complication rates.
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http://dx.doi.org/10.1007/s11060-020-03531-7DOI Listing
June 2020

Clinical outcome following cerebral AVM hemorrhage.

Acta Neurochir (Wien) 2020 07 8;162(7):1759-1766. Epub 2020 May 8.

Department of Surgery, Div. of Neurosurgery, National University Hospital, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore.

Background: A significant difference exists between the published results reporting the clinical outcome following brain arteriovenous malformation (AVM) ruptures. Information about the outcome following hemorrhage in an AVM population treated with radiosurgery could provide additional information to assess the risk of mortality and morbidity following an AVM hemorrhage.

Methods: Clinical outcome was studied in 383 patients, the largest patient population yet studied, who suffered from a symptomatic hemorrhage after Gamma Knife® surgery (GKS) but before confirmed AVM obliteration. The impact of different patient, AVM, and treatment parameters on the clinical outcome was analyzed. The aim was to generate outcome predictions by comparing our data to and combining them with earlier published results.

Results: No relation was found between clinical outcome and treatment parameters, indicating that the results are applicable also on untreated AVMs. Twenty-one percent of the patients died, 45% developed or experienced worsening of neurological sequelae, and 35% recovered completely after the hemorrhage. Old age was a predictor of poor outcome. Sex, AVM location, AVM volume, and history of prior hemorrhage did not influence the outcome. The mortality rate was comparable to earlier published prospective data, but higher than that found in retrospective studies.

Conclusions: The mortality rates in earlier published retrospective series as well as in studies focusing on clinical outcome following AVM hemorrhage significantly underestimate the risk for a mortal outcome following an AVM hemorrhage. Based on our findings, an AVM rupture has around 20% likelihood to result in mortality, 45% likelihood to result in a minor or major deficit, and 35% likelihood of complete recovery. The findings are probably applicable also for AVM ruptures in general. The cumulative mortality and morbidity rates 25 years after diagnosis were estimated to be around 40% in a patient with a patent AVM.
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http://dx.doi.org/10.1007/s00701-020-04380-zDOI Listing
July 2020

Stereotactic radiosurgery for central neurocytomas: an international multicenter retrospective cohort study.

J Neurosurg 2020 Apr 3:1-10. Epub 2020 Apr 3.

1Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia.

Objective: Central neurocytomas (CNs) are uncommon intraventricular tumors, and their rarity renders the risk-to-benefit profile of stereotactic radiosurgery (SRS) unknown. The aim of this multicenter, retrospective cohort study was to evaluate the outcomes of SRS for CNs and identify predictive factors.

Methods: The authors retrospectively analyzed a cohort of patients with CNs treated with SRS at 10 centers between 1994 and 2018. Tumor recurrences were classified as local or distant. Adverse radiation effects (AREs) and the need for a CSF shunt were also evaluated.

Results: The study cohort comprised 60 patients (median age 30 years), 92% of whom had undergone prior resection or biopsy and 8% received their diagnosis based on imaging alone. The median tumor volume and margin dose were 5.9 cm3 and 13 Gy, respectively. After a median clinical follow-up of 61 months, post-SRS tumor recurrence occurred in 8 patients (13%). The 5- and 10-year local tumor control rates were 93% and 87%, respectively. The 5- and 10-year progression-free survival rates were 89% and 80%, respectively. AREs were observed in 4 patients (7%), but only 1 was symptomatic (2%). Two patients underwent post-SRS tumor resection (3%). Prior radiotherapy was a predictor of distant tumor recurrence (p = 0.044). Larger tumor volume was associated with pre-SRS shunt surgery (p = 0.022).

Conclusions: Treatment of appropriately selected CNs with SRS achieves good tumor control rates with a reasonable complication profile. Distant tumor recurrence and dissemination were observed in a small proportion of patients, which underscores the importance of close post-SRS surveillance of CN patients. Patients with larger CNs are more likely to require shunt surgery before SRS.
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http://dx.doi.org/10.3171/2020.1.JNS191515DOI Listing
April 2020

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

Eur J Radiol 2020 Apr 6;125:108866. Epub 2020 Feb 6.

School of Medicine, National Yang Ming University, Taipei, Taiwan; Neurological Institute, Department of Neurosurgery, Taipei Veterans General Hospital, Taipei, Taiwan.

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.
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http://dx.doi.org/10.1016/j.ejrad.2020.108866DOI Listing
April 2020

Radiomics as prognostic factor in brain metastases treated with Gamma Knife radiosurgery.

J Neurooncol 2020 Feb 4;146(3):439-449. Epub 2020 Feb 4.

Professional Master Program in Artificial Intelligence in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Purpose: Gamma Knife radiosurgery (GKRS) is a non-invasive procedure for the treatment of brain metastases. This study sought to determine whether radiomic features of brain metastases derived from pre-GKRS magnetic resonance imaging (MRI) could be used in conjunction with clinical variables to predict the effectiveness of GKRS in achieving local tumor control.

Methods: We retrospectively analyzed 161 patients with non-small cell lung cancer (576 brain metastases) who underwent GKRS for brain metastases. The database included clinical data and pre-GKRS MRI. Brain metastases were demarcated by experienced neurosurgeons, and radiomic features of each brain metastasis were extracted. Consensus clustering was used for feature selection. Cox proportional hazards models and cause-specific proportional hazards models were used to correlate clinical variables and radiomic features with local control of brain metastases after GKRS.

Results: Multivariate Cox proportional hazards model revealed that higher zone percentage (hazard ratio, HR 0.712; P = .022) was independently associated with superior local tumor control. Similarly, multivariate cause-specific proportional hazards model revealed that higher zone percentage (HR 0.699; P = .014) was independently associated with superior local tumor control.

Conclusions: The zone percentage of brain metastases, a radiomic feature derived from pre-GKRS contrast-enhanced T1-weighted MRIs, was found to be an independent prognostic factor of local tumor control following GKRS in patients with non-small cell lung cancer and brain metastases. Radiomic features indicate the biological basis and characteristics of tumors and could potentially be used as surrogate biomarkers for predicting tumor prognosis following GKRS.
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http://dx.doi.org/10.1007/s11060-019-03343-4DOI Listing
February 2020

Gamma Knife radiosurgery for cerebral cavernous malformation.

Sci Rep 2019 12 24;9(1):19743. Epub 2019 Dec 24.

Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

This is a retrospective study examining the efficacy and safety of Gamma Knife radiosurgery (GKS) in treating patients with cerebral cavernous malformations (CCMs). Between 1993 and 2018, 261 patients with 331 symptomatic CCMs were treated by GKS. The median age was 39.9 years and females were predominant (54%). The median volume of CCMs was 3.1 mL. The median margin dose was 11.9 Gy treat to a median isodose level of 59%. Median clinical and imaging follow-up times were 69 and 61 months, respectively. After the initial hemorrhage that led to CCM diagnosis, 136 hemorrhages occurred in the period prior to GKS (annual incidence = 23.6%). After GKS, 15 symptomatic hemorrhages occurred within the first 2 years of follow-up (annual incidence = 3.22%), and 37 symptomatic hemorrhages occurred after the first 2 years of follow-up (annual incidence = 3.16%). Symptomatic radiation-induced complication was encountered in 8 patients (3.1%). Mortality related to GKS occurred in 1 patient (0.4%). In conclusion, GKS decreased the risk of hemorrhage in CCM patients presenting with symptomatic hemorrhage. GKS is a viable alternative treatment option for patients with surgically-inaccessible CCMs or significant medical comorbidities.
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http://dx.doi.org/10.1038/s41598-019-56119-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930272PMC
December 2019

Dose response and architecture in volume staged radiosurgery for large arteriovenous malformations: A multi-institutional study.

Radiother Oncol 2020 03 10;144:180-188. Epub 2019 Dec 10.

University of California - San Francisco School of Medicine, Department of Neurosurgery, United States.

Background: Optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. Volume-staged stereotactic radiosurgery (VS-SRS) provides an effective option for these high-risk lesions, but optimizing treatment for these recalcitrant and rare lesions has proven difficult.

Methods: This is a multi-centered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. We evaluated near complete response (nCR), obliteration, cure, and overall survival.

Results: With a median age of 33 years old at the time of first SRS volume stage, patients received 2-4 total volume stages and a median follow up of 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cc (range: 7.7-94.4 cc) with a median margin dose per stage of 17 Gy (range: 12-20 Gy). Total AVM volume, margin dose per stage, compact nidus, lack of prior embolization, and lack of thalamic location involvement were all associated with improved outcomes. Dose >/= 17.5 Gy was strongly associated with improved rates of nCR, obliteration, and cure. With dose >/= 17.5 Gy, 5- and 10-year cure rates were 33.7% and 76.8% in evaluable patients compared to 23.7% and 34.7% of patients with 17 Gy and 6.4% and 20.6% with <17 Gy per volume-stage (p = 0.004). Obliteration rates in diffuse nidus architecture with <17 Gy were particularly poor with none achieving obliteration compared to 32.3% with doses >/= 17 Gy at 5 years (p = 0.007). Comparatively, lesions with a compact nidus architecture exhibited obliteration rates at 5 years were 10.7% vs 9.3% vs 26.6% for dose >17 Gy vs 17 Gy vs >/=17.5 Gy.

Conclusion: VS-SRS is an option for upfront treatment of large AVMs. Higher dose was associated with improved rates of nCR, obliteration, and cure suggesting that larger volumetric responses may facilitate salvage therapy and optimize the chance for cure.
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http://dx.doi.org/10.1016/j.radonc.2019.09.019DOI Listing
March 2020

Stagnant Venous Outflow Predicts Brain Arteriovenous Malformation Obliteration After Gamma Knife Radiosurgery Without Prior Intervention.

Neurosurgery 2020 08;87(2):338-347

Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: Gamma Knife radiosurgery (GKRS) obliterates 65% to 82% of brain arteriovenous malformations (BAVMs).

Objective: To explore the impact of hemodynamics on GKRS outcomes.

Methods: We retrospectively (2011-2017) included 98 patients with BAVMs who had received GKRS alone. Two evaluators, blinded to the outcomes, analyzed the pre-GKRS angiography and magnetic resonance images to obtain the morphological characteristics and quantitative digital subtraction angiography (QDSA) parameters. The venous stasis index was defined as the inflow gradient divided by the absolute value of the outflow gradient. Patients' follow-up magnetic resonance or digital subtraction angiography images were evaluated for the presence of complete obliteration (CO). Cox regression and Kaplan-Meier analyses were conducted to determine the correlations between the parameters and outcomes.

Results: Among the 98 patients, 63 (63.4%) achieved CO after GKRS at a median latency period of 31 mo. In multivariable analyses with adjustments for age and sex, increased BAVM volume (hazard ratio (HR) 0.949, P = .022) was an independent characteristic predictor, and venous stenosis (HR 2.595, P = .009), venous rerouting (HR 0.375, P = .022), and larger stasis index (HR 1.227, P = .025) were independent angiographic predictors of CO. BAVMs with a stasis index of >1.71 had a higher 36-mo probability of CO than those with a stasis index of ≤1.71 (61.1% vs 26.7%, P < .001).

Conclusion: BAVMs with a larger stasis index, indicating more stagnant venous outflow, may predict obliteration after GKRS. QDSA analysis may help in predicting BAVM treatment outcomes and making therapeutic decisions.
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http://dx.doi.org/10.1093/neuros/nyz507DOI Listing
August 2020

Outcomes of stereotactic radiosurgery for pilocytic astrocytoma: an international multiinstitutional study.

J Neurosurg 2019 Nov 29:1-9. Epub 2019 Nov 29.

13Rose-Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland, Ohio.

Objective: The current standard initial therapy for pilocytic astrocytoma is maximal safe resection. Radiation therapy is considered for residual, recurrent, or unresectable pilocytic astrocytomas. However, the optimal radiation strategy has not yet been established. Here, the authors describe the outcomes of stereotactic radiosurgery (SRS) for pilocytic astrocytoma in a large multiinstitutional cohort.

Methods: An institutional review board-approved multiinstitutional database of patients treated with Gamma Knife radiosurgery (GKRS) between 1990 and 2016 was queried. Data were gathered from 9 participating International Radiosurgery Research Foundation (IRRF) centers. Patients with a histological diagnosis of pilocytic astrocytoma treated using a single session of GKRS and with at least 6 months of follow-up were included in the analysis.

Results: A total of 141 patients were analyzed in the study. The median patient age was 14 years (range 2-84 years) at the time of GKRS. The median follow-up was 67.3 months. Thirty-nine percent of patients underwent SRS as the initial therapy, whereas 61% underwent SRS as salvage treatment. The median tumor volume was 3.45 cm3. The tumor location was the brainstem in 30% of cases, with a nonbrainstem location in the remainder. Five- and 10-year overall survival rates at the last follow-up were 95.7% and 92.5%, respectively. Five- and 10-year progression-free survival (PFS) rates were 74.0% and 69.7%, respectively. On univariate analysis, an age < 18 years, tumor volumes < 4.5 cm3, and no prior radiotherapy or chemotherapy were identified as positive prognostic factors for improved PFS. On multivariate analysis, only prior radiotherapy was significant for worse PFS.

Conclusions: This represents the largest study of single-session GKRS for pilocytic astrocytoma to date. Favorable long-term PFS and overall survival were observed with GKRS. Further prospective studies should be performed to evaluate appropriate radiosurgery dosing, timing, and sequencing of treatment along with their impact on toxicity and the quality of life of patients with pilocytic astrocytoma.
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http://dx.doi.org/10.3171/2019.9.JNS191335DOI Listing
November 2019

Role of Gamma Knife Radiosurgery in Small Cell Lung Cancer: A Multi-Institutional Retrospective Study of the International Radiosurgery Research Foundation (IRRF).

Neurosurgery 2020 09;87(4):664-671

Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Background: Despite a high incidence of brain metastases in patients with small-cell lung cancer (SCLC), limited data exist on the use of stereotactic radiosurgery (SRS), specifically Gamma Knife™ radiosurgery (Elekta AB), for SCLC brain metastases.

Objective: To provide a detailed analysis of SCLC patients treated with SRS, focusing on local failure, distant brain failure, and overall survival (OS).

Methods: A multi-institutional retrospective review was performed on 293 patients undergoing SRS for SCLC brain metastases at 10 medical centers from 1991 to 2017. Data collection was performed according to individual institutional review boards, and analyses were performed using binary logistic regression, Cox-proportional hazard models, Kaplan-Meier survival analysis, and competing risks analysis.

Results: Two hundred thirty-two (79%) patients received SRS as salvage following prior whole-brain irradiation (WBRT) or prophylactic cranial irradiation, with a median marginal dose of 18 Gy. At median follow-up after SRS of 6.4 and 18.0 mo for surviving patients, the 1-yr local failure, distant brain failure, and OS were 31%, 49%, and 28%. The interval between WBRT and SRS was predictive of improved OS for patients receiving SRS more than 1 yr after initial treatment (21%, <1 yr vs 36%, >1 yr, P = .01). On multivariate analysis, older age was the only significant predictor for OS (hazard ratio 1.63, 95% CI 1.16-2.29, P = .005).

Conclusion: SRS plays an important role in the management of brain metastases from SCLC, especially in salvage therapy following WBRT. Ongoing prospective trials will better assess the value of radiosurgery in the primary management of SCLC brain metastases and potentially challenge the standard application of WBRT in SCLC patients.
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http://dx.doi.org/10.1093/neuros/nyz428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780439PMC
September 2020

Risk Prediction for Early Mortality in Patients with Newly Diagnosed Primary CNS Lymphoma.

J Cancer 2019 5;10(17):3958-3966. Epub 2019 Jul 5.

Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Overall survival of patients with primary CNS lymphoma (PCNSL) has improved since the introduction of immunochemotherapy. However, up to 10-15% of PCNSL patients still die shortly after diagnosis. In the present study, we aimed to investigate the risk factors of early mortality (death within 60 days after diagnosis) in patients with PCNSL. We included newly diagnosed PCNSL patients in a tertiary medical center in Taiwan between January 1, 2002 and May 31, 2018. Clinical risk factors were collected and compared between PCNSL patients who had and did not have early mortality. A total of 133 consecutive patients with PCNSL were included in this study. Approximately 9.8% of the PCNSL patients had early mortality. In multivariate analysis, age ≥ 80 (adjusted hazard ratio [HR] 3.34, 95% confidence interval [CI] 1.01-11.04, = 0.048) and involvement of the basal ganglia (adjusted HR 4.85, 95% CI 1.47-15.95, = 0.009) were identified as independent risk factors of early mortality. Use of MTX-based chemotherapy served as an independent protective factor for early mortality (adjusted HR 0.19, 95% CI 0.05-0.67, = 0.010). Infection and tumor-associated mass effect contributed most to early mortality. Early mortality is not uncommon in patients with PCNSL. Identification of patients with higher risk may help clinicians with initiating appropriate surveillance and management.
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http://dx.doi.org/10.7150/jca.32467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692612PMC
July 2019

The benefit and risk of stereotactic radiosurgery for prolactinomas: an international multicenter cohort study.

J Neurosurg 2019 Aug 2:1-10. Epub 2019 Aug 2.

1Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia.

Objective: The most common functioning pituitary adenoma is prolactinoma. Patients with medically refractory or residual/recurrent tumors that are not amenable to resection can be treated with stereotactic radiosurgery (SRS). The aim of this multicenter study was to evaluate the role of SRS for treating prolactinomas.

Methods: This retrospective study included prolactinomas treated with SRS between 1997 and 2016 at ten institutions. Patients' clinical and treatment parameters were investigated. Patients were considered to be in endocrine remission when they had a normal level of prolactin (PRL) without requiring dopamine agonist medications. Endocrine control was defined as endocrine remission or a controlled PRL level ≤ 30 ng/ml with dopamine agonist therapy. Other outcomes were evaluated including new-onset hormone deficiency, tumor recurrence, and new neurological complications.

Results: The study cohort comprised 289 patients. The endocrine remission rates were 28%, 41%, and 54% at 3, 5, and 8 years after SRS, respectively. Following SRS, 25% of patients (72/289) had new hormone deficiency. Sixty-three percent of the patients (127/201) with available data attained endocrine control. Three percent of patients (9/269) had a new visual complication after SRS. Five percent of the patients (13/285) were recorded as having tumor progression. A pretreatment PRL level ≤ 270 ng/ml was a predictor of endocrine remission (p = 0.005, adjusted HR 0.487). An increasing margin dose resulted in better endocrine control after SRS (p = 0.033, adjusted OR 1.087).

Conclusions: In patients with medically refractory prolactinomas or a residual/recurrent prolactinoma, SRS affords remarkable therapeutic effects in endocrine remission, endocrine control, and tumor control. New-onset hypopituitarism is the most common adverse event.
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http://dx.doi.org/10.3171/2019.4.JNS183443DOI Listing
August 2019

Hypopituitarism after Gamma Knife radiosurgery for pituitary adenomas: a multicenter, international study

J Neurosurg 2018 11 9. Epub 2018 Nov 9.

Department of Neurosurgery, West Virginia University, Morgantown, West Virginia

Objective: Recurrent or residual adenomas are frequently treated with Gamma Knife radiosurgery (GKRS). The most common complication after GKRS for pituitary adenomas is hypopituitarism. In the current study, the authors detail the timing and types of hypopituitarism in a multicenter, international cohort of pituitary adenoma patients treated with GKRS.

Methods: Seventeen institutions pooled clinical data obtained from pituitary adenoma patients who were treated with GKRS from 1988 to 2016. Patients who had undergone prior radiotherapy were excluded. A total of 1023 patients met the study inclusion criteria. The treated lesions included 410 nonfunctioning pituitary adenomas (NFPAs), 262 cases of Cushing’s disease (CD), and 251 cases of acromegaly. The median follow-up was 51 months (range 6–246 months). Statistical analysis was performed using a Cox proportional hazards model to evaluate factors associated with the development of new-onset hypopituitarism.

Results: At last follow-up, 248 patients had developed new pituitary hormone deficiency (86 with NFPA, 66 with CD, and 96 with acromegaly). Among these patients, 150 (60.5%) had single and 98 (39.5%) had multiple hormone deficiencies. New hormonal changes included 82 cortisol (21.6%), 135 thyrotropin (35.6%), 92 gonadotropin (24.3%), 59 growth hormone (15.6%), and 11 vasopressin (2.9%) deficiencies. The actuarial 1-year, 3-year, 5-year, 7-year, and 10-year rates of hypopituitarism were 7.8%, 16.2%, 22.4%, 27.5%, and 31.3%, respectively. The median time to hypopituitarism onset was 39 months. In univariate analyses, an increased rate of new-onset hypopituitarism was significantly associated with a lower isodose line (p = 0.006, HR = 8.695), whole sellar targeting (p = 0.033, HR = 1.452), and treatment of a functional pituitary adenoma as compared with an NFPA (p = 0.008, HR = 1.510). In multivariate analyses, only a lower isodose line was found to be an independent predictor of new-onset hypopituitarism (p = 0.001, HR = 1.38).

Conclusions: Hypopituitarism remains the most common unintended effect of GKRS for a pituitary adenoma. Treating the target volume at an isodose line of 50% or greater and avoiding whole-sellar radiosurgery, unless necessary, will likely mitigate the risk of post-GKRS hypopituitarism. Follow-up of these patients is required to detect and treat latent endocrinopathies.
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http://dx.doi.org/10.3171/2018.5.JNS18509DOI Listing
November 2018

Epidermal growth factor receptor mutations: association with favorable local tumor control following Gamma Knife radiosurgery in patients with non-small cell lung cancer and brain metastases.

J Neurosurg 2019 Jun 21:1-8. Epub 2019 Jun 21.

1Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital.

Objective: The presence of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) has been associated with elevated radiosensitivity in vitro. However, results from clinical studies on radiosensitivity in cases of NSCLC with EGFR mutations are inconclusive. This paper presents a retrospective analysis of patients with NSCLC who underwent regular follow-up imaging after radiotherapy for brain metastases (BMs). The authors also investigated the influence of EGFR mutations on the efficacy of Gamma Knife radiosurgery (GKRS).

Methods: This study included 264 patients (1069 BMs) who underwent GKRS treatment and for whom EGFR mutation status, demographics, performance status, and tumor characteristics were available. Radiological images were obtained at 3 months after GKRS and at 3-month intervals thereafter. Kaplan-Meier plots and Cox regression analysis were used to correlate EGFR mutation status and other clinical features with tumor control and overall survival.

Results: The tumor control rates and overall 12-month survival rates were 87.8% and 65.5%, respectively. Tumor control rates in the EGFR mutant group versus the EGFR wild-type group were 90.5% versus 79.4% at 12 months and 75.0% versus 24.5% at 24 months. During the 2-year follow-up period after SRS, the intracranial response rate in the EGFR mutant group was approximately 3-fold higher than that in the wild-type group (p < 0.001). Cox regression multivariate analysis identified EGFR mutation status, extracranial metastasis, primary tumor control, and prescribed margin dose as predictors of tumor control (p = 0.004, p < 0.001, p = 0.004, and p = 0.026, respectively). Treatment with a combination of GKRS and tyrosine kinase inhibitors (TKIs) was the most important predictor of overall survival (p < 0.001).

Conclusions: The current study demonstrated that, among patients with NSCLC-BMs, EGFR mutations were independent prognostic factors of tumor control. It was also determined that a combination of GKRS and TKI had the most pronounced effect on prolonging survival after SRS. In select patient groups, treatment with SRS in conjunction with EGFR-TKIs provided effective tumor control for NSCLC-BMs.
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http://dx.doi.org/10.3171/2019.4.JNS19446DOI Listing
June 2019