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Wen-Yuh Chung, David Hung-Chi Pan, Cheng-Ying Shiau, Wan-Yuo Guo and Ling-Wei Wang

Object. The goal of this study was to elucidate the role of gamma knife radiosurgery (GKS) and adjuvant stereotactic procedures by assessing the outcome of 31 consecutive patients harboring craniopharyngiomas treated between March 1993 and December 1999.

Methods. There were 31 consecutive patients with craniopharyngiomas: 18 were men and 13 were women. The mean age was 32 years (range 3–69 years). The mean tumor volume was 9 cm3 (range 0.3–28 cm3). The prescription dose to the tumor margin varied from 9.5 to 16 Gy. The visual pathways received 8 Gy or less. Three patients underwent stereotactic aspiration to decompress the cystic component before GKS. The tumor response was classified by percentage reduction of tumor volume as calculated based on magnetic resonance imaging studies. Clinical outcome was evaluated according to improvement and dependence on replacement therapy.

An initial postoperative volume increase with enlargement of a cystic component was found in three patients. They were treated by adjuvant stereotactic aspiration and/or Ommaya reservoir implantation. Tumor control was achieved in 87% of patients and 84% had fair to excellent clinical outcome in an average follow-up period of 36 months. Treatment failure due to uncontrolled tumor progression was seen in four patients at 26, 33, 49, and 55 months, respectively, after GKS. Only one patient was found to have a mildly restricted visual field; no additional endocrinological impairment or neurological deterioration could be attributed to the treatment. There was no treatment-related mortality.

Conclusions. Multimodality management of patients with craniopharyngiomas seemed to provide a better quality of patient survival and greater long-term tumor control. It is suggested that GKS accompanied by adjuvant stereotactic procedures should be used as an alternative in treating recurrent or residual craniopharyngiomas if further microsurgical excision cannot promise a cure.

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D. Hung-Chi Pan, Wan-Yuo Guo, Wen-Yuh Chung, Cheng-Ying Shiau, Yue-Cune Chang and Ling-Wei Wang

Object. A consecutive series of 240 patients with arteriovenous malformations (AVMs) treated by gamma knife radiosurgery (GKS) between March 1993 and March 1999 was evaluated to assess the efficacy and safety of radiosurgery for cerebral AVMs larger than 10 cm3 in volume.

Methods. Seventy-six patients (32%) had AVM nidus volumes of more than 10 cm3. During radiosurgery, targeting and delineation of AVM nidi were based on integrated stereotactic magnetic resonance (MR) imaging and x-ray angiography. The radiation treatment was performed using multiple small isocenters to improve conformity of the treatment volume. The mean dose inside the nidus was kept between 20 Gy and 24 Gy. The margin dose ranged between 15 to 18 Gy placed at the 55 to 60% isodose centers. Follow up ranged from 12 to 73 months.

There was complete obliteration in 24 patients with an AVM volume of more than 10 cm3 and in 91 patients with an AVM volume of less than 10 cm3. The latency for complete obliteration in larger-volume AVMs was significantly longer. In Kaplan—Meier analysis, the complete obliteration rate in 40 months was 77% in AVMs with volumes between 10 to 15 cm3, as compared with 25% for AVMs with a volume of more than 15 cm3. In the latter, the obliteration rate had increased to 58% at 50 months. The follow-up MR images revealed that large-volume AVMs had higher incidences of postradiosurgical edema, petechiae, and hemorrhage. The bleeding rate before cure was 9.2% (seven of 76) for AVMs with a volume exceeding 10 cm3, and 1.8% (three of 164) for AVMs with a volume less than 10 cm3. Although focal edema was more frequently found in large AVMs, most of the cases were reversible. Permanent neurological complications were found in 3.9% (three of 76) of the patients with an AVM volume of more than 10 cm3, 3.8% (three of 80) of those with AVM volume of 3 to 10 cm3, and 2.4% (two of 84) of those with an AVM volume less than 3 cm3. These differences in complications rate were not significant.

Conclusions. Recent improvement of radiosurgery in conjunction with stereotactic MR targeting and multiplanar dose planning has permitted the treatment of larger AVMs. It is suggested that gamma knife radiosurgery is effective for treating AVMs as large as 30 cm3 in volume with an acceptable risk.

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Kang-Du Liu, Wen-Yuh Chung, Hsiu-Mei Wu, Cheng-Ying Shiau, Ling-Wei Wang, Wan-You Guo and David Hung-Chi Pan

Object. The authors sought to determine the value of gamma knife surgery (GKS) in the treatment of cavernous hemangiomas (CHs).

Methods. Between 1993 and 2002, a total of 125 patients with symptomatic CHs were treated with GKS. Ninety-seven patients presented with bleeding and 45 of these had at least two bleeding episodes. Thirteen patients presented with seizures combined with hemorrhage, and 15 patients presented with seizures alone. The mean margin dose of radiation was 12.1 Gy and the mean follow-up time was 5.4 years.

In the 112 patients who had bled the number of rebleeds after GKS was 32. These rebleeds were defined both clinically and based on magnetic resonance imaging for an annual rebleeding rate of 32 episodes/492 patient-years or 6.5%. Twenty-three of the 32 rebleeding episodes occurred within 2 years after GKS. Nine episodes occurred after 2 years; thus, the annual rebleeding rate after GKS was 10.3% for the first 2 years and 3.3% thereafter (p = 0.0038). In the 45 patients with at least two bleeding episodes before GKS, the rebleeding rate dropped from 29.2% (55 episodes/188 patient-years) before treatment to 5% (10 episodes/197 patient-years) after treatment (p < 0.0001). Among the 28 patients who presented with seizures, 15 (53%) had good outcomes (Engel Grades I and II). In this study of 125 patients, symptomatic radiation-induced complications developed in only three patients.

Conclusions. Gamma knife surgery can effectively reduce the rebleeding rate after the first symptomatic hemorrhage in patients with CH. In addition, GKS may be useful in reducing the severity of seizures in patients with CH.

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David Hung-chi Pan, Wen-yuh Chung, Wan-yuo Guo, Hsiu-mei Wu, Kang-du Liu, Cheng-ying Shiau and Ling-wei Wang

Object. The aim of this study was to assess the efficacy and safety of radiosurgery for the treatment of dural arteriovenous fistulas (DAVFs) located in the region of the transverse—sigmoid sinus.

Methods. A series of 20 patients with DAVFs located in the transverse—sigmoid sinus, who were treated with gamma knife surgery between June 1995 and June 2000, was evaluated. According to the Cognard classification, the DAVF was Type I in four patients, Type IIa in seven, Type IIb in two, and combined Type IIa+b in seven. Nine patients had previously been treated with surgery and/or embolization, whereas 11 patients underwent radiosurgery alone. Radiosurgery was performed using multiple-isocenter irradiation of the delineated DAVF nidus. The target volume ranged from 1.7 to 40.7 cm3. The margin dose delivered to the nidus ranged from 16.5 to 19 Gy at a 50 to 70% isodose level.

Nineteen patients were available for follow-up review, the duration of which ranged from 6 to 58 months (median 19 months). Of the 19 patients, 14 (74%) were cured of their symptoms. At follow up, magnetic resonance imaging and/or angiography demonstrated complete obliteration of the DAVF in 11 patients (58%), subtotal obliteration (95% reduction of the nidus) in three (16%), and partial obliteration in another five (26%). There was no neurological complication related to the treatment. One patient experienced a recurrence of the DAVF 18 months after angiographic confirmation of total obliteration, and underwent a second course of radiosurgery.

Conclusions. Stereotactic radiosurgery provides a safe and effective option for the treatment of DAVFs involving the transverse and sigmoid sinuses. For some aggressive DAVFs with extensive retrograde cortical venous drainage, however, a combination of endovascular embolization and surgery may be necessary.

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Chih-Chun Wu, Wan-Yuo Guo, Wen-Yuh Chung, Hisu-Mei Wu, Chung-Jung Lin, Cheng-Chia Lee, Kang-Du Liu and Huai-che Yang

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.

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Chia-An Wu, Huai-Che Yang, Yong-Sin Hu, Hsiu-Mei Wu, Chung-Jung Lin, Chao-Bao Luo, Wan-Yuo Guo, Cheng-Chia Lee, Kang-Du Liu and Wen-Yuh Chung

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.

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Te Ming Lin, Huai Che Yang, Cheng Chia Lee, Hsiu Mei Wu, Yong Sin Hu, Chao Bao Luo, Wan Yuo Guo, Yi Hsuan Kao, Wen Yuh Chung and Chung Jung Lin

OBJECTIVE

Assessments of hemorrhage risk based on angioarchitecture have yielded inconsistent results, and quantitative hemodynamic studies have been limited to small numbers of patients. The authors examined whether cerebral hemodynamic analysis using quantitative digital subtraction angiography (QDSA) can outperform conventional DSA angioarchitecture analysis in evaluating the risk of hemorrhage associated with supratentorial arteriovenous malformations (AVMs).

METHODS

A cross-sectional study was performed by retrospectively reviewing adult supratentorial AVM patients who had undergone both DSA and MRI studies between 2011 and 2017. Angioarchitecture characteristics, DSA parameters, age, sex, and nidus volume were analyzed using univariate and multivariate logistic regression, and QDSA software analysis was performed on DSA images. Based on the QDSA analysis, a stasis index, defined as the inflow gradient divided by the absolute value of the outflow gradient, was determined. The receiver operating characteristic (ROC) curve was used to compare diagnostic performances of conventional DSA angioarchitecture analysis and analysis using hemodynamic parameters based on QDSA.

RESULTS

A total of 119 supratentorial AVM patients were included. After adjustment for age at diagnosis, sex, and nidus volume, the exclusive deep venous drainage (p < 0.01), observed through conventional angioarchitecture examination using DSA, and the stasis index of the most dominant drainage vein (p = 0.02), measured with QDSA hemodynamic analysis, were independent risk factors for hemorrhage. The areas under the ROC curves for the conventional DSA method (0.75) and QDSA hemodynamics analysis (0.73) were similar. A venous stasis index greater than 2.18 discriminated the hemorrhage group with a sensitivity of 52.6% and a specificity of 81.5%.

CONCLUSIONS

In QDSA, a higher stasis index of the most dominant drainage vein is an objective warning sign associated with supratentorial AVM rupture. Risk assessments of AVMs using QDSA and conventional DSA angioarchitecture were equivalent. Because QDSA is a complementary noninvasive approach without extra radiation or contrast media, comprehensive hemorrhagic risk assessment of cerebral AVMs should include both DSA angioarchitecture and QDSA analyses.

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Cheng-Chia Lee, Hideyuki Kano, Huai-Che Yang, Zhiyuan Xu, Chun-Po Yen, Wen-Yuh Chung, David Hung-Chi Pan, L. Dade Lunsford and Jason P. Sheehan

Object

Nonfunctioning pituitary adenomas (NFAs) are the most common type of pituitary adenoma and, when symptomatic, typically require surgical removal as an initial means of management. Gamma Knife radiosurgery (GKRS) is an alternative therapeutic strategy for patients whose comorbidities substantially increase the risks of resection. In this report, the authors evaluated the efficacy and safety of initial GKRS for NFAs.

Methods

An international group of three academic Gamma Knife centers retrospectively reviewed outcome data in 569 patients with NFAs.

Results

Forty-one patients (7.2%) underwent GKRS as primary management for their NFAs because of an advanced age, multiple comorbidities, or patient preference. The median age at the time of radiosurgery was 69 years. Thirty-seven percent of the patients had hypopituitarism before GKRS. Patients received a median tumor margin dose of 12 Gy (range 6.2–25.0 Gy) at a median isodose of 50%. The overall tumor control rate was 92.7%, and the actuarial tumor control rate was 94% and 85% at 5 and 10 years postradiosurgery, respectively. Three patients with tumor growth or symptom progression underwent resection at 3, 3, and 96 months after GKRS, respectively. New or worsened hypopituitarism developed in 10 patients (24%) at a median interval of 37 months after GKRS. One patient suffered new-onset cranial nerve palsy. No other radiosurgical complications were noted. Delayed hypopituitarism was observed more often in patients who had received a tumor margin dose > 18 Gy (p = 0.038) and a maximum dose > 36 Gy (p = 0.025).

Conclusions

In this study, GKRS resulted in long-term control of NFAs in 85% of patients at 10 years. This experience suggests that GKRS provides long-term tumor control with an acceptable risk profile. This approach may be especially valuable in older patients, those with multiple comorbidities, and those who have endocrine-inactive tumors without visual compromise due to mass effect of the adenoma.

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Cheng-Chia Lee, David Hung-Chi Pan, Wen-Yuh Chung, Kang-Du Liu, Huai-Che Yang, Hsiu-Mei Wu, Wan-Yuo Guo and Yang-Hsin Shih

Object

The authors retrospectively reviewed the efficacy and safety of Gamma Knife surgery (GKS) in patients with brainstem cavernous malformations (CMs). The CMs had bled repeatedly and placed the patients at high risk with respect to surgical intervention.

Methods

Between 1993 and 2010, 49 patients with symptomatic CMs were treated by GKS. The mean age in these patients was 37.8 years, and the predominant sex was female (59.2%). All 49 patients experienced at least 2 instances of repeated bleeding before GKS; these hemorrhages caused neurological deficits including cranial nerve deficits, hemiparesis, hemisensory deficits, spasticity, chorea or athetosis, and consciousness disturbance.

Results

The mean size of the CMs at the time of GKS was 3.2 cm3 (range 0.1–14.6 cm3). The mean radiation dose directed to the lesion was 11 Gy with an isodose level at 60.0%. The mean clinical and imaging follow-up time was 40.6 months (range 1.0–150.7 months). Forty-five patients participated in regularly scheduled follow-up. Twenty-nine patients (59.2%) were followed up for > 2 years, and 16 (32.7%) were followed up for < 2 years. The pre-GKS annual hemorrhage rate was 31.3% (69 symptomatic hemorrhages during a total of 220.3 patient-years). After GKS, 3 episodes of symptomatic hemorrhage were observed within the first 2 years of follow-up (4.29% annual hemorrhage rate), and 3 episodes of symptomatic hemorrhage were observed after the first 2 years of follow-up (3.64% annual hemorrhage rate). In this study of 49 patients, symptomatic radiation-induced complications developed in only 2 patients (4.1%; cyst formation in 1 patient and perifocal edema with neurological deficits in the other patient). There were no deaths in this group.

Conclusions

Gamma Knife surgery is effective in reducing the rate of recurrent hemorrhage. In the authors' experience, it was possible to control bleeding using a low-dose treatment. In addition, there were few symptomatic radiation-induced complications. As a result, the authors believe that GKS is a good alternative treatment for brainstem CMs.

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Cheng-Chia Lee, Hsiu-Mei Wu, Wen-Yuh Chung, Ching-Jen Chen, David Hung-Chi Pan and Sanford P. C. Hsu

Object

Resection of vestibular schwannoma (VS) after Gamma Knife surgery (GKS) is infrequently performed. The goals of this study were to analyze and discuss the neurological outcomes and technical challenges of VS resection and to explore strategies for treating tumors that progress after GKS.

Methods

In total, 708 patients with VS underwent GKS between 1993 and 2012 at Taipei Veterans General Hospital. The post-GKS clinical courses, neurological presentations, and radiological changes in these patients were analyzed. Six hundred patients with imaging follow-up of at least 1 year after GKS treatment were included in this study.

Results

Thirteen patients (2.2%) underwent microsurgery on average 36.8 months (range 3–107 months) after GKS. The indications for the surgery included symptomatic adverse radiation effects (in 4 patients), tumor progression (in 6), and cyst development (in 3). No morbidity or death as a result of the surgery was observed. At the last follow-up evaluation, all patients, except 1 patient with a malignant tumor, had stable or near-normal facial function.

Conclusions

For the few VS cases that require resection after radiosurgery, maximal tumor resection can be achieved with modern skull-based techniques and refined neuromonitoring without affecting facial nerve function.