Acute necrosis after Gamma Knife surgery in vestibular schwannoma leading to multiple cranial nerve palsies

We discuss a rare acute complication after Gamma Knife therapy (Elekta AB, Stockholm, Sweden) in a single patient. A 52-year-old woman presented with vertigo, facial weakness and hearing loss emerging 48 hours following Gamma Knife radiosurgery for a right-sided vestibular schwannoma. Neurological examination 6 days after symptom onset showed right-sided facial palsy, spontaneous left-beating nystagmus and pathologic head-impulse testing to the right. Pure-tone audiogram revealed right-sided sensorineural hearing loss. A diagnosis of acute vestibulocochlear and facial neuropathy was made. Brain MRI demonstrated focal contrast sparing within the schwannoma, likely related to acute radiation necrosis. Acute multiple cranial neuropathies of the cerebellopontine angle after Gamma Knife treatment should raise suspicion of acute tissue damage within the schwannoma and should result in urgent MRI. Treatment with steroids may be considered based on accompanying swelling and edema.     

伽玛刀治疗颅内肿瘤的病理组织学研究

目的观察伽玛刀治疗颅内肿瘤的病理组织学变化,探讨伽玛刀治疗的放射生物学效应机制。方法对46例颅内肿瘤伽玛刀照射后的手术标本行光镜、电镜的病理形态学变化观察,并采用S-P法对上述肿瘤标本和10例正常脑组织血管标本行免疫组织化学染色,观察受照射肿瘤血管的CD34、α-SMA的表达,根据染色强度行对比分析。结果伽玛刀照射后的肿瘤细胞均有不同程度的凝固性坏死,肿瘤间质纤维化,血管内皮细胞肿胀、固缩、脱落,内皮增生,肿瘤血管扩张、充血,血管壁普遍出现增厚,管腔闭塞。可伴有炎性细胞浸润或出血。肿瘤的周边区域可观察到早期凋亡细胞。免疫组化的结果显示正常脑组织血管中CD34、α-SMA明显呈阳性,而受照射的肿瘤组织中CD34的反应性明显减少或呈阴性。α-SMA在大多数肿瘤组织中仍呈强阳性反应。结论伽玛刀治疗颅内肿瘤的放射生物学效应机制主要为肿瘤细胞的直接杀伤效应与血管效应的双重作用;伽玛刀照射诱导肿瘤细胞凋亡在伽玛刀治疗中起到一定作用。     

Leksell—C型伽玛刀治疗听神经瘤的长期疗效分析

目的分析Leksell—C型伽玛刀治疗听神经的长期疗效。方法回顾性分析长期随访的64例听神经瘤的临床资料。其中曾行开颅手术17例．面神经功能正常53例,具备有用听力41例。肿瘤体积0．2—33．9cm^3,平均7．7cm^3;治疗周边剂量11．0-14．0 Gy,平均12．7Gy：等剂量曲线40％-60％,靶点数2～15个,平均6个。结果随访46～81个月,平均62．2个月。肿瘤缩小52例,稳定9例;肿瘤增大3例,其中2例在3年后再次行伽玛刀治疗,随访显示肿瘤缩小,另1例在治疗后2年行开颅手术。发生面神经功能损伤2例,保留有用听力29例。发生三叉神经功能障碍8例（其中一过性损伤6例,损伤率为3．1％）。结论Leksell—C型伽玛刀放射外科治疗听神经瘤具有良好的肿瘤控制率和有用听力保留率,神经功能损伤发生率低,值得临床推广应用。     

伽玛刀治疗听神经瘤中、长期疗效分析

目的总结评价伽玛刀(γ刀)放射外科治疗听神经瘤的中长期效果。方法78例患者平均年龄45.0±17.9岁,男性35例,女性43例;单侧病变74例,双侧4例;20例曾行手术治疗;57例γ刀治疗前存在有用听力;肿瘤容积0.11～27.8ml,平均10.8ml;边缘剂量10～14Gy,平均12.27Gy,中心剂量21～30Gy,平均24.90Gy。结果随访22～96个月,平均58.3±22.9个月;63例(80.8%)肿瘤缩小,12例(15.4%)大小无变化,3例(3.8%)肿瘤增大;47例患者有用听力得到保留,其中13(22.8%)例较术前明显改善;3例(3.8%)出现患侧面瘫;5例(6.4%)出现三叉神经功能部分受损。结论γ刀治疗听神经瘤中、长期疗效分析显示既可控制肿瘤生长又取得较高的神经功能保留率,值得推广。     

Calcified vestibular schwannoma in the cerebellopontine angle

Although vestibular schwannoma is a common tumor in the cerebellopontine angle, calcified vestibular schwannoma is rare. A 59-year-old woman with sudden onset epileptic seizures, was referred to Hokkaido Neurosurgical Memorial Hospital. Neurological examination revealed left Bruns nystagmus, left deafness and left cerebellar ataxia. Brain MRI revealed a mass, about 3cm in diameter, in the left cerebellopontine angle. The mass showed heterogeneous intensity on T1- and T2-weighted and fluid-attenuated inversion recovery (FLAIR) images. Hydrocephalus was seen. On CT scan, the tumor was calcified. Preoperatively, vestibular schwannoma, meningioma, cavernous hemangioma, or thrombosed giant aneurysm were considered as differential diagnoses. The pathological diagnosis was schwannoma. For a calcified mass in the cerebellopontine angle, vestibular schwannoma should be considered in the differential diagnosis to plan appropriate treatment strategies.     

Mask-based immobilization in Gamma Knife stereotactic radiosurgery

The Gamma Knife Icon (Elekta AB, Stockholm) is a cobalt-based stereotactic radiosurgery (SRS) unit to support the use of a thermoplastic mask in lieu of a rigid frame, using an onboard cone-beam CT (CBCT) and an intrafraction motion management system (IFMM). We retrospectively reviewed 124 patients treated with Gamma Knife SRS from January 2018 to December 2019 at our institution using a mask-based immobilization system. Patient and treatment characteristics were collected and summarized as well as interfraction shifts and treatment-related outcomes. This dataset includes 124 patients with an associated 358 intracranial tumors. Twenty-four patients presented with primary brain tumors, which included 14 meningiomas and 10 other histologies, with 100 patients having brain metastases. Sixty tumors were post-operative, while 298 were intact. The median dose for primary tumors was 25 Gy in 5 fractions. Median doses to metastases were 20 Gy in 1 fraction, 27 Gy in 3 fractions, and 25 Gy in 5 fractions. Median interfraction CBCT shifts were submillimeter. Median patient follow-up was 6.28 months. 91% of patients with metastases maintained local control. Our early clinical experience has demonstrated limited toxicity profiles and high patient tolerance, which suggests that mask-based Gamma Knife SRS provides a safe alternative option for frameless SRS. Patients with large target volumes where fractionation is preferred or with small target volumes in non-eloquent areas can be considered for this approach. Response rates are encouraging, and continued follow-up is necessary to investigate long-term control and survival.     

The option of Linac-based radiosurgery in a Gamma Knife radiosurgery center

Objective

Due to the fundamental differences in treatment delivery, linear-accelerator-based radiosurgery can be complementary to Gamma Knife (GK) for intracranial lesions. We reviewed the effect of adding GK to an existing linear accelerator (Linac)-based radiosurgery practice and analyzed case selections for the two modalities.

Patients and methods

UC Davis Medical Center installed a Leksell Gamma Knife Model C in October 2003 to supplement an established Linac-based radiosurgery program. Radiosurgery indications for the 15 months before and after installation were compared.

Results

Radiosurgery cases expanded by twofold from 68 patients before GK installation to 139 after, with 106 treated by GK and 33 by Linac. Besides a major increase for trigeminal neuralgia and a general growth for acoustic neuroma, meningioma and brain metastases, case numbers for glioma and arteriovenous malformation (AVM) remained stable. Considering case selections for Linac, glioma decreased from 28 to 18%, while meningioma and metastases increased from 9 to 21% and 38–46%, respectively. The Linac patients receiving fractionated treatment also increased from 37 to 61%.

Conclusions

While the majority of patients were treated with GK, a significant proportion was judged to be suited for Linac treatment. This latter group included particularly patients who benefit from fractionated therapy.     

Gamma Knife radiosurgery in the management of brainstem metastases

Background

Metastases to the brainstem portend a poor prognosis and present a challenge in clinical management. Surgical resection is rarely a viable option.

Methods

Post-treatment MRI scans of patients with brainstem metastases treated with radiosurgery were used to determine local control and disease progression. Median survival was calculated using Kaplan–Meier analysis. Univariate and multivariate analyses were performed using log-rank test and Cox proportional hazards model, respectively.

Results

Thirty-two consecutive patients with brainstem metastasis underwent Gamma Knife radiosurgery. Median age was 50 years. Median tumor volume was 0.71 cm³ and median tumor margin dose was 13 Gy. Seventeen of 32 patients received WBRT prior to stereotactic radiosurgery. Median survival was 5.2 months. There was a statistically significant difference in survival based on RTOG recursive partition analysis (RPA) class. Median survival of patients categorized as RPA class I was 19.2 months, RPA class II was 8.4 months, and RPA class III was 1.9 months. The overall local tumor control rate was 87.5%. There were no acute complications following stereotactic radiosurgery and no evidence of radiation necrosis noted on post-treatment MRI scans.

Conclusion

Stereotactic radiosurgery is an effective treatment for brainstem metastases and should be considered especially for patients with good performance status.     

Growth rate of vestibular schwannoma

Vestibular schwannoma (VS) is the most common tumor in the extra-axial posterior fossa compartment in adults. Growth rate is paramount to decision making regarding treatment and follow up of these tumors. We conducted a comprehensive review of the literature to answer four questions: What percentage of newly diagnosed VS will grow on follow-up? What factors correlate to tumor growth? What is the “normal” growth rate for sporadic VS? What factors characterize VS with rapid growth? Thirty-seven reports, with more than 4000 patients, fit our review criteria. One third of newly diagnosed VS will grow on follow-up of 1–3 years. However, after 5 years, up to one half will grow. Patient age and sex do not influence growth of VS. Hearing loss and vertigo at presentation do not predict tumor growth. It is unclear whether balance disturbance or tinnitus predict tumor growth. Tumor size and location do not predict tumor growth. Growth in the first year of observation is a strong predictor of tumor growth. The average growth rate of a VS is 0.99–1.11 mm/year. However, the expected growth rate for VS that have been shown to grow at first follow-up is 3 mm/year. Factors that may predict tumor growth of above 4 mm/year are cystic and hemorrhagic features in the tumor, and hormonal treatment. VS grow at an average 1 mm/year. VS that have been shown to grow at first follow-up should be considered for treatment, unless contraindicated. Long term follow-up is recommended for VS.     

Long term outcome of Gamma Knife radiosurgery for metastatic brain tumors

Gamma Knife radiosurgery (GKRS; Elekta AB, Stockholm, Sweden) has emerged as an important treatment option for metastatic brain tumors (MBT). However, the long term outcome of GKRS on MBT is not well understood. We reviewed the treatment of MBT with GKRS at our institution. We performed a retrospective review (2000–2013) of 298 patients with MBT who received GKRS. The study population was monitored clinically and radiographically after GKRS treatment. Survival benefits and predictive factors of the outcome were analyzed using the Kaplan–Meier test and Cox regression model, respectively. GKRS in MBT showed significant variation in tumor growth control (decreased in 135 [45%] patients, arrested growth in 91 [37%] patients and increased tumor size in 72 [24%] patients). The median survival in the study population was 17 months. Overall and progression free survival after 3 years were 25% and 45%, respectively. The predictive factors for improving survival in the patients with MBT were recursive partitioning analysis class I (p < 0.0001), absence of hydrocephalus (p < 0.0001), Karnofsky Performance Status (KPS) >80 (p = 0.007) and absence of recurrent MBT (p = 0.01). Forty (12%), 15 (4.3%) and two (0.6%) patients required GKRS, resection and whole brain radiation, respectively, after initial GKRS due to tumor progression and worsening of signs and symptoms. Our findings revealed that GKRS offers a high rate of tumor control and good survival benefits in both new and recurrent patients with MBT. Thus, GKRS is an effective treatment option for new patients with MBT, as well as an adjuvant therapy in patients with recurrent MBT.     

Fatal glioblastoma after Gamma Knife radiosurgery for arteriovenous malformation in a child

We describe a fatal case of glioblastoma multiforme that was induced by Gamma Knife radiosurgery (GKS; Elekta AB, Stockholm, Sweden) for an arteriovenous malformation (AVM). A 4-year-old girl presented with repeated convulsions. Imaging studies revealed an AVM located in the right thalamus. One year after initial symptoms, GKS was performed to obliterate the nidus. The maximum and marginal radiation doses were 32 and 16 Gy, respectively. Seventy months after GKS, the patient represented with severe headache. MRI showed a poorly demarcated tumor with heterogeneous gadolinium enhancement in the right thalamus and adjacent to the white matter of the temporal lobe. After a generalised convulsion, the patient deteriorated into a deep coma. CT scans showed severe brain swelling with intratumoral hemorrhage. An emergency craniotomy was performed, and the hematoma was removed. During this surgery, a tumor mass, which was found adjacent to the hematoma, was resected. Microscopic examination revealed glioblastoma multiforme. Despite intensive treatment, the patient died 1 month after surgery. A GKS-induced secondary tumor is a rare but serious complication. It is important to be aware of the adverse effects of GKS, including secondary neoplasms, before its clinical application, especially in young patients.     

Systematic review of quality of life in the management of vestibular schwannoma

Vestibular schwannoma (VS) is a benign tumour arising from the vestibular component of the vestibulocochlear nerve. Treatment protocols range from observation to microsurgical resection (MS) or radiation therapy using focused delivery techniques: either stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT). Most reported outcome measures explore medically orientated results such as extent of resection or facial nerve function and do not give any insight into how the initial disease, the treatment or operative complications impinge upon the patient's quality of life (QoL). The primary aim of this review was to appraise the quality of research concerning the measurement of QoL in patients with VS. A systematic review was performed including trials of patients with newly diagnosed VS undergoing MS, SRT/SRS, or observation with a measure of QoL. Only trials of prospective design were included. Excluded trials included participants with recurrent disease or comorbidities, and studies reporting patients with VS in association with neurofibromatosis type 2. Each trial for inclusion was assessed for bias and underwent formal data extraction. Between 1973 and 2010, 47 unique trials were identified with eight trials of prospective design. All included studies were prospective non-randomised, observational convenience sampled trials. No randomised control trials or systematic reviews were identified. The most common QoL measure used was the Short Form Questionnaire (SF-36), although it has not been validated in VS. The included trials suggest that the treatment protocols of MS and SRS/SRT are of equal efficacy with regard to impact on QoL; however, the trials were hetereogenous and suffered from a variety of methodological deficiencies. Given this heterogeneity, no meta-analysis was able to be performed. The available literature on QoL in the treatment of VS suffers from significant methodological weaknesses making it difficult to make any assessment as to the efficacy on QoL of available treatment options for VS. Further well-designed, randomised prospective research is necessary to understand this condition, its effect on QoL and how QoL outcomes may be used alongside clinical indicators in making treatment decisions.     

Factors influencing local tumor control after Gamma Knife radiosurgery for intracranial metastases from breast cancer

Because evaluation of Gamma Knife radiosurgery (GKRS) for brain metastases (METs) has mainly been based on overall or progression-free survival rates, that is, patients’ general condition and control of the primary disease, we focused on factors influencing local tumor control after GKRS for METs from breast cancer. Data were retrospectively collected from our institution’s records of patients who had undergone GKRS twice or more for METs from breast cancer. Failed GKRS was defined as a tumor needing re-treatment by further GKRS or having already been treated by other modalities prior to later GKRS procedures. Influences of various factors on local tumor control were examined. GKRS was performed on 623 tumors in 123 sessions in 90 patients. Median follow up was 9 months (range 1–41 months). According to multivariate analysis, use of HER2-targeting agents, (hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.18–0.99, p = 0.049), five or more lesions (HR 0.24, 95% CI 0.11–0.51, p < 0.001), volume >1.2 cm³ (HR 3.12, 95% CI 1.62–6.02, p < 0.001), use of GK model B (HR 2.53, 95% CI 1.28–4.98, p = 0.0076), and prescribed dosage ⩾18 Gy (HR 0.19, 95% CI 0.01–0.51, p < 0.001) were predictors of failed GKRS. Patients with METs from breast cancer with HER2-positive tumors, five or more lesions, and tumors of volume ⩽1.2 cm³ are good candidates for GKRS. GK model C and Perfexion achieve better local tumor control than does GK model B. The recommended dosage is ⩾18 Gy.     

伽玛刀治疗听神经瘤(附98例分析)

目的 评价伽玛刀治疗听神经的效果。方法 应用OUR旋转式伽玛刀治疗听神经98例。肿瘤直径512～29．7min．平均18.8mm。采用多个放射中心联合照射，周边等剂量曲线为45％-70％，边缘剂量10-13Gy。结果 81例获14。84个月随访，平均39个月。MRI示41例（50．6％）肿瘤缩小，38例（46.9％）无变化，2例（2．5％）增大；25例（30.9％）肿瘤中心失增强。无面瘫和面部麻木，听力保留率59.2％。结论 伽玛刀对听神经瘤有较高的肿瘤控制率，并能保留有用听力，对面神经、三又神经损伤小，是小至中等大小听神经瘤可供选择的治疗方法，及术后残余和复发肿瘤的重要辅助治疗手段。     

前庭神经雪旺细胞瘤和蛛网膜关系的术中观察

目的 探讨前庭神经雪旺细胞瘤和蛛网膜之间的关系以及神经功能的保护。方法 手术中观察蛛网膜、肿瘤和神经的关系。结果 肿瘤的后面、上下极表面有蛛网膜覆盖，脑干侧、肿瘤和面听神经之间没有蛛网膜间隔。结论 前庭神经雪旺细胞瘤是蛛网膜内位肿瘤，肿瘤表面的蛛网膜是桥小脑角池固有的蛛网膜，强调明视下的神经分离和肿瘤切除。     

伽玛刀放射治疗听神经瘤的长期疗效分析

目的总结评价伽玛刀放射治疗对听神经瘤生长的控制作用和对肿瘤周围的颅神经功能变化的影响。方法从1997年至2005年我科伽玛刀中心采用多中心点照射治疗159例（164个）听神经瘤,其中137例有完整的随访资料。MRI随访6～96个月,平均37.2个月;临床随访6～116个月,平均36.4个月。单纯行伽玛刀治疗86例,开颅手术后再行伽玛刀治疗51例。结果肿瘤控制率为94.16%;肿瘤体积增大8例（5.84%）。术前有听力的106例患者中听力保留率为72.64%,听力下降率为27.36%。面神经功能保留率为95.50%,三叉神经功能保留率为94.16%。结论伽玛刀治疗听神经瘤有良好的控制效果,并发症少,对肿瘤周围颅神经有较高的功能保留作用。     

Two cases of cystic enlargement of vestibular schwannoma as a late complication following gamma knife surgery

Cyst formation is the most common long-term complication after gamma knife surgery (GKS) for cerebral arteriovenous malformations; however, this rarely occurs after GKS for vestibular schwannoma (VS). We describe two patients that developed aggressive, symptomatic large cysts at more than 4 and 12 years after GKS for VS, although the tumor control for these patients had been acceptable at 3 and 11 years, respectively. During the surgery, a reddish lesion, which was distinct from the surrounding tumor, was observed. The microscopic examination of the reddish lesion revealed dilated capillary vessels and hemorrhage, which was compatible with late radiation changes; these were usually seen in arteriovenous malformations following radiosurgery. The present patients indicated that cyst formation and enlargement may occur as a late complication following GKS even in extra-axial benign tumors such as VS.     

A single institutional outcome analysis of Gamma Knife radiosurgery for single or multiple brain metastases

Although Gamma Knife stereotactic radiosurgery (SRS) is widely used for metastatic brain tumors, optimal patient selection and treatment strategy continue to be investigated. The aim of this study was to provide treatment results with Gamma Knife SRS and to establish prognostic factors. Of the 54 patients treated from 1990 to 1997, 51 patients were evaluable. There were 28 males and 23 females, with a median age of 60 years. Median Karnofsky Index was 80. There were 19 non-small cell lung cancers, eight colon cancers, six renal cell cancers, five ovarian cancers, four gastric cancers, three breast cancers, and six others. Primary tumors were controlled in 33 patients, and extracranial tumors were absent in 25 patients. Sixty-eight metastatic brain tumors in 37 patients underwent SRS as an initial treatment for the brain metastasis. Brain metastasis was solitary in 32 patients. Conventional radiation was combined with SRS in 29 patients, 24 of whom received whole brain radiotherapy. Eight patients had some form of surgical resection. Median survival time was 7.4 months. Five-year actuarial survival and local control rates were 16 and 52%, respectively. Median duration time of keeping pretreatment quality of life was 6.9 months. On a multivariate analysis, uncontrolled primary tumor, combined conventional radiotherapy, and performance status were statistically significant prognostic factors. Four patients who underwent whole brain radiation developed low grade dementia.