Treatment Options for Leptomeningeal Metastases of Solid Cancers: Literature Review and Personal Experience.

Leptomeningeal metastases (LM) may complicate the clinical course of any solid cancer or hematological malignancy. Diagnosis of such cases requires a multifaceted approach, including careful evaluation of the clinical history, detailed neurological examination, advanced imaging studies, and related laboratory data analysis. Therapeutic options for management of LM have not been standardized yet. Conventional intrathecal chemotherapy with or without involved-field fractionated radiotherapy has only modest efficacy, and the prognosis of most patients remains grim. Therefore, development of new, more aggressive multimodal treatment strategies is definitely needed. Immune checkpoint inhibitors-in particular, molecular targeted therapy-have demonstrated promising results in selected groups of patients. There may be an important role for stereotactic radiosurgery as well. Because organization of prospective randomized multi-institutional trials on treatment of LM of solid cancers may be problematic, practical guidelines for optimal therapeutic strategies in such cases should be established on the basis of integrated results of small-scale prospective and retrospective studies.

Impact of breast cancer subtype on clinical outcomes after Gamma Knife radiosurgery for brain metastases from breast cancer: a multi-institutional retrospective study (JLGK1702).

INTRODUCTION: Brain metastasis (BM) is one of the most important issues in the management of breast cancer (BC), since BMs are associated with neurological deficits. However, the importance of BC subtypes remains unclear for BM treated with Gamma Knife radiosurgery (GKS). Thus, we conducted a multicenter retrospective study to compare clinical outcomes based on BC subtypes, with the aim of developing an optimal treatment strategy. METHODS: We studied 439 patients with breast cancer and 1-10 BM from 16 GKS facilities in Japan. Overall survival (OS) was analyzed by the Kaplan-Meier method, and cumulative incidences of systemic death (SD), neurologic death (ND), and tumor progression were estimated by competing risk analysis. RESULTS: OS differed among subtypes. The median OS time (months) after GKS was 10.4 in triple-negative (TN), 13.7 in Luminal, 31.4 in HER2, and 35.8 in Luminal-HER2 subtype BC (p < 0.0001). On multivariate analysis, poor control of the primary disease (hazard ratio [HR] = 1.84, p < 0.0001), active extracranial disease (HR = 2.76, p < 0.0001), neurological symptoms (HR 1.44, p = 0.01), and HER2 negativity (HR = 2.66, p < 0.0001) were significantly associated with worse OS. HER2 positivity was an independent risk factor for local recurrence (p = 0.03) but associated with lower rates of ND (p = 0.03). TN histology was associated with higher rates of distant brain failure (p = 0.03). CONCLUSIONS: HER2 positivity is related to the longer OS after SRS; however, we should pay attention to preventing recurrence in Luminal-HER2 patients. Also, TN patients require meticulous follow-up observation to detect distant metastases and/or LMD.

Salvage gamma knife radiosurgery for active brain metastases from small-cell lung cancer after whole-brain radiation therapy: a retrospective multi-institutional study (JLGK1701).

PURPOSE: To evaluate the efficacy of gamma knife radiosurgery (GKS) for brain metastases (BMs) from small-cell lung cancer after whole-brain radiotherapy (WBRT). METHODS: We retrospectively analyzed the usefulness and safety of GKS in 163 patients from 15 institutions with 1-10 active BMs after WBRT. The usefulness and safety of GKS were evaluated using statistical methods. RESULTS: The median age was 66 years, and 79.1% of patients were men. The median number and largest diameter of BM were 2.0 and 1.4 cm, respectively. WBRT was administered prophylactically in 46.6% of patients. The median overall survival (OS) was 9.3 months, and the neurologic mortality was 20.0%. Crude incidences of local control failure and new lesion appearance were 36.6% and 64.9%, respectively. A BM diameter ≥ 1.0 cm was a significant risk factor for local progression (hazard ratio [HR] 2.556, P = 0.039) and neurologic death (HR 4.940, P = 0.031). Leukoencephalopathy at the final follow-up was more prevalent in the therapeutic WBRT group than in the prophylactic group (P = 0.019). The symptom improvement rate was 61.3%, and neurological function was preserved for a median of 7.6 months. Therapeutic WBRT was not a significant risk factor for OS, neurological death, local control, or functional deterioration (P = 0.273, 0.490, 0.779, and 0.560, respectively). Symptomatic radiation-related adverse effects occurred in 7.4% of patients. CONCLUSIONS: GKS can safely preserve neurological function and prevent neurologic death in patients with 1-10 small, active BMs after prophylactic and therapeutic WBRT.

[Posterior Approach for Cervical Spondylotic Myelopathy in Patients Older than 80 Years of Age].

OBJECTIVE: We aimed to investigate the characteristics and operative results of elderly patients with cervical spondylotic myelopathy(aged ≧80 years)treated using the posterior approach. METHODS: Between April 2010 and December 2018, 21 patients aged ≧80 years(older group:8 men and 13 women;age range, 80-90 years)who underwent laminoplasty were reviewed and compared with 23 patients aged <80 years(younger group;13 men and 10 women;age range, 42-79 years)who underwent laminoplasty. The following data were obtained from chart reviews:age;sex;cervical canal stenosis level;time to operation;symptoms(e.g., gait disturbance);comorbidities(hypertension, diabetes mellitus, cancer, heart disease, ischemic cerebrovascular disease, and lumbar canal stenosis);antithrombotic drug use;cardiac, pulmonary, and renal functions;operative time;volume of blood loss during the operation;postoperative delirium;and follow-up period. Neurological deficits before and after the surgery were assessed using the neurosurgical cervical spine scale(NCSS). Data were statistically analyzed, and p-values <0.05 were considered statistically significant. RESULTS: The operative time, symptoms(hypertension), renal function, and preoperative NCSS score were significantly different between the older and younger groups. Meanwhile, most variables showed no significant differences between the groups. Although the preoperative NCSS score was lower in the older group, there was no significant difference in the degree of improvement in the NCSS score after surgery. CONCLUSIONS: The findings of this study suggest that we should not hesitate to perform surgery for cervical spondylotic myelopathy in elderly patients with favorable cardiorespiratory function.

[Surgical Results of Lumbar Degenerative Disease with Foot Drop].

Drop foot is associated with various diseases, such as peripheral nerve disease, lumbar degenerative disease, metabolic disease, and endocrine disease. Among lumbar degenerative diseases, lumbar disc herniation and lumbar canal stenosis are most commonly reported. We report the surgical outcomes of patients with drop foot caused by lumbar degenerative diseases. Between 2008 and 2018, we encountered 24 cases of drop foot in patients who underwent surgery of the lumbar lesion. The mean age was 69.5 years(49-88 years). Fourteen patients were male and ten were female. The mean time interval between the onset of drop foot and surgery was 51.5 days(from 7 days to 1 year). Drop foot, as a clinically significant muscle weakness, was defined at levels of manual muscle test(MMT)3 or lower. Responsible lesions for drop foot were canal stenosis at L4/5 in 8 cases, disc herniation at L4/5 in 10 cases, disc herniation at L5/S1 in 5 cases, and far-out syndrome in 1. One case involved drop foot bilaterally. Muscle weakness improved by surgery at levels of MMT 4 or greater in 16 cases(66.7%). Six cases of complete paresis or tibialis anterior muscle atrophy preoperatively resulted in no improvement;however, neuralgia was relieved in all. Twelve of 15 cases(80%)of lumbar disc herniation and 4 of 10 cases(40%)of lumbar canal stenosis resulted in improvement. Between disc herniation and canal stenosis, the surgical success rate was not statistically different. Age and the time interval between the onset and surgery were also not significant factors of the outcome. Surgical intervention seems to be beneficial even in cases of severe muscle weakness since pain relief can be expected, which leads to improvement in gait.

[Pseudoaneurysm of Neck External Carotid Artery Related to Chiropractic Manipulation].

A 55-year-old man presented with progressive pain and expanding swelling in his right neck. He had no history of trauma or infectious disease. The patient had undergone chiropractic manipulations once in a month and the last manipulation was done one day before the admission to our hospital. On examination by laryngeal endoscopy, a swelling was found on the posterior wall of the pharynx on the right side. The right piriform fossa was invisible. CT revealed hematoma in the posterior wall of the right oropharynx compressing the airway tract. Aneurysm-like enhanced lesion was also seen near the right common carotid artery. Ultrasound imaging revealed a fistula of approximately 1.2 mm at the posterior wall of the external carotid artery and inflow image of blood to the aneurysm of a diameter of approximately 12 mm. No dissection or stenosis of the artery was found. Jet inflow of blood into the aneurysm was confirmed by angiography. T1-weighted MR imaging revealed presence of hematoma on the posterior wall of the pharynx and the aneurysm was recognized by gadolinium-enhancement. We performed emergency surgery to remove the aneurysm while preserving the patency of the external carotid artery. The pin-hole fistula was sutured and the wall of the aneurysm was removed. Histopathological assessment of the rissue revealed pseudoaneurysm. The patient was discharged after 12 days without deficit. Progressively growing aneurysm of the external carotid artery is caused by various factors and early intervention is recommended. Although, currently, intravascular surgery is commonly indicated, direct surgery is also feasible and has advantages with regard to pathological diagnosis and complete repair of the parent artery.

A Novel Rac1-GSPT1 Signaling Pathway Controls Astrogliosis Following Central Nervous System Injury.

Astrogliosis (i.e. glial scar), which is comprised primarily of proliferated astrocytes at the lesion site and migrated astrocytes from neighboring regions, is one of the key reactions in determining outcomes after CNS injury. In an effort to identify potential molecules/pathways that regulate astrogliosis, we sought to determine whether Rac/Rac-mediated signaling in astrocytes represents a novel candidate for therapeutic intervention following CNS injury. For these studies, we generated mice with Rac1 deletion under the control of the GFAP (glial fibrillary acidic protein) promoter (GFAP-Cre;Rac1flox/flox). GFAP-Cre;Rac1flox/flox (Rac1-KO) mice exhibited better recovery after spinal cord injury and exhibited reduced astrogliosis at the lesion site relative to control. Reduced astrogliosis was also observed in Rac1-KO mice following microbeam irradiation-induced injury. Moreover, knockdown (KD) or KO of Rac1 in astrocytes (LN229 cells, primary astrocytes, or primary astrocytes from Rac1-KO mice) led to delayed cell cycle progression and reduced cell migration. Rac1-KD or Rac1-KO astrocytes additionally had decreased levels of GSPT1 (G1 to S phase transition 1) expression and reduced responses of IL-1ß and GSPT1 to LPS treatment, indicating that IL-1ß and GSPT1 are downstream molecules of Rac1 associated with inflammatory condition. Furthermore, GSPT1-KD astrocytes had cell cycle delay, with no effect on cell migration. The cell cycle delay induced by Rac1-KD was rescued by overexpression of GSPT1. Based on these results, we propose that Rac1-GSPT1 represents a novel signaling axis in astrocytes that accelerates proliferation in response to inflammation, which is one important factor in the development of astrogliosis/glial scar following CNS injury.

Gamma Knife Radiosurgery for Metastatic Brain Tumors from Malignant Melanomas: A Japanese Multi-Institutional Cooperative and Retrospective Cohort Study (JLGK1501).

BACKGROUND: The incidences of metastatic brain tumors from malignant melanomas have increased and survival has been prolonged by novel molecular targeted agents and immunotherapy. However, malignant melanomas are uncommon in Asian populations. OBJECTIVES: We retrospectively analyzed treatment efficacy and identified prognostic factors impacting tumor control and survival in Japanese melanoma patients with brain metastases treated with gamma knife radiosurgery (GKRS). METHODS: We retrospectively reviewed the medical records of 177 patients with 1,500 tumors who underwent GKRS for brain metastases from malignant melanomas. This study was conducted by the Japanese Leksell Gamma Knife Society (JLGK1501). RESULTS: Six and 12 months after GKRS, the cumulative incidences of local tumor recurrence were 9.2 and 13.8%. Intratumoral hemorrhage (p < 0.0001) and larger tumor volume (p = 0.001) in GKRS were associated with significantly poorer local control outcomes. The use of immune checkpoint inhibitors before GKRS was significantly associated with symptomatic adverse events (p = 0.037). The median overall survival time after the initial GKRS was 7.3 months. Lower Karnofsky performance status scores (p = 0.016), uncontrolled primary cancer (p < 0.0001), and multiple brain metastases (p = 0.014) significantly influenced unfavorable overall survival outcomes. The cumulative incidences of neurological death 6 and 12 months after GKRS were 9.7 and 17.4%, those of neurological deterioration were 14.2 and 19.6%, and those of new tumor appearance were 34.5 and 40.5%. CONCLUSIONS: The results of the present multicenter study suggest that GKRS is a relatively effective and safe modality for control of tumor progression in Japanese patients with brain metastases from malignant melanomas.

[Two Cases of Bilateral Orbital Metastases of Breast Cancer].

Two cases of breast cancer with bilateral orbital metastases associated with intracranial metastases are presented. Case 1:A 61-year-old woman who was diagnosed with breast cancer 14 years earlier presented with rapid deterioration of visual acuity, eye pain, and limitation of left-sided extraocular motility. Magnetic resonance(MR)images showed an enhanced lesion in the left orbital apex, ethmoid sinus, and right middle fossa. The first gamma knife radiotherapy(35 Gy, 5 Fr)was performed successfully, but was followed by recurrence 18 months later in the right intraorbital, where newly formed iso-intensity masses in the extraconal compartment were found. The second gamma knife radiosurgery was performed for three masses(20 Gy). Case 2:A 35-year-old woman with breast cancer who was diagnosed 22 months earlier was treated for meningeal carcinomatosis by whole-brain radiation(30 Gy, 10 Fr)and intrathecal chemotherapy. Eight months later, swelling in both eyelids and limitation of extraocular motility developed rapidly. MR imaging revealed an infiltrating lesion in the cone with heterogenous signal that was encasing, but not infiltrating the optic nerves. The extraconal lesion extended into the soft tissue of the lower eye lid. She expired one week after diagnosis. With the increasing number of long-term survivors with breast cancer, intraorbital metastases may be found during the course of treatment for intracranial lesions. Understanding the unique clinical presentation and characteristic MR findings of this rare entity are emphasized.

A phase demodulation method with high spatial resolution for two-dimensional single-shot X-ray Talbot interferometry.

A new phase demodulation approach is proposed that uses windowed Fourier transforms to achieve high spatial resolution in fringe pattern analysis with a high signal-to-noise ratio for single-shot X-ray grating-based interferometry. Conventionally, Fourier transforms have been used to demodulate single-fringe patterns, but this requires a fringe pattern with a long period to obtain an acceptable signal-to-noise ratio among the demodulated parameters. However, by controlling the signal-to-noise ratio, the spatial resolution of demodulated parameters is degraded below that obtained from the phase-stepping method, which requires several images to obtain these parameters. In this paper, we introduce the use of a windowed Fourier transform with a process for analyzing the objective spectrum in isolation from other spectra on the Fourier space to overcome the limitations of the Fourier transform method. It is proved that with suitable assumptions the objective spectrum is isolated theoretically, and the spatial resolution is improved by practically accepting the limitations from the assumptions. We demonstrate the validity of the proposed method by comparing the modulation transfer function of a synthetic phantom with the conventional FT method. The proposed method is also valid on practical data obtained by an experimental setup, by which it is demonstrated that a high spatial resolution with high signal-to-noise ratio can be achieved by our proposed method.

Sparse phase-stepping in two-dimensional x-ray phase contrast imaging.

We have developed a sparse phase-stepping (SPS) method for x-ray Talbot-Lau interferometry, which first constructs a SPS intensity pattern of fewer images than the conventional phase-stepping (PS) method and then fills the data gap with neighboring pixels for phase retrieval. The SPS method is highly beneficial in practice since the fundamental difference in spatial resolution between the SPS and PS methods becomes negligible due to the blur caused by an interferometer. The concept of the SPS method has been proved by the experiment using a small effective source size. Furthermore, the experiment using a large effective source size has verified that in practical situations the SPS method can reduce the required number of images for phase retrieval and still offer the retrieved images with as high a spatial resolution as the PS method.

Optimization of X-ray microplanar beam radiation therapy for deep-seated tumors by a simulation study.

A Monte Carlo simulation was applied to study the energy dependence on the transverse dose distribution of microplanar beam radiation therapy (MRT) for deep-seated tumors. The distribution was found to be the peak (in-beam) dose and the decay from the edge of the beam down to the valley. The area below the same valley dose level (valley region) was decreased with the increase in the energy of X-rays at the same beam separation. To optimize the MRT, we made the following two assumptions: the therapeutic gain may be attributed to the efficient recovery of normal tissue caused by the beam separation; and a key factor for the efficient recovery of normal tissue depends on the area size of the valley region. Based on these assumptions and the results of the simulated dose distribution, we concluded that the optimum X-ray energy was in the range of 100-300 keV depending on the effective peak dose to the target tumors and/or tolerable surface dose. In addition, we proposed parameters to be studied for the optimization of MRT to deep-seated tumors.

Stereotactic radiotherapy of radiation-induced meningioma previously irradiated retrobulbar for Graves' ophthalmopathy: A case report.

A 69-year-old woman was diagnosed with an asymptomatic intracranial tumor nine years ago and has been followed with annual MR imaging studies. Two years ago, the tumor had grown in size, requiring treatment. She experienced ophthalmopathy due to hyperthyroidism 27 years ago and was treated with 20 Gy in 10 fractions using parallel opposed beams to her bilateral posterior eyeballs, supplemented with steroid pulse therapy. The tumor originated in the medial aspect of the right sphenoid border and compressed the temporal lobe, while bone infiltration was observed, partially extending to the soft tissue outside the maxillary sinus. The tumor was removed by craniotomy. The pathological diagnosis was atypical meningioma (WHO grade II). Four months postsurgery, the resection cavity's tumor exhibited growth inclination, necessitating Gamma Knife radiosurgery. Radiation planning was executed at a marginal tumor dose of 30 Gy in 5 fractions. Since the optic nerve had been previously exposed to radiation, a plan was devised to minimize radiation exposure. The dose on the optic nerve was limited to 6.9 Gy in 5 fractions. She did not experience any visual or visual field disruptions postradiation. This is a case of radiation-induced meningioma resulting from radiation therapy for Graves' ophthalmopathy and is the first reported case of a grade II meningioma. The patient's condition calls for adjuvant radiation therapy following surgical removal. Accordingly, a radiation treatment plan that safeguards the optic nerve, which was previously exposed to radiation, was deemed indispensable.

Facial Nerve Neurolymphomatosis That Extends to Both the Brainstem and Extracranial Regions.

A 73-year-old female developed right facial paralysis of House-Brackmann (H-B) grade III and was diagnosed with Bell's palsy. After three months of steroid therapy, she developed progressive hearing loss, and an MRI revealed a tumor in the right internal auditory canal. Within a few months, the right facial nerve palsy recurred, and the patient was treated with Gamma Knife radiosurgery. The tumor in the irradiated region disappeared, but new dysphagia was observed, and a right parotid gland tumor was detected for the first time. Tumors of the right parotid gland and the digastric muscle of the jaw were surgically resected, and a diagnosis of diffuse large B-cell lymphoma was made. The tumor had invaded the cranial nerves and brainstem region, and the patient did not wish to undergo further medical therapy. This was a case of malignant lymphoma that started as facial paralysis and invaded the brainstem, and testing for possible lymphoma at an early stage prior to radiotherapy was desirable.

Long-term recurrence after surgery for schwannoma of the cauda equina.

Background: Cauda equina tumors are rare primary spinal tumors. Histologically, the most common tumor arising from the cauda equina is a schwannoma. However, little is known about the long-term postoperative outcomes of cauda equina schwannoma. Here, we reviewed the median-to-long-term postoperative outcomes of eight of our own patients with schwannomas of the cauda equina. Methods: Between 2007 and 2020, we, retrospectively, reviewed eight patients with cauda equina schwannomas (CESs) undergoing nine operations at our institution. There were five males and three females averaging 56.5 years of age who were followed for over 40 postoperative months. The study included assessment of the following variables: the modified McCormick scale, tumor size, location, extent of resection, treatment of the tumor involving nerve roots, and postoperative observational follow-up. Results: Gross-total resection was achieved in all eight patients; none received adjuvant therapy. The involved nerve roots were completely sacrificed in seven patients and partially resected in one. During a median follow-up of 108 months, only one patient sustained a tumor recurrence 164 months following the index surgery. Conclusion: CESs may recur more than 10 years after the original surgery. Radical resection of the tumor, including complete removal of the involved nerve root during the index surgery, and long-term postoperative follow-up is, therefore, essential.

Gamma knife radiosurgery cured hydrocephalus in non-hemorrhagic brain stem arteriovenous malformation.

A 13-year-old boy, with a history of intermittent headache and transient diplopia, was found to have non-hemorrhagic cerebral arteriovenous malformation in the midbrain tegmental region associated with hydrocephalus. Gamma knife radiosurgery was performed at 16 Gy with 75% marginal dose. Posttreatment course was uneventful. Follow-up MR imaging at one year after the treatment revealed complete disappearance of the abnormal vascular flow voids. The size of each ventricle at the treatment and at one year after treatment were as follows; 60.2 cc and 20.9 cc in the lateral ventricles, 3.7 cc and 2.7 cc in the third ventricle. The hydrocephalus might be caused by obstructive mechanism but mostly by high venous pressure due to the shunt blood flow. The goal of treatment for hydrocephalus should be nidus obstruction and normalizing the vascular flow.

Endovascular Treatment Strategy for Acute Basilar Artery Occlusion with Unexpected Right-Sided Aortic Arch.

A right-sided aortic arch (RAA) is a rare variant of the aortic arch found. We present a case of endovascular treatment (EVT) for acute basilar artery (BA) occlusion with an RAA. A 70-year-old man developed acute ischemic stroke due to BA occlusion. During urgent EVT for BA occlusion with an RAA, which was observed unexpectedly, navigation of the catheter to the target vessel was achieved as a result of an early change in the access route. Flexible treatment strategies are warranted for cases of unexpected anatomical variant in the fight against time for emergent cases, such as acute ischemic stroke.

Outcomes of Gamma Knife radiosurgery for skull base chondrosarcomas: a multi-institutional retrospective study.

OBJECTIVE: Radiotherapy has an essential role in the management of skull base chondrosarcomas (SBCs) after resection. This multi-institutional study evaluated the outcomes of Gamma Knife radiosurgery (GKRS) for histopathologically proven SBCs. METHODS: Data of patients who underwent GKRS for SBCs at Gamma Knife centers in Japan were retrospectively collected. Patients without a histopathological diagnosis and those who had intracranial metastases from extracranial chondrosarcomas were excluded. Histologically, grade III and some nonconventional variants were identified as aggressive types. The cumulative local control rates (LCRs) and disease-specific survival (DSS) rates were calculated using the Kaplan-Meier method. Factors potentially affecting the LCR were evaluated using the Cox proportional hazards model for bivariate and multivariate analyses. The incidence of radiation-induced adverse effects (RAEs) was calculated as crude rates, and factors associated with RAEs were examined using Fisher's exact test. RESULTS: Fifty-one patients were enrolled, with a median age of 38 years. Thirty patients (59%) were treated with upfront GKRS for residual SBCs after resection (n = 27) or biopsy (n = 3), and 21 (41%) underwent GKRS as a salvage treatment for recurrence. The median tumor volume was 8 cm3. The overall LCRs were 87% at 3 years, 78% at 5 years, and 67% at 10 years after GKRS. A better LCR was associated with a higher prescription dose (p = 0.039) and no history of repeated recurrence before GKRS (p = 0.024). The LCRs among patients with the nonaggressive histological type and treatment with ≥ 16 Gy were 88% at 3 years, 83% at 5 years, and 83% at 10 years. The overall survival rates after GKRS were 96% at 5 years and 83% at 10 years. Although RAEs were observed in 3 patients (6%), no severe RAEs with Common Terminology Criteria for Adverse Events grade 3 or higher were identified. No significant factor was associated with RAEs. CONCLUSIONS: GKRS for SBCs has a favorably low risk of RAEs and could be a reasonable therapeutic option for SBC in multimodality management. A sufficient GKRS prescription dose is necessary for higher LCRs. Histological grading and subtype evaluations are important for excluding exceptional SBCs. Patients with conventional SBCs have a long life expectancy and should be observed for life after treatment.

A Practical Grading Scale for Predicting Outcomes of Radiosurgery for Dural Arteriovenous Fistulas: JLGK 1802 Study.

BACKGROUND AND PURPOSE: To assess the long-term outcomes of intracranial dural arteriovenous fistula (DAVF) treated with stereotactic radiosurgery (SRS) alone or embolization and SRS (Emb-SRS) and to develop a grading system for predicting DAVF obliteration. METHODS: This multi-institutional retrospective study included 200 patients with DAVF treated with SRS or Emb-SRS. We investigated the long-term obliteration rate and obliteration-associated factors. We developed a new grading system to estimate the obliteration rate. Additionally, we compared the outcomes of SRS and Emb-SRS by using propensity score matching. RESULTS: The 3- and 4-year obliteration rates were 66.3% and 78.8%, respectively. The post-SRS hemorrhage rate was 2%. In the matched cohort, the SRS and Emb-SRS groups did not differ in the rates of obliteration (P=0.54) or post-SRS hemorrhage (P=0.50). In multivariable analysis, DAVF location and cortical venous reflux (CVR) were independently associated with obliteration. The new grading system assigned 2, 1, and 0 points to DAVFs in the anterior skull base or middle fossa, DAVFs with CVR or DAVFs in the superior sagittal sinus or tentorium, and DAVFs without these factors, respectively. Using the total points, patients were stratified into the highest (0 points), intermediate (1 point), or lowest (≥2 points) obliteration rate groups that exhibited 4-year obliteration rates of 94.4%, 71.3%, and 60.4%, respectively (P<0.01). CONCLUSIONS: SRS-based therapy achieved DAVF obliteration in more than three-quarters of the patients at 4 years of age. Our grading system can stratify the obliteration rate and may guide physicians in treatment selection.

A narrow microbeam is more effective for tumor growth suppression than a wide microbeam: an in vivo study using implanted human glioma cells.

The tumoricidal mechanisms of microbeam radiation therapy, and the more recently proposed minibeam radiation therapy, for the treatment of brain tumors are as yet unclear. Moreover, from among the various parameters of beam geometry the impact of changing the beam width is unknown. In this study, suppression of tumor growth in human glioma cells implanted in mice was evaluated experimentally using microbeams of two different widths: a conventional narrow beam (20 µm width, 100 µm center-to-center distance) and a wide beam (100 µm width, 500 µm center-to-center distance). The tumor growth ratio was compared and acute cell death was studied histologically. With cross-planar irradiation, tumor growth was significantly suppressed between days 4 and 28 after 20 µm microbeam irradiation, whereas tumor growth was suppressed, and not significantly so, only between days 4 and 18 after 100 µm microbeam irradiation. Immunohistochemistry using TUNEL staining showed no increase in TUNEL-positive cells with either microbeam at 24 and 72 h post-irradiation. The 20 µm microbeam was found to be more tumoricidal than the 100 µm microbeam, and the effect was not related to apoptotic cell death. The underlying mechanism may be functional tissue deterioration rather than direct cellular damage in the beam path.