Relapse patterns and radiation dose exposure in IDH wild-type glioblastoma at first radiographic recurrence following chemoradiation.

PURPOSE: To quantify the radiation dose distribution and lesion morphometry (shape) at baseline, prior to chemoradiation, and at the time of radiographic recurrence in patients with glioblastoma (GBM). METHODS: The IMRT dose distribution, location of the center of mass, sphericity, and solidity of the contrast enhancing tumor at baseline and the time of tumor recurrence was quantified in 48 IDH wild-type GBM who underwent postoperative IMRT (2 Gy daily for total of 60 Gy) with concomitant and adjuvant temozolomide. RESULTS: Average radiation dose within enhancing tumor at baseline and recurrence was ≥ 60 Gy. Centroid location of the enhancing tumor shifted an average of 11.3 mm at the time of recurrence with respect to pre-IMRT location. A positive correlation was observed between change in centroid location and PFS in MGMT methylated patients (P = 0.0007) and Cox multivariate regression confirmed centroid distance from baseline was associated with PFS when accounting for clinical factors (P = 0.0189). Lesion solidity was higher at recurrence compared to baseline (P = 0.0118). Tumors that progressed > 12 weeks after IMRT were significantly more spherical (P = 0.0094). CONCLUSION: Most GBMs recur local within therapeutic IMRT doses; however, tumors with longer PFS occurred further from the original tumor location and were more solid and/or nodular.

Comparison of treatment results between 3- and 2-stage Gamma Knife radiosurgery for large brain metastases: a retrospective multi-institutional study.

OBJECTIVE: In order to obtain better local tumor control for large (i.e., > 3 cm in diameter or > 10 cm3 in volume) brain metastases (BMs), 3-stage and 2-stage Gamma Knife surgery (GKS) procedures, rather than a palliative dose of stereotactic radiosurgery, have been proposed. Here, authors conducted a retrospective multi-institutional study to compare treatment results between 3-stage and 2-stage GKS for large BMs. METHODS: This retrospective multi-institutional study involved 335 patients from 19 Gamma Knife facilities in Japan. Major inclusion criteria were 1) newly diagnosed BMs, 2) largest tumor volume of 10.0-33.5 cm3, 3) cumulative intracranial tumor volume ≤ 50 cm3, 4) no leptomeningeal dissemination, 5) no more than 10 tumors, and 6) Karnofsky Performance Status 70% or better. Prescription doses were restricted to between 9.0 and 11.0 Gy in 3-stage GKS and between 11.8 and 14.2 Gy in 2-stage GKS. The total treatment interval had to be within 6 weeks, with at least 12 days between procedures. There were 114 cases in the 3-stage group and 221 in the 2-stage group. Because of the disproportion in patient numbers and the pre-GKS clinical factors between these two GKS groups, a case-matched study was performed using the propensity score matching method. Ultimately, 212 patients (106 from each group) were selected for the case-matched study. Overall survival, tumor progression, neurological death, and radiation-related adverse events were analyzed. RESULTS: In the case-matched cohort, post-GKS median survival time tended to be longer in the 3-stage group (15.9 months) than in the 2-stage group (11.7 months), but the difference was not statistically significant (p = 0.65). The cumulative incidences of tumor progression (21.6% vs 16.7% at 1 year, p = 0.31), neurological death (5.1% vs 6.0% at 1 year, p = 0.58), or serious radiation-related adverse events (3.0% vs 4.0% at 1 year, p = 0.49) did not differ significantly. CONCLUSIONS: This retrospective multi-institutional study showed no differences between 3-stage and 2-stage GKS in terms of overall survival, tumor progression, neurological death, and radiation-related adverse events. Both 3-stage and 2-stage GKS performed according to the aforementioned protocols are good treatment options in selected patients with large BMs.

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.

De Novo Arteriovenous Malformation after Aneurysm Clipping.

We report a 73-year-old woman with de novo arteriovenous malformations (AVMs) that developed in the ipsilateral parietal lobe after craniotomy and aneurysm clipping. While intracerebral AVMs are considered to be congenital lesions, there have been several reported cases of acquired AVM arising after ischemic or traumatic episodes. We summarize previously reported cases of such acquired 'de novo' AVMs with a discussion of some pathophysiological responses or factors suggested to promote their development.

Identification of hemodynamically compromised regions by means of cerebral blood volume mapping utilizing computed tomography perfusion imaging.

The aim of the study was to evaluate the potential role of computed tomography perfusion (CTP) imaging in identifying hemodynamically compromised regions in patients with occlusive cerebrovascular disease. Twelve patients diagnosed with either occlusion or severe stenosis of the internal carotid artery or the M1 portion of the middle cerebral artery underwent CTP imaging. The data was analyzed by an automated ROI-determining software. Patients were classified into two subgroups: an asymptomatic group consisting of three patients in whom perfusion pressure distal to the site of occlusion/stenosis (PPdis) could be maintained in spite of the arterial occlusion/stenosis, and a symptomatic group consisting of nine patients in whom PPdis could not be maintained enough to avoid watershed infarction. Four CTP-related parameters were independently compared between the two groups. Significant differences were determined using a two-sample t-test. When statistically significant differences were identified, cut-off points were calculated using ROC curves. Analysis revealed statistically significant differences between the asymptomatic and symptomatic subgroups only in the measure of relCBV (p=0.028). Higher relCBV values were observed in the symptomatic subgroup. ROC curve analysis revealed 1.059 to be the optimal relCBV cut-off value for distinguishing between the asymptomatic and symptomatic subgroups. The data revealed that, in patients whose PPdis is maintained, relCBV remains around 1.00. Conversely, in patients whose PPdis decreased, relCBV increased. From these findings, we conclude that elevation of relCBV as observed using CTP imaging accurately reflects the extent of compensatory vasodilatation involvement and can identify hemodynamically compromised regions.

Spatial Relationship between Hypoglossal Schwannoma and the Vertebral Artery Using the Far-Lateral Approach.

In hypoglossal schwannoma removal via the far-lateral approach needs care as the vertebral arteries are usually adjacent to the tumors. Thus, it is important to understand their location respective to schwannoma to conduct a safe surgery. We reviewed the data of eight patients with hypoglossal schwannoma who underwent surgery in Keio University Hospital in 2005-2013. There were five males and three females (mean age at initial presentation was 48.6 years, range 38-72 years). We especially focused on the spatial relationship between the vertebral artery and the tumor, and evaluated their spatial relationship from intraoperative findings. All eight hypoglossal schwannomas included in the current study were type B according to Kaye's classification. As for spatial relationship between the tumor and the vertebral artery, in six out of eight cases, the vertebral artery was located inside or beneath the tumor; in contrast, in the other two cases, it was pushed out by the tumor and identified just after dural opening. Through the far-lateral approach, we found that the vertebral artery was located inside or beneath in most hypoglossal schwannoma; however, the vertebral artery was occasionally located on the tumor surface. From an anatomical perspective, we speculate this unique location of the vertebral artery in these cases is due to the unusual course of the hypoglossal nerve of tumor origin.

The process of change in hemodynamics after revascularization in the ischemic brain.

In patients with a high-degree of internal carotid artery stenosis, cerebral hemodynamics and metabolism are compromised during ischemia. Revascularization improves cortical hemodynamics and oxygen metabolism during functional activity, but the process by which it occurs is still controversial. Therefore, using functional near-infrared spectroscopy (fNIRS), we investigated the process by which cerebral hemodynamics improve after revascularization surgery. Eight patients with severe carotid artery stenosis were examined using fNIRS during a motor task before and after surgery. We evaluated postoperative changes in total hemoglobin and deoxyhemoglobin (HbR), at 2 weeks after surgery, and again at 3 months after surgery. Parameters measured were the TTP (time to peak) value, defined as the time taken to reach 70% of the maximum total hemoglobin concentration, and the increase in HbR during the motor task. TTP was higher in four patients preoperatively, but this was no longer evident in two of the patients at 2 weeks after surgery. An increase in HbR during the task was observed in six patients before surgery, and was maintained at 2 weeks after surgery. However, in three of these patients, this increase was no longer evident 3 months later. These changes observed using fNIRS suggest that the increase in cerebral blood flow after revascularization surgery is followed by improvement in parenchymal vasodilation and neuronal oxygen metabolism.

Prediction of cerebrovascular reserve capacity by computed tomography perfusion using 320-row computed tomography.

BACKGROUND: Acetazolamide loading has been the "gold standard" for evaluating cerebrovascular reserve capacity (CVRC). However, life-threatening side effects of acetazolamide have recently been reported. The aim of the study was to identify alternative methods for evaluating CVRC. METHODS: We reviewed 6 patients who underwent both computed tomography perfusion (CTP) imaging and xenon CT (XeCT) imaging with and without acetazolamide loading during the same periods. The data were obtained as volume data using 320-row CT and applied to the automated region of interest-determining software and converted to standardized images. Correlations between CVRC and CTP parameters were analyzed by Pearson correlation coefficient analysis, and simple regression was used to assess the relationship between the data. When statistically significant, correlation between CVRC and any CTP data is identified, and cutoff points for CVRC 30% and 10% were calculated with receiver operating characteristic curves. RESULTS: Of 4 CTP parameters evaluated, statistically significant correlations were observed between time to peak (TTP) by CTP and CVRC (P < .0001, r = -.7228) calculated from XeCT. The regression line using CVRC as outcome variable (y) and using TTP as predictor variable (x) was y = -9.062x + 140.1. The cutoff value for the TTP for CVRC less than 10% was 12.56 seconds (sensitivity of 86% and specificity of 85%) and that for CVRC less than 30% was 9.34 seconds (sensitivity of 77% and specificity of 96%). CONCLUSIONS: TTP calculated from CTP data correlated well with the CVRC calculated from XeCT data. These results suggest that TTP calculated from CTP could be used to estimate CVRC in patients with occlusive cardiovascular disease.

Comparison of cerebral blood flow data obtained by computed tomography (CT) perfusion with that obtained by xenon CT using 320-row CT.

Cerebral blood flow (CBF) data obtained by computed tomography perfusion (CTP) imaging have been shown to be qualitative data rather than quantitative, in contrast with data obtained by other imaging methods, such as xenon CT (XeCT) imaging. Thus, interpatient comparisons of CBF values themselves obtained by CTP may be inaccurate. In this study, we have compared CBF ratios as well as CBF values obtained from CTP-CBF data to those obtained from XeCT-CBF data for the same patients to determine CTP-CBF parameters that can be used for interpatient comparisons. The data used in the present study were obtained as volume data using 320-row CT. The volume data were applied to an automated region of interest-determining software (3DSRT, version 3.5.2 ) and converted to 59 slices of 2 mm interval standardized images. In the present study, we reviewed 10 patients with occlusive cerebrovascular diseases (CVDs) undergoing both CTP and XeCT in the same period. Our study shows that ratios of CBF measurements, such as hemodynamic stress distribution (perforator-to-cortical flow ratio of middle cerebral artery [MCA] region) or the left/right ratio for the region of the MCA, calculated using CTP data have been shown to correlate well with the same ratios calculated using XeCT data. These results suggest that such CBF ratios could be useful for generating interpatient comparisons of CTP-CBF data obtained by 320-row CT among patients with occlusive CVD.

Transoral vs. endoscopic endonasal approach for clival/upper cervical chordoma.

The surgical results of 18 cases of clival/upper cervical chordoma treated in the last decade via the endoscopic endonasal approach (EEA, 9 cases) and the transoral-transpalatal approach (TO-TPA, 9 cases) were compared. Each group showed the same incidence of subdural invasion, with 5 cases each. The superior (frontal base) and lateral surgical fields were wider by EEA, but the inferior view lower than the cranio-vertebral junction (CVJ) was wider by TO-TPA. Gross total removal was achieved in 3 cases in the EEA group, but in only 1 case in the TO-TPA group. Differences in radicality might be due to the extent of the lateral and subdural overview. However for large tumors extending below the CVJ, TO-TPA was the only viable approach for surgical removal. Surgical complications were higher in the EEA (4 cases) than the TO-TPA group (1 case), and were mainly caused by aggressive management of subdural invasion in the EEA group. Post-operative oral intake was earlier and the operative time was shorter in the EEA group. The surgical results were more radical and less invasive in the EEA group than the TO-TPA group. However in tumors extending below the CVJ, the surgical field in EEA was limited, indicating the need to use the transoral route or a combination of routes. A higher complication rate following subdural management was a negative factor that requires improvement in the EEA group and two-staged EEA followed by a transcranial approach may be considered for the cases with subdural invasion.

Transoral vs. endoscopic endonasal approach for clival/upper cervical chordoma.

The surgical results of 18 cases of clival/upper cervical chordoma treated in the last decade via the endoscopic endonasal approach (EEA, 9 cases) and the transoral-transpalatal approach (TO-TPA, 9 cases) were compared. Each group showed the same incidence of subdural invasion, with 5 cases each. The superior (frontal base) and lateral surgical fields were wider by EEA, but the inferior view lower than the cranio-vertebral junction (CVJ) was wider by TO-TPA. Gross total removal was achieved in 3 cases in the EEA group, but in only 1 case in the TO-TPA group. Differences in radicality might be due to the extent of the lateral and subdural overview. However for large tumors extending below the CVJ, TO-TPA was the only viable approach for surgical removal. Surgical complications were higher in the EEA (4 cases) than the TO-TPA group (1 case), and were mainly caused by aggressive management of subdural invasion in the EEA group. Post-operative oral intake was earlier and the operative time was shorter in the EEA group. The surgical results were more radical and less invasive in the EEA group than the TO-TPA group. However in tumors extending below the CVJ, the surgical field in EEA was limited, indicating the need to use the transoral route or a combination of routes. A higher complication rate following subdural management was a negative factor that requires improvement in the EEA group and two-staged EEA followed by a transcranial approach may be considered for the cases with subdural invasion.

Supratentorial neurenteric cyst with spontaneous repetitive intracystic hemorrhage mimicking brain abscess: a case report.

Neurenteric cyst (NC) is a benign epithelial cyst (BEC) of endodermal origin that mostly occurs in the spinal subdural space or posterior cranial fossa. A 28-year-old male presented with a left frontal lobe NC associated with spontaneous repetitive intracystic hemorrhage, which was initially diagnosed and treated as a brain abscess. He presented with headache and disorientation, without underlying diseases. A cystic tumor was suspected because of a hypointense signal on diffusion-weighted magnetic resonance imaging (MRI). One day after admission, his condition deteriorated rapidly and emergency cyst aspiration was performed. A brown viscous liquid like bloody pus comprising many neutrophils and macrophages was obtained. Although culture was negative, we initially started antibiotic treatment because of cyst content characteristics and rapid clinical course compatible with brain abscess. He was discharged without neurological deficits, but occasionally complained of intense headache. Computed tomography/MRI showed repetitive intracystic hemorrhage and gradual re-enlargement of the lesion. He underwent radical cyst excision by frontal craniotomy 34 months after aspiration. The pathological diagnosis was NC. We believe this is the first report of a supratentorial NC with spontaneous repetitive intracystic hemorrhage. BECs, especially with intracystic hemorrhage, are difficult to be distinguished from brain abscesses. In cases of cystic lesions or presumed brain abscesses refractory to treatment with aspiration and/or antibiotics, BECs should be considered, and radical cyst wall removal should be considered a treatment option.

Cerebral perfusion change of venous hypertension on near-infrared spectroscopy signals after operation for dural arteriovenous fistula.

A dural arteriovenous fistula (AVF) is an arteriovenous shunt in the dura and is associated with a risk of intracranial hemorrhage and neurologic deficit. The morbidity of this disease depends on venous hypertension, and the classification of this disease is based on the pattern of venous drainage. The pattern of venous drainage relates to the clinical features of the disease, especially to the probability of intracranial hemorrhage. We report 1 case of dural AVF with retrograde leptomeningeal venous drainage. Cerebral hemodynamics were monitored using near-infrared spectroscopy imaging before, during, and after the 2-stage operative treatment. Preoperative functional near-infrared spectroscopy (fNIRS) showed an increase in deoxyhemoglobin (HbR) during a motor task. After partial coil embolization of the shunt points (stage 1), HbR increased during the first half of the task and decreased later, whereas oxyhemoglobin (HbO2) decreased in the first half of the task and increased later. After complete embolization (stage 2), fNIRS showed a pattern similar to that of a normal adult. The patient's symptoms improved gradually, and angiography showed a reduction of the retrograde venous drainage and venous congestion after this 2-stage operation. The reduction in venous hypertension may be the underlying mechanism behind the changes observed with fNIRS.

Hemorrhagic onset of cerebellar pilocytic astrocytoma in an adult: a case report and review of the literature implying a possible relation of degenerative vascular changes to the massive intratumoral hemorrhage.

Pilocytic astrocytoma (PA) is a low-grade astrocytic tumor arising predominantly during the first two decades of life. Hemorrhagic onset of PAs is uncommon, and the etiology of hemorrhage remains unclear. Here we report a case of hemorrhagic onset of cerebellar PA in a 29-year-old man who presented with a week-long history of headache and gait instability. Computed tomography and magnetic resonance imaging revealed a hemorrhagic tumor located in the right cerebellar hemisphere, and total resection was performed. Histological examination showed bipolar glial cell proliferation in a biphasic pattern in a compact area and a loose microcystic area with Rosenthal fibers and eosinophilic granular bodies, indicating PA. Prominent changes in tumor vasculature, including aggregation of sclerotic thick-walled and ectatic thin-walled vessels, was observed, and nodules of thrombi containing complex vascular proliferation suggesting recanalized thrombi formed in partially ruptured vessels were also found. Thus, rupture of these abnormal vessels appeared to be the cause of hemorrhage. Review of the literature revealed that age distribution of patients with hemorrhagic PAs tends to be older than that of patients with general PAs. These findings imply a possibility that degenerative changes in blood vessels in long-standing PAs might be related to the mechanisms of spontaneous intratumoral hemorrhage.

Extraaxial neurocytoma in the skull base.

Extraventricular neurocytoma is an uncommon neuronal tumor, located outside the cerebral ventricles, which shows histological features similar to those of central neurocytoma. Most extraventricular neurocytomas are situated in the intraaxial regions of the central nervous system. We report a rare case of an extraaxial neurocytoma in the sphenocavernous-petroclival region that was successfully treated by radiation therapy following partial removal and pathological evaluation of the tumor.

Parasagittal solitary fibrous tumor resembling hemangiopericytoma.

Solitary fibrous tumor (SFT) is a rare mesenchymal tumor in the central nervous system, and the clinical behavior of this tumor is similar to that of meningioma. We report the case of a Japanese woman with parasagittal SFT that resembled hemangiopericytoma (HPC). Histological examination revealed that the tumor was highly cellular, with cells containing oval- or spindle-shaped nuclei arranged in sheets or a pattern-less growth mode. Focal vascular proliferation was also observed. Some areas showed intercellular stroma containing remarkable eosinophilic collagens. Tumor cells showed a strong immunoreactivity for CD34 but were negative for S-100 protein and epithelial membrane antigen. MIB-1 labeling index of the tumor was 6.6%. Owing to the high cellularity, high MIB-1 labeling index, and focal vascular proliferation, it was difficult to distinguish this lesion from HPC. However, the tumor was finally diagnosed as SFT on the basis of the strong immunostaining for CD34 and absence of pericellular reticulin.

Spontaneous regression after standard transsphenoidal surgery in a huge pituitary adenoma with epidural extension.

A 59-year-old female presented with a huge non-functioning pituitary adenoma which mainly extended from the intrasellar region to the epidural space of the anterior cranial base, manifesting as a 2-year history of disturbance of the visual field. Transsphenoidal surgery was performed to decompress the optic pathway as the first step of a two-staged operation. Postoperative magnetic resonance images unexpectedly showed spontaneous regression of the major portion of the epidural tumor which had not been manipulated during the first operation. The reason for the spontaneous regression remains unclear.