Spinal cord diffuse midline glioma with postoperative acute swelling: A case report and review of literature.

Background: H3K27-altered diffuse midline glioma (DMG) is a newly classified disease according to the 5th edition of the World Health Organization classification of the central nervous system tumors. However, little is known about its progression pattern and the timing of surgical intervention, especially regarding spinal cord lesions. Case Description: A 26-year-old man presented with rapid muscle weakness progression in both upper and lower extremities and urinary dysfunction. Magnetic resonance imaging showed diffuse swelling of the cervicothoracic spinal cord. He underwent decompressive laminectomy with expansive duroplasty and tumor biopsy. The surgical specimen revealed DMG. Immediately after surgery, deterioration of limb paresis was observed, and the patient developed respiratory failure the day after surgery. Head-and-neck computed tomography on the 7th day after surgery showed spinal cord swelling and acute obstructive hydrocephalus. Conclusion: We report a rare case of a spinal DMG with acute postoperative swelling. Neurological deterioration in patients with spinal cord DMG is often exacerbated, so it is essential to suspect DMG at an early stage based on neuroimaging, and if surgery is performed on the edematous spinal cord, further rapid swelling can occur, as in the present case.

Preoperatively difficult-to-diagnose medulla oblongata germinoma: A case report and literature review.

Background: Intracranial germinomas are rare tumors, accounting for 0.5-2% of primary intracranial neoplasms. While they typically occur in the pineal gland, suprasellar region, basal ganglia, and thalamus, germinomas arising in the medulla oblongata are exceptionally rare. Diagnosis of medulla oblongata germinoma is challenging, potentially leading to misdiagnosis and poor prognosis. Case Description: We present a case of a 29-year-old man complaining of left leg numbness. Radiological findings revealed a contrast-enhanced lesion in the medulla oblongata. The patient underwent tumor biopsy, and intraoperative pathological diagnosis (IOD) suspected the diagnosis of medulla oblongata germinoma. He underwent chemoradiotherapy after confirming the diagnosis of germinoma. Intracranial germinoma arising in the medulla oblongata differs from germinomas in other locations due to its higher incidence in individuals in their 20s and a slight female predominance. Conclusion: When encountering lesions in the medulla oblongata, germinoma should be considered as one of the differential diagnoses, and surgical strategies including IOD should be planned accordingly.

The Influence of Aneurysm Size on the Outcomes of Endovascular Management for Aneurysmal Subarachnoid Hemorrhages: A Comparison of the Treatment Results of Patients with Large and Small Aneurysms.

The influence of aneurysm size on the outcomes of endovascular management (EM) for aneurysmal subarachnoid hemorrhages (aSAH) is poorly understood. To evaluate the outcomes of EM for ruptured large cerebral aneurysms, we retrospectively analyzed the medical records of patients with aSAH that were treated with coiling between 2013 and 2020 and compared the differences in outcomes depending on aneurysm size. A total of 469 patients with aSAH were included; 73 patients had aneurysms measuring ≥10 mm in diameter (group L), and 396 had aneurysms measuring <10 mm in diameter (group S). The median age; the percentage of patients that were classified as World Federation of Neurological Surgeons grade 1, 2, or 3; and the frequency of intracerebral hemorrhages differed significantly between group L and group S (p = 0.0105, p = 0.0075, and p = 0.0458, respectively). There were no significant differences in the frequencies of periprocedural hemorrhagic or ischemic events. Conversely, rebleeding after the initial treatment was significantly more common in group L than in group S (6.8% vs. 2.0%; p = 0.0372). The frequency of a modified Rankin Scale score of 0-2 at discharge was significantly lower (p = 0.0012) and the mortality rate was significantly higher (p = 0.0023) in group L than in group S. After propensity-score matching, there were no significant differences in complications and outcomes between the two groups. Rebleeding was more common in large aneurysm cases. However, propensity-score matching indicated that the outcomes of EM for aSAH may not be affected markedly by aneurysm size.

Difficulty of diagnosing a mucor-induced aneurysm arising in segment P4 of the posterior cerebral artery - A case report.

Background: Identification of causative pathogen for fungal aneurysm is frequently difficult. We reported the case of a fungal aneurysm caused by Mucor arising in segment P4 of the posterior cerebral artery (PCA) detected only by histopathological examination. Case Description: A 50-year-old female complained of nausea and vomiting. Computed tomography showed an intracranial hemorrhage in the left occipital lobe and acute hydrocephalus due to intraventricular hemorrhaging. Digital subtraction angiography performed after external drainage showed a cerebral aneurysm in segment P4 of the left PCA. Surgical excision of the aneurysm and end-to-end anastomosis of the PCA were performed. A histopathological examination revealed that the aneurysm had been caused by a Mucor infection. Conclusion: In fungal aneurysm cases, especially those involving Mucor infections, it is difficult to identify the causative fungal infection based on cultures, imaging, and serological tests. Therefore, surgical excision and histopathological diagnosis are important for diagnosing such cases if possible.

Coiling for Ruptured Aneurysms in the Vasospasm Period: Safety and Efficacy Based on a Propensity Score Analysis.

Objective: To evaluate the efficacy and safety of interventional radiology (IVR) for aneurysmal subarachnoid hemorrhage (SAH) later than 3 days after onset. Methods: A total of 71 patients between 2012 and 2017 who underwent endovascular coiling were divided into two groups according to the timing of treatment: Group E (treated within 3 days after onset) and group D (treated between 4 and 14 days after onset), and the outcomes between two groups were compared. A case-matched study was conducted to minimize the selection bias lying in this cohort. Results: There were 56 (78.9%) and 15 (21.1%) patients in groups E and D, respectively. In group D, all patients arrived at the hospital later than 3 days after onset. The rates of patients with WFNS grade 1, 2, 3 and the presence of vasospasm upon the access route to the targeted aneurysm at the time of IVR were significantly higher in group D than in group E (93.3% vs 60.7%; p = 0.027, 33.3% vs 3.6%; p = 0.0037, respectively). There were no significant differences in the rate of intraprocedural complications, symptomatic vasospasm, delayed cerebral infarction due to vasospasm, retreatment, or modified Rankin Scale (mRS) at discharge. After propensity score matching, there were no significant differences in the outcomes between two groups. Conclusion: Prompt coiling for patients with ruptured aneurysms who arrived later than 3 days after onset can be safely performed, even if they had vasospasm upon the access route.

The effects of antithrombotic therapy on head trauma and its management.

The number of patients with traumatic intracranial hemorrhage (tICH) that are taking antithrombotics (ATs), antiplatelets (APs) and/or anticoagulants (ACs), has increased, but the influence of it for outcome remains unclear. This study aimed to evaluate an influence of AT for tICH. We retrospectively reviewed all patients with tICH treated between 2012 and 2019, and analyzed demographics, neurological status, clinical course, radiological findings, and outcome data. A total of 393 patients with tICH were included; 117 were on AT therapy (group A) and 276 were not (group B). Fifty-one (43.6%) and 159 (57.6%) patients in groups A and B, respectively, exhibited mRS of 0-2 at discharge (p = 0.0113). Mortality at 30 days was significantly higher in group A than in group B (25.6% vs 16.3%, p = 0.0356). Multivariate analysis revealed that higher age (OR 32.7, p < 0.0001), female gender (OR 0.56, p = 0.0285), pre-injury vitamin K antagonist (VKA; OR 0.42, p = 0.0297), and hematoma enlargement (OR 0.27, p < 0.0001) were associated with unfavorable outcome. AP and direct oral anticoagulant were not. Hematoma enlargement was significantly higher in AC-users than in non-users. Pre-injury VKA was at high risk of poor prognosis for patients with tICH. To improve outcomes, the management of VKA seems to be important.

Hyperperfusion Syndrome Detected by 15O-Gas Positron Emission Tomography after Clipping of a Large Unruptured Internal Carotid Artery Aneurysm: A Case Report.

Cerebral hyperperfusion syndrome (CHS) after surgical clipping for cerebral aneurysm is a rare entity. The authors present a 76-year-old woman with a large left internal carotid-posterior communicating artery aneurysm. After successful clipping with temporary occlusion of the internal carotid artery, the patient exhibited motor aphasia. 15O-gas positron emission tomography (PET) showed extreme elevation of the regional cerebral blood flow (rCBF) along with a mildly decreased regional cerebral metabolic rate for oxygen (rCMRO2) and a remarkable decrease in the oxygen extraction fraction (OEF) in the territory of the ipsilateral superior trunk of the middle cerebral artery. These data indicated local hyperperfusion. She had fully recovered from the aphasia by postoperative day (POD) 18. PET showed normalization of CBF on POD 27. To our knowledge, this is the first case report to show hyperperfusion syndrome, clearly detected by 15O-gas PET, after aneurysmal neck clipping.

Applicability and limitations of a recently-proposed prognostic grading metric, initial brain metastasis velocity, for brain metastasis patients undergoing stereotactic radiosurgery.

PURPOSE: This study, based on our brain metastasis (BM) patients undergoing stereotactic radiosurgery (SRS) procedures, aimed to validate whether the recently-proposed prognostic grading system, initial brain metastasis velocity (iBMV, scoring the cumulative number of BMs at the time of SRS divided by time [years] since the initial primary cancer diagnosis), is generally applicable. METHODS: This was an institutional review board-approved, retrospective cohort study using our prospectively accumulated database including 3498 patients who underwent SRS for BMs during the 19.5-year-period between July, 1998 and December, 2017. We excluded four lost to follow-up, 24 for whom the day of primary cancer diagnosis was not available, 665 with synchronous presentation and 651 with pre-SRS radiotherapy and/or surgery, ultimately studying 2150 patients. Patients were categorized into two classes by iBMV scores, i.e., < 2.00 and ≥ 2.00. RESULTS: In a multivariable model, iBMV was directly associated with a higher risk of death (p < 0.0001). The median survival time of patients with iBMV scores < 2.00, 10.0 (95% CI; 9.2-10.9) months, was longer than that of patients with iBMV scores ≥ 2.00, 6.3 (5.6-6.7) months, showing a significant difference between the two groups (HR 1.599, 95% CI 1.458-1.753, p < 0.0001). The same results were obtained in patients with non-small cell lung, breast, kidney or other cancers. Among 608 patients who underwent repeat SRS for newly-developed BMs, iBMV score categories correlated well with brain metastasis velocity risk groups (p < 0.0001). CONCLUSIONS: Our present results support the validity of iBMV for predicting survival after SRS.

Long-term follow-up results of stereotactic radiosurgery for vestibular schwannomas larger than 8 cc.

BACKGROUND: Accumulated stereotactic radiosurgery (SRS) experience for large vestibular schwannomas (VSs) based on over 5 years of follow-up are as yet insufficient, and chronological volume changes have not been documented. METHOD: Among 402 patients treated between 1990 and 2015, tumor volumes exceeded 8 cc in 30 patients. We studied 19 patients with follow-up for more than 36 post-SRS months or until an event. Median tumor volume was 11.5 cc (range; 8.0 to 30.6). The target volume was basically covered with 12.0 Gy. RESULTS: The median magnetic resonance imaging and clinical follow-up periods were both 98 months (range 49 to 204). Tumor shrinkage was documented in 13 patients (72%), no change in 2 (11%), and growth in the other 3 (17%). Therefore, the crude growth control rate was 83%. All three patients with tumor enlargement needed salvage treatment. Thus, the crude clinical control rate was 84%. Actuarial further procedure-free rates were 91%, 83% and 76%, at the 60th, 120th, and 180th post-SRS month. Among six patients followed chronologically, transient tumor expansion was observed in three (43%) and two cystic VSs showed rapid tumor growth. Transient trigeminal neuropathy occurred in two patients (11%). No patients experienced facial nerve palsy. None of the six patients with useful hearing pre-SRS maintained serviceable hearing. Ventricular-peritoneal shunt placement was required in three patients. CONCLUSIONS: Long-term tumor control with SRS was moderately acceptable in large VSs. In terms of functional outcome, trigeminal neuropathies and facial palsies were rare. However, hearing preservation remains a challenge. In the long term, chronological tumor volumes were generally decreased after SRS. However, caution is required regarding rapid increases in tumor size, especially for cystic type VSs. Further studies are needed to optimize clinical positioning of SRS for large VSs.

Spontaneous Persistent Primitive Trigeminal Artery-Cavernous Sinus Fistula Successfully Treated by Multipronged Coil Embolization: Case Report and Literature Review.

BACKGROUND: A spontaneous persistent primitive trigeminal artery-cavernous sinus fistula (PCF) is extremely rare. Until recently, endovascular treatment for PCF involving transarterial and/or transvenous coil embolization of the cavernous sinus (with/without the persistent trigeminal artery) was commonly performed. However, it may result in remaining shunt flow or exacerbation of cranial nerve palsy. CASE DESCRIPTION: A 51-year-old woman presented with headache and left abducens palsy. Digital subtraction angiography demonstrated a direct fistula between the cavernous segment of the persistent primitive trigeminal artery (PPTA) and posterosuperior compartment of the left cavernous sinus (CS). Three microcatheters were guided into the fistula as follows: 1) through the PPTA to the CS from the left internal carotid artery, 2) through the PPTA to the CS from the basilar artery, and 3) through the CS to the PPTA from the internal jugular vein. Using the double-catheter technique in a multidirectional fashion, shunt occlusion was achieved with a small number of coils. No signs of recurrence were observed during the follow-up period. CONCLUSIONS: The multipronged approach is safe and effective for embolization of a small tortuous artery and shunt segment to avoid incomplete shunt occlusion.

Signal intensity increases in dentate nucleus/globus pallidus/pulvinar on unenhanced T1WI MR images after multiple examinations with gadodiamide.

BACKGROUND AND PURPOSE: Elevated signal intensity (SI) in the dentate nucleus (DN), globus pallidus (GP) and pulvinar (PUL) was reportedly observed on unenhanced T1-weighted (T1WI) magnetic resonance (MR) images in patients receiving multiple enhanced MR examinations. We aimed to clarify whether this phenomenon influences the long-term neurological status of patients. MATERIALS AND METHODS: We studied 196 radiosurgically treated patients undergoing ≥10 MR examinations using a single dose of gadodiamide and the same 1.5 Tesla MR unit. SI ratios were calculated by referencing the brainstem (BS) for the DN and the thalamus (TH) for the GP and PUL. We compared the SI ratios at the first, fifth, and 10th, and at the most recent examinations. The neurological symptoms of all 196 patients were assessed at each MR examination by one of the authors (MY). RESULTS: The DN/BS and GP/TH SI ratios were significantly increased at the fifth examination ( p < .0001, p = 0.0094) and, thereafter, gradually increased. Although the PUL/TH SI ratio was not significantly increased at the fifth examination ( p = 0.2515), a significant increase was noted at the 10th examination ( p < .0001). There were no significant predictive factors for DN/BS SI increases. Younger age, no brain metastasis, and normal estimated glomerular filtration rate were related to GP/TH SI ratio increases ( p = 0.0308, p = 0.0001, p = 0.0306). Higher age and total bilirubin level were related to an increased PUL/TH SI ratio ( p = 0.0276, p = 0.0097). No patients experienced gadodiamide-related health problems. CONCLUSIONS: Although the SI ratios rose as numbers of gadodiamide administrations increased, no adverse health effects have developed to date.

Validity of a Recently Proposed Prognostic Grading Index, Brain Metastasis Velocity, for Patients With Brain Metastasis Undergoing Multiple Radiosurgical Procedures.

PURPOSE: This study of our patients with brain metastasis who underwent multiple stereotactic radiosurgery (SRS) procedures aimed to validate whether the recently proposed prognostic grading system, brain metastasis velocity (BMV), is generally applicable. The BMV scores the cumulative number of new brain metastases that developed after the first SRS divided by time (years) since the initial SRS. Patients were categorized into 3 classes by their BMV scores (ie, ≤3, 4-13, and ≥14). METHODS AND MATERIALS: This retrospective cohort study was approved by the Tokyo Women's Medical University Institutional Review Board (number 1981). We used our prospectively accumulated database, which included 833 patients who underwent a second SRS procedure for newly detected lesions, using a gamma knife, for brain metastases. Patients who had whole-brain radiation therapy were excluded. The procedures took place during the 19-year period between July 1998 and June 2017. Furthermore, among the 833 patients, 250 underwent a third SRS procedure, and 88 had a fourth SRS procedure. RESULTS: The median survival times (MSTs) after the second SRS were 12.9 months (95% confidence interval [CI], 10.2-17.1) for the BMV group with a score of ≤3; 7.5 months (CI, 6.5-9.0) for the group scoring 4 to 13, and 5.1 months (CI, 4.0-5.6) for the group scoring ≥14 (P = .0001). The corresponding MSTs after the third SRS were 13.2 months (95% CI, 9.1-21.6), 8.0 months (CI, 6.2-11.2), and 5.7 months (CI, 4.8-7.8; P = .0001). Respective MSTs after the fourth SRS were 13.2 months (95% CI, 9.1-21.6), 8.0 months (CI, 6.2-11.2), and 5.7 months (CI, 4.8-7.8; P < .0001). The mean BMV score of patients with small cell lung cancer, 24.8, was significantly higher than that of patients with non-small cell lung cancer, 17.7 (P = .032). CONCLUSIONS: Our present results support the validity of BMV for predicting survival not only after the second SRS but also after the third and fourth SRS.

Postsurgical Salvage Radiosurgery for Nonfunctioning Pituitary Adenomas Touching/Compressing the Optic Chiasm: Median 13-Year Postirradiation Imaging Follow-up Results.

BACKGROUND: There is little information on long-term outcomes after salvage treatment by either surgery or stereotactic radiosurgery (SRS) for patients with recurrent/residual nonfunctioning pituitary adenomas (NFPAs). OBJECTIVE: To reappraise the efficacy and safety of SRS for patients with NFPAs touching/compressing the optic apparatus (OA). METHODS: We studied 27 patients (14 females, 13 males; mean age: 61 [range, 19-85] yr) who underwent SRS between 1998 and 2008 for NFPAs with such condition. The median tumor volume was 4.9 (range, 1.8-50.8) cc. To avoid excess irradiation to the OA, the lower part of the tumor was covered with a 50% or a 60% isodose gradient, ie 49% to 98% (mean, 84%; median, 88%) of the entire tumor received the selected doses. Median doses at the tumor periphery/OA were 7.6/11.0 (interquartile range [IQR], 5.8-9.1/10.1-11.8) Gy. RESULTS: Seven patients (26%) were confirmed to be deceased due to unrelated diseases at a median post-SRS period of 149 (IQR, 83-158) mo. Follow-up magnetic resonance imaging (MRI) showed tumor growth in 2 patients (7%) at the 11th and 134th post-SRS month; the former underwent surgery and the other SRS. Excluding these 2 patients, the latest follow-up MRI examinations, performed 13 to 238 (median: 168, IQR: 120-180) mo after SRS, showed no size changes in 5 (19%) and shrinkage in 20 (74%) patients. Cumulative incidences of tumor growth control were 96.3% and 91.8% at the 120th and 180th post-SRS month. None of our patients developed subjective symptoms suggesting SRS-induced optic neuropathy or endocrinological impairment. CONCLUSION: In patients with NFPAs touching/compressing the OA, SRS achieves good long-term results.

Three-stage Gamma Knife treatment for metastatic brain tumors larger than 10 cm3: a 2-institute study including re-analyses of earlier results using competing risk analysis.

OBJECTIVEThe results of 3-stage Gamma Knife treatment (3-st-GK-Tx) for relatively large brain metastases have previously been reported for a series of patients in Chiba, Japan (referred to in this study as the C-series). In the current study, the authors reappraised, using a competing risk analysis, the efficacy and safety of 3-st-GK-Tx by comparing their experience with that of the C-series.METHODSThis was a retrospective cohort study. Among 1767 patients undergoing GK radiosurgery for brain metastases at Mito Gamma House during the 2005-2015 period, 78 (34 female, 44 male; mean age 65 years, range 35-86 years) whose largest tumor was > 10 cm3, treated with 3-st-GK-Tx, were studied (referred to in this study as the M-series). The target volumes were covered with a 50% isodose gradient and irradiated with a peripheral dose of 10 Gy at each procedure. The interval between procedures was 2 weeks. Because competing risk analysis had not been employed in the published C-series, the authors reanalyzed the previously published data using this method.RESULTSThe overall median survival time after 3-st-GK-Tx was 8.3 months (95% CI 5.6-12.0 months) in the M-series and 8.6 months (95% CI 5.5-10.6 months) in the C-series (p = 0.41). Actuarial survival rates at the 6th and 12th post-3-st-GK-Tx months were, respectively, 55.1% and 35.2% in the M-series and 62.5% and 26.4% in the C-series (HR 1.175, 95% CI 0.790-1.728, p = 0.42). Cumulative incidences at the 12th post-3-st-GK-Tx, determined by competing risk analyses, of neurological deterioration (14.2% in C-series vs 12.8% in M-series), neurological death (7.2% vs 7.7%), local recurrence (4.8% vs 6.2%), repeat SRS (25.9% vs 18.0%), and SRS-related complications (2.3% vs 5.1%) did not differ significantly between the 2 series.CONCLUSIONSThere were no significant differences in post-3-st-GK-Tx results between the 2 series in terms of overall survival times, neurological death, maintained neurological status, local control, repeat SRS, and SRS-related complications. The previously published results (C-series) are considered to be validated by the M-series results.

Prognostic grading system specifically for elderly patients with brain metastases after stereotactic radiosurgery: a 2-institution study.

OBJECTIVEWith the aging of the population, increasing numbers of elderly patients with brain metastasis (BM) are undergoing stereotactic radiosurgery (SRS). Among recently reported prognostic grading indexes, only the basic score for brain metastases (BSBM) is applicable to patients 65 years or older. However, the major weakness of this system is that no BM-related factors are graded. This prompted the authors to develop a new grading system, the elderly-specific (ES)-BSBM.METHODSFor this IRB-approved, retrospective cohort study, the authors used their prospectively accumulated database comprising 3267 consecutive patients undergoing Gamma Knife SRS for BMs during the 1998-2016 period at the Mito GammaHouse. Among these 3267 patients, 1789 patients ≥ 65 years of age were studied (Yamamoto series [Y-series]). Another series of 1785 patients ≥ 65 years of age in whom Serizawa and colleagues performed Gamma Knife SRS during the same period (Serizawa series [S-series]) was used for validity testing of the ES-BSBM.RESULTSTwo factors were identified as strongly impacting longer survival after SRS by means of multivariable analysis using the Cox proportional hazard model with a stepwise selection procedure. These factors are the number of tumors (solitary vs multiple: HR 1.450, 95% CI 1.299-1.621; p < 0.0001) and cumulative tumor volume (≤ 15 cm3 vs > 15 cm3: HR 1.311, 95% CI 1.078-1.593; p = 0.0067). The new index is the addition of scores 0 and 1 for these 2 factors to the BSBM. The ES-BSBM system is based on categorization into 3 classes by adding these 2 scores to those of the original BSBM. Each ES-BSBM category has 2 possible scores. For the category ES-BSBM 4-5, the score is either 4 or 5; for ES-BSBM 2-3, the score is either 2 or 3; and for ES-BSBM 0-1, the score is either 0 or 1. In the Y-series, the median survival times (MSTs, months) after SRS were 17.5 (95% CI 15.4-19.3) in ES-BSBM 4-5, 6.9 (95% CI 6.4-7.4) in ES-BSBM 2-3, and 2.8 (95% CI 2.5-3.6) in ES-BSBM 0-1 (p < 0.0001). Also, in the S-series, MSTs were, respectively, 20.4 (95% CI 17.2-23.4), 7.9 (95% CI 7.4-8.5), and 3.2 (95% CI 2.8-3.6) (p < 0.0001). The ES-BSBM system was shown to be applicable to patients with all primary tumor types as well as to those 80 years or older.CONCLUSIONSThe authors found that the addition of the number of tumors and cumulative tumor volume as scoring factors to the BSBM system significantly improved the prognostic value of this index. The present study is strengthened by testing the ES-BSBM in a different patient group.

Clinical significance of conformity index and gradient index in patients undergoing stereotactic radiosurgery for a single metastatic tumor.

OBJECTIVEAlthough the conformity index (CI) and the gradient index (GI), which were proposed by Paddick and colleagues, are both logically considered to correlate with good posttreatment results after stereotactic radiosurgery (SRS), this hypothesis has not been confirmed clinically. The authors' aim was to reappraise whether high CI values correlate with reduced tumor progression rates, and whether low GI values correlate with reduced complication incidences.METHODSThis was an institutional review board-approved, retrospective cohort study conducted using a prospectively accumulated database including 3271 patients who underwent Gamma Knife SRS for brain metastases (BMs) during the 1998-2016 period. Among the 3271 patients, 925 with a single BM at the time of SRS (335 women and 590 men, mean age 66 [range 24-93] years) were studied. The mean/median CIs were 0.62/0.66 (interquartile range [IQR] 0.53-0.74, range 0.08-0.88) and the mean/median GIs were 3.20/3.09 (IQR 2.83-3.39, range 2.27-11.4).RESULTSSRS-related complications occurred in 38 patients (4.1%), with a median post-SRS interval of 11.5 (IQR 6.0-25.8, maximum 118.0) months. Cumulative incidences of post-SRS complications determined by a competing risk analysis were 2.2%, 3.2%, 3.6%, 3.8%, and 3.9% at the 12th, 24th, 36th, 48th, and 60th post-SRS month, respectively. Multivariable analyses showed that only two clinical factors (i.e., peripheral doses and brain volume receiving ≥ 12 Gy) correlated with complication rates. However, neither CIs nor GIs impacted the incidences of complications. Among the 925 patients, post-SRS MRI was performed at least once in 716 of them, who were thus eligible for local progression evaluation. Among these 716 patients, local progression was confirmed in 96 (13.4%), with a median post-SRS interval of 10.8 (IQR 6.7-19.5, maximum 59.8) months. Cumulative incidences of local progression determined by a competing risk analysis were 7.7%, 12.6%, 14.2%, 14.8%, and 15.3% at the 12th, 24th, 36th, 48th, and 60th post-SRS month, respectively. Multivariable analyses showed neurological symptoms, extracerebral metastases, repeat SRS, and CIs to correlate with incidences of local progression, whereas GIs had no impact on local tumor progression. Particularly, cumulative incidences of local progression were significantly lower in patients with CIs < 0.65 than in those with CIs ≥ 0.65 (adjusted hazard ratio 1.870, 95% confidence interval 1.299-2.843; p = 0.0034).CONCLUSIONSTo the authors' knowledge, this is the first analysis to focus on the clinical significance of CI and GI based on a large series of patients with BM. Contrary to the majority opinion that dose planning with higher CI and lower GI results in good post-SRS outcomes (i.e., low local progression rates and minimal complications), this study clearly showed that the lower the CIs were, the lower the local progression rates were, and that the GI did not impact complication rates.

Complications after stereotactic radiosurgery for brain metastases: Incidences, correlating factors, treatments and outcomes.

BACKGROUND AND PURPOSE: Complications after stereotactic radiosurgery (SRS) for brain metastases (BMs) were analyzed in detail using our database including nearly 3000 BM patients. MATERIALS AND METHODS: This was an institutional review board-approved, retrospective cohort study using our prospectively accumulated database including 3271 consecutive patients who underwent gamma knife SRS for BMs during the 1998-2016 period. Excluding four patients lost to follow-up, 112 with three-staged treatment and 189 with post-operative irradiation, 2966 who underwent a single-session of SRS only as radical irradiation were studied. RESULTS: The overall median survival time after SRS was 7.8 (95% CI; 7.4-8.1) months. Post-SRS complications occurred in 86 patients (2.9%) 1.9-211.4 (median; 24.0, IQR; 12.0-64.6) months after treatment. RTOG neurotoxicity grades were 2, 3 and 4 in 58, 25 and 3 patients, respectively. Cumulative incidences determined with a competing risk analysis were 1.4%, 2.2%, 2.4%, 2.6% and 2.9% at the 12th, 24th, 36th, 48th and 60th post-SRS month, respectively. Among various pre-SRS clinical factors and radiosurgical parameters, multivariable analyses demonstrated solitary tumor (Adjusted HR; 0.584, 95% CI; 0.381-0.894, p = 0.0133), controlled primary cancer (Adjusted HR; 2.595, 95% CI; 1.646-4.091, p < 0.0001), no extra-cerebral metastases (Adjusted HR; 1.608, 95% CI; 1.028-2.514, p = 0.0374), KPS ≥80% (Adjusted HR; 2.715, 95% CI; 1.245-5.924, p = 0.0121) and largest tumor volume ≥3.3 cc (Adjusted HR; 0.516, 95% CI; 0.318-0.836, p = 0.0072) to be independently significant predictors of a higher incidence of complications. CONCLUSION: The post-SRS complication incidence is acceptably low (2.9%). Meticulous long-term follow-up after SRS is crucial for all patients.

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.

Superior Prognostic Value of Cumulative Intracranial Tumor Volume Relative to Largest Intracranial Tumor Volume for Stereotactic Radiosurgery-Treated Brain Metastasis Patients.

BACKGROUND: Two intracranial tumor volume variables have been shown to prognosticate survival of stereotactic-radiosurgery-treated brain metastasis patients: the largest intracranial tumor volume (LITV) and the cumulative intracranial tumor volume (CITV). OBJECTIVE: To determine whether the prognostic value of the Scored Index for Radiosurgery (SIR) model can be improved by replacing one of its components-LITV-with CITV. METHODS: We compared LITV and CITV in terms of their survival prognostication using a series of multivariable models that included known components of the SIR: age, Karnofsky Performance Score, status of extracranial disease, and the number of brain metastases. Models were compared using established statistical measures, including the net reclassification improvement (NRI > 0) and integrated discrimination improvement (IDI). The analysis was performed in 2 independent cohorts, each consisting of ∼3000 patients. RESULTS: In both cohorts, CITV was shown to be independently predictive of patient survival. Replacement of LITV with CITV in the SIR model improved the model's ability to predict 1-yr survival. In the first cohort, the CITV model showed an NRI > 0 improvement of 0.2574 (95% confidence interval [CI] 0.1890-0.3257) and IDI of 0.0088 (95% CI 0.0057-0.0119) relative to the LITV model. In the second cohort, the CITV model showed a NRI > 0 of 0.2604 (95% CI 0.1796-0.3411) and IDI of 0.0051 (95% CI 0.0029-0.0073) relative to the LITV model. CONCLUSION: After accounting for covariates within the SIR model, CITV offers superior prognostic value relative to LITV for stereotactic radiosurgery-treated brain metastasis patients.

Follow-up results of brain metastasis patients undergoing repeat Gamma Knife radiosurgery.

OBJECTIVE Stereotactic radiosurgery (SRS) without upfront whole-brain radiotherapy (WBRT) has influenced recent treatment recommendations for brain metastasis patients. However, in brain metastasis patients who undergo SRS alone, new brain metastases inevitably appear with relatively high incidences during post-SRS follow-up. However, little is known about the second SRS results. The treatment results of second SRS were retrospectively reviewed, mainly for newly developed or, uncommonly, for recurrent brain metastases in order to reappraise the efficacy of this treatment strategy with a special focus on the maintenance of neurological status and safety. METHODS This was an institutional review board-approved, retrospective cohort study that used a prospectively accumulated database, including 3102 consecutive patients with brain metastases who underwent SRS between July 1998 and June 2015. Among these 3102 patients, 859 (376 female patients; median age 64 years; range 21-88 years) who underwent a second SRS without WBRT were studied with a focus on overall survival, neurological death, neurological deterioration, local recurrence, salvage SRS, and SRS-induced complications after the second SRS. Before the second SRS, the authors also investigated the clinical factors and radiosurgical parameters likely to influence these clinical outcomes. For the statistical analysis, the standard Kaplan-Meier method was used to determine post-second SRS survival and neurological death. A competing risk analysis was applied to estimate post-second SRS cumulative incidences of local recurrence, neurological deterioration, salvage SRS, and SRS-induced complications. RESULTS The post-second SRS median survival time was 7.4 months (95% CI 7.0-8.2 months). The actuarial survival rates were 58.2% and 34.7% at 6 and 12 months after the second SRS, respectively. Among 789 deceased patients, the causes of death could not be determined in 24 patients, but were confirmed in the remaining 765 patients to be nonbrain diseases in 654 (85.5%) patients and brain diseases in 111 (14.5%) patients. The actuarial neurological death-free survival rates were 94.4% and 86.6% at 6 and 12 months following the second SRS. Multivariable analysis revealed female sex, Karnofsky Performance Scale score of 80% or greater, better modified recursive partitioning analysis class, smaller tumor numbers, and higher peripheral dose to be significant predictive factors for longer survival. The cumulative incidences of local recurrence were 11.2% and 14.9% at 12 and 24 months after the second SRS. The crude incidence of neurological deterioration was 7.1%, and the respective cumulative incidences were 4.5%, 5.8%, 6.7%, 7.2%, and 7.5% at 12, 24, 36, 48, and 60 months after the second SRS. SRS-induced complications occurred in 25 patients (2.9%) after a median post-second SRS period of 16.8 months (range 0.6-95.0 months; interquartile range 5.6-29.3 months). The cumulative incidences of complications were 1.4%, 2.0%, 2.4%, 3.0%, and 3.0% at 12, 24, 36, 48, and 60 months after the second SRS, respectively. CONCLUSIONS Carefully selected patients with recurrent tumors-either new or locally recurrent-are favorable candidates for a second SRS, particularly in terms of neurological status maintenance and the safety of this treatment strategy.