Publications by authors named "Hitoshi Aiyama"

22 Publications

  • Page 1 of 1

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

Breast Cancer Res Treat 2020 Nov 1;184(1):149-159. Epub 2020 Aug 1.

Department of Neurological Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.

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.
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http://dx.doi.org/10.1007/s10549-020-05835-8DOI Listing
November 2020

Evaluation of First-line Radiosurgery vs Whole-Brain Radiotherapy for Small Cell Lung Cancer Brain Metastases: The FIRE-SCLC Cohort Study.

JAMA Oncol 2020 07;6(7):1028-1037

Department of Neurosurgery, New York University Langone Medical Center, New York.

Importance: Although stereotactic radiosurgery (SRS) is preferred for limited brain metastases from most histologies, whole-brain radiotherapy (WBRT) has remained the standard of care for patients with small cell lung cancer. Data on SRS are limited.

Objective: To characterize and compare first-line SRS outcomes (without prior WBRT or prophylactic cranial irradiation) with those of first-line WBRT.

Design, Setting, And Participants: FIRE-SCLC (First-line Radiosurgery for Small-Cell Lung Cancer) was a multicenter cohort study that analyzed SRS outcomes from 28 centers and a single-arm trial and compared these data with outcomes from a first-line WBRT cohort. Data were collected from October 26, 2017, to August 15, 2019, and analyzed from August 16, 2019, to November 6, 2019.

Interventions: SRS and WBRT for small cell lung cancer brain metastases.

Main Outcomes And Measures: Overall survival, time to central nervous system progression (TTCP), and central nervous system (CNS) progression-free survival (PFS) after SRS were evaluated and compared with WBRT outcomes, with adjustment for performance status, number of brain metastases, synchronicity, age, sex, and treatment year in multivariable and propensity score-matched analyses.

Results: In total, 710 patients (median [interquartile range] age, 68.5 [62-74] years; 531 men [74.8%]) who received SRS between 1994 and 2018 were analyzed. The median overall survival was 8.5 months, the median TTCP was 8.1 months, and the median CNS PFS was 5.0 months. When stratified by the number of brain metastases treated, the median overall survival was 11.0 months (95% CI, 8.9-13.4) for 1 lesion, 8.7 months (95% CI, 7.7-10.4) for 2 to 4 lesions, 8.0 months (95% CI, 6.4-9.6) for 5 to 10 lesions, and 5.5 months (95% CI, 4.3-7.6) for 11 or more lesions. Competing risk estimates were 7.0% (95% CI, 4.9%-9.2%) for local failures at 12 months and 41.6% (95% CI, 37.6%-45.7%) for distant CNS failures at 12 months. Leptomeningeal progression (46 of 425 patients [10.8%] with available data) and neurological mortality (80 of 647 patients [12.4%] with available data) were uncommon. On propensity score-matched analyses comparing SRS with WBRT, WBRT was associated with improved TTCP (hazard ratio, 0.38; 95% CI, 0.26-0.55; P < .001), without an improvement in overall survival (median, 6.5 months [95% CI, 5.5-8.0] for SRS vs 5.2 months [95% CI, 4.4-6.7] for WBRT; P = .003) or CNS PFS (median, 4.0 months for SRS vs 3.8 months for WBRT; P = .79). Multivariable analyses comparing SRS and WBRT, including subset analyses controlling for extracranial metastases and extracranial disease control status, demonstrated similar results.

Conclusions And Relevance: Results of this study suggest that the primary trade-offs associated with SRS without WBRT, including a shorter TTCP without a decrease in overall survival, are similar to those observed in settings in which SRS is already established.
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http://dx.doi.org/10.1001/jamaoncol.2020.1271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273318PMC
July 2020

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

J Neurooncol 2020 Mar 13;147(1):67-76. Epub 2020 Jan 13.

Department of Human Health Sciences, School of Medicine, Kyoto University, Kyoto, Japan.

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.
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http://dx.doi.org/10.1007/s11060-020-03397-9DOI Listing
March 2020

Treatment Outcomes of Burr-Hole Surgery for Chronic Subdural Hematoma in the Elderly Living Beyond Life Expectancy: A Study Comparing Cure, Recurrence, and Complications in Patients Aged ≥80 Years versus ≤79 Years.

World Neurosurg 2019 Dec 9;132:e812-e819. Epub 2019 Aug 9.

Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

Background: Few reports have focused on chronic subdural hematoma (CSDH) in the very elderly, who have lived beyond average life expectancy. Our aim is to appraise treatment outcomes of burr-hole craniotomy for CSDH in the elderly, focusing on cure, recurrence, and complications.

Methods: Fifty patients ≤79 years of age (group A) and 73 patients ≥80 years of age (group B) were studied. Recurrence was defined as requiring reoperation for hematoma regrowth or symptomatic failure. A cure was regarded as having been achieved in the absence of hematoma on postoperative computed tomography. Complications were defined as any harmful event related to the treatment procedure for CSDH.

Results: Cure was documented in 31 patients in group A (63%) and 24 patients in group B (33%) (P = 0.0017). Median intervals to cure were 2.76 and 3.73 months, respectively (P = 0.06). Cumulative cure rates were 51%/76% and 36%/59%, respectively, at the sixth/twelfth postoperative months. Recurrence was documented in 2 patients (4%) and 11 patients (15%), respectively (P = 0.07). Median intervals to recurrence were 0.81 and 1.25 months, respectively (P = 0.049). Cumulative recurrence-free rates were 96%/92% and 87%/75%, respectively, at the third/sixth postoperative months. Complications were observed in 2 patients (4%) and 4 patients (5%), respectively (P = 1.00).

Conclusions: With advancing age, CSDH might show a greater tendency to recur and a longer time is required to achieve a cure. However, complications developed only in high-risk patients. Thus, surgical treatment for CSDH in elderly patients, even those who have lived beyond life expectancy, might provide acceptably effective results.
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http://dx.doi.org/10.1016/j.wneu.2019.08.003DOI Listing
December 2019

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

J Neurooncol 2019 Jul 28;143(3):613-621. Epub 2019 May 28.

Katsuta Hospital Mito GammaHouse, 5125-2 Nakane, Hitachi-naka, Ibaraki, 312-0011, Japan.

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.
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http://dx.doi.org/10.1007/s11060-019-03199-8DOI Listing
July 2019

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

Acta Neurochir (Wien) 2019 07 24;161(7):1457-1465. Epub 2019 May 24.

Katsuta Hospital Mito GammaHouse, 5125-2 Nakane, Hitachi-naka, Ibaraki, 312-0011, Japan.

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.
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http://dx.doi.org/10.1007/s00701-019-03951-zDOI Listing
July 2019

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

J Neurosurg 2018 12;129(Suppl1):103-110

4Department of Neurosurgery, Tokyo Women's Medical University, Medical Center East, Tokyo.

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.
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http://dx.doi.org/10.3171/2018.6.GKS181314DOI Listing
December 2018

A novel method to determine the natural course of unruptured brain arteriovenous malformations without the need for follow-up information.

J Neurosurg 2018 12;129(Suppl1):10-16

1Division of Neurosurgery, Department of Surgery, National University Hospital, Singapore.

OBJECTIVEThere is a strong clinical need to accurately determine the average annual hemorrhage risk in unruptured brain arteriovenous malformations (AVMs). This need motivated the present initiative to use data from a uniquely large patient population and design a novel methodology to achieve a risk determination with unprecedented accuracy. The authors also aimed to determine the impact of sex, pregnancy, AVM volume, and location on the risk for AVM rupture.METHODSThe present study does not consider any specific management of the AVMs, but only uses the age distribution for the first hemorrhage, the shape of which becomes universal for a sufficiently large set of patients. For this purpose, the authors collected observations, including age at first hemorrhage and AVM size and location, in 3425 patients. The average annual risk for hemorrhage could then be determined from the simple relation that the number of patients with their first hemorrhage at a specific age equals the risk for hemorrhage times the number of patients at risk at that age. For a subset of the patients, the information regarding occurrence of AVM hemorrhage after treatment of the first hemorrhage was used for further analysis of the influence on risk from AVM location and pregnancy.RESULTSThe age distribution for the first AVM hemorrhage was used to determine the average annual risk for hemorrhage in unruptured AVMs at adult ages (25-60 years). It was concluded to be 3.1% ± 0.2% and unrelated to AVM volume but influenced by its location, with the highest risk for centrally located AVMs. The hemorrhage risk was found to be significantly higher for females in their fertile years.CONCLUSIONSThe present methodology allowed the authors to determine the average annual risk for the first AVM hemorrhage at 3.1% ± 0.2% without the need for individual patient follow-up. This methodology has potential also for other similar types of investigations. The conclusion that centrally located AVMs carry a higher risk was confirmed by follow-up information. Follow-up information was also used to conclude that pregnancy causes a substantially greater AVM hemorrhage risk. The age distribution for AVM hemorrhage is incompatible with AVMs present at birth having the same hemorrhage risk as AVMs in adults. Plausibly, they instead develop in the early years of life, possibly with a lower hemorrhage risk during that time period.
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http://dx.doi.org/10.3171/2018.7.GKS181278DOI Listing
December 2018

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

J Neurosurg 2018 12;129(Suppl1):95-102

2Department of Neurosurgery, Tokyo Women's Medical University Medical Center East, Tokyo.

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.
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http://dx.doi.org/10.3171/2018.7.GKS181458DOI Listing
December 2018

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.

J Neurosurg 2018 12;129(Suppl1):77-85

2Department of Neurosurgery, Tokyo Women's Medical University Medical Center East, Tokyo.

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.
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http://dx.doi.org/10.3171/2018.7.GKS181392DOI Listing
December 2018

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

Int J Radiat Oncol Biol Phys 2019 03 3;103(3):631-637. Epub 2018 Nov 3.

Katsuta Hospital Mito GammaHouse, Hitachi-naka, Japan.

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.
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http://dx.doi.org/10.1016/j.ijrobp.2018.10.036DOI Listing
March 2019

Prognostic Importance of Cumulative Intracranial Tumor Volume in Patients with Gastrointestinal Brain Metastasis Treated with Stereotactic Radiosurgery.

World Neurosurg 2019 Jan 9;121:e747-e754. Epub 2018 Oct 9.

Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, Minnesota, USA. Electronic address:

Background: The disease-specific Graded Prognostic Assessment (ds-GPA) for patients with gastrointestinal (GI) tract cancer brain metastases (BM) suggests Karnofsky Performance Status (KPS) as the only pertinent prognostic factor. We evaluated the prognostic importance of cumulative intracranial tumor volume (CITV).

Methods: KPS, CITV, and overall survival were collected from consecutive patients with stereotactic radiosurgery-treated GI BM. Patients were grouped into 2 independent cohorts for development and validation of the model (termed "exploratory" and "validation" cohorts). Analyses were performed using logistic regression, Cox proportional hazards models, Net Reclassification Index (NRI >0), integrated discrimination improvement (IDI >0), and Akaike information criterion.

Results: In univariable logistic regression models, both CITV and KPS were independently associated with patient survival. The association between CITV and overall survival remained robust after controlling for KPS (P < 0.001) in a multivariable Cox proportional hazards model. Based on NRI analysis of the exploratory cohort, we found that a CITV cutoff of 12 cm best augments the prognostic accuracy of GI-ds-GPA. In this analysis, incorporation of CITV (as < or ≥12 cm) improved prognostication of the GI-specific GPA model by NRI >0 of 0.397 (95% confidence interval [CI], 0.165-0.630; P < 0.001) and IDI of 0.019 (95% CI, 0.004-0.033; P = 0.013). We confirmed the prognostic usefulness of the CITV-incorporated GI-ds-GPA in an independent validation cohort, in which CITV incorporation improved prognostic usefulness with an NRI >0 of 0.478 (95% CI, 0.257-0.699; P < 0.001) and IDI of 0.028 (95% CI, 0.014-0.043; P < 0.001).

Conclusions: CITV is an important prognostic variable in patients with stereotactic radiosurgery-treated GI BM and augments the prognostic accuracy of the GI-ds-GPA index.
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http://dx.doi.org/10.1016/j.wneu.2018.09.209DOI Listing
January 2019

The NASSAU (New ASSessment of cerebral Arteriovenous Malformations yet Unruptured) Analysis: Are the Results From The ARUBA Trial Also Applicable to Unruptured Arteriovenous Malformations Deemed Suitable for Gamma Knife Surgery?

Neurosurgery 2019 07;85(1):E118-E124

Department of Surgery, Division of Neurosurgery, National University Hospital, Singapore, Singapore.

Background: The optimal management of unruptured brain arteriovenous malformations (AVMs) is controversial after the ARUBA trial.

Objective: To confirm or repudiate the ARUBA conclusion that "medical management only is superior to medical management with interventional therapy for unruptured brain arteriovenous malformations."

Methods: Data were collected from 1351 patients treated with Gamma Knife Surgery (GKS; Elekta AB, Stockholm, Sweden) for unruptured and untreated AVMs The follow-up was 8817 yr (median 5.0 and mean 6.5). The results of the analyses were compared to that found in patients randomized to medical management only in the ARUBA trial and extrapolated to a 10-yr time period. Our data were also compared to the natural course in a virtual AVM population for a 25-yr time period.

Results: The incidence of stroke was similar among ARUBA and our patients for the first 5 yr. Thereafter, the longer the follow-up, the relatively better outcome following treatment. Both the mortality rate and the incidence of permanent deficits in patients with small AVMs were the same as in untreated patients for the first 2 to 3 yr after GKS, after which GKS patients did better. Patients with large AVMs had a higher incidence of neurological deficits in the first 3 yr following GKS. The difference decreased thereafter, but the time until break even depended on the analysis method used and the assumed risk for hemorrhage in patent AVMs.

Conclusion: The ARUBA trial conclusion that medical management is superior to medical management with interventional therapy for all unruptured AVMs could be repudiated.
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http://dx.doi.org/10.1093/neuros/nyy391DOI Listing
July 2019

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

Radiother Oncol 2018 11 4;129(2):364-369. Epub 2018 Oct 4.

Katsuta Hospital Mito GammaHouse, Hitachi-naka, Japan.

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.
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http://dx.doi.org/10.1016/j.radonc.2018.08.018DOI Listing
November 2018

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

Neurosurgery 2019 10;85(4):476-485

Department of Neurosurgery, Tokyo Women's Medical University Medical Center East, Tokyo, Japan.

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.
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http://dx.doi.org/10.1093/neuros/nyy357DOI Listing
October 2019

Modern management for brain metastasis patients using stereotactic radiosurgery: literature review and the authors' gamma knife treatment experiences.

Cancer Manag Res 2018 5;10:1889-1899. Epub 2018 Jul 5.

Katsuta Hospital Mito Gamma House, Hitachi-Naka, Japan,

Historically, whole brain radiotherapy was administered to most patients with brain metastases. However, over the past three decades, stereotactic radiosurgery (SRS), targeted at individual cranial lesions, has been accepted widely. In this study, based on the authors' experiences along with published data, recent trends in SRS for brain metastases are discussed. This article focuses on the following issues: 1) How many tumors can or should be treated with SRS? 2) Two-/three-staged SRS for relatively large tumors, 3) post- or preoperative SRS, and 4) repeat SRS.
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http://dx.doi.org/10.2147/CMAR.S116718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038887PMC
July 2018

Improving the Prognostic Value of Disease-Specific Graded Prognostic Assessment Model for Renal Cell Carcinoma by Incorporation of Cumulative Intracranial Tumor Volume.

World Neurosurg 2017 Dec 25;108:151-156. Epub 2017 Jul 25.

Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota, USA. Electronic address:

Background: We tested the prognostic value of cumulative intracranial tumor volume (CITV) in the context of a disease-specific Graded Prognostic Assessment (ds-GPA) model for renal cell carcinoma (RCC) patients with brain metastasis (BM) treated with stereotactic radiosurgery (SRS).

Methods: Patient and tumor characteristics were collected from RCC cohorts with new BM who underwent SRS. Univariable and multivariable logistic regression model was used to test the prognostic value of CITV, Karnofsky Performance Score (KPS), and the number of BM. Net reclassification index (NRI) and integrated discrimination improvement (IDI) were used to assess whether CITV improved the prognostic utility of RCC ds-GPA.

Results: In univariable logistic regression models, CITV, KPS, and the number of BM were independently associated with RCC patient survival. In a multivariable Cox proportional hazard model, the association between CITV and survival remained robust after controlling for KPS and the number of BM (P = 0.042). The incorporation of the CITV into the RCC ds-GPA model (consisting of KPS and number of BM) improved prognostic accuracy with NRI >0 of 0.3156 (95% confidence interval [CI], 0.0883-0.5428; P = 0.0065) and IDI of 0.0151 (95% CI, 0.0036-0.0277; P = 0.0183). These findings were validated in an independent cohort of 107 SRS-treated RCC BM patients.

Conclusion: CITV is an important prognostic variable in SRS-treated RCC patients with BM. The prognostic value of the ds-GPA scale for RCC brain metastasis was enhanced by the incorporation of CITV.
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http://dx.doi.org/10.1016/j.wneu.2017.07.109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705321PMC
December 2017

Survival Patterns of 5750 Stereotactic Radiosurgery-Treated Patients with Brain Metastasis as a Function of the Number of Lesions.

World Neurosurg 2017 Nov 19;107:944-951.e1. Epub 2017 Jul 19.

Center for Translational and Applied Neuro-Oncology, Department of Neurosurgery, University of California, San Diego, La Jolla, California, USA; Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota, USA. Electronic address:

Background: The number of brain metastases (BMs) plays an important role in the decision between stereotactic radiosurgery (SRS) and whole-brain radiation therapy.

Methods: We analyzed the survival of 5750 SRS-treated patients with BM as a function of BM number. Survival analyses were performed with Kaplan-Meier analysis as well as univariate and multivariate Cox proportional hazards models.

Results: Patients with BMs were first categorized as those with 1, 2-4, and 5-10 BMs based on the scheme proposed by Yamamoto et al. (Lancet Oncology 2014). Median overall survival for patients with 1 BM was superior to those with 2-4 BMs (7.1 months vs. 6.4 months, P = 0.009), and survival of patients with 2-4 BMs did not differ from those with 5-10 BMs (6.4 months vs. 6.3 months, P = 0.170). The median survival of patients with >10 BMs was lower than those with 2-10 BMs (6.3 months vs. 5.5 months, P = 0.025). In a multivariate model that accounted for age, Karnofsky Performance Score, systemic disease status, tumor histology, and cumulative intracranial tumor volume, we observed a ∼10% increase in hazard of death when comparing patients with 1 versus 2-10 BMs (P < 0.001) or 10 versus >10 BMs (P < 0.001). When BM number was modeled as a continuous variable rather than using the classification by Yamamoto et al., we observed a step-wise 4% increase in the hazard of death for every increment of 6-7 BM (P < 0.001).

Conclusions: The contribution of BM number to overall survival is modest and should be considered as one of the many variables considered in the decision between SRS and whole-brain radiation therapy.
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http://dx.doi.org/10.1016/j.wneu.2017.07.062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5654648PMC
November 2017

Language areas involving the inferior temporal cortex on intraoperative mapping in a bilingual patient with glioblastoma.

Neurol Med Chir (Tokyo) 2013 ;53(4):256-8

Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.

A 40-year-old bilingual man underwent removal of glioblastoma multiforme with intraoperative language mapping, mainly using the picture-naming and auditory responsive-naming tasks under cortical stimulation. Multiple language areas were identified, including one located in the middle of the inferior temporal cortex (ITC). Individual mapping for glioma patients must be performed because language areas might be located in various and unexpected regions, including the ITC.
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http://dx.doi.org/10.2176/nmc.53.256DOI Listing
February 2014

Reinforcement of pericranium as a dural substitute by fibrin sealant.

Acta Neurochir (Wien) 2011 Nov 6;153(11):2251-4. Epub 2011 Jul 6.

Department of Neurosurgery, NTT Medical Center Tokyo, Shinagawa-ku, Japan.

Background: For dural plasty, several kinds of substitute materials are used clinically. Among these materials, pericranium is often used as a dural substitute since it is autologous and easy to harvest. However, it is rather thin and fragile, which makes it difficult to suture onto peripheral dura mater, especially when the defect is large.

Objective: We present a simple method of reinforcing the pericranium with fibrin sealant, which facilitates easier handling and suturing of the pericranium.

Methods: Fifteen patients who underwent surgical removal of meningioma, metastatic brain tumor and glioma attached to the dura mater were included in this analysis. To close the defects, we use 'fibrin-sealed pericranium'. Herein we describe the method we employed in these cases. First, a standard skin flap is made by dissecting the subgaleal layer, leaving the periosteum on the bone. Second, fibrin sealant is evenly applied to the pericranium. Finally, the pericranium is cut along the reinforced area and dissected from the bone. The harvested pericranium is then used for closure of the dural defect. Some of these patients received further treatment as needed according to each pathology. The fibrin-sealed pericranium was examined histopathologically.

Results: Fibrin-sealing of pericranium made it durable enough to be handled and sutured easily. There were no significant complications or treatment failures, such as infection or CSF leakage.

Conclusions: Reinforcement of the pericranium with fibrin sealant is a simple and easy method to reduce the stress of dural plasty.
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http://dx.doi.org/10.1007/s00701-011-1077-3DOI Listing
November 2011

Simulation of and training for cerebral aneurysm clipping with 3-dimensional models.

Neurosurgery 2009 Oct;65(4):719-25; discussion 725-6

Department of Neurosurgery, Kanto Medical Center, NTT EC, Tokyo, Japan.

Objective: With improvements in endovascular techniques, fewer aneurysms are treated by surgical clipping, and those aneurysms targeted for open surgery are often complex and difficult to treat. We devised a hollow, 3-dimensional (3D) model of individual cerebral aneurysms for preoperative simulation and surgical training. The methods and initial experience with this model system are presented.

Methods: The 3D hollow aneurysm models of 3 retrospective and 8 prospective cases were made with a prototyping technique according to data from 3D computed tomographic angiograms of each patient. Commercially available titanium clips used in our routine surgery were applied, and the internal lumen was observed with an endoscope to confirm the patency of parent vessels. The actual surgery was performed later.

Results: In the 8 prospective cases, the clips were applied during surgery in the same direction and configuration as in the preoperative simulation. Fine adjustments were necessary in each case, and 2 patients needed additional clips to occlude the atherosclerotic aneurysmal wall. With these 3D models, it was easy for neurosurgical trainees to grasp the vascular configuration and the concept of neck occlusion. Practicing surgery with these models also improved their handling of the instruments used during aneurysm surgery, such as clips and appliers.

Conclusion: Using the hollow 3D models to simulate clipping preoperatively, we could treat the aneurysms confidently during live surgery. These models allow easy and concrete recognition of the 3D configuration of aneurysms and parent vessels.
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http://dx.doi.org/10.1227/01.NEU.0000354350.88899.07DOI Listing
October 2009

[Case of enlargement of an intradiploic epidermoid cyst by a head contusion].

Brain Nerve 2009 Jun;61(6):707-10

Department o f Neurosurgery, National Hospital Organization Sendai Medical Center, 2-8-8 Miyagino-ku, Sendai 983-8520, Japan.

We report a case of enlargement of a intradiploic epidermoid cyst following head trauma in a 19-year-old man. The patient had a swelling on the right side of his forehead from the time of his birth. He sustained a bruise in this region when he was 15 years old, following which the swelling gradually enlarged. When the diameter of the mass increased to 5 cm, he visited our hospital. Computed tomography (CT) scan of the head showed a subcutaneous mass of low density extending from the diploe to the outer tables of the skull. Magnetic resonance imaging (MRI) showed a hyperintense mass in both T1- and T2-weighted images. During the operation, we found a tumor that was intradiploic and had a thin capsule. The effusion from the tumor resembled an old hematoma, and the tumor did not involve the paranasal sinuses. We concluded the operation by performing cranioplasty using artificial bone. Histological examination revealed that the thin capsule consisted of stratified squamous epithelium and ciliated epithelium. Needle-like cholesterol crystals and hemosiderosis were seen shown in the granulation-like tissue. On the basis of these findings, we diagnosed the mass to bean intradiploic epidermoid cyst and thought that it might have grown following head trauma associated with chronic hemorrhage. This paper reviews the differential diagnosis and pathologic findings of the intradiploic epidermoid cyst along with some previously published cases.
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June 2009