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Iwao Yamakami, Seiro Ito and Yoshinori Higuchi

Object

Management of small acoustic neuromas (ANs) consists of 3 options: observation with imaging follow-up, radiosurgery, and/or tumor removal. The authors report the long-term outcomes and preservation of function after retrosigmoid tumor removal in 44 patients and clarify the management paradigm for small ANs.

Methods

A total of 44 consecutively enrolled patients with small ANs and preserved hearing underwent retrosigmoid tumor removal in an attempt to preserve hearing and facial function by use of intraoperative auditory monitoring of auditory brainstem responses (ABRs) and cochlear nerve compound action potentials (CNAPs). All patients were younger than 70 years of age, had a small AN (purely intracanalicular/cerebellopontine angle tumor ≤ 15 mm), and had serviceable hearing preoperatively. According to the guidelines of the Committee on Hearing and Equilibrium of the American Academy of Otolaryngology–Head and Neck Surgery Foundation, preoperative hearing levels of the 44 patients were as follows: Class A, 19 patients; Class B, 17; and Class C, 8. The surgical technique for curative tumor removal with preservation of hearing and facial function included sharp dissection and debulking of the tumor, reconstruction of the internal auditory canal, and wide removal of internal auditory canal dura.

Results

For all patients, tumors were totally removed without incidence of facial palsy, death, or other complications. Total tumor removal was confirmed by the first postoperative Gd-enhanced MRI performed 12 months after surgery. Postoperative hearing levels were Class A, 5 patients; Class B, 21; Class C, 11; and Class D, 7. Postoperatively, serviceable (Class A, B, or C) and useful (Class A or B) levels of hearing were preserved for 84% and 72% of patients, respectively. Better preoperative hearing resulted in higher rates of postoperative hearing preservation (p = 0.01); preservation rates were 95% among patients with preoperative Class A hearing, 88% among Class B, and 50% among Class C. Reliable monitoring was more frequently provided by CNAPs than by ABRs (66% vs 32%, p < 0.01), and consistently reliable auditory monitoring was significantly associated with better rates of preservation of useful hearing. Long-term follow-up by MRI with Gd administration (81 ± 43 months [range 5–181 months]; median 7 years) showed no tumor recurrence, and although the preserved hearing declined minimally over the long-term postoperative follow-up period (from 39 ± 15 dB to 45 ± 11 dB in 5.1 ± 3.1 years), 80% of useful hearing and 100% of serviceable hearing remained at the same level.

Conclusions

As a result of a surgical technique that involved sharp dissection and internal auditory canal reconstruction with intraoperative auditory monitoring, retrosigmoid removal of small ANs can lead to successful curative tumor removal without long-term recurrence and with excellent functional outcome. Thus, the authors suggest that tumor removal should be the first-line management strategy for younger patients with small ANs and preserved hearing.

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Shinji Matsuda, Osamu Nagano, Toru Serizawa, Yoshinori Higuchi and Junichi Ono

Object

Gamma Knife surgery (GKS) is an effective treatment option for intractable trigeminal neuralgia (TN). The incidence of trigeminal nerve dysfunction, such as facial numbness or dysesthesia, has been reported to be higher than previously published, and the degree and prognosis of trigeminal nerve dysfunction has not been well evaluated. The authors evaluated the incidence, timing, degree, and outcome of trigeminal nerve dysfunction after GKS for TN.

Methods

One hundred four patients with medically refractory TN were treated by GKS. Thirty-nine patients were men and 65 were women; their median age at GKS was 74 years. Using a single isocenter and a 4-mm collimator, 80 or 90 Gy was directed to the trigeminal nerve root. Follow-up data were obtained at clinical examinations every 3–6 months after GKS. Each patient's pain-control status and degree of trigeminal nerve dysfunction were recorded. The incidence, timing, and degree of dysfunction (assessed using the Barrow Neurological Institute facial numbness scale [BNI-N]) and the prognosis and factors related to trigeminal nerve dysfunction were analyzed.

Results

The median duration of follow-up in these patients was 37 months (range 6–121 months). At the final clinical visit, a pain-free status was still observed in 71 patients (68.3%). In 51 patients (49.0%), new or increased trigeminal nerve dysfunction developed at a median of 10.5 months (range 4–68 months) after GKS. In 24 patients (23.1%), this dysfunction was categorized as BNI-N Score II, in 20 patients (19.2%) as BNI-N Score III, and in 7 patients (6.7%) as BNI-N Score IV. Among those patients, 18 patients, including 3 patients with BNI-N Score IV, experienced improvement in nerve dysfunction between 24 and 108 months after GKS (median 52.5 months). At the final clinical visit, 43 patients (41.3%) reported having some trigeminal nerve dysfunction: in 26 patients (25.0%) this was categorized as BNI-N Score II, in 13 patients (12.5%) as BNI-N Score III, and in 4 patients (3.8%) as BNI-N Score IV. The only independent factor that was correlated to all trigeminal nerve dysfunction and also specifically to bothersome trigeminal nerve dysfunction was pain-free status at the final clinic visit.

Conclusions

The incidence of trigeminal nerve dysfunction after GKS for TN was 49%. The severity of the dysfunction improved in one-third of the afflicted patients, even in those with severe dysesthesia at long-term follow-up. A strong relationship between TN and good pain control was identified.

Free access

Masaaki Yamamoto, Atsuya Akabane, Yuji Matsumaru, Yoshinori Higuchi, Hidetoshi Kasuya and Yoichi Urakawa

Object

Little information is available on staged Gamma Knife surgery (GKS) with an interval of 3 years or more when used to treat arteriovenous malformations (AVMs) with volumes larger than 10 cm3. The goal of this study was to increase knowledge in this area by reporting the authors' experience.

Methods

The authors describe an institutional review board–approved retrospective study in which they examined databases including information on 250 patients who consecutively underwent GKS for cerebral AVMs during a 16-year period (1988–2004). Among the 250 patients the authors identified 31 patients (12.4%, 15 female and 16 male patients with a mean age of 29 years [range 10–63 years]) in whom 2-stage GKS was intentionally planned at the time of initial treatment because the volume of the AVM nidus was larger than 10 cm3. The most common presentation was bleeding (14 patients), followed by seizures (9 patients), incidental findings (7 patients), and headache with scintillation (1 patient). One patient underwent GKS for the treatment of 2 AVMs simultaneously, and thus 32 AVMs are included in this study. The mean nidus volume was 16.2 cm3 (maximum 55.8 cm3). In all 31 patients, relatively low radiation doses (12–16 Gy directed at the periphery of the lesion) were intentionally used for the first GKS. The second GKS was scheduled for at least 36 months after the first.

Results

Complete nidus obliteration was obtained after the first GKS in 1 patient. To date, 26 patients have undergone a second procedure with a post-GKS mean interval of 41 months (range 24–83 months); 2 other patients refused to undergo the second GKS, and no further treatment was given because of severe morbidity in 1 case and death due to bleeding in the other case. Among the 26 patients who did undergo a second procedure, 3 patients refused follow-up digital subtraction (DS) angiography, another is scheduled for follow-up DS angiography, and 2 patients died, one of bleeding and the other of an unknown cause. The remaining 20 patients underwent follow-up DS angiography. Complete nidus obliteration was confirmed in 13 patients (65.0%) and remarkable nidus shrinkage in the other 7 patients (35.0%). In 2 of these 7 patients, a third GKS achieved complete nidus obliteration. Therefore, the cumulative complete obliteration rate in this series was 76.2% (16 of 21 eligible patients). Seven patients (22.6%) experienced bleeding. The bleeding rates were 9.7%, 16.1%, 16.1%, and 26.1%, respectively, at 1, 2, 5, and 10 years post-GKS. There were 2 deaths and 3 cases of morbidity (persistent coma, mild hemimotor weakness, and hemianopsia in 1 patient each). Hemorrhage did not produce neurological deficits in the other 2 patients. During the mean post-GKS follow-up period of 105 months (range 42–229 months) to date, mild symptomatic GKS-related complications occurred in 2 patients (6.5%); these were classified as Radiation Oncology Group Neurotoxicity Grade 1 in 1 patient and Grade 2 in the other. Among various pre-GKS clinical factors, univariate analysis showed only patient age to impact complications (hazard ratio 0.675, 95% CI 0.306–0.942, p = 0.0085). The rate of complications in the pediatric cases was 33.3%, whereas that in the adolescent and adult cases was 0% (p = 0.0323).

Conclusions

Although a final conclusion awaits further studies and patient follow-up, these results suggest 2-stage GKS to be beneficial even for relatively large AVMs.

Free access

Toru Serizawa, Yoshinori Higuchi, Osamu Nagano, Tatsuo Hirai, Junichi Ono, Naokatsu Saeki and Akifumi Miyakawa

Object

The authors conducted validity testing of the 5 major reported indices for radiosurgically treated brain metastases— the original Radiation Therapy Oncology Group's Recursive Partitioning Analysis (RPA), the Score Index for Radiosurgery in Brain Metastases (SIR), the Basic Score for Brain Metastases (BSBM), the Graded Prognostic Assessment (GPA), and the subclassification of RPA Class II proposed by Yamamoto—in nearly 2500 cases treated with Gamma Knife surgery (GKS), focusing on the preservation of neurological function as well as the traditional endpoint of overall survival.

Methods

The authors analyzed data from 2445 cases treated with GKS by the first author (T.S.), the primary surgeon. The patient group consisted of 1716 patients treated between January 1998 and March 2008 (the Chiba series) and 729 patients treated between April 2008 and December 2011 (the Tokyo series). The interval from the date of GKS until the date of the patient's death (overall survival) and impaired activities of daily living (qualitative survival) were calculated using the Kaplan-Meier method, while the absolute risk for two adjacent classes of each grading system and both hazard ratios and 95% confidence intervals were estimated using the Cox proportional hazards model.

Results

For overall survival, there were highly statistically significant differences between each two adjacent patient groups characterized by class or score (all p values < 0.001), except for GPA Scores 3.5–4.0 and 3.0. The SIR showed the best statistical results for predicting preservation of neurological function. Although no other grading systems yielded statistically significant differences in qualitative survival, the BSBM and the modified RPA appeared to be better than the original RPA and GPA.

Conclusions

The modified RPA subclassification, proposed by Yamamoto, is well balanced in scoring simplicity with respect to case number distribution and statistical results for overall survival. However, a new or revised grading system is necessary for predicting qualitative survival and for selecting the optimal treatment for patients with brain metastasis treated by GKS.

Free access

Masaaki Yamamoto, Takuya Kawabe, Yasunori Sato, Yoshinori Higuchi, Tadashi Nariai, Bierta E. Barfod, Hidetoshi Kasuya and Yoichi Urakawa

Object

Although stereotactic radiosurgery (SRS) alone for patients with 4–5 or more tumors is not a standard treatment, a trend for patients with 5 or more tumors to undergo SRS alone is already apparent. The authors' aim in the present study was to reappraise whether SRS results for ≥ 5 tumors differ from those for 1–4 tumors.

Methods

This institutional review board–approved retrospective cohort study used the authors' database of prospectively accumulated data that included 2553 consecutive patients who underwent SRS, not in combination with concurrent whole-brain radiotherapy, for brain metastases (METs) between 1998 and 2011. These 2553 patients were divided into 2 groups: 1553 with tumor numbers of 1–4 (Group A) and 1000 with ≥ 5 tumors (Group B). Because there was considerable bias in pre-SRS clinical factors between Groups A and B, a case-matched study was conducted. Ultimately, 1096 patients (548 each in Groups A and B) were selected. The standard Kaplan-Meier method was used to determine post-SRS survival and the post-SRS neurological death–free survival times. Competing risk analysis was applied to estimate cumulative incidences of local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-induced complications.

Results

The post-SRS median survival time was significantly longer in the 548 Group A patients (7.9 months, 95% CI 7.0–8.9 months) than in the 548 Group B patients (7.0 months 95% [CI 6.2–7.8 months], HR 1.176 [95% CI 1.039–1.331], p = 0.01). However, incidences of neurological death were very similar: 10.6% in Group A and 8.2% in Group B (p = 0.21). There was no significant difference between the groups in neurological death–free survival intervals (HR 0.945, 95% CI 0.636–1.394, p = 0.77). Furthermore, competing risk analyses showed that there were no significant differences between the groups in cumulative incidences of local recurrence (HR 0.577, 95% CI 0.312–1.069, p = 0.08), repeat SRS (HR 1.133, 95% CI 0.910–1.409, p = 0.26), neurological deterioration (HR 1.868, 95% CI 0.608–1.240, p = 0.44), and major SRS-related complications (HR 1.105, 95% CI 0.490–2.496, p = 0.81).

In the authors' cohort, age ≤ 65 years, female sex, a Karnofsky Performance Scale score ≥ 80%, cumulative tumor volume ≤ 10 cm3, controlled primary cancer, no extracerebral METs, and neurologically asymptomatic status were significant factors favoring longer survival equally in both groups.

Conclusions

This retrospective study suggests that increased tumor number is an unfavorable factor for longer survival. However, the post-SRS median survival time difference, 0.9 months, between the two groups is not clinically meaningful. Furthermore, patients with 5 or more METs have noninferior results compared to patients with 1–4 tumors, in terms of neurological death, local recurrence, repeat SRS, maintenance of good neurological state, and SRS-related complications. A randomized controlled trial should be conducted to test this hypothesis.

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Toru Serizawa, Yoshinori Higuchi, Junichi Ono, Shinji Matsuda, Osamu Nagano, Yasuo Iwadate and Naokatsu Saeki

Object

The authors analyzed the effectiveness of Gamma Knife surgery (GKS) for metastatic brain tumors without adjuvant prophylactic whole-brain radiotherapy (WBRT). Salvage GKS was performed as the sole treatment for new distant lesions.

Methods

Among 1127 patients in whom new brain metastases had been diagnosed, 97 who met one or more of the following three criteria were excluded from the study: any surgically inaccessible huge (≥ 35 mm) lesion; tumor number and size requiring an internal skull dose exceeding 10 J; or symptomatic carcinomatous meningitis. Thus, 1030 consecutive patients formed the basis for this study. Huge tumors were totally removed, whereas smaller lesions were treated with GKS. No adjuvant WBRT was given prior to GKS, and new distant lesions were appropriately retreated with GKS. Overall, neurological and new lesion–free survival curves were calculated and the prognostic values of covariates were obtained. In total, 1853 separate GKS sessions were required to treat 10,163 lesions.The patients' median overall survival period was 8.6 months. Neurological survival and new lesion–free rates at 1 year were 89.1 and 49.3%, respectively. In a multivariate analysis, the significant factors for poor prognosis were the development of more than four new brain metastases and active extracranial disease.

Conclusions

In meeting the goal of preventing neurological death and maintaining activities of daily living for patients with brain metastases, GKS alone provides excellent palliation without prophylactic WBRT. New distant lesions were quite well controlled with GKS salvage treatment alone.

Free access

Masaaki Yamamoto, Takuya Kawabe, Yasunori Sato, Yoshinori Higuchi, Tadashi Nariai, Shinya Watanabe and Hidetoshi Kasuya

Object

Although stereotactic radiosurgery (SRS) alone is not a standard treatment for patients with 4–5 tumors or more, a recent trend has been for patients with 5 or more, or even 10 or more, tumors to undergo SRS alone. The aim of this study was to reappraise whether the treatment results for SRS alone for patients with 10 or more tumors differ from those for patients with 2–9 tumors.

Methods

This was an institutional review board–approved, retrospective cohort study that gathered data from the Katsuta Hospital Mito GammaHouse prospectively accumulated database. Data were collected for 2553 patients who consecutively had undergone Gamma Knife SRS alone, without whole-brain radiotherapy (WBRT), for newly diagnosed (mostly) or recurrent (uncommonly) brain metastases during 1998–2011. Of these 2553 patients, 739 (28.9%) with a single tumor were excluded, leaving 1814 with multiple metastases in the study. These 1814 patients were divided into 2 groups: those with 2–9 tumors (Group A, 1254 patients) and those with 10 or more tumors (Group B, 560 patients). Because of considerable bias in pre-SRS clinical factors between groups A and B, a case-matched study, which used the propensity score matching method, was conducted for clinical factors (i.e., age, sex, primary tumor state, extracerebral metastases, Karnofsky Performance Status, neurological symptoms, prior procedures [surgery and WBRT], volume of the largest tumor, and peripheral doses). Ultimately, 720 patients (360 in each group) were selected. The standard Kaplan-Meier method was used to determine post-SRS survival times and post-SRS neurological death–free survival times. Competing risk analysis was applied to estimate cumulative incidence for local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-induced complications.

Results

Post-SRS median survival times did not differ significantly between the 2 groups (6.8 months for Group A vs 6.0 months for Group B; hazard ratio [HR] 1.133, 95% CI 0.974–1.319, p = 0.10). Furthermore, rates of neurological death were very similar: 10.0% for group A and 9.4% for group B (p = 0.89); neurological death–free survival times did not differ significantly between the 2 groups (HR 1.073, 95% CI 0.649–1.771, p = 0.78). The cumulative incidence of local recurrence (HR 0.425, 95% CI 0.0.181–0.990, p = 0.04) and repeat SRS for new lesions (HR 0.732, 95% CI 0.554–0.870, p = 0.03) were significantly lower for Group B than for Group A patients. No significant differences between the groups were found for cumulative incidence for neurological deterioration (HR 0.994, 95% CI 0.607–1.469, p = 0.80) or SRS-related complications (HR 0.541, 95% CI 0.138–2.112, p = 0.38).

Conclusions

Post-SRS treatment results (i.e., median survival time; neurological death–free survival times; and cumulative incidence for local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-related complications) were not inferior (neither less effective nor less safe) for patients in Group B than for those in Group A. We conclude that carefully selected patients with 10 or more tumors are not unfavorable candidates for SRS alone. A randomized controlled trial should be conducted to test this hypothesis.

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Toshio Machida, Yoshinori Higuchi, Shigeki Nakano, Masaki Izumi, Satoshi Ishige, Atsushi Fujikawa, Yuichi Akaogi, Junichiro Shimada and Junichi Ono

OBJECTIVE

Encephalo-myo-synangiosis (EMS) is an effective revascularization procedure for the treatment of moyamoya disease (MMD). However, the temporalis muscle used for EMS sometimes swells and causes ischemic complications by compressing the underlying brain. This study aimed to elucidate the effect of sagittal splitting (SS) of the muscle for prevention of ischemic complications and its impact on the postoperative development of collateral vessels.

METHODS

In this historical case-control study, we analyzed 60 hemispheres in adult patients with MMD who underwent EMS using the temporalis muscle from December 1998 to November 2017. The muscle was divided anteroposteriorly by coronal splitting, and the anterior, posterior, or both parts of the muscle were used for EMS in 17, 4, and 39 hemispheres, respectively. In cases performed after 2006, the muscle was halved by SS, and the medial half was used for EMS to reduce the muscle volume (n = 47). The degree of postoperative muscle swelling was evaluated by measuring the maximum thickness of the muscle on CT scans obtained 3 to 7 days after surgery. The collateral developments of the anterior deep temporal artery (aDTA), posterior deep temporal artery (pDTA), and middle temporal artery (MTA) were assessed using digital subtraction angiography and MR angiography performed 6 months or more after surgery.

RESULTS

SS significantly reduced the temporalis muscle thickness from 12.1 ± 5.0 mm to 7.1 ± 3.0 mm (p < 0.01). Neurological deterioration due to the swollen temporalis muscle developed in 4 of the 13 hemispheres without SS (cerebral infarction in 1, reversible neurological deficit in 2, and convulsion in 1) but in none with SS. There were no significant differences in the postoperative collateral developments of the aDTA, pDTA, and MTA between hemispheres with and without SS. The MTA more frequently developed in hemispheres with EMS in which the posterior part of the muscle was used (30/37) than those in which this part was not used (4/16) (p < 0.01).

CONCLUSIONS

SS of the temporalis muscle might prevent neurological deterioration caused by the swollen temporalis muscle by reducing its volume without inhibiting the development of the collateral vessels.

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Osamu Nagano, Yoshinori Higuchi, Toru Serizawa, Junichi Ono, Shinji Matsuda, Iwao Yamakami and Naokatsu Saeki

Object

The authors prospectively analyzed volume changes in vestibular schwannomas (VSs) after stereotactic radiosurgery.

Methods

One hundred consecutive patients with unilateral VS treated with Gamma Knife surgery (GKS) at Chiba Cardiovascular Center between 1998 and 2006 were analyzed in this study. For each lesion the Gd-enhanced volume was measured serially every 3 months in the 1st year, then every 6 months thereafter, using volumetric software. The frequency and degree of transient tumor expansion were documented and possible prognostic factors were analyzed. Concurrently, neurological deterioration involving trigeminal, facial, and cochlear nerve functions were also assessed.

Results

The mean observation period was 65 months (range 25–100 months). There were 32 men and 68 women, whose mean age was 59.1 years (range 29–80 years). Tumor volumes at GKS averaged 2.7 cm3 (range 0.1–13.2 cm3), and the lesions were irradiated at the mean 52.2% isodose line for the tumor margin (range 50–67%), with a mean dose of 12.2 Gy (range 10.5–13 Gy) at the periphery. The tumor volume was increased by 23% at 3 months and 27% at 6 months. Tumors shrank to their initial size over a mean period of 12 months. The maximum volume increase was < 10% (no significant increase) in 26 patients, 10–30% in 23, 30–50% in 22, 50–100% in 16, and > 100% in 13. The peak tumor expansion averaged 47% (range 0–613%). A high-dose (≥ 3.5 Gy/min) treatment appears to be the greatest risk factor for transient tumor expansion, although the difference did not reach statistical significance. Transient facial palsy and facial dysesthesia correlated strongly with tumor expansion, but only half of the hearing loss was coincident with this phenomenon.

Conclusions

Transient expansion of VSs after GKS was found to be much more frequent than previously reported, strongly suggesting a correlation with deterioration of facial and trigeminal nerve functions.

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Toru Serizawa, Masaaki Yamamoto, Osamu Nagano, Yoshinori Higuchi, Shinji Matsuda, Junichi Ono, Yasuo Iwadate and Naokatsu Saeki

Object

The authors compared results of Gamma Knife surgery (GKS) for brain metastases obtained at 2 institutions in Japan.

Methods

They analyzed a consecutive series of 2390 patients with brain metastases who underwent GKS from 1998 through 2005 in 2 institutes (1181 patients in Chiba; 1209 in Mito). In the 2 facilities, 1 neurosurgeon each was responsible for diagnosis, patient selection, GKS procedures, and follow-up (T.S. in Chiba, M.Y. in Mito). Even if tumor numbers exceeded 4, all visible lesions were irradiated with a total skull integral dose (TSID) of ≤ 10–12 J. No prophylactic whole-brain radiotherapy (WBRT) was applied. If new distant lesions were detected, salvage GKS was appropriately performed.

Results

The distributions of patient and treatment factors did not differ between institutes. The most common primary tumors were lung cancer (1572 patients), followed by gastrointestinal tract (316), breast (211), kidney (113), and other cancers (159). The median survival periods were 7.7 months in Chiba and 7.0 months in Mito (p = 0.0635). The significant poor prognostic factors for overall survival were active extracranial disease status, male sex, and low initial Karnofsky Performance Scale score on multivariate analysis (all p < 0.0001). The neurological survival rates at 1 year were 86.6% in Chiba and 84.2% in Mito (p = 0.3310).

Conclusions

This 2-institute study demonstrated no significant institutional differences in any of the treatment result items. Gamma Knife surgery for brain metastases without prophylactic WBRT prevents neurological death and allows a patient to maintain good brain condition. However, there is 1 important patient selection criterion: regardless of how many tumors there are, all lesions can be irradiated with a TSID of ≤12 J.