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Yoshiyasu Iwai, Kazuhiro Yamanaka and Hidetoshi Ikeda

Object

In this study, the authors evaluate the long-term results after Gamma Knife radiosurgery of cranial base meningiomas. This study is a follow-up to their previously published report on the early results.

Methods

Between January 1994 and December 2001, the authors treated benign cranial base meningiomas in 108 patients using low-dose Gamma Knife radiosurgery. The tumor volumes ranged from 1.7 to 55.3 cm3 (median 8.1 cm3), and the radiosurgery doses ranged from 8 to 12 Gy (median 12 Gy) to the tumor margin.

Results

The mean duration of follow-up was 86.1 months (range 20–144 months). Tumor volume decreased in 50 patients (46%), remained stable in 51 patients (47%), and increased (local failure) in 7 patients (6%). Eleven patients experienced tumor recurrence outside the treatment field. Among these patients, marginal failure was seen in 5 and distant recurrence was seen in 6. Seven patients were thought to have malignant transformation based on histological or radiological characteristics of the lesion. The actuarial progression-free survival rate, including malignant transformation and outside recurrence, was 93% at 5 years and 83% at 10 years. Neurological status improved in 16 patients (15%). Permanent radiation injury occurred in 7 patients (6%).

Conclusions

Gamma Knife radiosurgery is a safe and effective treatment for cranial base meningiomas as demonstrated with a long-term follow-up period of > 7 years. Surgeons must be aware of the possibility of treatment failure, defined as local failure, marginal failure, and malignant transformation; however, this may be the natural course of meningiomas and not related to radiosurgery.

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Masaki Komiyama, Kazuhiro Yamanaka, Toshihiro Yasui and Masanori Kan

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Naohiro Tsuyuguchi, Ichiro Sunada, Yoshiyasu Iwai, Kazuhiro Yamanaka, Kiyoaki Tanaka, Toshihiro Takami, Yumiko Otsuka, Shinichi Sakamoto, Kenji Ohata, Takeo Goto and Mitsuhiro Hara

Object. In this study the authors examined how to differentiate radiation necrosis from recurrent metastatic brain tumor following stereotactic radiosurgery by using positron emission tomography (PET) with l-[methyl-11C]methionine (MET).

Methods. In 21 adult patients with suspected recurrent metastatic brain tumor or radiation injury, MET-PET scans were obtained. These patients had previously undergone stereotactic radiosurgery and subsequent contrast-enhanced magnetic resonance (MR) examinations before nuclear medicine imaging. Positron emission tomography images were obtained as a static scan of 10 minutes performed 20 minutes after injection of 370 MBq of MET. On MET-PET scans, the portion of the tumor with the highest accumulation of MET was selected as the region of interest (ROI), and the ratio of tumor tissue to normal tissue (T/N) was defined as the mean counts of radioisotope per pixel in the tumor divided by the mean counts per pixel in normal gray matter. The standardized uptake value (SUV) was calculated using the same ROI in the tumor. The accuracy of the MET-PET scan was evaluated by correlating findings with results of subsequent histological analysis (11 cases) or, in cases in which surgery or biopsy was not performed, with subsequent clinical course and MR imaging findings (10 cases).

Histological examinations performed in 11 cases showed viable tumor cells with necrosis in nine and necrosis with no viable tumor cells in two. Another 10 cases were characterized as radiation necrosis because the patients exhibited stable neurological symptoms with no sign of massive enlargement of the lesion on follow-up MR images after 5 months. The mean T/N was 1.15 in the radiation necrosis group (12 cases) and 1.62 in the tumor recurrence group (nine cases). The mean SUV was 1.78 in the necrosis group and 2.5 in the recurrence group. There were statistically significant differences between the recurrence and necrosis groups in T/N and SUV. Furthermore, the borderline T/N value was 1.42 according to a 2 × 2 factorial table (high T/N or low T/N, recurrence or necrosis). From this result, the sensitivity and specificity of MET-PET scanning in detecting tumor recurrence were determined to be 77.8 and 100%, respectively.

Conclusions. The use of MET-PET scanning is a sensitive and accurate technique for differentiating between metastatic brain tumor recurrence and radiation necrosis following stereotactic radiosurgery. This study reveals important information for creating strategies to treat postradiation reactions.

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Kazuhiro Yamanaka, Toshiya Tachibana, Tokuhide Moriyama, Fumiaki Okada, Keishi Maruo, Shinichi Inoue, Yutaka Horinouchi and Shinichi Yoshiya

Object

Postoperative C-5 palsy is known as a common complication after cervical laminoplasty. The authors of this article have encountered postoperative C-5 palsy more often when laminoplasty was combined with instrumented posterior spinal fusion than when it was performed alone. The purpose of this clinical study was to examine the incidence of fifth cervical nerve root palsy (C-5 palsy) and surgical results in patients with cervical myelopathy who had undergone laminoplasty with or without instrumented spinal fusion.

Methods

The authors retrospectively studied patients with cervical myelopathy who had undergone laminoplasty with or without instrumented posterior spinal fusion.

Results

Clinical data on 58 patients were evaluated and analyzed. Preoperative diagnoses were cervical spondylotic myelopathy or ossification of the posterior longitudinal ligament of the cervical spine. Twenty-four patients with spondylolisthesis or kyphosis underwent laminoplasty combined with posterior spinal fusion using instrumented lateral mass fixation (fusion group), while the remaining 34 patients underwent laminoplasty without posterior spinal fusion (no-fusion group). In the fusion group, C-5 palsy developed in 6 patients; in the no-fusion group, it occurred in only 1 patient. There was a significant difference in the rate of this complication between the 2 groups. In the fusion group, local kyphosis and spondylolisthesis level were reduced at the fusion level, and all patients with C-5 palsy underwent C4–5 spinal fusion.

Conclusions

The incidence of postoperative C-5 palsy is significantly higher after laminoplasty when it is combined with spinal fusion. Correction of kyphosis and spondylolisthesis using posterior instrumentation may be a risk factor for iatrogenic intervertebral foraminal stenosis leading to C-5 palsy.

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Takashi Shuto, Atsuya Akabane, Masaaki Yamamoto, Toru Serizawa, Yoshinori Higuchi, Yasunori Sato, Jun Kawagishi, Kazuhiro Yamanaka, Hidefumi Jokura, Shoji Yomo, Osamu Nagano and Hidefumi Aoyama

OBJECTIVE

Previous Japanese Leksell Gamma Knife Society studies (JLGK0901) demonstrated the noninferiority of stereotactic radiosurgery (SRS) alone as the initial treatment for patients with 5–10 brain metastases (BMs) compared with those with 2–4 BMs in terms of overall survival and most secondary endpoints. The authors studied the aforementioned treatment outcomes in a subset of patients with BMs from non–small cell lung cancer (NSCLC).

METHODS

Patients with initially diagnosed BMs treated with SRS alone were enrolled in this prospective observational study. Major inclusion criteria were the existence of up to 10 tumors with a maximum diameter of less than 3 cm each, a cumulative tumor volume of less than 15 cm3, and no leptomeningeal dissemination in patients with a Karnofsky Performance Scale score of 70% or better.

RESULTS

Among 1194 eligible patients, 784 with NSCLC were categorized into 3 groups: group A (1 tumor, n = 299), group B (2–4 tumors, n = 342), and group C (5–10 tumors, n = 143). The median survival times were 13.9 months in group A, 12.3 months in group B, and 12.8 months in group C. The survival curves of groups B and C were very similar (hazard ratio [HR] 1.037; 95% CI 0.842–1.277; p < 0.0001, noninferiority test). The crude and cumulative incidence rates of neurological death, deterioration of neurological function, newly appearing lesions, and leptomeningeal dissemination did not differ significantly between groups B and C. SRS-induced complications occurred in 145 (12.1%) patients during the median post-SRS period of 9.3 months (IQR 4.1–17.4 months), including 46, 54, 29, 11, and 5 patients with a Common Terminology Criteria for Adverse Events v3.0 grade 1, 2, 3, 4, or 5 complication, respectively. The cumulative incidence rates of adverse effects in groups A, B, and C 60 months after SRS were 13.5%, 10.0%, and 12.6%, respectively (group B vs C: HR 1.344; 95% CI 0.768–2.352; p = 0.299). The 60-month post-SRS rates of neurocognitive function preservation were 85.7% or higher, and no significant differences among the 3 groups were found.

CONCLUSIONS

In this subset analysis of patients with NSCLC, the noninferiority of SRS alone for the treatment of 5–10 versus 2–4 BMs was confirmed again in terms of overall survival and secondary endpoints. In particular, the incidence of neither post-SRS complications nor neurocognitive function preservation differed significantly between groups B and C. These findings further strengthen the already-reported noninferiority hypothesis of SRS alone for the treatment of patients with 5–10 BMs.

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Toru Serizawa, Masaaki Yamamoto, Yoshinori Higuchi, Yasunori Sato, Takashi Shuto, Atsuya Akabane, Hidefumi Jokura, Shoji Yomo, Osamu Nagano, Jun Kawagishi and Kazuhiro Yamanaka

OBJECTIVE

The Japanese Leksell Gamma Knife (JLGK)0901 study proved the efficacy of Gamma Knife radiosurgery (GKRS) in patients with 5–10 brain metastases (BMs) as compared to those with 2–4, showing noninferiority in overall survival and other secondary endpoints. However, the difference in local tumor progression between patients with 2–4 and those with 5–10 BMs has not been sufficiently examined for this data set. Thus, the authors reappraised this issue, employing the updated JLGK0901 data set with detailed observation via enhanced MRI. They applied sophisticated statistical methods to analyze the data.

METHODS

This was a prospective observational study of 1194 patients harboring 1–10 BMs treated with GKRS alone. Patients were categorized into groups A (single BM, 455 cases), B (2–4 BMs, 531 cases), and C (5–10 BMs, 208 cases). Local tumor progression was defined as a 20% increase in the maximum diameter of the enhanced lesion as compared to its smallest documented maximum diameter on enhanced MRI. The authors compared cumulative incidence differences determined by competing risk analysis and also conducted propensity score matching.

RESULTS

Local tumor progression was observed in 212 patients (17.8% overall, groups A/B/C: 93/89/30 patients). Cumulative incidences of local tumor progression in groups A, B, and C were 15.2%, 10.6%, and 8.7% at 1 year after GKRS; 20.1%, 16.9%, and 13.5% at 3 years; and 21.4%, 17.4%, and not available at 5 years, respectively. There were no significant differences in local tumor progression between groups B and C. Local tumor progression was classified as tumor recurrence in 139 patients (groups A/B/C: 68/53/18 patients), radiation necrosis in 67 (24/31/12), and mixed/undetermined lesions in 6 (1/5/0). There were no significant differences in tumor recurrence or radiation necrosis between groups B and C. Multivariate analysis using the Fine-Gray proportional hazards model revealed age < 65 years, neurological symptoms, tumor volume ≥ 1 cm3, and prescription dose < 22 Gy to be significant poor prognostic factors for local tumor progression. In the subset of 558 case-matched patients (186 in each group), there were no significant differences between groups B and C in local tumor progression, nor in tumor recurrence or radiation necrosis.

CONCLUSIONS

Local tumor progression incidences did not differ between groups B and C. This study proved that tumor progression after GKRS without whole-brain radiation therapy for patients with 5–10 BMs was satisfactorily treated with the doses prescribed according to the JLGK0901 study protocol and that results were not inferior to those in patients with a single or 2–4 BMs.

Clinical trial registration no.: UMIN000001812 (umin.ac.jp)