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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.

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Yoshishige Nagaseki, Tohru Shibazaki, Tatsuo Hirai, Yasuhiro Kawashima, Masafumi Hirato, Hirochiyo Wada, Mizuho Miyazaki and Chihiro Ohye

✓ The authors report the results of a long-term follow-up study of the effects of the physiologically defined selective VIM (nucleus ventralis intermedius)-thalamotomy on tremor of Parkinson's disease in 27 patients and essential tremor in 16 patients. The follow-up period ranged from 3.25 to 10 years (mean 6.58 years). In 43 patients a total of 50 operations (including four bilateral operations and three reoperations) were carried out. The early (2 to 4 weeks after surgery) and late effects on the tremors were determined clinically and electromyographically. Fourteen parkinsonian cases were treated with minimal lesions (about 40 cu mm). Their late results were very similar to the early results: in 10, the tremors were completely abolished, three had a slight residual tremor, and one underwent reoperation 3 months after the first surgery. Eleven essential tremor cases were treated with minimal lesions. Six of these tremors were completely abolished, four patients had slight residual tremors, and one patient with a recurrence underwent reoperation 2 years after the initial surgery. In these 23 successful operations with minimal lesions (excluding two cases with reoperation), the tremor was abolished without discernible long-lasting side effects. The other 23 operations on 16 patients with Parkinson's disease (including one reoperation) and on seven with essential tremor (one of whom also had a minimal lesion on the other side) involved relatively large lesions. In this group, the surgery was successful in almost every case. It was concluded that radiographically and physiologically monitored selective VIM-thalamotomy for parkinsonian and essential tremor is effective even when lesioning is minimal. Moreover, the beneficial effect is maintained over a long period of time.

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Toru Serizawa, Yoshinori Higuchi, Osamu Nagano, Shinji Matsuda, Kyoko Aoyagi, Junichi Ono, Naokatsu Saeki, Yasuo Iwadate, Tatsuo Hirai, Shinya Takemoto and Yuta Shibamoto

OBJECTIVE

The neurological prognostic score (NPS) was recently proposed as a means for predicting neurological outcomes, such as the preservation of neurological function and the prevention of neurological death, in brain metastasis patients treated with Gamma Knife radiosurgery (GKRS). NPS consists of 2 groups: Group A patients were expected to have better neurological outcomes, and Group B patients were expected to have poorer outcomes. NPS robustness was tested in various situations.

METHODS

In total, 3040 patients with brain metastases that were treated with GKRS were analyzed. The cumulative incidence of the loss of neurological function independence (i.e., neurological deterioration) was estimated using competing risk analysis, and NPS was compared between Groups A and B by employing Gray's model. NPS was tested to determine if it can be applied to 5 cancer categories—non–small cell lung cancer, small cell lung cancer, gastrointestinal tract cancer, breast cancer, and other cancers—as well as if it can be incorporated into the 5 major grading systems: recursive partitioning analysis (RPA), score index for stereotactic radiosurgery (SIR), basic score for brain metastases (BSBM), graded prognostic assessment (GPA), and modified-RPA (M-RPA).

RESULTS

There were 2263 patients in NPS Group A and 777 patients in Group B. Neurological deterioration was observed in 586 patients (19.2%). The cumulative incidences of neurological deterioration were 9.5% versus 21.0%, 14.1% versus 25.4%, and 17.6% versus 27.8% in NPS Groups A and B at 1, 2, and 5 years, respectively. Significant differences were detected between the NPS groups in all cancer categories. There were significant differences between NPS Groups A and B for all classes in terms of the BSBM, GPA, and M-RPA systems, but the differences failed to reach statistical significance in terms of RPA Class I and SIR Class 0 to 3.

CONCLUSIONS

The NPS was verified as being highly applicable to all cancer categories and almost all classes for the 5 grading systems in terms of neurological function independence. This NPS system appears to be quite robust in various situations for brain metastasis patients treated with GKRS.

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

Object

The Basic Score for Brain Metastases (BSBM) proposed by Lorenzoni and colleagues is one of the best grading systems for predicting survival periods after stereotactic radiosurgery (SRS) for brain metastases. However, it includes no brain factors and cannot predict neurological outcomes, such as preservation of neurological function and prevention of neurological death. Herein, the authors propose a modified BSBM, adding 4 brain factors to the original BSBM, enabling prediction of neurological outcomes, as well as of overall survival, in patients undergoing SRS.

Methods

To serve as neurological prognostic scores (NPSs), the authors scored 4 significant brain factors for both preservation of neurological function (qualitative survival) and prevention of neurological death (neurological survival) as 0 or 1 as described in the following: > 10 brain tumors = 0 or ≤ 10 = 1, total tumor volume > 15 cm3 = 0 or ≤ 15 cm3 = 1, MRI findings of localized meningeal dissemination (yes = 0 or no = 1), and neurological symptoms (yes = 0 or no = 1). According to the sum of NPSs, patients were classified into 2 subgroups: Subgroup A with a total NPS of 3 or 4 and Subgroup B with an NPS of 0, 1, or 2. The authors defined the modified BSBM according to the NPS subgroup classification applied to the original BSBM groups. The validity of this modified BSBM in 2838 consecutive patients with brain metastases treated with SRS was verified.

Results

Patients included 1868 with cancer of the lung (including 1604 with non–small cell lung cancer), 355 of the gastrointestinal tract, 305 of the breast, 176 of the urogenital tract, and 134 with other cancers. Subgroup A had 2089 patients and Subgroup B 749. Median overall survival times were 2.6 months in BSBM 0 (382 patients), 5.7 in BSBM 1 (1143), 11.4 in BSBM 2 (1011) and 21.7 in BSBM 3 (302), and pairwise differences between the BSBM groups were statistically significant (all p < 0.0001). One-year qualitative survival rates were 64.6% (modified BSBM 0A, 204 patients), 45.0% (0B, 178), 82.5% (1A, 825), 63.3% (1B, 318), 86.4% (2A, 792), 73.7% (2B, 219), 91.4% (3A, 268), and 73.5% (3B, 34). One-year neurological survival rates were 82.6% (0A), 52.4% (0B), 90.5% (1A), 78.1% (1B), 91.1% (2A), 83.2% (2B), 93.9% (3A), and 76.3% (3B), where A and B identify the subgroup. Statistically significant differences in both qualitative and neurological survivals between Subgroups A and B were detected in all BSBM groups.

Conclusions

The authors' new index, the modified BSBM, was found to be excellent for predicting neurological outcomes, independently of life expectancy, in SRS-treated patients with brain metastases.

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Toru Serizawa, Masaaki Yamamoto, Yasunori Sato, Yoshinori Higuchi, Osamu Nagano, Takuya Kawabe, Shinji Matsuda, Junichi Ono, Naokatsu Saeki, Manabu Hatano and Tatsuo Hirai

Object

The authors retrospectively reviewed the results of Gamma Knife surgery (GKS) used as the sole treatment for brain metastases in patients who met the eligibility criteria for the ongoing JLGK0901 multi-institutional prospective trial. They also discuss the anticipated results of the JLGK0901 study.

Methods

Data from 1508 consecutive cases were analyzed. All of the patients were treated at the Gamma Knife House of Chiba Cardiovascular Center or the Mito Gamma House of Katsuta Hospital between 1998 and 2007 and met the following JLGK0901 inclusion criteria: 1) newly diagnosed brain metastases, 2) 1–10 brain lesions, 3) less than 10 cm3 volume of the largest tumor, 4) no more than 15 cm3 total tumor volume, 5) no findings of CSF dissemination, and 6) no impairment of activities of daily living (Karnofsky Performance Scale score < 70) due to extracranial disease. At the initial treatment, all visible lesions were irradiated with GKS without upfront whole-brain radiation therapy. Thereafter, gadolinium-enhanced MR imaging was performed every 2–3 months, and new distant lesions were appropriately retreated with GKS. Patients were divided into groups according to numbers of tumors: Group A, single lesions (565 cases); Group B, 2–4 tumors (577 cases); and Group C, 5–10 tumors (366 cases). The differences in overall survival (OS) were compared between groups.

Results

The median age of the patients was 66 years (range 19–96 years). There were 963 men and 545 women. The primary tumors were in the lung in 1114 patients, gastrointestinal tract in 179, breast in 105, urinary tract in 66, and other sites in 44. The overall mean survival time was 0.78 years (0.99 years for Group A, 0.68 years for Group B, and 0.62 years for Group C). The differences between Groups A and B (p < 0.0001) and between Groups B and C (p = 0.0312) were statistically significant. Multivariate analysis revealed significant prognostic factors for OS to be sex (poor prognostic factor: male, p < 0.0001), recursive partitioning analysis class (Class I vs Class II and Class II vs III, both p < 0.0001), primary site (lung vs breast, p = 0.0047), and number of tumors (Group A vs Group B, p < 0.0001). However, no statistically difference was detected between Groups B and C (p = 0.1027, hazard ratio 1.124, 95% CI 0.999–1.265).

Conclusions

The results of this retrospective analysis revealed an upper CI of 1.265 for the hazard ratio, which was lower than the 1.3 initially set by the JLGK0901 study. The JLGK0901 study is anticipated to show noninferiority of GKS as sole treatment for patients with 5–10 brain metastases compared with those with 2–4 in terms of OS.