樋口 佳則

PURPOSE: Recent advances in targeted therapy have prolonged overall survival (OS) for patients with lung cancer. The impact of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) on brain metastases (BM) treated with stereotactic radiosurgery (SRS) has not, however, been fully elucidated. We investigated the influence of post-SRS EGFR-TKI use on the efficacy and toxicity of SRS for BM from lung adenocarcinoma. METHODS: We used the updated dataset of the Japanese Leksell Gamma Knife (JLGK) 0901 study, which proved the efficacy of Gamma Knife SRS in patients with BM. Propensity score matching (PSM) analysis was employed to determine the impact of concurrent or post-SRS EGFR-TKI use on OS, neurological death, intracranial disease recurrence and SRS-related adverse events. RESULTS: Among 1194 patients registered in the JLGK0901 study, 608 eligible lung adenocarcinoma patients were identified and 238 (39%) had received EGFR-TKI concurrently or during the post-SRS clinical course. After PSM, there were 200 patient pairs with/without post-SRS EGFR-TKI use. EGFR-TKI use was associated with longer OS (median 25.5 vs. 11.0 months, HR 0.60, 95% CI 0.48-0.75, p < 0.001), although the long-term OS curves eventually crossed. Distant intracranial recurrence was more likely in patients receiving EGFR-TKI (HR 1.45, 95% CI 1.12-1.89, p = 0.005). Neurological death, local recurrence and SRS-related adverse event rates did not differ significantly between the two groups. CONCLUSIONS: Although patients receiving EGFR-TKI concurrently or after SRS had significantly longer OS, the local treatment efficacy and toxicity of SRS did not differ between patients with/without EGFR-TKI use.

BACKGROUND: The surgical resection of large supracerebellar hemangioblastomas (SHBs) is exceptionally challenging due to their vascularity and deep anatomic location and is associated with a high risk of postoperative complications and mortality. Access to the posterior incisural space can be achieved by either an infratentorial supracerebellar approach or occipital transtentorial approach (OTA). However, the optimal surgical strategy has not yet been established. Here, we report 2 cases of large SHBs that were successfully and safely resected via a unilateral OTA with multimodal assistance. CASE DESCRIPTION: Two patients presented to our hospital with ataxia due to large, solid SHBs. After preoperative embolization, gross total resection of the SHBs was achieved via an OTA. Furthermore, endoscopic assistance was used to resect the remnant portion of the tumor in the second patient. Both patients experienced transient ataxia but were discharged from the hospital without serious complications. CONCLUSIONS: The combination of an OTA with preoperative embolization and endoscopic assistance may reduce the intraoperative risk and contribute to improved outcome in patients with such clinically challenging tumors.

PURPOSE: Stereotactic radiosurgery (SRS) has been increasingly used for elderly patients with brain metastases (BMs). However, no studies based on a large sample size have been reported. To compare SRS treatment results between elderly and non-elderly patients, we performed a subset study of elderly patients using our prospectively-accumulated multi-institution study database (JLGK0901 Study, Lancet Oncol 15:387-395, 2014). METHODS: During the 2009-2011 period, 1194 eligible patients undergoing gamma knife SRS alone for newly diagnosed BMs were enrolled in this study from 23 gamma knife facilities in Japan. Observation was discontinued at the end of 2013. The 1194 patients were divided into the two age groups, 693 elderly ( ≥ 65 years) and 501 non-elderly ( < 65 years) patients. Our study protocol neither set an upper age limit nor required dose de-escalation. RESULTS: Median post-SRS survival time was significantly shorter in the elderly than in the non-elderly patient group (10.3 vs 14.3 months, HR 1.380, 95% CI 1.218-1.563, p < 0.0001). However, regarding all secondary endpoints including neurological death, neurological deterioration, SRS-related complications, leukoencephalopathy, local recurrence, newly-developed tumors, meningeal dissemination, salvage SRS, whole brain radiotherapy and surgery and decreased mini-mental state examination scores, the elderly patient group was not inferior to the non-elderly patient group. In the 693 elderly patients, there was no post-SRS median survival time difference between those with 5-10 versus 2-4 tumors (10.8 vs 8.9 months, HR 0.936, 95% CI 0.744-1.167, p = 0.5601). CONCLUSIONS: We conclude that elderly BM patients are not unfavorable candidates for SRS alone treatment.

腫瘍体積が10ml以上の大きな脳転移に対するガンマナイフによる三期的および二期的照射の治療成績を比較検討した。本試験参加19施設において総計1441例のガンマナイフによる段階的照射が施行され、このうち335例(三期114例、二期的照射221例)が登録された。生存期間中央値は三期群15.1ヵ月、二期群12.0ヵ月と三期群の方が長い傾向にあったが有意差を認めなかった。その他のすべての副次評価項目において両群間に有意差を認めなかった。Propensity score matchを用いて最終的に212例(両群106例)を選択し評価したところ、生存期間中央値は三期群15.9ヵ月、二期群11.7ヵ月と三期群の方が長い傾向にあったが有意差を認めなかった。1年における累積腫瘍増大発生頻度は三期群21.6%、二期群16.7%で有意差を認めなかった。その他、腫瘍再発、放射線壊死、神経死、有害事象においても両群間に有意差を認めなかった。

A 41-year-old man was diagnosed with chronic pulmonary thromboembolism and underwent pulmonary thromboendarterectomy (PTE) with deep hypothermia and circulatory arrest. Five days after the operation, chorea emerged in the lower extremities. The patient was referred to our hospital for disabling chorea 16 years after PTE. Neurological examination revealed choreatic movements in the four extremities. Brain magnetic resonance images indicated atrophy in the bilateral head of the caudate nuclei. The patient underwent deep brain stimulation (DBS) of the bilateral globus pallidus interna (GPi). Continuous GPi-DBS diminished the choreatic movements. GPi-DBS may be a treatment option for sustained choreatic movements after PTE.

【目的】パーキンソン病(PD)に対する視床下核脳深部刺激療法(STN-DBS)による運動症状の改善は明らかではあるが、経時的な体幹症状・高次脳機能の変化は議論の余地が残り、時に包括的な管理が必要となる。当施設では神経内科・リハビリテーション科・精神科とともに術前適応判断から術後評価まで行っており、その評価結果および自宅療養が困難となるまでの期間とその原因を検討した。【方法】DBSを目的に紹介されたPD 141例を対象とし、術前適応判断および術後評価結果を検討した。またSTN-DBS術後自宅での療養が不可能となるまでの期間を競合リスク解析により評価した。【結果】術前評価により手術適応とされた症例は65例であり、適応とならなかった理由は薬物治療再調整が最も多かった。このうち57例でSTN-DBSが施行された。DBS術後症例の経過観察期間中央値は58.1(IQR31〜86)ヵ月で、術後5年で29.2%が自宅での療養が困難となっていた。PD発症が55歳以上あるいは65歳超でDBSを施行した例で施設入所または長期入院までの期間が有意に短く、その原因は認知機能障害、体幹症状の進行などであった。【結語】PDに対するDBSにおいては多科による包括的な評価と管理が重要である。また、対象患者の高齢化により術後比較的早期に自宅での療養が困難となることが想定され、地域医療も含めた多職種連携が必要と考えられる。(著者抄録)

ガンマナイフ治療(GKS)を施行した脳転移患者における神経死(ND)および全身死(SD)のリスクを評価する新しいツールND・SDリスクアセスメントを提案し、その有用性について検討した。GKSを施行した脳転移患者連続3436例を対象とした。449例(13.1%)の生存、2987例(86.9%)の死亡を確認した。死亡2987例中、NDは480例(16.1%)、SDは2507例(83.9%)と判定された。GKS後1〜5年における累積発生率はNDで8.7%、12.6%、14.1%、14.9%、15.5%、SDで53.4%、68.7%、74.7%、77.8%、79.3%であった。多変量解析の結果、NDに対する頭蓋内予後影響因子として、頭蓋内総腫瘍体積、造影MRIの限局性髄液播種所見、腫瘍最大径が独立して有意であった。一方、SDに対する頭蓋外予後影響因子は、性別、初診時KPS score、原病巣制御、頭蓋外転移、遺伝子変異が独立して有意であった。

ガンマナイフ治療を施行した乳癌脳転移症例のうちGenetic Phenotype(GP)の情報の得られた394例を対象に、全生存、全身死、神経死、神経機能低下について検討した。Basal(HER2/ER/PRともに陰性)88例、Luminal A(HER2陰性、ERまたはPR陽性)105例、Luminal B(HER2陽性、ERまたはPR陽性)95例、HER2(HER2陽性、ER/PRともに陰性)106例であり、4群間の患者背景に有意差を認めなかった。102例(25.9%)の生存、292例(74.1%)の死亡を確認し、全生存中央値はBasal 7.4ヵ月、Luminal A 12.6ヵ月、HER2 14.5ヵ月、Luminal B 22.3ヵ月で4群間に有意差を認めた。全身死について神経死を競合リスクとしてGP別に評価したところ、ガンマナイフ治療後3年での累積発生頻度はBasal 74.4%、Luminal A 74.2%、HER2 55.2%、Luminal B 51.4%であり、4群間に有意差を認め、特にHER2陽性群では有意に発生頻度が低かった。さらに、神経死について全身死を競合リスクとしてGP別に評価したところ、ホルモン受容体陽性群で有意に発生頻度が低かった。

Background Hypotension is a significant risk factor for the development of ischemic complication following revascularization surgery for moyamoya disease (MMD). However, it is currently unknown whether autonomic dysfunction also plays a role. Case Description Here we report a case of MMD in which hypotension due to autonomic dysfunction caused postoperative cerebral ischemia. A 30-year-old female patient with MMD had a history of transient right hemiparesis following laughter. Single-photon emission computed tomography showed impaired cerebral blood flow (CBF) in both cerebral hemispheres, so she underwent revascularization surgery in her left cerebral hemisphere. She awoke from anesthesia uneventfully however, 1 hour after the surgery her blood pressure suddenly dropped to 90/40 mm Hg and she became comatose. A perfusion computed tomography scan demonstrated a widespread reduction in CBF in the left hemisphere. Bezold-Jarisch reflex was thought to be the cause of the hypotension. Following treatment with a vasopressor agent, her BP increased and her consciousness rapidly recovered. The reduced CBF had almost completely recovered the next day. Head-up tilt test conducted 2 weeks after surgery demonstrated latent vasopressor-type autonomic dysfunction, which was possibly another cause of the hypotension. She was discharged from the hospital, and the laughter-induced hemiparesis gradually resolved. Conclusion Situational neurologic deterioration in patients with MMD suggests latent autonomic dysfunction, which may be a risk factor for postoperative ischemic complications.

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.

Purpose: The JLGK0901 study showed the noninferiority of stereotactic radiosurgery (SRS) alone as initial treatment of 5 to 10 brain metastases (BMs) compared with 2 to 4 BMs in terms of overall survival and most secondary endpoints (Lancet Oncol 2014; 15: 387-95). However, observation periods were not long enough to allow confirmation of the long-term safety of SRS alone in patients with 5 to 10 BMs. Methods and Materials: This was a prospective observational study of Gamma Knife SRS-treated patients with 1 to 10 newly diagnosed BMs enrolled at 23 facilities between March 1, 2009, and February 15, 2012. Results: The 1194 eligible patients were categorized into the following groups: group A, 1 tumor (n=455); group B, 2 to 4 tumors (n=531); and group C, 5 to 10 tumors (n=208). Cumulative rates of Mini-Mental State Examination (MMSE) score maintenance (MMSE score decrease &lt;3 from baseline) determined with a competing risk analysis of groups A, B, and C were 93%, 91%, and 92%, respectively, at the 12th month after SRS; 91%, 89%, and 91%, respectively, at the 24th month; 89%, 88%, and 89%, respectively, at the 36th month; and 87%, 86%, and 89%, respectively, at the 48th month (hazard ratio [HR] of group A vs group B, 0.719; 95% confidence interval [CI], 0.437-1.172; PZ. 18; HR of group B vs group C, 1.280; 95% CI, 0.696-2.508; PZ. 43). During observations ranging from 0.3 to 67.5 months (median, 12.0 months; interquartile range, 5.826.5 months), as of December 2014, 145 patients (12.1%) had SRS-induced complications. Cumulative complication incidences by competing risk analysis for groups A, B, and C were 7%, 8%, and 6%, respectively, at the 12th month after SRS; 10%, 11%, and 11%, respectively, at the 24th month; 11%, 11%, and 12%, respectively, at the 36th month; and 12%, 12%, and 13%, respectively, at the 48th month (HR of group A vs group B, 0.850; 95% CI, 0.592-1.220; P=. 38; HR of group B vs group C, 1.052; 95% CI, 0.666-1.662, P=. 83). Leukoencephalopathy occurred in 12 of the 1074 patients (1.1%) with follow-up magnetic resonance imaging and was detected after salvage whole-brain radiation therapy in 11 of these 12 patients. In these 11 patients, leukoencephalopathy was detected by magnetic resonance imaging 5.2 to 21.2 months (median, 11.0 months; interquartile range, 7.0-14.4 months) after whole-brain radiation therapy. Conclusions: Neither MMSE score maintenance nor post-SRS complication incidence differed among groups A, B, and C. This longer-term follow-up study further supports the already-reported noninferiority hypothesis of SRS alone for patients with 5 to 10 BMs versus 2 to 4 BMs. (C) 2017 Elsevier Inc. All rights reserved.

【目的・背景】重粒子線治療は本邦が実運用に成功した技術である。我々は重粒子線治療後に誘発された二次性腫瘍の初の臨床2症例を経験し一昨年および昨年,国際学会にて発表した。本研究では,その臨床検体を用いた解析から染色体構造の変化を捉え得たので報告する。【症例報告】症例1:外耳道癌に対する重粒子線照射の4年後,片麻痺・失語・てんかん発作で発症した側頭葉病変で,摘出した腫瘤の病理は原疾患(扁平上皮がん)と全く異なる,海綿状血管腫であった。周囲脳には硝子化など放射線誘発性変化を伴っており,これら複数所見より重粒子線により発生した腫瘍であることが示された。症例2:上顎洞未分化癌への重粒子線照射の13年後,歯痛・頬腫脹・てんかん発作で発症した,眼窩から中頭蓋窩(側頭葉先端)まで拡がる腫瘍で,生検により重粒子線による二次性の骨肉腫と病理診断された。腫瘍は広範に浸潤しており,耳鼻咽喉科および脳外科による合同手術を行った。【結果】G-band染色ならびに腫瘍CGH+SNPアレイによる分析を行ったところ,欠失・逆位・転座を含む複数の染色体構造異常を見出だすことができた。【考察・今後の計画】以上より,X線・ガンマ線照射後に報告のある誘発腫瘍が,重粒子線治療後にも起こりうることを証明した。また,重粒子線誘発腫瘍においてgeneticな変化が起きている可能性を示した。但し同一腫瘍検体内に複数の個別の変異が含まれていることからは,構造変化を伴わず現時点で検出できていない共通する遺伝子異常が存在している可能性も示唆され,今後は塩基配列決定などにて,詳細な変異部位,更には腫瘍関連遺伝子の同定を目指す。(著者抄録)

Introduction: We aimed to examine temporal changes in health-related quality of life (HRQOL) and its relationship with motor and cognitive functions in patients with Parkinson's disease (PD) after subthalamic nucleus deep brain stimulation (STN-DBS). Methods: In total, 31 patients with PD were enrolled in this study (mean age: 66.7 +/- 0.9 years; mean disease duration: 11.6 +/- 3.7 years). Participants completed the Unified Parkinson's Disease Rating Scale and the Parkinson's Disease Questionnaire-39. Cognitive function was assessed using the Mini Mental State Examination, the Frontal Assessment Battery, and the Montreal Cognitive Assessment. Postoperative evaluation was performed at three months, one year, three years, and five years after surgery; temporal changes in the correlation between HRQOL and motor and cognitive functions were evaluated at all follow-up periods. Results: All patients completed postoperative clinical evaluations after three months, after one year. Of the 31 participants, twelve completed postoperative clinical evaluations after three years and seven after five years. Motor functions showed significant improvement over the five-year follow-up period. The mobility subdomain of the HRQOL worsened whereas the total score did not change significantly over years. Cognitive functions were not significantly impaired during follow-up periods. HRQOL was basically not significantly correlated with motor and cognitive functions during the follow-up period. Conclusions: The mobility subdomain of the HRQOL worsened after surgery, and the improvement in motor functions was basically not correlated with HRQOL after STN-DBS in patients with PD. Cognitive functions were not significantly impaired during follow-up periods. (C) 2017 Published by Elsevier B.V.

Background and Purpose-Venous oxygen saturation (SO2) is measured in medical fields to assess tissue circulation insufficiency. This study aimed to elucidate the use of a cortical venous redness measurement to evaluate hemodynamic changes during revascularization surgery for patients with moyamoya disease. Methods-In this retrospective case-series analysis, we first quantitatively measured and correlated SO2 and R intensity of 24-bit color digital red-green-blue pictures of blood samples from 3 volunteers. Subsequently, based on intraoperative digital pictures of 29 patients with moyamoya disease, we measured the R intensities of a cortical vein near the anastomosis site before and after anastomosis. Cerebral blood flow (CBF) at the site was measured using a single-photon emission computed tomography before and 1 to 3 days after surgery. Venous R intensity and CBF were measured twice by 4 raters, and their correlations were examined using generalized linear mixed effect model and linear regression analysis. Results-A strong linear correlation was found between blood R intensity and its SO2 (coefficients, 0.522; 95% confidence interval, 0.364-0.680, using generalized linear mixed effect model). Venous R intensity before the anastomosis was not correlated with preoperative CBF (coefficients, 0.000352; 95% confidence interval, -0.000369 to 0.00107, by generalized linear mixed effect); however, the increases in venous R intensity after anastomosis were correlated with postoperative increases in CBF (R-2, 0.367; 95% confidence interval, 0.116-0.618 to 0.548; 95% confidence interval, 0.331-0.764, by linear regression analysis). Conclusions-Cortical venous redness represented impaired CBF and could be a useful parameter for assessing hemodynamic changes during revascularization surgery.

Functional radiosurgery has advanced steadily during the past half century since the development of the gamma knife technique for treating intractable cancer pain. Applications of radiosurgery for intracranial diseases have increased with a focus on understanding radiobiology. Currently, the use of gamma knife radiosurgery to ablate deep brain structures is not widespread because visualization of the functional targets remains difficult despite the increased availability of advanced neuroimaging technology. Moreover, most existing reports have a small sample size or are retrospective. However, increased experience with intraoperative neurophysiological evaluations in radiofrequency thalamotomy and deep brain stimulation supports anatomical and neurophysiological approaches to the ventralis intermedius nucleus. Two recent prospective studies have promoted the clinical application of functional radiosurgery for movement disorders. For example, unilateral gamma knife thalamotomy is a potential alternative to radiofrequency thalamotomy and deep brain stimulation techniques for intractable tremor patients with contraindications for surgery. Despite the promising efficacy of gamma knife thalamotomy, however, these studies did not include sufficient follow-up to confirm long-term effects. Herein, we review the radiobiology literature, various techniques, and the treatment efficacy of gamma knife radiosurgery for patients with movement disorders. Future research should focus on randomized controlled studies and long-term effects. (C) 2016 International Parkinson and Movement Disorder Society

We aimed to reappraise whether post-stereotactic radiosurgery (SRS) results for brain metastases differ between patients with and without neurological symptoms. This was an institutional review board-approved, retrospective cohort study using our prospectively accumulated database including 2825 consecutive BM patients undergoing gamma knife SRS alone during the 15-year period since July 1998. The 2825 patients were divided into two groups; neurologically asymptomatic [group A, 1374 patients (48.6 %)] and neurologically symptomatic [group B, 1451 (51.4 %)]. Because there was considerable bias in pre-SRS clinical factors between groups A and B, a case-matched study was conducted. Ultimately, 1644 patients (822 in each group) were selected. The standard Kaplan-Meier method was used to determine post-SRS survival. Competing risk analysis was applied to estimate cumulative incidences of neurological death, neurological deterioration, local recurrence, re-SRS for new lesions and SRS-induced complications. Post-SRS median survival times (MSTs) did not differ between the two groups; 7.8 months in group A versus 7.4 months in group B patients (HR 1.064, 95 % CI 0.963-1.177, p = 0.22). However, cumulative incidences of neurological death (HR 1.637, 95 % CI 1.174-2.281, p = 0.0036) and neurological deterioration (HR 1.425, 95 % CI 1.073-1.894, p = 0.014) were significantly lower in the group A than in the group B patients. Neurologically asymptomatic patients undergoing SRS for BM had better results than symptomatic patients in terms of both maintenance of good neurological state and prolonged neurological survival. Thus, we conclude that screening computed tomography/magnetic resonance imaging is highly beneficial for managing cancer patients.

ObjectivesThis study aims to compare the surgical and functional outcomes of superolateral orbitotomy (group A) and conventional superior orbitotomy (group B) for benign orbital tumors. DesignA retrospective review of 31 consecutive orbital tumor surgeries with the fronto-orbital approach was conducted. SettingProcedures were performed at two institutions by a single surgeon. ParticipantsA total of 31 orbital tumor patients participated in this study. Overall, 11 intraconal and 2 extraconal tumors in group A and 11 intraconal and 7 extraconal tumors in group B were resected by superolateral orbitotomy, respectively. Main Outcome MeasuresDemographic information, pre- and postoperative neurological findings and neuroimaging data, and pathological data were collected. Surgical and functional outcomes were compared and statistically analyzed between the two different surgical procedures. ResultsThe surgical outcomes were not significantly different between the two groups. In patients with intraconal tumors, the functional outcome was significantly better in group A than in group B. ConclusionSuperolateral orbitotomy provides better functional outcomes.

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