Mixed pial and dural arteriovenous fistula after craniotomy: case report and literature review.

Dural arteriovenous fistula (AVF) is known to occur after craniotomy, but mixed pial and dural AVF after craniotomy has not been reported. A 45-year-old man who had undergone surgical clipping of an unruptured aneurysm 2 years previously presented with small subcortical hemorrhage from mixed pial and dural AVF. Surgical disconnection could not be cured completely due to the granulomatous tissue around the aneurysm, and the presence of an undetected shunt. Postoperative digital subtraction angiography showed a new pial AVF supplied by the middle cerebral artery pial branches. Many branches were associated with the remnant aneurysm and pial AVF, so we did not try to embolize the fistula. Gamma knife surgery was performed as adjuvant radiotherapy, which achieved angiographically complete occlusion of the shunt points. Multimodal approaches including surgery, endovascular intervention, and radiotherapy are needed for radiological and clinical cure of mixed pial and dural AVF. Long-term follow up is essential.

Pituitary Radiosurgery for Management of Intractable Pain: Tokyo Women's Medical University Experience and Literature Review.

Surgical or chemical hypophysectomy has historically shown good effectiveness in management of intractable pain but has often been accompanied by serious complications. In contrast, high-dose irradiation of the pituitary gland and stalk provides comparable analgesic effects and is associated with minimal morbidity. Although its physiological mechanism remains elusive, pituitary radiosurgery using the Gamma Knife has demonstrated high clinical efficacy and safety in cases of both cancer pain and noncancer pain. According to the available data, this treatment provides at least a temporary analgesic effect in >80% of patients, usually within hours to days after the procedure. Although the pain relief is most prominent and durable in cases of metastatic bone disease, it is not limited to that pathological condition or to cases of hormone-dependent cancers. Nevertheless, the low-quality studies reported to date cannot support any meaningful clinical recommendations on use of pituitary radiosurgery. Therefore, additional well-elaborated clinical and basic investigations, preferably performed in a multi-institutional and prospective fashion, are clearly needed and may bolster further developments of this highly promising treatment modality.

Gamma Knife Radiosurgery for Symptomatic Cavernous Malformations: Tokyo Women's Medical University Experience.

OBJECTIVE: This retrospective study evaluated the results of Gamma Knife surgery (GKS) for symptomatic cavernous malformations (CM) of the brain. METHODS: From 1993 till 2014, 11 patients (mean age 44 years) with a symptomatic CM underwent GKS at Tokyo Women's Medical University. In six cases, the disease manifested with hemorrhaging. Seizures and a neurological deficit were noted in four patients each. The CM were located in the brainstem (in 5 cases), basal ganglia (in 2 cases), thalamus (in 2 cases), and cerebral lobe (in 2 cases). The mean lesion volume was 1.46 cc. The mean marginal dose was 15.3 Gy. The mean length of follow-up after GKS was 78.5 months. RESULTS: At the last follow-up, the general status was considered excellent, fair, and poor in 8 patients (73%), 1 patient (9%), and 2 patients (18%), respectively. The annual hemorrhage rates per case-year were 2.94% from birth till GKS, 20.20% from the first hemorrhage till GKS, 4.54% within the first 2 years after GKS, and 1.39% within the entire follow-up period after GKS. Two patients attained seizure-free status after treatment. CONCLUSION: GKS may be considered as a possible management option for symptomatic CM, since it reduces the subsequent hemorrhage risk after the initial bleeding episode. Moreover, in some patients, cessation of symptomatic epilepsy after treatment may be expected.

Outcome After Resection of Craniopharyngiomas and the Important Role of Stereotactic Radiosurgery in Their Management.

OBJECTIVE: Experience with management of craniopharyngiomas (CPH) was evaluated retrospectively. METHODS: Between 1981 and 2012, 100 patients underwent removal of a CPH (the main surgical group), and an original tumor grading system was applied to these cases. The mean length of follow-up was 121 months. Additionally, 17 patients underwent removal of a CPH between 2012 and 2017 (the supplementary surgical group), and in 6 of them, CyberKnife radiosurgery was performed on a residual tumor (in 5 cases) or at the time of recurrence (in 1 case). RESULTS: In the main surgical group, the gross total resection (GTR) rate was 81%. The early and late disease-specific postoperative mortality rates were 0% and 2%, respectively. Tumor recurrence was never noted after GTR. There was a statistically significant increase in the Karnofsky Performance Scale (KPS) score after surgery. The tumor surgical grade was inversely associated with both the pre- and postoperative KPS scores, and was lower in cases operated on via the transnasal transsphenoidal approach, but was unrelated to the GTR rate. In the supplementary surgical group, the GTR rate was 65%. CyberKnife radiosurgery consistently resulted in tumor shrinkage. CONCLUSION: GTR is the preferred management option for CPH. The original surgical grading system developed at Tokyo Women's Medical University may be helpful for clinical decision-making. CyberKnife radiosurgery for residual and recurrent CPH is associated with high tumor response rates.

Gamma Knife Radiosurgery for Pituitary Adenomas Invading the Cavernous Sinus: Tokyo Women's Medical University Experience.

Total surgical removal of a pituitary adenoma (PA) invading the cavernous sinus (CS) is challenging and carries a significant risk of postoperative complications. As an alternative treatment strategy, after incomplete resection, such tumors may undergo stereotactic radiosurgery-in particular, Gamma Knife surgery (GKS). Treatment planning based on advanced neuroimaging (e.g., thin-slice 3-dimensional postcontrast constructive interference in steady state (CISS) images) allows clear visualization of the target microanatomy, which results in highly conformal and selective radiation delivery to the lesion with preservation of adjacent functionally important neurovascular structures. In the Tokyo Women's Medical University experience of GKS for 43 nonfunctioning and 46 hormone-secreting PA invading the CS, with a minimum follow-up period of 5 years (mean 76 months, range 60-118 months), the tumor control rate has reached 97%, and a significant volume reduction (≥50%) has been seen in 24% of lesions. In cases of hormone-secreting neoplasms, normalization (in 18 patients; 39%) or improvement (in 22 patients; 48%) of endocrinological function has been noted. Importantly, such effects have been sufficiently durable. Complications have been extremely rare and limited to transient cranial nerve palsy (in 2% of cases). Notably, no patient in our series has had a new pituitary hormone deficit after irradiation. Thus, subtotal resection followed by GKS may be considered a valuable alternative to aggressive surgery for a PA invading the CS.

Gamma Knife Radiosurgery for Metastatic Brain Tumors from Malignant Melanomas: A Japanese Multi-Institutional Cooperative and Retrospective Cohort Study (JLGK1501).

BACKGROUND: The incidences of metastatic brain tumors from malignant melanomas have increased and survival has been prolonged by novel molecular targeted agents and immunotherapy. However, malignant melanomas are uncommon in Asian populations. OBJECTIVES: We retrospectively analyzed treatment efficacy and identified prognostic factors impacting tumor control and survival in Japanese melanoma patients with brain metastases treated with gamma knife radiosurgery (GKRS). METHODS: We retrospectively reviewed the medical records of 177 patients with 1,500 tumors who underwent GKRS for brain metastases from malignant melanomas. This study was conducted by the Japanese Leksell Gamma Knife Society (JLGK1501). RESULTS: Six and 12 months after GKRS, the cumulative incidences of local tumor recurrence were 9.2 and 13.8%. Intratumoral hemorrhage (p < 0.0001) and larger tumor volume (p = 0.001) in GKRS were associated with significantly poorer local control outcomes. The use of immune checkpoint inhibitors before GKRS was significantly associated with symptomatic adverse events (p = 0.037). The median overall survival time after the initial GKRS was 7.3 months. Lower Karnofsky performance status scores (p = 0.016), uncontrolled primary cancer (p < 0.0001), and multiple brain metastases (p = 0.014) significantly influenced unfavorable overall survival outcomes. The cumulative incidences of neurological death 6 and 12 months after GKRS were 9.7 and 17.4%, those of neurological deterioration were 14.2 and 19.6%, and those of new tumor appearance were 34.5 and 40.5%. CONCLUSIONS: The results of the present multicenter study suggest that GKRS is a relatively effective and safe modality for control of tumor progression in Japanese patients with brain metastases from malignant melanomas.

Safety and efficacy of Gamma Knife radiosurgery in hypothalamic hamartomas with severe epilepsies: A prospective trial in 48 patients and review of the literature.

Epilepsies associated with hypothalamic hamartomas (HHs) are frequently drug resistant with severe psychiatric and cognitive comorbidities. We performed a prospective trial to evaluate the safety and efficacy of Gamma Knife radiosurgery (GKS). Between October 1999 and October 2007, a total of 57 patients were investigated, included and treated by GKS in Timone University Hospital. Preoperative workup and 3-year postoperative evaluation consisted of seizure diary, neuropsychological, psychiatric, endocrinologic, visual field, and visual acuity examinations. Follow-up of >3 years was available for 48 patients. Topologic type was type I in 11 patients, type II in 15, type III in 17, type IV in one, type V in one, type VI in one, and mixed type in 2. The median marginal dose was 17 Gy (min 14 and max 25 Gy). The median target volume was 398 mm3 (28-1,600 mm3 ). Due to partial results, 28 patients (58.3%) required a second treatment. The median follow-up was 71 months (36-153 months). At last follow-up, the rate of Engel class I outcome was 39.6%, Engel class II was 29.2% (I+II 68.8%), and Engel class III was 20%. Global psychiatric comorbidity was considered cured in 28%, improved in 56%, stable in 8%, and continued to worsen in 8%. No permanent neurologic side effect was reported (in particular, no memory deficit). Nondisabling transient poikilothermia was observed in three patients (6.2%). A transient increase of seizure frequency was reported in 8 patients (16.6%) with a median duration of 30 days (9-90 days). Microsurgery was proposed because of insufficient efficacy of GKS in seven patients (14.5%) with a postoperative Engel class I-II in 28.6%. This prospective trial demonstrates very good long-term safety and efficacy of GKS for 2 patients. Beyond seizure reduction, the improvement of psychiatric and cognitive comorbidities along with better school performance and social functioning, being better socially integrated, having friends having a social life, working, participating to group activities turn out to be major benefits of GKS in this group of patients with frequently catastrophic epilepsy.

Is upfront stereotactic radiosurgery a rational treatment option for very elderly patients with brain metastases? A retrospective analysis of 106 consecutive patients age 80 years and older.

BACKGROUND: Advanced age has been shown to be a factor predicting poor survival in patients with brain metastases (BM). There have been only a few studies focusing on stereotactic radiosurgery (SRS) for elderly BM patients. The present study aimed to investigate the efficacy and limitations of SRS for very elderly BM patients. METHODS: This was a retrospective observational study analyzing 106 consecutive patients (69 males/37 females) age 80 years and older who received upfront Gamma Knife SRS for BM between January 2009 and October 2015. The median age was 84 years, and the median Karnofsky performance status (KPS) was 70. Fifty-two patients had a solitary BM, and others multiple BM. The median cumulative tumor volume was 3.9 mL and the median dose prescribed was 20 Gy. Overall survival (OS), neurological death rates and distant and local intracranial tumor control rates were analyzed. RESULTS: No patients were lost to follow-up. Six-month and 12-month OS rates were 54% and 32%, respectively. The median OS time was 7.1 months. Competing risks analysis showed that 6-month and 12-month neurological death rates were 8% and 11%, respectively. In total, 245 / 311 tumors (79%) in 82 patients (77%) with sufficient radiological follow-up data were evaluated. Six-month and 12-month distant BM recurrence rates (per patient) after SRS were 17% and 25%, respectively. Six-month and 12-month rates of local tumor control (per lesion) were 94% and 89%, respectively. Repeat SRS, salvage WBRT and surgical resection were subsequently required in 25, 4 and 1 patient, respectively. Proportional hazard regression analysis showed that KPS ≥ 70 (HR: 0.444, P < .001), controlled primary disease/no extracranial metastases (HR: 0.361, P < .001) and female sex (HR: 0.569, P = 0.028) were independent factors predicting better OS. Similarly, tumor volume (>2 mL) was the only factor predicting a higher rate of local control failure (HR: 12.8, P = 0.003). CONCLUSIONS: The present study suggested an upfront SRS strategy to offer a feasible and effective treatment option for very elderly patients with limited BM. In the majority of patients, neurological death could be delayed or even prevented.

Salvage stereotactic radiosurgery with adjuvant use of bevacizumab for heavily treated recurrent brain metastases: a preliminary report.

It is not uncommon for brain metastasis (BM) treated with stereotactic radiosurgery (SRS) to demonstrate radiographic enlargement, with the patient developing neurological deficits attributable to a lesion at the site of SRS. The management of both local recurrence and radiation-induced necrosis (RN) poses a significant therapeutic dilemma, if surgical resection is not feasible, and effective therapies have yet to be established. This preliminary study introduces our initial experience with salvage SRS using adjuvant bevacizumab for this refractory entity. We retrospectively reviewed five patients who had received salvage SRS using adjuvant bevacizumab for recurrent BM complicated by RN. The diagnosis was based on clinical features, serial imaging studies and/or histopathological findings. Patients underwent salvage SRS followed by the first cycle of bevacizumab (7.5-10 mg/kg intravenous). Bevacizumab was repeated every 3-4 weeks until tumor progression or significant toxic events. The number of bevacizumab doses ranged from 2 to 16 (median 4). Follow-up MR imaging demonstrated a clear radiographic response in all lesions. Neurological symptoms improved in three patients and stabilized in two. In two patients, bevacizumab treatment was discontinued due to anemia and gastrointestinal bleeding, respectively. At the time of data analysis, four patients had died and the other was still alive. The causes of death were neurological decline and systemic disease progression in two patients each. Salvage SRS with adjuvant bevacizumab use appeared to provide an adequate radiographic response as well as neurological palliation for selected patients with heavily treated recurrent BM complicated by RN.

Is stereotactic radiosurgery a rational treatment option for brain metastases from small cell lung cancer? A retrospective analysis of 70 consecutive patients.

BACKGROUND: Because of the high likelihood of multiple brain metastases (BM) from small cell lung cancer (SCLC), the role of focal treatment using stereotactic radiosurgery (SRS) has yet to be determined. We aimed to evaluate the efficacy and limitations of upfront and salvage SRS for patients with BM from SCLC. METHODS: This was a retrospective and observational study analyzing 70 consecutive patients with BM from SCLC who received SRS. The median age was 68 years, and the median Karnofsky performance status (KPS) was 90. Forty-six (66%) and 24 (34%) patients underwent SRS as the upfront and salvage treatment after prophylactic or therapeutic whole brain radiotherapy (WBRT), respectively. Overall survival (OS), neurological death-free survival, remote and local tumor recurrence rates were analyzed. RESULTS: None of our patients were lost to follow-up and the median follow-up was 7.8 months. One-and 2-year OS rates were 43% and 15%, respectively. The median OS time was 7.8 months. One-and 2-year neurological death-free survival rates were 94% and 84%, respectively. In total, 219/292 tumors (75%) in 60 patients (86 %) with sufficient radiological follow-up data were evaluated. Six-and 12-month rates of remote BM relapse were 25% and 47%, respectively. Six-and 12-month rates of local control failure were 4% and 23%, respectively. Repeat SRS, salvage WBRT and microsurgery were subsequently required in 30, 8 and one patient, respectively. Symptomatic radiation injury, treated conservatively, developed in 3 patients. CONCLUSIONS: The present study suggested SRS to be a potentially effective and minimally invasive treatment option for BM from SCLC either alone or after failed WBRT. Although repeat salvage treatment was needed in nearly half of patients to achieve control of distant BM, such continuation of radiotherapeutic management might contribute to reducing the rate of neurological death.

Modern Gamma Knife radiosurgery of vestibular schwannomas: treatment concept, volumetric tumor response, and functional results.

The objective of the present study was longitudinal evaluation of the volumetric tumor response and functional results after Gamma Knife radiosurgery of vestibular schwannomas, performed according to the modern standards of treatment. From October 2003 to September 2007, 133 consecutive patients with vestibular schwannomas were treated according to the concept of robotic Gamma Knife microradiosurgery, which is based on precise irradiation of the lesion, sparing adjacent structures, and delivery of the high radiation energy to the target. Multiple small-sized isocenters located within the border of the neoplasm were applied. The mean marginal dose was 11.5 Gy (range, 11-12 Gy). In total, 126 cases with a minimum posttreatment follow-up of 2 years (range, 2-7 years; median, 4 years) were analyzed. Temporary enlargement was noted in 25% of tumors at 6 months after radiosurgery. At 3 years of follow-up, tumor shrinkage, stabilization, and increase in volume were marked in 73%, 23%, and 4% of cases, respectively. All progressing lesions spontaneously stabilized later on and did not require additional management. In 3% of patients, transitory impairment of the facial nerve function was marked; however, neither its permanent dysfunction nor trigeminal neuropathy attributed to radiosurgery was noted. Impairment of hearing compared to its pretreatment level was revealed in 4%, 12%, 13%, and 16% of patients at 6 months, 1 year, 2 years, and 3 years after radiosurgery, respectively, and this trend was statistically significant (P = 0.0042). Overall, 77% of patients with serviceable hearing before treatment preserved it 3 years thereafter. In conclusion, modern Gamma Knife radiosurgery provides effective and safe management of vestibular schwannomas. Nevertheless, possible temporary tumor enlargement, delay of its growth arrest, transient dysfunction of the cranial nerves, and gradual deterioration of hearing after irradiation should be always taken into consideration.

Proposed therapeutic strategy for adult low-grade glioma based on aggressive tumor resection.

OBJECT There is no standard therapeutic strategy for low-grade glioma (LGG). The authors hypothesized that adjuvant therapy might not be necessary for LGG cases in which total radiological resection was achieved. Accordingly, they established a treatment strategy based on the extent of resection (EOR) and the MIB-1 index: patients with a high EOR and low MIB-1 index were observed without postoperative treatment, whereas those with a low EOR and/or high MIB-1 index received radiotherapy (RT) and/or chemotherapy. In the present retrospective study, the authors reviewed clinical data on patients with primarily diagnosed LGGs who had been treated according to the above-mentioned strategy, and they validated the treatment policy. Given their results, they will establish a new treatment strategy for LGGs stratified by EOR, histological subtype, and molecular status. METHODS One hundred fifty-three patients with diagnosed LGG who had undergone resection or biopsy at Tokyo Women's Medical University between January 2000 and August 2010 were analyzed. The patients consisted of 84 men and 69 women, all with ages ≥ 15 years. A total of 146 patients underwent surgical removal of the tumor, and 7 patients underwent biopsy. RESULTS Postoperative RT and nitrosourea-based chemotherapy were administered in 48 and 35 patients, respectively. Extent of resection was significantly associated with both overall survival (OS; p = 0.0096) and progression-free survival (PFS; p = 0.0007) in patients with diffuse astrocytoma but not in those with oligodendroglial subtypes. Chemotherapy significantly prolonged PFS, especially in patients with oligodendroglial subtypes (p = 0.0009). Patients with a mutant IDH1 gene had significantly longer OS (p = 0.034). Multivariate analysis did not identify MIB-1 index or RT as prognostic factors, but it did identify chemotherapy as a prognostic factor for PFS and EOR as a prognostic factor for OS and PFS. CONCLUSIONS The findings demonstrated that EOR was significantly correlated with patient survival; thus, one should aim for maximum tumor resection. In addition, patients with a higher EOR can be safely observed without adjuvant therapy. For patients with partial resection, postoperative chemotherapy should be administered for those with oligodendroglial subtypes, and repeat resection should be considered for those with astrocytic tumors. More aggressive treatment with RT and chemotherapy may be required for patients with a poor prognosis, such as those with diffuse astrocytoma, 1p/19q nondeleted tumors, or IDH1 wild-type oligodendroglial tumors with partial resection.

Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study.

BACKGROUND: We aimed to examine whether stereotactic radiosurgery without whole-brain radiotherapy (WBRT) as the initial treatment for patients with five to ten brain metastases is non-inferior to that for patients with two to four brain metastases in terms of overall survival. METHODS: This prospective observational study enrolled patients with one to ten newly diagnosed brain metastases (largest tumour <10 mL in volume and <3 cm in longest diameter; total cumulative volume ≤15 mL) and a Karnofsky performance status score of 70 or higher from 23 facilities in Japan. Standard stereotactic radiosurgery procedures were used in all patients; tumour volumes smaller than 4 mL were irradiated with 22 Gy at the lesion periphery and those that were 4-10 mL with 20 Gy. The primary endpoint was overall survival, for which the non-inferiority margin for the comparison of outcomes in patients with two to four brain metastases with those of patients with five to ten brain metastases was set as the value of the upper 95% CI for a hazard ratio (HR) of 1·30, and all data were analysed by intention to treat. The study was finalised on Dec 31, 2012, for analysis of the primary endpoint; however, monitoring of stereotactic radiosurgery-induced complications and neurocognitive function assessment will continue for the censored subset until the end of 2014. This study is registered with the University Medical Information Network Clinical Trial Registry, number 000001812. FINDINGS: We enrolled 1194 eligible patients between March 1, 2009, and Feb 15, 2012. Median overall survival after stereotactic radiosurgery was 13·9 months [95% CI 12·0-15·6] in the 455 patients with one tumour, 10·8 months [9·4-12·4] in the 531 patients with two to four tumours, and 10·8 months [9·1-12·7] in the 208 patients with five to ten tumours. Overall survival did not differ between the patients with two to four tumours and those with five to ten (HR 0·97, 95% CI 0·81-1·18 [less than non-inferiority margin], p=0·78; pnon-inferiority<0·0001). Stereotactic radiosurgery-induced adverse events occurred in 101 (8%) patients; nine (2%) patients with one tumour had one or more grade 3-4 event compared with 13 (2%) patients with two to four tumours and six (3%) patients with five to ten tumours. The proportion of patients who had one or more treatment-related adverse event of any grade did not differ significantly between the two groups of patients with multiple tumours (50 [9%] patients with two to four tumours vs 18 [9%] with five to ten; p=0·89). Four patients died, mainly of complications relating to stereotactic radiosurgery (two with one tumour and one each in the other two groups). INTERPRETATION: Our results suggest that stereotactic radiosurgery without WBRT in patients with five to ten brain metastases is non-inferior to that in patients with two to four brain metastases. Considering the minimal invasiveness of stereotactic radiosurgery and the fewer side-effects than with WBRT, stereotactic radiosurgery might be a suitable alternative for patients with up to ten brain metastases. FUNDING: Japan Brain Foundation.

The efficacy and limitations of stereotactic radiosurgery as a salvage treatment after failed whole brain radiotherapy for brain metastases.

The aim of the present study was to evaluate the efficacy and limitations of repeat stereotactic radiosurgery (SRS) salvage for patients with recurrence of brain metastases (BM) after whole brain radiotherapy (WBRT). This is a retrospective, observational, single-center trial analyzing 77 consecutive patients with recurrent BM who were treated primarily with WBRT. All patients underwent SRS as salvage treatment. Median age was 62 years, and median Karnofsky performance status (KPS) was 80. The median interval between the starting date of WBRT and radiosurgery was 10.6 months. One, two and more than two SRS sessions were required in 42, 13 and 22 patients, respectively. The median total planning target volume (PTV) was 8.1 mL and the median dose prescribed was 20 Gy. The median follow-up was 7.7 months. 1- and 2-year neurological death-free survival (NS) rates were 87 and 78 %, respectively. Competing risk analysis demonstrated active extra-central nervous system (CNS) disease [Hazard ratio (HR) 0.236, P = 0.041] and total PTV on initial SRS (≥ 5 mL) (HR 4.22, P = 0.033) to be associated with the NS rate. 1- and 2-year overall survival (OS) rates were 41 and 11 %, respectively. The median OS time was 8.2 months. Active extra-CNS disease (HR 1.94, P = 0.034) and high KPS (≥ 90) (HR 0.409, P = 0.006) were associated with the OS rate. In total, 798 tumors (75 %) in 66 patients (86 %) with sufficient radiological follow-up data were evaluated. 1- and 2-year metastasis local control rates were 76.6 and 57.9 %, respectively. Prescribed dose (≥ 20 Gy) (HR 0.326, P < 0.001), tumor volume (≥ 2 mL) (HR 1.98, P = 0.007) and metastases from breast cancer (HR 0.435, P < 0.001) were independent predictive factors for local tumor control. Repeat salvage SRS for recurrent BM after WBRT appeared to be a safe and effective treatment. In the majority of patients, even those with numerous BM, neurological death could be delayed or even prevented.

Impacts of HER2-overexpression and molecular targeting therapy on the efficacy of stereotactic radiosurgery for brain metastases from breast cancer.

Advances in chemotherapy for breast cancer (BC) have prolonged overall survival, especially for patients with human epidermal growth factor receptor-2 (HER2) positive cancer. We evaluated the effectiveness and limitations of stereotactic radiosurgery (SRS) for brain metastases (BM) from BC in conjunction with molecular targeting chemotherapy. Outcomes were retrospectively reviewed in 80 consecutive patients who underwent gamma knife SRS for BM from BC between January 2009 and February 2012. The overall survival (OS), neurological death-free survival (NS) and local tumor control endpoints were calculated, and prognostic factors were investigated using proportional hazards models. In 40 patients with HER2-overexpression, treatment results were compared between two sub-groups: lapatinib-based therapy (24 patients) versus non-lapatinib-based therapy (16 patients). The rates of 1- and 2-year OS after SRS were 50 and 26 %, respectively. The median survival time (MST) was 11.4 months. HER2-overexpression (P < 0.001), recursive partitioning analysis class (P = 0.018) and total planning target volume on initial SRS (P = 0.004) were associated with OS. The MSTs in HER2-positive and -negative patients were 16.6 and 7.1 months, respectively (P = 0.001). The rates of 1- and 2-year NS were 90 and 78 %, respectively. The rates of 1- and 2-year local tumor control were 84 and 70 %, respectively. Factors associated with local tumor control included lesion volume (P < 0.001) and peripheral dose (P = 0.003). In sub-analysis of patients with HER2-overexpression, lapatinib-based chemotherapy was also associated with better local tumor control (P = 0.002). The 1-year local tumor control rate of the lapatinib group was significantly better than that of the non-lapatinib group (86 vs. 69 %, P < 0.001). SRS is a safe and effective management option for selected patients with BM from BC. Patients with HER2-overexpressing tumors were found to be a distinct subgroup for which a longer survival time can be expected. Synergistic anti-tumor effects of lapatinib on BM in conjunction with SRS were suggested.

How to control propofol infusion in pediatric patients undergoing gamma knife radiosurgery.

INTRODUCTION: Although Gamma Knife radiosurgery (GKS) is commonly performed under local anesthesia, general anesthesia is sometimes required. The authors previously reported a remote-controlled patient management system consisting of propofol-based general anesthesia with a target-controlled infusion (TCI) that we designed for pediatric GKS. However, a commercially available propofol TCI system has age and weight limitations (<16 years and <30 kg). We examined a manually controlled regimen of propofol appropriate for pediatric GKS. METHODS: A pharmacokinetic model of the TIVA Trainer© with Paedfusor's parameter was used. A manually controlled infusion scheme to achieve a sufficient level of propofol for pediatric GKS was examined in five models ranging from 10 to 30 kg. RESULTS: Following a loading dose of 3.0 mg/kg, the combination of continuous infusion of 14, 12, 10, and 8 mg/kg/h resulted in a target concentration of 3.0-4.0 µg/ml, the required level for pediatric GKS. CONCLUSION: Propofol titration is a key issue in GKS. Manual infusion is less accurate than TCI, but the combination of a small bolus and continuous infusion might be a substitute. Considering the characteristics of propofol pharmacokinetics in children, co-administration of opioids is recommended.

Optimal visualization of multiple brain metastases for gamma knife radiosurgery.

BACKGROUND: Optimal management of metastatic brain disease requires precise detection and detailed characterization of all intracranial lesions. METHODS: We analyzed an experience with 3200 brain MRI investigations performed at 1.5 T and 3.0 T for identification and/or evaluation of intracranial metastases. Usually axial T1- and T2-weighted images and contrast-enhanced T1-weighted images in axial and coronal and/or sagittal projections were obtained. Fluid-attenuated inversion recovery and diffusion-weighted imaging were sometimes used as well. Routinely, 0.2 mmol/kg of gadoteridol (ProHance®) was administered intravenously, but the dose was reduced to 0.1 mmol/kg in elderly patients or in patients with mild renal dysfunction. FINDINGS: Magnetic resonance imaging (MRI) provided excellent information on tumor location; interrelations with functionally important intracranial structures; type of growth; vascularity; recent, old or multiple hemorrhages within or in the vicinity of the mass; presence of peritumoral edema; necrotic changes; subarachnoid dissemination; meningeal carcinomatosis. However, without administration of gadoteridol or without contrast enhancement, small metastatic tumors could not be reliably distinguished from brain lacunes. Some metastases (malignant melanoma, thyroid cancer, endocrine carcinoma, small cell lung carcinoma) may demonstrate specific neuroimaging features. Non-metastatic -multiple brain lesions caused by vascular, inflammatory, demyelinative or lymphoproliferative diseases require a thorough differential diagnosis with metastatic brain tumors based not only on neuroimaging but on additional analysis of various clinical data. CONCLUSION: Contemporary MRI techniques provide excellent options for detection, detailed characterization, and differential diagnosis of metastatic brain tumors, which is extremely important when choosing the optimal treatment strategy, particularly with Gamma Knife radiosurgery.

Concept of robotic gamma knife microradiosurgery and results of its clinical application in benign skull base tumors.

The availability of advanced computer-aided robotized devices for the Gamma Knife (i.e., an automatic positioning system and PerfeXion) resulted in significant changes in radiosurgical treatment strategy. The possibility of applying irradiation precisely and the significantly improved software for treatment planning led to the development of the original concept of robotic Gamma Knife microradiosurgery, which is comprised of the following: (1) precise irradiation of the lesion with regard to conformity and selectivity; (2) intentional avoidance of excessive irradiation of functionally important anatomical structures, particularly cranial nerves, located both within the target and in its vicinity; (3) delivery of sufficient radiation energy to the tumor with a goal of shrinking it while keeping the dose at the margins low enough to prevent complications. Realization of such treatment principles requires detailed evaluation of the microanatomy of the target area, which is achieved with an advanced neuroimaging protocol. From 2003, we applied the described microradiosurgical concept in our clinic for patients with benign skull base tumors. Overall, 75 % of neoplasms demonstrated shrinkage, and 47 % showed ≥50 % and more volume reduction. Treatment-related complications were encountered in only 6 % of patients and were mainly related to transient cranial nerve palsy. Just 2 % of neoplasms showed regrowth after irradiation. In conclusion, applying the microradiosurgical principles based on advanced neuroimaging and highly precise treatment planning is beneficial for patients, providing a high rate of tumor shrinkage and a low morbidity rate.

Gamma knife treatment strategy for metastatic brain tumors.

From 1993 to 2011, a total of 3,095 patients with brain metastases underwent Gamma Knife radiosurgery (GKS) at Tokyo Women's Medical University. Follow-up information on 2,283 of these patients was available for retrospective analysis. The cases were separated into three groups according to the treatment period, the model of the Gamma Knife used, main goals of treatment, and technical nuances of radiosurgery. In the latest cohort of patients treated with the Leksell Gamma Knife model 4C with automatic positioning system, an optimized treatment strategy was applied. It was based on highly selective dose planning, with the use of multiple small isocenters located within the bulk of the mass, which was done for prevention of the excessive irradiation of the perilesional brain and avoidance of its posttreatment edema. In cases of large cystic tumors, selective coverage of the contrast-enhancing capsule with chain-like application of multiple small isocenters was done. Introduction of the new treatment strategy did not affect the 1-year tumor control rate, which was consistently >90 %. However, it did result in a statistically significant reduction of severe posttreatment peritumoral brain edema (from 15.5 % to 6.3 %; P < 0.0001). In conclusion, recent technical and methodological achievements of GKS seemingly do not affect its high efficacy in cases of brain metastasis with regard to tumor control. However, it may result in a prominent reduction of treatment-associated -morbidity, which is particularly important in patients with large and/or critically located neoplasm.