Preplanned Partial Surgical Removal Followed by Low-Dose Gamma Knife Radiosurgery for Large Vestibular Schwannomas.

OBJECTIVE: The present study evaluated outcomes after preplanned partial surgical removal of a large vestibular schwannoma (VS) followed by low-dose Gamma Knife surgery (GKS). METHODS: Between January 2000 and May 2015, 47 patients with a unilateral VS (median maximum diameter 32 mm) underwent preplanned partial tumor removal at our clinic. GKS for a residual lesion was done within a median time interval of 3 months. The median prescription dose was 12 Gy. The median length of subsequent follow-up was 74 months. RESULTS: The actuarial tumor growth control rates without a need for additional management at 3, 5, and 15 years after GKS were 92%, 86%, and 86%, respectively. At the time of the last follow-up, the function of the ipsilateral facial nerve corresponded to House-Brackmann grade I in 92% of patients. Significant improvement of ipsilateral hearing was noted in two patients after partial tumor removal and in one after GKS. Among 16 patients who presented with ipsilateral serviceable hearing, it was preserved immediately after surgery in 81% of cases and at the time of the last follow-up in 44%. Salvage surgical treatment was required in 9% of patients. CONCLUSION: Preplanned partial surgical removal followed by low-dose GKS provides a high level of functional preservation in patients with a large VS.

Salvage gamma knife radiosurgery for active brain metastases from small-cell lung cancer after whole-brain radiation therapy: a retrospective multi-institutional study (JLGK1701).

PURPOSE: To evaluate the efficacy of gamma knife radiosurgery (GKS) for brain metastases (BMs) from small-cell lung cancer after whole-brain radiotherapy (WBRT). METHODS: We retrospectively analyzed the usefulness and safety of GKS in 163 patients from 15 institutions with 1-10 active BMs after WBRT. The usefulness and safety of GKS were evaluated using statistical methods. RESULTS: The median age was 66 years, and 79.1% of patients were men. The median number and largest diameter of BM were 2.0 and 1.4 cm, respectively. WBRT was administered prophylactically in 46.6% of patients. The median overall survival (OS) was 9.3 months, and the neurologic mortality was 20.0%. Crude incidences of local control failure and new lesion appearance were 36.6% and 64.9%, respectively. A BM diameter ≥ 1.0 cm was a significant risk factor for local progression (hazard ratio [HR] 2.556, P = 0.039) and neurologic death (HR 4.940, P = 0.031). Leukoencephalopathy at the final follow-up was more prevalent in the therapeutic WBRT group than in the prophylactic group (P = 0.019). The symptom improvement rate was 61.3%, and neurological function was preserved for a median of 7.6 months. Therapeutic WBRT was not a significant risk factor for OS, neurological death, local control, or functional deterioration (P = 0.273, 0.490, 0.779, and 0.560, respectively). Symptomatic radiation-related adverse effects occurred in 7.4% of patients. CONCLUSIONS: GKS can safely preserve neurological function and prevent neurologic death in patients with 1-10 small, active BMs after prophylactic and therapeutic WBRT.

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.

Pediatric thalamic glioma with H3F3A K27M mutation, which was detected before and after malignant transformation: a case report.

PURPOSE: Histone H3.3 (H3F3A) mutation in the codon for lysine 27 (K27M) has been found as driver mutations in pediatric glioblastoma and has been suggested to play critical roles in the pathogenesis of thalamic gliomas and diffuse intrinsic pontine gliomas. We report a case of thalamic glioma with H3F3A K27M mutation, which was detected in both the primary tumor diagnosed as diffuse astrocytoma obtained during the first surgery and also in the tumor diagnosed as anaplastic astrocytoma obtained at the second surgery. CASE PRESENTATION: A 14-year-old girl presented with mild headache. Magnetic resonance imaging (MRI) showed a small intraaxial lesion in the left thalamus, which increased in size. Stereotactic tumor biopsy was performed 2 years after the initial diagnosis, and a pathological diagnosis of diffuse astrocytoma (WHO grade 2) was made. The tumor grew further and showed contrast enhancement on MRI despite 16 months of chemotherapy. Surgical removal via the transcallosal approach was then performed, and postoperative pathological diagnosis was anaplastic astrocytoma (WHO grade 3), indicating malignant transformation of the tumor. Molecular diagnosis of tumor tissue obtained at first and second surgeries revealed H3F3A K27M mutation in both primary and secondary specimens. CONCLUSION: This report demonstrates minute neuroradiological and pathological features of malignant transformation from thalamic low grade glioma with H3F3A K27M mutation. It is noteworthy that this mutation was found in this case when the tumor was still a low-grade glioma. Tissue sampling for genetic analysis is useful in patients with thalamic gliomas to predict the clinical course and efficacy of treatments.

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.

[An endoscopic transnasal transsphenoidal biopsy for pituitary gland Langerhans cell histiocytosis in a child: a case report].

Endoscopic transnasal transsphenoidal surgery is gaining wide acceptance as the first-line treatment of pituitary tumors in adults, as this procedure is minimally invasive and associated with good outcomes. On the other hand, conventional transcranial and sublabial approaches are chosen for infants as their small anatomical structures pose some difficulty. This study reports on the case of a 5-year-old boy who had a Langerhans cell histiocytosis appearing in the sella. The biopsy was performed using the endoscopic transnasal transsphenoidal approach, and the patient has not exhibited any post-operative complications. Although the patient was a fairly young child, the endoscopic transnasal transsphenoidal approach resulted in fewer complications as compared to the transcranial and translabial approaches. Otolaryngologists, therefore, should view this approach more positively. The indication for pediatric skull base diseases can be expected to expand to include endoscopic transnasal surgery.

Cerebral Arteriovenous Malformation With Ipsilateral Middle Cerebral Artery Occlusion: A Case Report.

We report the case of a 29-year-old man who presented with a sudden headache. Computed tomography showed a small intraventricular hemorrhage in the left lateral ventricle. Cerebral angiograms suggested rupture of a coexisting feeder aneurysm in the left temporal cerebral arteriovenous malformation (AVM). The left proximal middle cerebral artery, a major feeding artery, was occluded near the AVM, with development of abnormal blood supply, such as in moyamoya-like vessels to the nidus. After endovascular embolization of the coexisting feeder aneurysm and feeding arteries, the patient underwent volume-staged Gamma Knife radiosurgery (GKS). Follow-up angiograms performed 4.5 years after the last GKS confirmed complete disappearance of the AVM. Around 4.8 years after GKS, the patient required surgical intervention to develop delayed cyst formation; however, the postoperative course was uneventful.

Gamma Knife Radiosurgery for Metastatic Brain Tumors from Uterine Cervical and Endometrial Carcinomas: Histopathological Analysis of Survival and Local Control. A Japanese Multi-Institutional Cooperative and Retrospective Cohort Study.

OBJECTIVE: A retrospective comparative analysis of the outcomes of gamma knife radiosurgery (GKRS) for brain metastases from uterine cervical carcinoma (CC) and endometrial carcinoma (EC), investigated the efficacy and prognostic factors for survival and local tumor control. Histopathological analysis was also performed. METHODS: The authors retrospectively reviewed 61 patients with 260 tumors of CC and 73 patients with 302 tumors of EC who had undergone GKRS. RESULTS: The survival times after GKRS had no difference between CC and EC. Uncontrolled primary cancer was significant unfavorable factor. CC resulted in significantly higher neurological death and post-GKRS neurological deterioration. New lesions appeared intracranially after GKRS, with no significant difference between CC and EC. Local tumor control rates at 6, 12, and 24 months after GKRS were 90.0%, 86.6%, and 78.0% for CC and 92.2%, 87.9%, and 86.4% for EC. Primary cancer of CC, more than 7 cm3 volume, and prescription dose less than 20 Gy were significantly correlated in control failure. Local tumor control rates were significantly lower for squamous cell carcinoma in CC. No significant differences were found between histopathological subtypes of EC. CONCLUSIONS: This study established a relationship between the efficacy of GKRS for CC and EC brain metastases and the histopathological. Though, survival time after GKRS has no difference between CC and EC, CC was significantly higher neurogenic death and neurological deterioration after GKRS. Squamous cell carcinoma had a significantly lower rate of local tumor control among all CC, thereby resulting in CC having lower local tumor control than EC.

Gamma Knife radiosurgery for metastatic brain tumors from ovarian cancer: histopathological analysis of survival and local control. A Japanese multi-institutional cooperative and retrospective cohort study.

OBJECTIVE: Brain metastasis is rare in ovarian cancer patients. The results of Gamma Knife radiosurgery (GKRS) for the treatment of patients with brain metastases from ovarian cancer were retrospectively analyzed to derive the efficacy and prognostic factors for survival and local tumor control. Further histopathological analysis was also performed. METHODS: The authors retrospectively reviewed the medical records of 118 patients with 566 tumors who had undergone GKRS at the 10 GKRS institutions in Japan. RESULTS: After the initial GKRS, the median overall survival time was 18.1 months. Multivariate analysis showed that uncontrolled primary cancer (p = 0.003) and multiple intracranial metastases (p = 0.034) were significant unfavorable factors. Ten patients died of uncontrolled brain metastases at a median of 17.1 months. The 6-, 12-, and 24-month neurological death rates were 3.2%, 4.6%, and 11.9%, respectively. The 6-, 12-, and 24-month neurological deterioration rates were 7.2%, 13.5%, and 31.4%, respectively. The 6-, 12-, and 24-month distant brain control failure rates were 20.6%, 40.2%, and 42.3%, respectively. Median tumor volume was 1.6 cm3 and marginal dose was 20 Gy. The 6-, 12-, and 24-month local tumor control rates were 97.6%, 95.2%, and 88.0%, respectively. Peritumoral edema (p = 0.043), more than 7-cm3 volume (p = 0.021), and prescription dose less than 18 Gy (p = 0.014) were factors that were significantly correlated in local tumor control failure. Eight patients had symptomatic radiation injury. The 6-, 12-, and 24-month GKRS-related complication rates were 3.3%, 7.8%, and 12.2%, respectively. Primary ovarian cancer was histopathologically diagnosed for 313 tumors in 69 patients. Serous adenocarcinoma was found in 37 patients and other types in 32 patients. Median survival times were 32.3 months for the serous type and 17.4 months for other types after initial GKRS. Patients with serous-type tumors survived significantly longer than patients with other types (p = 0.039). The 6-, 12-, and 24-month local tumor control rates were 100%, 98.8%, and 98.8%, respectively. Serous-type tumors were a significantly good prognosis factor for local tumor control after GKRS (p = 0.005). CONCLUSIONS: This study established a relationship between the efficacy of GKRS treatment for brain metastases and the histological type of primary ovarian cancer. GKRS for ovarian cancer brain metastasis can provide satisfactory survival and local control, especially in cases of serous adenocarcinoma.

A Practical Grading Scale for Predicting Outcomes of Radiosurgery for Dural Arteriovenous Fistulas: JLGK 1802 Study.

BACKGROUND AND PURPOSE: To assess the long-term outcomes of intracranial dural arteriovenous fistula (DAVF) treated with stereotactic radiosurgery (SRS) alone or embolization and SRS (Emb-SRS) and to develop a grading system for predicting DAVF obliteration. METHODS: This multi-institutional retrospective study included 200 patients with DAVF treated with SRS or Emb-SRS. We investigated the long-term obliteration rate and obliteration-associated factors. We developed a new grading system to estimate the obliteration rate. Additionally, we compared the outcomes of SRS and Emb-SRS by using propensity score matching. RESULTS: The 3- and 4-year obliteration rates were 66.3% and 78.8%, respectively. The post-SRS hemorrhage rate was 2%. In the matched cohort, the SRS and Emb-SRS groups did not differ in the rates of obliteration (P=0.54) or post-SRS hemorrhage (P=0.50). In multivariable analysis, DAVF location and cortical venous reflux (CVR) were independently associated with obliteration. The new grading system assigned 2, 1, and 0 points to DAVFs in the anterior skull base or middle fossa, DAVFs with CVR or DAVFs in the superior sagittal sinus or tentorium, and DAVFs without these factors, respectively. Using the total points, patients were stratified into the highest (0 points), intermediate (1 point), or lowest (≥2 points) obliteration rate groups that exhibited 4-year obliteration rates of 94.4%, 71.3%, and 60.4%, respectively (P<0.01). CONCLUSIONS: SRS-based therapy achieved DAVF obliteration in more than three-quarters of the patients at 4 years of age. Our grading system can stratify the obliteration rate and may guide physicians in treatment selection.

[Transsphenoidal surgery for pituitary tumors from microsurgery to the endoscopic surgery: single surgeon's experience].

We reviewed results of the surgical outcome of pituitary tumors treated via the transsphenoidal approach between January, 1994 and January, 2010 at our institution. This data included 100 patients (124 procedures) treated through the sublabial transsphenoidal approach and 45 patients (54 procedures) treated through the endoscopic endonasal (bilateral nostrils) transsphenoidal approach performed by a single surgeon. The extent of tumor removal was significantly improved with endoscopic surgery; adjuvant gamma knife radiosurgery was needed for 65% of patients undergoing microsurgery vs. 30% for patients who had endoscopic surgery (p<0.0001). Patients who underwent endoscopic surgery had less intraoperative blood loss (mean volume: 100 mL for microsurgery patients vs. 30 mL for endoscopic surgery patients, p<0.0001), less pain, and less need for postoperative hormone replacement therapy (19% for microsurgery patients vs. 6% for endoscopic surgery patients; p<0.05). CSF leakage and meningitis were experienced in one microsurgery patient (1%) and one endoscopic surgery patient (2.2%). Endoscopic surgery is a reasonable alternative to microsurgery and our experience supports the concept that an otolaryngologist/neurosurgeon team skilled in endoscopic techniques and pituitary surgery can safely make the transition from microsurgery to endoscopic surgery.

Gamma Knife Radiosurgery for Concurrent Trigeminal Neuralgia and Glossopharyngeal Neuralgia.

An 82-year-old female had suffered right facial pain since 37 years of her age. The trigeminal neuralgia (TN) was controlled by carbamazepine and peripheral nerve block. The local block was effective for two to three years once performed, and as it became less effective, the patient took carbamazepine. Four months before gamma knife radiosurgery (GKRS), TN worsened. Analysis of her blood sample revealed autoimmune hemolytic anemia. It was suspected to be related to carbamazepine, and the patient stopped taking carbamazepine. The patient suffered pharyngeal pain and had difficulty swallowing for two months before GKRS. Tube feeding was started one month before GKRS. The patient was considered in pain due to TN and glossopharyngeal neuralgia (GPN). We performed GKRS continuously on the right cisternal portion of the trigeminal nerve at a maximum radiosurgical dose of 85 Gy for TN, and on the right cisternal portion of the glossopharyngeal nerve at a maximum dose of 80 Gy for GPN on the same day. The facial pain improved the day after GKRS. Seven days after treatment, the patient could swallow without pharyngeal pain, and the gastric tube was removed. Thirteen months after GKRS, the TN re-occurred but was controlled by carbamazepine 400 mg per day. GPN did not recur at that time. Simultaneous GKRS for concurrent TN and GPN is a less invasive and useful treatment option for non-candidates for surgical interventions.

Gamma Knife Surgery for Residual or Recurrent Craniopharyngioma After Surgical Resection: A Multi-institutional Retrospective Study in Japan.

Objective The optimal treatment for a craniopharyngioma has been controversial. Complete resection is ideal, but it has been difficult to obtain total resection in many cases because of intimate proximity to critical structures such as the optic pathway, hypothalamus, and pituitary gland. A growing number of studies have demonstrated the utility of radiosurgery in controlling residual or recurrent craniopharyngioma. However, most of them are small series. The aim of this multi-institutional study was to clarify the efficacy and safety of Gamma Knife (Elekta, Stockholm, Sweden) surgery for patients with a craniopharyngioma. Methods This was a multi-institutional retrospective study by 16 medical centers of the Japan Leksell Gamma Knife Society. Data on patients with craniopharyngiomas treated with Gamma Knife Surgery (GKS) between 1991 and 2013 were obtained from individual institutional review board-approved databases at each center. A total of 242 patients with craniopharyngioma were included in this study. The mean age of the patients was 41 (range, 3 to 86) years. The median follow-up time was 61.4 months (range, 3 to 180 months). The mean radiosurgery target volume was 3.1 ml (range, 0.03-22.3 ml), and the mean marginal dose was 11.4 Gy (range, 8-20.4 Gy). Results Two-hundred twenty patients were alive at the time of the last follow-up visit. The three-, five-, and 10-year overall survival rates after GKS were 95.4%, 92.5%, and 82.0%, respectively. The three-, five-, and 10-year progression-free survival rates after GKS were 73.1%, 62.2%, and 42.6% respectively. The rate of radiation-induced complications was 6.2%. Conclusion GKS is effective for controlling the tumor growth of craniopharyngiomas with an acceptable complication rate.

[Experience in the treatment for intracranial arteriovenous shunts in children].

PURPOSE: To report our experiences in the treatment for intracranial arteriovenous shunts (AV shunts) in the pediatric population. MATERIAL AND METHODS: Twelve children with intracranial AV shunts were treated with endovascular embolization between December 1993 and March 2008. These comprised two cases of vein of Galen aneurysmal malformation, three of dural sinus malformation, two of infantile dural AV shunt, five of pial AV fistula including two of vein of Galen aneurysmal dilatation. There were eleven boys and one girl. The age at the first embolization ranged from day 0 to 9 years. We reviewed their clinical features and outcomes. RESULTS: Six patients including four neonates presented with congestive heart failure, one infant with macrocrania and three children with headache, seizure or ataxia. The number of endovascular embolization ranged from one to five per patient. These included eighteen transarterial embolizations and ten transvenous embolizations. All patients except for one who died eventually from pulmonary hemorrhage showed improvement in their symptoms. Although only five patients achieved complete occlusion of AV shunts, six patients including them developed normally. CONCLUSION: Intracranial AV shunts in the pediatric population present characteristic clinical features depending on the age of the presentation. Endovascular embolization is currently the treatment of choice for them. It is more important to obtain normal development than to achieve normal morphological appearance. It is also important to understand the difference of pathophysiological features of these diseases in the pediatric and adult population.

Intracavernous Hemangiopericytoma: Case Report and Review of the Literature.

Intracavernous hemangiopericytoma/solitary fibrous tumor is an extremely rare tumor, with only seven cases reported. We present a case of intracavernous hemangiopericytoma/solitary fibrous tumor and review all cases reported in the literature. A 67-year-old man experienced numbness over the left half of the face. Magnetic resonance imaging revealed a left intracavernous tumor extending into Meckel's cave and the posterior fossa. We performed gamma knife surgery (GKS) which a prescribed dose to the tumor of 12 Gy, but tumor recurred 43 months after GKS. We performed partial tumor resection via a subtemporal interdural approach. The pathological diagnosis was hemangiopericytoma. Postoperatively, we performed second GKS with a prescribed dose of 15 Gy. Diplopia and ptosis improved markedly and the tumor initially reduced in size, but tumor regrowth was seen again 29 months after second GKS. Third GKS was performed with a prescribed dose of 15 Gy. Recurrence was not seen at 18 months after third GKS, but was identified about 2 years after third GKS. We performed fourth GKS with a prescribed dose to the residual tumor of 16 Gy. We report a rare case of intracavernous hemangiopericytoma originating in the cavernous sinus, but distinguishing between hemangiopericytoma and schwannoma is difficult for round, intracavernous tumors showing homogeneous enhancement without flow voids. GKS might be one of the options for residual and recurrent intracavernous hemangiopericytomas.

Staged Gamma Knife Radiosurgery for Large Skull Base Meningiomas.

PURPOSE: The authors have been treating skull base meningiomas using relatively low-dose gamma knife radiosurgery (GKS, ≤ 12 Gy) with acceptable tumor growth control and low morbidity. In the present study, volume-staged, low-dose GKS was performed for large skull base meningiomas with a maximum diameter > 4 cm. In this article, a treatment strategy for volume-staged GKS and results for large skull base meningiomas are described. METHODS: Data from 27 patients with large skull base meningiomas histopathologically diagnosed as WHO grade I or diagnosed by imaging, who underwent volume-staged GKS between March 1995 and September 2018, were reviewed. Among these patients, 24 were followed-up for > six months. The tumor was located in the parasellar region in nine patients, cavernous sinus region in four, petroclival region in four, petrocavernous sinus region in four, cerebellopontine angle region in two, and in the tent in one. The mean tumor diameters ranged from 31 to 47.8 mm (median 39.4 mm), with tumor volumes between 14.7 and 49.5 cm3 (median 27.5 cm3). RESULTS: The prescribed radiation dose was 8-12 Gy (median 10 Gy). The treatment interval between the first and second GKS was three to nine months (median 5.5 months). The median duration of follow-up after the first GKS was 84 months (range 6-204 months). Tumor volume decreased in nine (37.5%) patients, remained stable in nine (37.5%), and increased (local failure) in six (25%). The actuarial progression-free local control rate was 88% at three years, 78% at five years, 70% at 10 years, and 70% at 15 years. Neurological status improved in three (12.5%) patients, was unchanged in 16 (66.5%), and deteriorated in five (21%). Permanent radiation injury occurred in one (4%) patient. CONCLUSION: Volume-staged GKS demonstrated the usefulness for large skull meningiomas > 4 cm in diameter, over a long-term follow-up period.

Diagnostic accuracy of 11C-methionine PET for differentiation of recurrent brain tumors from radiation necrosis after radiotherapy.

UNLABELLED: We evaluated the diagnostic accuracy of PET with l-methyl-(11)C-methionine ((11)C-MET) for the differentiation of recurrent brain tumors from radiation necrosis. METHODS: Seventy-seven patients who had been previously treated with radiotherapy after primary treatment for metastatic brain tumor (n=51) or glioma (n=26) were studied to clarify the diagnostic performance of (11)C-MET PET in differentiating between recurrent brain tumors and radiation necrosis. A total of 88 PET scans with (11)C-MET were obtained; sometimes more than one scan was obtained when there was an indication of recurrent brain tumor or radiation necrosis. A definitive diagnosis was made on the basis of pathologic examination for recurrent brain tumors and on the basis of pathologic examination or clinical course for radiation necrosis. Several indices characterizing the lesions were determined; these included mean and maximum standardized uptake values (SUV(mean) and SUV(max), respectively) and the ratios of lesion uptake to contralateral normal frontal-lobe gray matter uptake corresponding to the SUV(mean) and the SUV(max) (L/N(mean) and L/N(max), respectively). Receiver-operating-characteristic (ROC) curve analysis was used to determine the optimal index of (11)C-MET PET and cutoff values for the differential diagnosis of tumor recurrence and radiation necrosis. RESULTS: The values of each index of (11)C-MET PET tended to be higher for tumor recurrence than for radiation necrosis. There were significant differences between tumor recurrence and radiation necrosis in all of the indices except for the L/N(max) for glioma. ROC analysis indicated that the L/N(mean) was the most informative index for differentiating between tumor recurrence and radiation necrosis. An L/N(mean) of greater than 1.41 provided the best sensitivity and specificity for metastatic brain tumor (79% and 75%, respectively), and an L/N(mean) of greater than 1.58 provided the best sensitivity and specificity for glioma (75% and 75%, respectively). CONCLUSION: (11)C-MET PET can provide quantitative values to aid in the differentiation of tumor recurrence from radiation necrosis, although these values do not appear to be absolute indicators. Quantitative analysis of (11)C-MET PET data may be helpful in managing irradiated brain tumors.

Gamma Knife radiosurgery for skull base meningioma: long-term results of low-dose treatment.

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.

A case of hypopituitarism due to inflammatory myofibroblastic tumor of the sella turnica.

An 18-year-old man with 4-year history of central diabetes insipidus and partial pituitary dysfunction was admitted to our hospital because of headache and nasal discharge. Magnetic resonance imaging (MRI) revealed abnormal mass in the sella turnica invading into the cavernous sinus and sinus maxillaries along with thickened tentorium cerebelli. Histopathology of the mass in the sinus maxillaries revealed spindle-shaped cells arranged in a fascicular pattern with varied myxoid and collagenized regions with various inflammatory cells. Immunostaining revealed the spindle-shaped cells were positive for smooth muscle actin. These features were identical to those of inflammatory myofibroblastic tumor (IMT). He was diagnosed with IMT in the sella turnica and other regions. Corticosteroid therapy improved clinical symptoms and follow-up MRI revealed amelioration of the thickened tentorium cerebelli. However, the other lesions were unchanged and pituitary dysfunction did not improve. Although rare, IMT should be considered in the differential diagnosis of a sellar mass. Early treatment with corticosteroid therapy may reduce the risk of disease progression.

Boost radiosurgery for treatment of brain metastases after surgical resections.

BACKGROUND: We evaluated results of resection surgery followed by boost radiosurgery for the treatment of brain metastases. METHODS: We treated 21 patients (13 male, 8 female) with surgical resection (subtotal or total) followed by boost radiosurgery. The mean patient age was 61 years (range, 41-80 years); supratentorial lesions were treated in 12 patients, and posterior fossa lesions were treated in 9 patients. The most common primary cancers were lung (24%) and colon (24%). Fifty-three percent of patients had brain metastases only, whereas 47% had extracranial metastases. The radiosurgery dose plan was designed to radiate the operative cavity; the mean treatment volume (50% isodose) was 10.7 mL (range, 3.4-23.3 mL), and the mean marginal dose was 17 Gy (range, 13-20 Gy). RESULTS: Local control was achieved in 16 (76%) patients. However, new intracranial lesions developed in 10 patients, and meningeal carcinomatosis occurred in 5 patients. Local tumor recurrence occurred more often for patients treated with lower radiotherapy doses (<18 vs > or =18 Gy, P = .03), and meningeal carcinomatosis occurred more often in patients with posterior fossa lesions (P = 0.05). Gamma knife radiosurgery was performed in 13 patients, and whole-brain radiation was performed in 2 patients. No patients experienced symptomatic radiation injury, and the median survival time was 20 months. CONCLUSIONS: Although boost radiosurgery is less invasive and reduces morbidity, the radiosurgical dose must be higher than 18 Gy for the treatment to be most effective. Treatment of lesions of the posterior fossa must be considered carefully because of the higher frequency of meningeal carcinomatosis. Also, we recommend that the surgeons who operate on the metastatic tumors must try to decrease the resected cavity volume and to prevent cerebrospinal fluid dissemination at the operation for posterior fossa lesions.