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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Gamma Knife Radiosurgery for Trigeminal Neuralgia Associated with Osteogenesis Imperfecta.

BACKGROUND: Trigeminal neuralgia is a rare feature of basilar impression, a complication of osteochondrodysplasic disorders. Microvascular decompression is difficult in medically refractory cases. Gamma knife radiosurgery (GKS) is effective for classical trigeminal neuralgia, and we first applied this GKS for a patient suffering from trigeminal neuralgia with basilar impression complicated by osteogenesis imperfecta. CASE DESCRIPTION: An 18-year-old man with type I osteogenesis imperfecta presented with a 2-year history of typical left trigeminal neuralgia affecting the ophthalmic, maxillary, and mandibular nerves. His condition was poorly controlled by carbamazepine and pregabalin. Magnetic resonance imaging confirmed severe basilar impression and an elongated cisternal portion of the left trigeminal nerve. GKS was performed under local anesthesia. The middle part of the cisternal portion of the left trigeminal nerve was chosen as the radiosurgical target, despite the lack of neurovascular compression. The maximum radiosurgical dose was 85 Gy, using a single 4-mm collimator. The patient's trigeminal neuralgia improved by 1 month after GKS, and at 21 months after GKS he remained free of pain and medications. CONCLUSIONS: We report a case of trigeminal neuralgia resulting from severe basilar impression. Conventional microvascular decompression would not have been an appropriate treatment for this patient, so GKS was used. GKS is a simple and effective option even in cases with severe cranial deformity.

Gamma Knife radiosurgery for brain metastases from pulmonary large cell neuroendocrine carcinoma: a Japanese multi-institutional cooperative study (JLGK1401).

OBJECTIVE In 1999, the World Health Organization categorized large cell neuroendocrine carcinoma (LCNEC) of the lung as a variant of large cell carcinoma, and LCNEC now accounts for 3% of all lung cancers. Although LCNEC is categorized among the non-small cell lung cancers, its biological behavior has recently been suggested to be very similar to that of a small cell pulmonary malignancy. The clinical outcome for patients with LCNEC is generally poor, and the optimal treatment for this malignancy has not yet been established. Little information is available regarding management of LCNEC patients with brain metastases (METs). This study aimed to evaluate the efficacy of Gamma Knife radiosurgery (GKRS) for patients with brain METs from LCNEC. METHODS The Japanese Leksell Gamma Knife Society planned this retrospective study in which 21 Gamma Knife centers in Japan participated. Data from 101 patients were reviewed for this study. Most of the patients with LCNEC were men (80%), and the mean age was 67 years (range 39-84 years). Primary lung tumors were reported as well controlled in one-third of the patients. More than half of the patients had extracranial METs. Brain metastasis and lung cancer had been detected simultaneously in 25% of the patients. Before GKRS, brain METs had manifested with neurological symptoms in 37 patients. Additionally, prior to GKRS, resection was performed in 17 patients and radiation therapy in 10. A small cell lung carcinoma-based chemotherapy regimen was chosen for 48 patients. The median lesion number was 3 (range 1-33). The median cumulative tumor volume was 3.5 cm3, and the median radiation dose was 20.0 Gy. For statistical analysis, the standard Kaplan-Meier method was used to determine post-GKRS survival. Competing risk analysis was applied to estimate GKRS cumulative incidences of maintenance of neurological function and death, local recurrence, appearance of new lesions, and complications. RESULTS The overall median survival time (MST) was 9.6 months. MSTs for patients classified according to the modified recursive partitioning analysis (RPA) system were 25.7, 11.0, and 5.9 months for Class 1+2a (20 patients), Class 2b (28), and Class 3 (46), respectively. At 12 months after GKRS, neurological death-free and deterioration-free survival rates were 93% and 87%, respectively. Follow-up imaging studies were available in 78 patients. The tumor control rate was 86% at 12 months after GKRS. CONCLUSIONS The present study suggests that GKRS is an effective treatment for LCNEC patients with brain METs, particularly in terms of maintaining neurological status.

Delayed cyst formations and/or expanding hematomas developing after Gamma Knife surgery for cerebral arteriovenous malformations.

The authors retrospectively analyzed cyst formations and expanding haematomas (EHs) that developed after Gamma Knife surgery (GKS) for arteriovenous malformations (AVMs), and evaluated the treatment results of these lesions. Cyst formations and/or EHs which developed after GKS for AVMs were identified in 20 patients (5.0%) out of 404 patients who underwent this procedure. There were nine patients with cyst formations, two with EHs and nine with cyst formations with EHs. These lesions developed between 36 and 192months (median 99months) after GKS. The median nidus volume was 4.7ml (range, 1.8-14.2ml) and the median prescribed margin dose was 20Gy (range, 15-23Gy). The multivariate analysis showed no correlation between the appearance of cyst formations and/or EHs and the patients' age, sex, nidus volume, margin dose, repeated GKS, nidus obliteration, pre-GKS embolization and prior hemorrhage. Surgical treatment was required in nine patients. Eight patients had total removal of the angiomatous lesions (EHs or nodular lesions that were detected as enhancement part on MRI) via a craniotomy and one had a cyst aspiration. There was no recurrence of the lesions in all the patients that underwent a craniotomy. In the patient treated with a cyst aspiration, regrowth of the cyst formation occurred. Surgical treatment should be considered for symptomatic lesions and we recommend total removal of the angiomatous lesions to achieve a complete cure.

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.

Functional Outcomes of Salvage Surgery for Vestibular Schwannomas after Failed Gamma Knife Radiosurgery.

OBJECTIVE: We reviewed our experience with salvage surgery following failed gamma knife radiosurgery (GKS) for vestibular schwannomas. METHODS: The study comprised 18 patients with unilateral vestibular schwannomas. The median prescribed radiation dose was 12 Gy (range, 10-12.5 Gy). Nine patients had regrowth after GKS, and 9 had regrowth after surgical resection plus GKS. The median interval between GKS and surgical resection was 26 months (range: 4-66 months). The maximum tumor diameter of all patients ranged 25-43 mm (median 35.5 mm). The tumor was removed subtotally in 2 patients and partially in the other 16 patients. The median follow-up period after surgical resection was 60 months (range: 12-144 months). RESULTS: Among the 17 patients with preoperative preserved facial nerve function (House-Brackmann [HB] grade I-III), 14 of them (82%) had an HB score of grade I at the last follow-up. There were no differences in facial nerve preservation between those with failed GKS and those with failed GKS plus surgery (78% vs. 100%, P = 0.156). At the post-salvage surgery follow-up, the residual tumor was unchanged or decreased in 15 patients (83%) and increased in 3 patients (17%). CONCLUSION: A surgical indication after GKS should be carefully considered because of the natural regression of transient tumor expansion with time, and surgical resection is limited to subtotal or partial removal for functional preservation. Careful follow-up is necessary in patients with tumor regrowth several years after GKS due to delayed radiation effects.

Treatment Results of Gamma Knife Radiosurgery for Central Neurocytoma: Report of a Japanese Multi-Institutional Cooperative Study.

OBJECTIVE: Central neurocytoma (CN) is a rare benign neuronal tumor, and a limited number of reports have described the usefulness of radiosurgery for a relatively large group of patients. We evaluated the effectiveness and outcomes of Gamma Knife radiosurgery (GKS) for CN in a Japanese multi-institutional study. METHODS: We performed retrospective analysis of 36 patients with CN who were treated with GKS in 12 institutes in Japan. All patients underwent surgery before GKS. The median tumor volume at GKS was 4.9 mL (range, 0.07-23.4 mL), and the median radiation dose prescribed to the tumor margin was 15 Gy (range, 10-20 Gy). The median follow-up period was 54.5 months (range, 3-180 months). RESULTS: The local tumor progression-free survival rates at 5 and 10 years were 94% and 86%, respectively. Three patients developed distant dissemination 16-90 months later. Overall progression-free survival was unrelated to the prescribed dose (<15 Gy vs. ≥15 Gy, P = 0.62), tumor size (<6 mL vs. ≥6 mL, P = 0.46), gender (P = 0.36), age (<30 vs. ≥30 years, P = 0.37), target of GKS (residual vs. recurrence, P = 0.90), and type of enhancement (homogeneous vs. inhomogeneous, P = 0.19). Two permanent complications occurred with 1 intratumoral hemorrhage and 1 radiation injury. CONCLUSIONS: GKS is effective for CN because of its high rate of long-term local tumor control. GKS may have a potential role as a primary treatment for asymptomatic, relatively small tumors in the absence of hydrocephalus without surgical resection.

Gamma Knife surgery for patients with jugular foramen schwannomas: a multiinstitutional retrospective study in Japan.

OBJECTIVE This study aimed to explore the efficacy and safety of stereotactic radiosurgery in patients with jugular foramen schwannomas (JFSs). METHODS This study was a multiinstitutional retrospective analysis of 117 patients with JFSs who were treated with Gamma Knife surgery (GKS) at 18 medical centers of the Japan Leksell Gamma Knife Society. The median age of the patients was 53 years. Fifty-six patients underwent GKS as their initial treatment, while 61 patients had previously undergone resection. At the time of GKS, 46 patients (39%) had hoarseness, 45 (38%) had hearing disturbances, and 43 (36%) had swallowing disturbances. Eighty-five tumors (73%) were solid, and 32 (27%) had cystic components. The median tumor volume was 4.9 cm3, and the median prescription dose administered to the tumor margin was 12 Gy. Five patients were treated with fractionated GKS and maximum and marginal doses of 42 and 21 Gy, respectively, using a 3-fraction schedule. RESULTS The median follow-up period was 52 months. The last follow-up images showed partial remission in 62 patients (53%), stable tumors in 42 patients (36%), and tumor progression in 13 patients (11%). The actuarial 3- and 5-year progression-free survival (PFS) rates were 91% and 89%, respectively. The multivariate analysis showed that pre-GKS brainstem edema and dumbbell-shaped tumors significantly affected PFS. During the follow-up period, 20 patients (17%) developed some degree of symptomatic deterioration. This condition was transient in 12 (10%) of these patients and persistent in 8 patients (7%). The cause of the persistent deterioration was tumor progression in 4 patients (3%) and adverse radiation effects in 4 patients (3%), including 2 patients with hearing deterioration, 1 patient with swallowing disturbance, and 1 patient with hearing deterioration and hypoglossal nerve palsy. However, the preexisting hoarseness and swallowing disturbances improved in 66% and 63% of the patients, respectively. CONCLUSIONS GKS resulted in good tumor control in patients with either primary or residual JFSs. Although some patients experienced some degree of symptomatic deterioration after treatment, persistent adverse radiation effects were seen in only 3% of the entire series at the last follow-up. Lower cranial nerve deficits were extremely rare adverse radiation effects, and preexisting hoarseness and swallowing disturbances improved in two-thirds of patients. These results indicated that GKS was a safe and reasonable alternative to surgical resection in selected patients with JFSs.

Gamma Knife surgery for patients with facial nerve schwannomas: a multiinstitutional retrospective study in Japan.

OBJECTIVE: The aim of this study was to explore the efficacy and safety of stereotactic radiosurgery for patients with facial nerve schwannomas (FNSs). METHODS: This study was a multiinstitutional retrospective analysis of 42 patients with FNSs treated with Gamma Knife surgery (GKS) at 1 of 10 medical centers of the Japan Leksell Gamma Knife Society (JLGK1301). The median age of the patients was 50 years. Twenty-nine patients underwent GKS as the initial treatment, and 13 patients had previously undergone surgery. At the time of the GKS, 33 (79%) patients had some degree of facial palsy, and 21 (50%) did not retain serviceable hearing. Thirty-five (83%) tumors were solid, and 7 (17%) had cystic components. The median tumor volume was 2.5 cm(3), and the median prescription dose to the tumor margin was 12 Gy. RESULTS: The median follow-up period was 48 months. The last follow-up images showed partial remission in 23 patients and stable tumors in 19 patients. Only 1 patient experienced tumor progression at 60 months, but repeat GKS led to tumor shrinkage. The actuarial 3- and 5-year progression-free survival rates were 100% and 92%, respectively. During the follow-up period, 8 patients presented with newly developed or worsened preexisting facial palsy. The condition was transient in 3 of these patients. At the last clinical follow-up, facial nerve function improved in 8 (19%) patients, remained stable in 29 (69%), and worsened in 5 (12%; House-Brackmann Grade III in 4 patients, Grade IV in 1 patient). With respect to hearing function, 18 (90%) of 20 evaluated patients with a pure tone average of ≤ 50 dB before treatment retained serviceable hearing. CONCLUSIONS: GKS is a safe and effective treatment option for patients with either primary or residual FNSs. All patients, including 1 patient who required repeat GKS, achieved good tumor control at the last follow-up. The incidence of newly developed or worsened preexisting facial palsy was 12% at the last clinical follow-up. In addition, the risk of hearing deterioration as an adverse effect of radiation was low. These results suggest that GKS is a safe alternative to resection.

Pituitary metastases: current practice in Japan.

OBJECT: With advancement of cancer treatment and development of neuroimaging techniques, contemporary clinical pictures of pituitary metastases (PMs) must have changed from past reports. The goal of this paper was to elucidate the clinical features of PMs and current clinical practice related to those lesions. In this retrospective study, questionnaires were sent to 87 physicians who had treated PMs in Japan. RESULTS: Between 1995 and 2010, 201 patients with PMs were treated by the participating physicians. The diagnosis of PM was histologically verified in 69 patients (34.3%). In the other 132 patients (65.7%), the PM was diagnosed by their physicians based on neuroimaging findings and clinical courses. The most frequent primary tumor was lung (36.8%), followed by breast (22.9%) and kidney (7.0%) cancer. The average interval between diagnosis of primary cancer and detection of PM was 2.8 ± 3.9 (SD) years. Major symptoms at diagnosis were visual disturbance in 30.3%, diabetes insipidus in 27.4%, fatigue in 25.4%, headache in 20.4%, and double vision in 17.4%. Major neuroimaging features were mass lesion in the pituitary stalk (63.3%), constriction of tumor at the diaphragmatic hiatus (44.7%), hypothalamic mass lesion (17.4%), and hyperintensity in the optic tract (11.4%). Surgical treatment was performed in 26.9% of patients, and 74.6% had radiation therapy; 80.0% of patients who underwent radiotherapy had stereotactic radiotherapy. The median survival time was 12.9 months in total. Contributing factors for good prognosis calculated by Cox proportional hazard analysis were younger age, late metastasis to the pituitary gland, smaller PM size, and radiation therapy. The Kaplan-Meier survival was significantly better in patients with breast cancer and renal cell cancer than in those with lung cancer. CONCLUSIONS: At the time of this writing, approximately 60% (120/201) of PMs had been treated by stereotactic radiation therapy in Japan. The median survival time was much longer than that reported in past series. To confirm the changes of clinical features and medical practice, a prospective and population-based survey is mandatory.