Tumor Habitat Analysis Using Longitudinal Physiological MRI to Predict Tumor Recurrence After Stereotactic Radiosurgery for Brain Metastasis

Objective@#It is difficult to predict the treatment response of tissue after stereotactic radiosurgery (SRS) because radiation necrosis (RN) and tumor recurrence can coexist. Our study aimed to predict tumor recurrence, including the recurrence site, after SRS of brain metastasis by performing a longitudinal tumor habitat analysis. @*Materials and Methods@#Two consecutive multiparametric MRI examinations were performed for 83 adults (mean age, 59.0 years; range, 27–82 years; 44 male and 39 female) with 103 SRS-treated brain metastases. Tumor habitats based on contrastenhanced T1- and T2-weighted images (structural habitats) and those based on the apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) images (physiological habitats) were defined using k-means voxel-wise clustering. The reference standard was based on the pathology or Response Assessment in Neuro-Oncologycriteria for brain metastases (RANO-BM). The association between parameters of single-time or longitudinal tumor habitat and the time to recurrence and the site of recurrence were evaluated using the Cox proportional hazards regression analysis and Dice similarity coefficient, respectively. @*Results@#The mean interval between the two MRI examinations was 99 days. The longitudinal analysis showed that an increase in the hypovascular cellular habitat (low ADC and low CBV) was associated with the risk of recurrence (hazard ratio [HR], 2.68; 95% confidence interval [CI], 1.46–4.91; P = 0.001). During the single-time analysis, a solid low-enhancing habitat (low T2 and low contrast-enhanced T1 signal) was associated with the risk of recurrence (HR, 1.54; 95% CI, 1.01–2.35; P= 0.045). A hypovascular cellular habitat was indicative of the future recurrence site (Dice similarity coefficient = 0.423). @*Conclusion@#After SRS of brain metastases, an increased hypovascular cellular habitat observed using a longitudinal MRI analysis was associated with the risk of recurrence (i.e., treatment resistance) and was indicative of recurrence site. A tumor habitat analysis may help guide future treatments for patients with brain metastases.

Clinical Implications of the Mitotic Index as a Predictive Factor for Malignant Transformation of Atypical Meningiomas

Objective@#: Intracranial atypical meningiomas have a poor prognosis and high rates of recurrence. Moreover, up to one-third of the recurrences undergo high-grade transformation into malignant meningiomas. We aimed to investigate the clinical factors that can predict the propensity of malignant transformation from atypical to anaplastic meningiomas. @*Methods@#: Between 2001 and 2018, all patients with atypical meningioma, in whom the tumors had undergone malignant transformation to anaplastic meningioma, were included. The patients’ medical records documenting the diagnosis of atypical meningioma prior to malignant transformation were reviewed to identify the predictors of transformation. The control group comprised 56 patients with atypical meningiomas who were first diagnosed between January 2017 and December 2018 and had no malignant transformation. @*Results@#: Nine patients in whom the atypical meningiomas underwent malignant transformation were included. The median time interval from diagnosis of atypical meningioma to malignant transformation was 19 months (range, 7–78). The study group showed a significant difference in heterogeneous enhancement (77.8% vs. 33.9%), bone invasion (55.6% vs. 12.5%), mitotic index (MI; 14.8±4.9 vs. 3.5±3.9), and Ki-67 index (20.7±13.9 vs. 9.5±7.1) compared with the control group. In multivariate analysis, increased MI (odds ratio, 1.436; 95% confidence interval, 1.127–1.900; p=0.004) was the only significant factor for predicting malignant transformation. @*Conclusion@#: An increased MI within atypical meningiomas might be used as a predictor of malignant transformation. Tumors at high risk for malignant transformation might require more attentive surveillance and management than other atypical meningiomas.

Posterior Fossa Teratomas in Adults : A Systematic Review

Objective@#: The occurrence of posterior fossa teratomas in adulthood is extremely rare. In this study, we aimed to report our experience with two cases of posterior fossa mature teratoma in adults who underwent surgical resection. We also performed a systematic review of published papers available to date. @*Methods@#: We retrospectively reviewed the electronic medical records of patients who had onset of posterior fossa teratomas in adulthood at our institute between 1995 and 2020. We evaluated the clinical, radiographic, and pathological features of mature teratomas at the posterior fossa in adulthood. Furthermore, we searched the PubMed, EMBASE, and Web of Science database and reviewed published articles. @*Results@#: We found 507 articles on database review; of them, 102 were duplicates and 389 were excluded based on the inclusion criteria. Finally, 16 cases of posterior fossa from the web search and related articles. Subsequently, we added two cases that underwent surgery at our institute. We analyzed a total of 18 cases of mature teratomas. Headache was the most common (55.6%) symptom. The teratomas showed heterogeneous signals on magnetic resonance imaging. Thirteen patients (72.2%) had lesion at midline, five patients (27.8%) had calcification. Surgical resection was performed in all patients. No studies reported recurrence after resection. @*Conclusion@#: The occurrence of posterior fossa teratomas in adulthood is difficult to diagnose at the initial stage. Radiographic diagnosis alone can lead to misdiagnosis. Pathological confirmation is essential. Surgical resection is a curative option for posterior fossa teratomas in adulthood.

Treatment Outcome of Hydrocephalus Associated with Vestibular Schwannoma

Background@#and Purpose Managing hydrocephalus in patients with vestibular schwannoma (VS) is controversial. We evaluated the clinical factors associated with hydrocephalus. @*Methods@#Between 2000 and 2019, 562 patients with VS were treated at our institute. We applied endoscopic third ventriculostomy (ETV), external ventricular drainage (EVD), and ventriculoperitoneal (VP) shunts to patients with hydrocephalus. The relationships of patient, tumor, and surgical variables with the hydrocephalus outcome were assessed. @*Results@#Preoperative hydrocephalus (Evans ratio ≥0.3) was present in 128 patients. Six patients who received a preresectional VP shunt were excluded after analyzing the hydrocephalus outcome. Seven of the remaining 122 patients had severe hydrocephalus (Evans ratio ≥0.4). Primary tumor resection, VP shunting, ETV, and EVD were performed in 60, 6, 57, and 5 patients, respectively. The hydrocephalus treatment failure rate was highest in the EVD group. Persistent hydrocephalus was present in five (8%) and seven (12%) patients in the primary resection and ETV groups, respectively. Multivariate analysis revealed that severe hydrocephalus, the cystic tumor, and the extent of resection (subtotal resection or partial resection) were associated with hydrocephalus treatment failure. @*Conclusions@#Larger ventricles and a higher cystic portion are predictive of persistent hydrocephalus. We recommend attempting near-total tumor resection in patients with VS.

Treatment Outcome of Hydrocephalus Associated with Vestibular Schwannoma

Background@#and Purpose Managing hydrocephalus in patients with vestibular schwannoma (VS) is controversial. We evaluated the clinical factors associated with hydrocephalus. @*Methods@#Between 2000 and 2019, 562 patients with VS were treated at our institute. We applied endoscopic third ventriculostomy (ETV), external ventricular drainage (EVD), and ventriculoperitoneal (VP) shunts to patients with hydrocephalus. The relationships of patient, tumor, and surgical variables with the hydrocephalus outcome were assessed. @*Results@#Preoperative hydrocephalus (Evans ratio ≥0.3) was present in 128 patients. Six patients who received a preresectional VP shunt were excluded after analyzing the hydrocephalus outcome. Seven of the remaining 122 patients had severe hydrocephalus (Evans ratio ≥0.4). Primary tumor resection, VP shunting, ETV, and EVD were performed in 60, 6, 57, and 5 patients, respectively. The hydrocephalus treatment failure rate was highest in the EVD group. Persistent hydrocephalus was present in five (8%) and seven (12%) patients in the primary resection and ETV groups, respectively. Multivariate analysis revealed that severe hydrocephalus, the cystic tumor, and the extent of resection (subtotal resection or partial resection) were associated with hydrocephalus treatment failure. @*Conclusions@#Larger ventricles and a higher cystic portion are predictive of persistent hydrocephalus. We recommend attempting near-total tumor resection in patients with VS.

Thyroid-Stimulating Hormone-Secreting Pituitary Adenomas : Single Institutional Experience of 14 Consecutive Cases

Objective@#: Thyroid-stimulating hormone (TSH)-secreting pituitary adenoma (PA) is an extremely rare functioning form of PA that accounts for 0.7–2% of all such cases. The previously reported outcomes of the surgical removal of TSH-PA are poor. Owing to its extremely low incidence, most available reports on TSH-PA are case reports or small case series. Thus, we investigated the clinical and endocrinological outcomes of surgically treated TSH-PA through our institutional series. @*Methods@#: We retrospectively reviewed 14 consecutive cases of surgically treated TSH-PA, focusing on the clinical, radiological, surgical, and endocrinological data. @*Results@#: There were seven male (50%) and seven female (50%) patients. The mean age was 42.5 years (range, 19–63). The mean tumor size was 16.6 mm (range, 4–30). Optic chiasm compression was noted in six patients (42.9%), and no patient showed cavernous sinus invasion. Thirteen of 14 patients (92.8%) underwent transnasal transsphenoidal approach (TSA), and one patient underwent TSA followed by transcranial approach for residual tumor removal. Thirteen of 14 patients (92.8%) showed endocrinological remission; all patients who experienced remission showed subnormal levels of TSH (<0.4 μU/mL) on postoperative day 2. Recurrence occurred in two patients (14.2%). One patient underwent subsequent revision transnasal TSA for recurrent tumor removal, and the other patient underwent gamma knife radiosurgery for recurrence. @*Conclusion@#: Surgical treatment showed excellent surgical outcomes. The TSH level in the immediate postoperative period may be a predictor for endocrinological remission.

Short-term Effect of Gamma Knife Radiosurgery for a Choroidal Tumor

Purpose@#To evaluate the effectiveness and safety of treating choroidal melanoma and cancer that has metastasized to the choroid with gamma knife radiosurgery (GKR). @*Methods@#We performed a retrospective chart review that included 10 eyes of eight patients with a diagnosis of choroidal tumors who underwent GKR between January 2016 and February 2019 and who had at least one month follow-up visit. @*Results@#The mean patient age was 57.9 ± 14.6 years (range, 32-83 years). The choroidal tumor group included six choroidal metastases and four choroidal melanomas. The mean follow-up period after GKR was 7.0 ± 4.3 months (range, 2-13 months). The mean cumulative marginal dose was 25.36 ± 7.35 Gy (range, 16-45 Gy). Pre- and postoperative magnetic resonance imaging revealed a reduction in tumor volume in eight of the 10 eyes and five of them presented with improved visual symptoms. One patient showed increased tumor volume; however, a new choroidal lesion was not observed. Another patient showed no reduction in tumor size; however, the pain had worsened, and the eye was enucleated. The mean maximum tumor diameter decreased from 1.60 ± 0.37 cm before to 1.22 ± 0.47 cm after GKR (p = 0.004), and the mean minimum diameter decreased from 0.62 ± 0.27 cm before to 0.38 ± 0.35 cm after GKR (p = 0.031). No radiation-induced optic neuropathy, retinopathy, or cataracts was observed in any of the cases during the follow-up period. @*Conclusions@#GKR was shown to be safe for choroidal lesions identified in orbital magnetic resonance imaging with a reduction in the size of choroidal tumors and eyeball preservation expected with this treatment approach.

Short-term Effect of Gamma Knife Radiosurgery for a Choroidal Tumor

Purpose@#To evaluate the effectiveness and safety of treating choroidal melanoma and cancer that has metastasized to the choroid with gamma knife radiosurgery (GKR). @*Methods@#We performed a retrospective chart review that included 10 eyes of eight patients with a diagnosis of choroidal tumors who underwent GKR between January 2016 and February 2019 and who had at least one month follow-up visit. @*Results@#The mean patient age was 57.9 ± 14.6 years (range, 32-83 years). The choroidal tumor group included six choroidal metastases and four choroidal melanomas. The mean follow-up period after GKR was 7.0 ± 4.3 months (range, 2-13 months). The mean cumulative marginal dose was 25.36 ± 7.35 Gy (range, 16-45 Gy). Pre- and postoperative magnetic resonance imaging revealed a reduction in tumor volume in eight of the 10 eyes and five of them presented with improved visual symptoms. One patient showed increased tumor volume; however, a new choroidal lesion was not observed. Another patient showed no reduction in tumor size; however, the pain had worsened, and the eye was enucleated. The mean maximum tumor diameter decreased from 1.60 ± 0.37 cm before to 1.22 ± 0.47 cm after GKR (p = 0.004), and the mean minimum diameter decreased from 0.62 ± 0.27 cm before to 0.38 ± 0.35 cm after GKR (p = 0.031). No radiation-induced optic neuropathy, retinopathy, or cataracts was observed in any of the cases during the follow-up period. @*Conclusions@#GKR was shown to be safe for choroidal lesions identified in orbital magnetic resonance imaging with a reduction in the size of choroidal tumors and eyeball preservation expected with this treatment approach.

Cyberknife Dosimetric Planning Using a Dose-Limiting Shell Method for Brain Metastases

OBJECTIVE: We investigated the effect of optimization in dose-limiting shell method on the dosimetric quality of CyberKnife (CK) plans in treating brain metastases (BMs).METHODS: We selected 19 BMs previously treated using CK between 2014 and 2015. The original CK plans (CKoriginal) had been produced using 1 to 3 dose-limiting shells : one at the prescription isodose level (PIDL) for dose conformity and the others at lowisodose levels (10–30% of prescription dose) for dose spillage. In each case, a modified CK plan (CKmodified) was generated using 5 dose-limiting shells : one at the PIDL, another at intermediate isodose level (50% of prescription dose) for steeper dose fall-off, and the others at low-isodose levels, with an optimized shell-dilation size based on our experience. A Gamma Knife (GK) plan was also produced using the original contour set. Thus, three data sets of dosimetric parameters were generated and compared.RESULTS: There were no differences in the conformity indices among the CKoriginal, CKmodified, and GK plans (mean 1.22, 1.18, and 1.24, respectively; p=0.079) and tumor coverage (mean 99.5%, 99.5%, and 99.4%, respectively; p=0.177), whereas the CKmodified plans produced significantly smaller normal tissue volumes receiving 50% of prescription dose than those produced by the CKoriginal plans (p < 0.001), with no statistical differences in those volumes compared with GK plans (p=0.345).CONCLUSION: These results indicate that significantly steeper dose fall-off is able to be achieved in the CK system by optimizing the shell function while maintaining high conformity of dose to tumor.

Gamma Knife Radiosurgery for Metastatic Brain Tumors with Exophytic Hemorrhage

OBJECTIVE: Metastatic brain tumors (MBTs) often present with intracerebral hemorrhage. Although Gamma Knife surgery (GKS) is a valid treatment option for hemorrhagic MBTs, its efficacy is unclear. To achieve oncologic control and reduce radiation toxicity, we used a radiosurgical targeting technique that confines the tumor core within the hematoma when performing GKS in patients with such tumors. We reviewed our experience in this endeavor, focusing on local tumor control and treatment-associated morbidities.METHODS: From 2007 to 2014, 13 patients with hemorrhagic MBTs were treated via GKS using our targeting technique. The median marginal dose prescribed was 23 Gy (range, 20–25). GKS was performed approximately 2 weeks after tumor bleeding to allow the patient’s condition to stabilize.RESULTS: The primary sites of the MBTs included the liver (n=7), lung (n=2), kidney (n=1), and stomach (n=1); in two cases, the primary tumor was a melanoma. The mean tumor volume was 4.00 cm³ (range, 0.74–11.0). The mean overall survival duration after GKS was 12.5 months (range, 3–29), and three patients are still alive at the time of the review. The local tumor control rate was 92% (tumor disappearance 23%, tumor regression 46%, and stable disease 23%). There was one (8%) instance of local recurrence, which occurred 11 months after GKS in the solid portion of the tumor. No GKS-related complications were observed.CONCLUSION: Our experience shows that GKS performed in conjunction with our targeting technique safely and effectively treats hemorrhagic MBTs. The success of this technique may reflect the presence of scattered metastatic tumor cells in the hematoma that do not proliferate owing to the inadequate microenvironment of the hematoma. We suggest that GKS can be a useful treatment option for patients with hemorrhagic MBTs that are not amenable to surgery.

Cyberknife Dosimetric Planning Using a Dose-Limiting Shell Method for Brain Metastases

OBJECTIVE: We investigated the effect of optimization in dose-limiting shell method on the dosimetric quality of CyberKnife (CK) plans in treating brain metastases (BMs). METHODS: We selected 19 BMs previously treated using CK between 2014 and 2015. The original CK plans (CKoriginal) had been produced using 1 to 3 dose-limiting shells : one at the prescription isodose level (PIDL) for dose conformity and the others at lowisodose levels (10–30% of prescription dose) for dose spillage. In each case, a modified CK plan (CKmodified) was generated using 5 dose-limiting shells : one at the PIDL, another at intermediate isodose level (50% of prescription dose) for steeper dose fall-off, and the others at low-isodose levels, with an optimized shell-dilation size based on our experience. A Gamma Knife (GK) plan was also produced using the original contour set. Thus, three data sets of dosimetric parameters were generated and compared. RESULTS: There were no differences in the conformity indices among the CKoriginal, CKmodified, and GK plans (mean 1.22, 1.18, and 1.24, respectively; p=0.079) and tumor coverage (mean 99.5%, 99.5%, and 99.4%, respectively; p=0.177), whereas the CKmodified plans produced significantly smaller normal tissue volumes receiving 50% of prescription dose than those produced by the CKoriginal plans (p < 0.001), with no statistical differences in those volumes compared with GK plans (p=0.345). CONCLUSION: These results indicate that significantly steeper dose fall-off is able to be achieved in the CK system by optimizing the shell function while maintaining high conformity of dose to tumor.

Gamma Knife Radiosurgery for Metastatic Brain Tumors with Exophytic Hemorrhage

OBJECTIVE: Metastatic brain tumors (MBTs) often present with intracerebral hemorrhage. Although Gamma Knife surgery (GKS) is a valid treatment option for hemorrhagic MBTs, its efficacy is unclear. To achieve oncologic control and reduce radiation toxicity, we used a radiosurgical targeting technique that confines the tumor core within the hematoma when performing GKS in patients with such tumors. We reviewed our experience in this endeavor, focusing on local tumor control and treatment-associated morbidities. METHODS: From 2007 to 2014, 13 patients with hemorrhagic MBTs were treated via GKS using our targeting technique. The median marginal dose prescribed was 23 Gy (range, 20–25). GKS was performed approximately 2 weeks after tumor bleeding to allow the patient’s condition to stabilize. RESULTS: The primary sites of the MBTs included the liver (n=7), lung (n=2), kidney (n=1), and stomach (n=1); in two cases, the primary tumor was a melanoma. The mean tumor volume was 4.00 cm³ (range, 0.74–11.0). The mean overall survival duration after GKS was 12.5 months (range, 3–29), and three patients are still alive at the time of the review. The local tumor control rate was 92% (tumor disappearance 23%, tumor regression 46%, and stable disease 23%). There was one (8%) instance of local recurrence, which occurred 11 months after GKS in the solid portion of the tumor. No GKS-related complications were observed. CONCLUSION: Our experience shows that GKS performed in conjunction with our targeting technique safely and effectively treats hemorrhagic MBTs. The success of this technique may reflect the presence of scattered metastatic tumor cells in the hematoma that do not proliferate owing to the inadequate microenvironment of the hematoma. We suggest that GKS can be a useful treatment option for patients with hemorrhagic MBTs that are not amenable to surgery.

Concurrent Chemoradiotherapy with Temozolomide Followed by Adjuvant Temozolomide for Newly Diagnosed Glioblastoma Patients: A Retrospective Multicenter Observation Study in Korea / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to investigate the feasibility and survival benefits of combined treatment with radiotherapy and adjuvant temozolomide (TMZ) in a Korean sample. MATERIALS AND METHODS: A total of 750 Korean patients with histologically confirmed glioblastoma multiforme, who received concurrent chemoradiotherapy with TMZ (CCRT) and adjuvant TMZ from January 2006 until June 2011, were analyzed retrospectively. RESULTS: After the first operation, a gross total resection (GTR), subtotal resection (STR), partial resection (PR), biopsy alone were achieved in 388 (51.7%), 159 (21.2%), 96 (12.8%), and 107 (14.3%) patients, respectively. The methylation status of O6-methylguanine-DNA methyltransferase (MGMT) was reviewed retrospectively in 217 patients. The median follow-up period was 16.3 months and the median overall survival (OS) was 17.5 months. The actuarial survival rates at the 1-, 3-, and 5-year OS were 72.1%, 21.0%, and 9.0%, respectively. The median progression-free survival (PFS) was 10.1 months, and the actuarial PFS at 1-, 3-, and 5-year PFS were 42.2%, 13.0%, and 7.8%, respectively. The patients who received GTR showed a significantly longer OS and PFS than those who received STR, PR, or biopsy alone, regardless of the methylation status of the MGMT promoter. Patients with a methylated MGMT promoter also showed a significantly longer OS and PFS than those with an unmethylated MGMT promoter. Patients who received more than six cycles of adjuvant TMZ had a longer OS and PFS than those who received six or fewer cycles. Hematologic toxicity of grade 3 or 4 was observed in 8.4% of patients during the CCRT period and in 10.2% during the adjuvant TMZ period. CONCLUSION: Patients treated with CCRT followed by adjuvant TMZ had more favorable survival rates and tolerable toxicity than those who did not undergo this treatment.

Clinical Outcomes of Gamma Knife Radiosurgery for Metastatic Brain Tumors from Gynecologic Cancer : Prognostic Factors in Local Treatment Failure and Survival

OBJECTIVE: Brain metastases in gynecologic cancer (ovarian, endometrial, and cervical cancer) patients are rare, and the efficacy of Gamma Knife Radiosurgery (GKRS) to treat these had not been evaluated. We assessed the efficacy of GKRS and prognostic factors for tumor control and survival in brain metastasis from gynecologic cancers. METHODS: This retrospective study was approved by the institutional review board. From May 1995 to October 2012, 26 women (mean age 51.3 years, range 27-70 years) with metastatic brain tumors from gynecologic cancer were treated with GKRS. We reviewed their outcomes, radiological responses, and clinical status. RESULTS: In total 24 patients (59 lesions) were available for follow-up imaging. The median follow-up time was 9 months. The mean treated tumor volume at the time of GKRS was 8185 mm³ (range 10-19500 mm³), and the median dose delivered to the tumor margin was 25 Gy (range, 10-30 Gy). A local tumor control rate was 89.8% (53 of 59 tumors). The median overall survival was 9.5 months after GKRS (range, 1-102 months). Age-associated multivariate analysis indicated that the Karnofsky performance status (KPS), the recursive partitioning analysis (RPA) classification, and the number of treated lesions were significant prognostic factors for overall survival (HR=0.162, p=0.008, HR=0.107, p=0.038, and HR=2.897, p=0.045, respectively). CONCLUSION: GKRS is safe and effective for the management of brain metastasis from gynecologic cancers. The clinical status of the patient is important in determining the overall survival time.

Upfront Stereotactic Radiosurgery for Pineal Parenchymal Tumors in Adults

OBJECTIVE: Pineal parenchymal tumors (PPTs) in adults are rare, and knowledge regarding their optimal management and treatment outcome is limited. Herein, we present the clinical results of our series of PPTs other than pineoblastomas managed by stereotactic radiosurgery (SRS) at upfront setting. METHODS: Between 1997 and 2014, nine consecutive adult patients with the diagnosis of PPTs, either pineocytoma or pineal parenchymal tumor of intermediate differentiation, were treated with SRS. There were 6 men and 3 women. The median age was 39 years (range, 31-53 years). All of the patients presented with symptoms of hydrocephalus. Endoscopic third ventriculostomy and biopsy was done for initial management. After histologic diagnosis, patients were treated with Gamma Knife with the mean dose of 13.3 Gy (n=3) or fractionated Cyberknife with 32 Gy (n=6). RESULTS: After a mean follow-up of 78.6 months (range, 14-223 months), all patients were alive and all of their tumors were locally controlled except for one instance of cerebrospinal fluid seeding metastasis. On magnetic resonance images, tumor size decreased in all patients, resulting in complete response in 3 patients and partial response in 6. One patient had experienced temporary memory impairment after SRS, which improved spontaneously. CONCLUSION: SRS is effective and safe for PPTs in adults and can be considered as a useful alternative to surgical resection at upfront setting.

Effects of an Epithelial Growth Factor Receptor-Tyrosine Kinase Inhibitor Add-on in Stereotactic Radiosurgery for Brain Metastases Originating from Non-Small-Cell Lung Cancer

OBJECTIVE: This study was aimed at optimizing the treatment of non-small-cell lung cancer (NSCLC) patients who are candidates for stereotactic radiosurgery (SRS) for brain metastases and harbor activating epithelial growth factor receptor (EGFR) mutations. METHODS: We retrospectively reviewed the medical records from 2005 to 2010 of NSCLC patients with brain metastases harboring an activating EGFR mutation. Patients who received a combination therapy of SRS and EGFR-tyrosine kinase inhibitor (TKI) for brain metastases and those who received SRS without EGFR-TKI were compared. The primary endpoint was progression-free survival (PFS) of the brain metastases. RESULTS: Thirty-one patients were eligible for enrolment in this study (SRS with TKI, 18; SRS without TKI, 13). Twenty-two patients (71.0%) were women and the median overall age was 56.0 years. PFS of brain lesions was not significantly prolonged in SRS with TKI treatment group than in SRS without TKI group (17.0 months vs. 9.0 months, p=0.45). Local tumor control rate was 83.3% in the combination therapy group, and 61.5% in the SRS monotherapy group (p=0.23). There were no severe adverse events related with treatment in both groups. CONCLUSIONS: Therapeutic outcome of concurrent SRS and TKI treatment was not superior to SRS monotherapy, however, there was no additive adverse events related with combined treatment.

Efficacy and Safety of Fractionated Stereotactic Radiosurgery for Large Brain Metastases

OBJECTIVE: To investigate the efficacy and safety of fractionated stereotactic radiosurgery for large brain metastases (BMs). METHODS: Between June 2011 and December 2013, a total of 38 large BMs >3.0 cm in 37 patients were treated with fractionated Cyberknife radiosurgery. These patients comprised 16 men (43.2%) and 21 women, with a median age of 60 years (range, 38-75 years). BMs originated from the lung (n=19, 51.4%), the gastrointestinal tract (n=10, 27.0%), the breast (n=5, 13.5%), and other tissues (n=3, 8.1%). The median tumor volume was 17.6 cc (range, 9.4-49.6 cc). For Cyberknife treatment, a median peripheral dose of 35 Gy (range, 30-41 Gy) was delivered in 3 to 5 fractions. RESULTS: With a median follow-up of 10 months (range, 1-37 months), the crude local tumor control (LTC) rate was 86.8% and the estimated LTC rates at 12 and 24 months were 87.0% and 65.2%, respectively. The median overall survival (OS) and progression-free survival (PFS) rates were 16 and 11 months, respectively. The estimated OS and PFS rates at 6, 12, and 18 months were 81.1% and 65.5%, 56.8% and 44.9%, and 40.7% and 25.7%, respectively. Patient performance status and preoperative focal neurologic deficits improved in 20 of 35 (57.1%) and 12 of 17 patients (70.6%), respectively. Radiation necrosis with a toxicity grade of 2 or 3 occurred in 6 lesions (15.8%). CONCLUSION: These results suggest a promising role of fractionated stereotactic radiosurgery in treating large BMs in terms of both efficacy and safety.

Peritumoral Brain Edema after Stereotactic Radiosurgery for Asymptomatic Intracranial Meningiomas: Risks and Pattern of Evolution

OBJECTIVE: To investigate the risks and pattern of evolution of peritumoral brain edema (PTE) after stereotactic radiosurgery (SRS) for asymptomatic intracranial meningiomas. METHODS: A retrospective study was conducted on 320 patients (median age 56 years, range 24-87 years) who underwent primary Gamma Knife radiosurgery for asymptomatic meningiomas between 1998 and 2012. The median tumor volume was 2.7 cc (range 0.2-10.5 cc) and the median follow-up was 48 months (range 24-168 months). Volumetric data sets for tumors and PTE on serial MRIs were analyzed. The edema index (EI) was defined as the ratio of the volume of PTE including tumor to the tumor volume, and the relative edema indices (rEIs) were calculated from serial EIs normalized against the baseline EI. Risk factors for PTE were analyzed using logistic regression. RESULTS: Newly developed or increased PTE was noted in 49 patients (15.3%), among whom it was symptomatic in 28 patients (8.8%). Tumor volume larger than 4.2 cc (p4.2 cc), of hemispheric location, or with pre-treatment PTE. PTE usually develops within months, reaches its maximum degree until a year, and resolves within 2 years after SRS.

Is the Complete Resection of Craniopharyngiomas in Adults Feasible Considering Both the Oncologic and Functional Outcomes?

OBJECTIVE: To assess the impact of the complete resection of craniopharyngioma (CP) in adults on oncologic and functional outcomes. METHODS: We retrospectively analyzed 82 patients with CP who were surgically treated by the same neurosurgeon at our institution between January 1994 and December 2012. RESULTS: Gross total resection (GTR) was achieved in 71 patients (86.6%), near total resection (NTR) in 7 patients (8.5%), and subtotal resection (STR) in 3 patients (3.7%). The disease-specific overall survival rate was 100% with the exclusion of 2 surgery-related mortalities. The overall recurrence rate was 12.2% (10 of 82 patients), however the recurrence rate according to extent of resection (EOR) was 9.9% (7 of 71 patients) after GTR, 14.3% (1 of 7 patients) after NTR, and 66.7% (2 of 3 patients) after STR. The overall recurrence-free survival (RFS) rates at 5 and 10 years were 87.0% and 76.8%, respectively. Postoperatively, most patients (86.3%) needed hormone replacement for at least 1 hypothalamic-pituitary axis. Vision improved in 56.4% of the patients with preoperative abnormal vision, but deteriorated in 27.4% of patients. Hypothalamic dysfunction developed in 32.9% of patients. There were no significant differences in the risks of pituitary dysfunction, visual deterioration, or hypothalamic dysfunction between the groups with complete vs. incomplete removal. The overall rate of postoperative complications was 22.0%, which did not differ between groups (p=0.053). CONCLUSION: The complete removal of a CP at first surgery can provide a chance for a cure with acceptable morbidity and mortality risks.

Treatment and Outcomes for Gangliogliomas: A Single-Center Review of 16 Patients

BACKGROUND: Ganglioglioma is a rare and slowly growing benign tumor. We investigated the outcomes of patients who underwent different combination treatments. METHODS: Between 1998 and 2012, 16 patients, including 11 men and 5 women, with a median age of 12.5 years (range, 2.5-65 years) were treated for intracranial gangliogliomas at our institution. The median follow-up period was 5.7 years (range, 48 days-15.6 years). Fifteen cases were included in the outcome assessment because one patient was lost to follow-up. Complete resection was achieved in 8 (53%) patients. Six (40%) patients underwent incomplete resection with or without adjuvant radiotherapy, and one patient with a brainstem tumor underwent only stereotactic biopsy. RESULTS: Gangliogliomas predominantly affected young (87.5%), male patients and most frequently presented with seizures (64%). Of eight patients who underwent complete resection, seven did not show recurrence, whereas only three of six with incomplete resection showed no recurrence. Four patients with recurrence received salvage treatments (two repeat surgeries and two radiosurgeries). A tumor control rate of 93% (14/15) was achieved at the last follow-up. No recurrence or malignant changes were observed after a median follow-up of 12 and 4.5 years in four patients who received gamma knife (GK) radiosurgery as adjuvant and salvage treatment. CONCLUSION: Complete resection produced the best outcomes and incomplete resection followed by adjuvant or salvage treatments showed favorable outcomes. In patients who are not eligible for complete resection because of tumor location or potential neurologic deficits following surgery, GK radiosurgery should be considered for the treatment of residual or recurrent tumors.