Impact of boost sequence in concurrent chemo-radiotherapy on newly diagnosed IDH-wildtype glioblastoma multiforme.

BACKGROUND: The standard of care for glioblastoma multiforme (GBM) is maximal surgical resection followed by conventional fractionated concurrent chemoradiotherapy (CCRT) with a total dose of 60 Gy. However, there is currently no consensus on the optimal boost technique for CCRT in GBM. METHODS: We conducted a retrospective review of 398 patients treated with CCRT between 2016 and 2021, using data from two institutional databases. Patients were divided into two groups: those receiving sequential boost (SEB, N = 119) and those receiving simultaneous integrated boost (SIB, N = 279). The primary endpoint was overall survival (OS). To minimize differences between the SIB and SEB groups, we conducted propensity score matching (PSM) analysis. RESULTS: The median follow-up period was 18.6 months. Before PSM, SEB showed better OS compared to SIB (2-year, 55.6% vs. 44.5%, p = 0.014). However, after PSM, there was no significant difference between two groups (2-year, 55.6% vs. 51.5%, p = 0.300). The boost sequence was not associated with inferior OS before and after PSM (all p-values > 0.05). Additionally, the rates of symptomatic pseudo-progression were similar between the two groups (odds ratio: 1.75, p = 0.055). CONCLUSIONS: This study found no significant difference in OS between SEB and SIB for GBM patients treated with CCRT. Further research is needed to validate these findings and to determine the optimal boost techniques for this patient population.

A single-center prospective study regarding time to return to activities of daily living after craniotomy for brain tumors.

BACKGROUND: There are few studies on the time to return to activities of daily living (ADL) after craniotomy in patients with brain tumors. This study aimed to investigate the duration before returning to ADLs after craniotomy for brain tumors and present data that can provide information and guidelines on the appropriate time needed. METHODS: Patients (n = 183 of 234) who underwent craniotomy for brain tumors between April 2021 and July 2021 capable of self-care upon discharge were enrolled, and data of 158 were collected. The start time of 85 ADL items was prospectively investigated for 4 months postoperatively, using the self-recording sheet. RESULTS: Over 89% and 87% of the patients performed basic ADL items within a month and instrumental ADL items within 2 months (medians: within 18 days), except for a few. Regarding work, 50% of the patients returned within 4 months. Washing hair with a wound was performed at 18 days of median value, after 4 months of dyeing/perming hair, 6 days of drinking coffee/tea, after 4 months of air travel, and 40 days of complementary and alternative medicine. In patients with infratentorial tumors or surgical problems, return times were much later for various items. CONCLUSIONS: It is possible to provide practical information and guidelines on the duration to return to ADL after craniotomy in brain tumor patients. These study findings also reduce uncertainty about recovery and daily life and help patients return to their daily life at the appropriate time, thereby maintaining function and daily well-being after surgery.

Bevacizumab plus irinotecan with or without gamma knife radiosurgery after failure of concurrent chemo-radiotherapy for high-grade glioma.

INTRODUCTION: Concurrent chemo-radiotherapy (CCRT) with temozolomide (TMZ) is a standard first-line treatment for high-grade glioma. However, if CCRT with TMZ treatment fails, second-line treatment options have limited value. Bevacizumab plus irinotecan is the only available treatment option for such patients. The role of gamma knife radiosurgery (GKS) in patients with high-grade gliomas is not well-established. In this study, we evaluated the efficacy and safety of bevacizumab plus irinotecan with or without GKS in the treatment of high-grade glioma patients who progressed after initially being treated with CCRT with TMZ. METHODS: We collected clinical data of patients with biopsy-proven high-grade glioma (glioblastoma multiforme (GBM) or anaplastic astrocytoma) who were treated at Samsung Medical Center from January 2015 to December 2020, retrospectively. We evaluated the overall survival (OS), progression-free survival (PFS), and safety of bevacizumab plus irinotecan with or without GKS. RESULTS: In total, 203 patients were diagnosed with high-grade glioma, including GBM and anaplastic astrocytoma. The median OS was 8.73 months (95% confidence interval [CI]: 7.27-10.18), and the median PFS was 4.36 months (95% CI: 3.75-4.97). Sixty-eight (33.4%) patients underwent GKS prior to bevacizumab plus irinotecan treatment, which led to a significantly prolonged OS (10.13 months, 95% CI: 8.65-11.60 vs. 8.26 months, 95% CI: 7.01-9.51, p = 0.012). The most common adverse events of any grade were neutropenia (36.9%) and thrombocytopenia (22.6%). However, the incidence of adverse events in patients who underwent GKS prior to bevacizumab plus irinotecan was not different compared with those in patients who did not undergo GKS. CONCLUSIONS: Bevacizumab plus irinotecan was well-tolerated and moderately effective in patients with high-grade gliomas. The addition of GKS prior to bevacizumab plus irinotecan led to a significant OS benefit with a manageable safety profile. GKS prior to bevacizumab plus irinotecan can therefore be considered a potential treatment option for these patients.

Combined endoscopic endonasal and transorbital multiportal approach for complex skull base lesions involving multiple compartments.

PURPOSE: This study defines the specific areas that connect the surgical corridors of the endoscopic endonasal (EEA) and transorbital approach (TOA) to identify adequate clinical applications and perspectives of this combined multiportal approach. METHODS: Consecutive patients who underwent combined EEA and TOA procedures for various pathologies involving multiple compartments of the skull base were enrolled. RESULTS: A total of eight patients (2 chondrosarcomas, 2 meningiomas, 2 schwannomas, 1 glioma, and 1 traumatic optic neuropathy) were included between August 2016 and April 2021. The cavernous sinus (CS) was targeted as the connection area of the combined approach in four patients with tumors infiltrating the middle cranial fossa (MCF) and central skull base through the CS. For two patients with MCF tumors extending into the infratemporal fossa (ITF), the horizontal portion of the greater sphenoid wing and the foramen ovale were utilized as the connection area. In the remaining 2 patients, connection was achieved through the optic canal (OC). Gross total and near total resection was achieved in 5 patients with tumors, and circumferential removal of bone composing the OC was performed in one patient with traumatic compressive optic neuropathy. Postoperative complications included one cardiac arrest due to underlying cardiovascular disease and one case of oculomotor nerve palsy. CONCLUSIONS: The combined EEA and TOA procedure is a useful strategy for complex lesions involving multiple compartments of the skull base. Herein, we identified the specific areas connecting the two surgical approaches, allowing a common path for EEA and TOA procedures.

Early hormonal recovery following endoscopic transsphenoidal surgery for silent non-functioning pituitary adenomas with hormone dysfunction.

PURPOSE: The role of transsphenoidal surgery in the recovery of preexisting hormone dysfunction from pituitary tumors remains controversial. This study aimed to investigate the incidence of hormone dysfunction among asymptomatic non-functioning pituitary adenomas and their recovery following endoscopic transsphenoidal surgery. METHODS: Eligibility criteria included age under 80 years, presence of a non-functioning pituitary adenoma compressing the normal gland resulting in deviation of the stalk, absence of visual symptoms, and availability for regular follow-up using MRI and pre- and post-operative endocrinological assessments. 182 patients with silent non-functioning pituitary adenomas were included in this study between March 2014 and December 2018. All patients underwent endoscopic transsphenoidal surgery and complete hormonal evaluation, with basal hormone assays and a combined pituitary function test before and after surgery until the end of last follow-up. RESULTS: Preoperative assessment of hormonal function revealed that 124 of 182 patients (68.1%) had at least a single hormone dysfunction preoperatively. Among these, 61 of 124 (49.2%) had a dysfunction in a single axis, and 63 (50.8%) had a hormone dysfunction in two or more axes. Overall, the median endocrinological follow-up duration was 15.0 months (6-57 months). At 1 month following surgery, 91 patients (73.4%) with hormone dysfunction experienced improvement in at least a single hormone axis. Prolactin was the most common hormone among those that recovered at the last follow up (92.8% improvement) followed by growth hormone (GH, 50.0%), thyroid stimulating hormone (TSH, 50.0%), gonadotropin (Gn, 46.9%), and adrenocorticotropic hormone (ACTH, 45.0%). Time to recovery varied from 1.1 months (for prolactin) to 2.2 months (for gonadotropin, and ACTH). In patients with preoperative deficiency in GH, and ACTH, postoperative transient diabetes insipidus was associated with poor recovery (GH: HR = 0.50, p = 0.048; ACTH: HR = 0.39, p = 0.023). CONCLUSIONS: Non-functioning pituitary adenomas with silent hormone dysfunction are often overlooked by clinicians and patients. We suggest that even silent hormone dysfunction in patients with non-functioning pituitary adenomas can be improved with effective surgical decompression and these tumors may be potential indications of endoscopic transsphenoidal surgery.

Comparison between retrosigmoid and translabyrinthine approaches for large vestibular schwannoma: focus on cerebellar injury and morbidities.

This study aimed to compare the surgical outcomes and morbidities of retrosigmoid and translabyrinthine approaches for large vestibular schwannoma (VS), with a focus on cerebellar injury and morbidities. Eighty-six consecutive patients with large VS, with a maximal extrameatal diameter > 3.0 cm, were reviewed between August 2010 and September 2018. The surgical outcomes, operating time, volume change of perioperative cerebellar edema, and inpatient rehabilitation related to cerebellar morbidities were compared between the two approaches. In total, 53 and 33 patients underwent the retrosigmoid and translabyrinthine approaches, respectively. The median follow-up time was 34.5 months. Surgical outcomes, including the extent of resection, tumor recurrence, and facial nerve preservation, showed no significant differences between the two groups. Patients who underwent the retrosigmoid approach showed a marginal trend for postoperative lower cranial nerve (LCN) dysfunction (P = 0.068). Although the approaching procedure time was longer in the translabyrinthine group, the tumor resection time was significantly longer in the retrosigmoid group (P = 0.001). The median change in the volume of the perioperative cerebellar edema was significantly larger in the retrosigmoid group (P < 0.001) and significantly related to the retrosigmoid approach, solid VS, and tumor resection time. Most cerebellar and LCN deficits were transient; however, the patients in the retrosigmoid group underwent inpatient rehabilitation more than those in the translabyrinthine group (P = 0.018). Both surgical approaches show equivalent surgical outcomes. Notably, the translabyrinthine approach for large VS has advantages in that it reduces cerebellar injury and related morbidities.

Stereotactic radiosurgery for orbital cavernous venous malformation: a single center's experience for 15 years.

BACKGROUND: Stereotactic radiosurgery such as Gamma Knife radiosurgery (GKRS) has been shown to have a good treatment effect for orbital cavernous venous malformation (CVM). However, radiation-induced retinopathy or optic neuropathy is a vision-threatening complication of orbital irradiation. Predicting the post-treatment visual outcome is critical. METHODS: Clinical and radiological outcomes were investigated in 30 patients who underwent GKRS for orbital CVM between July 2005 and February 2020. Measurement of peripapillary retinal nerve fiber layer (pRNFL) thickness using optical coherence tomography (OCT) was obtained in 14 patients. RESULTS: The median clinical and radiological follow-up periods were 46.6 months (range, 15.9-105.8) and 27.5 months (range, 15.4-105.8), respectively. Twenty-eight patients underwent multisession (4 fractions) GKRS. The median cumulative marginal dose was 20 Gy (range, 16-24). Two patients underwent single-session GKRS. Marginal doses were 15 Gy and 10.5 Gy in each patient. The volume of CVM decreased in 29 (97%) patients. Visual acuity was improved in 6 (20%) patients and was stable in 22 (73%) patients. Visual field defect and exophthalmos were improved in all patients. Serial investigation of OCT showed no statistically significant difference in pRNFL thickness after GKRS. Patients with normal average pRNFL thickness showed better visual recovery than patients with thin average pRNFL thickness. CONCLUSIONS: GKRS is an effective and safe treatment option for orbital CVM. The pRNFL thickness before GKRS can be a prognostic indicator for visual recovery in orbital CVM after GKRS.

Optimal Volume of the Residual Tumor to Predict Long-term Tumor Control Using Stereotactic Radiosurgery after Facial Nerve-preserving Surgery for Vestibular Schwannomas.

BACKGROUND: Intended subtotal resection (STR) followed by adjuvant gamma knife radiosurgery (GKRS) has emerged as an effective treatment option for facial nerve (FN) preservation in vestibular schwannomas (VSs). This study aimed to identify the optimal cut-off volume of residual VS to predict favorable outcomes in terms of both tumor control and FN preservation. METHODS: This retrospective study assessed the patients who underwent adjuvant GKRS for residual VS after microsurgery. A total of 68 patients who had been followed up for ≥ 24 months after GKRS were included. Tumor progression was defined as an increase in tumor volume (TV) of ≥ 20%. House-Brackmann grades I and II were considered to indicate good FN function. RESULTS: The median residual TV was 2.5 cm³ (range: 0.3-27.4). The median follow-up period after the first adjuvant GKRS was 64 months (range: 25.7-152.4). Eight (12%) patients showed tumor progression. In multivariate analyses, residual TV was associated with tumor progression (P = 0.003; hazard ratio [HR], 1.229; 95% confidence interval [CI], 1.075-1.405). A residual TV of 6.4 cm³ was identified as the cut-off volume for showing the greatest difference in progression-free survival (PFS). The 5-year PFS rates in the group with residual TVs of < 6.4 cm³ (54 patients) and that with residual TVs of ≥ 6.4 cm³ (14 patients) were 93.3% and 69.3%, respectively (P = 0.014). A good FN outcome was achieved in 57 (84%) patients. Residual TV was not associated with good FN function during the immediate postoperative period (P = 0.695; odds ratio [OR], 1.024; 95% CI, 0.908-1.156) or at the last follow-up (P = 0.755; OR, 0.980; 95% CI, 0.866-1.110). CONCLUSION: In this study, residual TV was associated with tumor progression in VS after adjuvant GKRS following STR. As preservation of FN function is not correlated with the extent of resection, optimal volume reduction is imperative to achieve long-term tumor control. Our findings will help surgeons predict the prognosis of residual VS after FN-preserving surgery.

Gamma Knife Radiosurgery as a Primary Treatment for Nonfunctioning Pituitary Adenoma Invading the Cavernous Sinus.

OBJECTIVES: Surgical resection of nonfunctioning pituitary adenoma (NFPA) invading the cavernous sinus (CS) remains a challenging and significant factor associated with incomplete resection. The residual tumor in CS is usually treated with adjuvant stereotactic radiosurgery (SRS), but there is little information concerning SRS as an initial treatment for CS-invading NFPA. In this study, we investigated the tumor control rate and clinical outcomes of the patients who received primary gamma knife radiosurgery (GKRS) for CS-invading NFPA. METHODS: This was a single-institute retrospective analysis of 11 patients. CS invasion of tumor was categorized using the modified Knosp grading system. The median tumor volume and maximal diameter were 1.6 cm3 (range 0.4-6.5) and 17.2 mm (range 11.6-23.3), respectively. The median clinical follow-up period was 48.5 months (range 16.4-177.8). The median prescription dose at tumor margin was 15 Gy (range 11-25) and median prescription isodose was 50% (range 45-50). The maximum radiation dose to optic chiasm and optic nerve were 7.2 Gy (range 3.4-9.2) and 7.5 Gy (range 4.5-11.5), respectively. RESULTS: Tumor control was achieved in all patients. The median tumor volume and maximal diameter at last follow-up were 0.4 cm3 (range 0.1-2.3) and 11.4 mm (range 4.7-19.5), respectively. The median volume reduction rate was 52% (range 33-88). Six patients showed downgrading of modified Knosp grade after GKRS. No patients developed GKRS-related complications such as hypopituitarism or visual disturbance. CONCLUSIONS: SRS may be an alternative primary treatment option for CS-invading NFPA if there is no urgent and absolute indication for surgery such as optic apparatus compression.

Hypermutagenesis in untreated adult gliomas due to inherited mismatch mutations.

Hypermutagenesis refers to marked increase in the number of mutations due to continuous mutagenic process. Hypermutated tumors, have being found in several tumor types, are associated with inherited or acquired alterations in the DNA repair pathways. Hypermutation has been observed in a subset of adult glioma patients as a direct result of temozolomide(TMZ)-induced mutagenesis. In our study, we have identified a rare subset of treatment-naïve adult gliomas with de novo hypermutator phenotype and explored the evolution of spontaneous and treatment-induced hypermutagenesis. We conducted Whole-Exome Sequencing (WES), Whole-Transcriptome Sequencing (WTS), and Single-Cell Sequencing (SCS) of TMZ-naïve and post-TMZ-treated hypermutated tumors to identify distinct clinical or genomic manifestations that contribute to the development of hypermutation in untreated adult gliomas. TMZ-naïve hypermutated tumors were marked by absence of IDH1 somatic mutation and MGMT promoter (pMGMT) methylation, two genomic traits that were significantly associated with the TMZ-induced hypermutagenic event in glioblastoma, and harbored inherited alterations in the mismatch repair (MMR) machinery. The immediate family members of the TMZ-naive hypermutated glioma patients were also previous diagnosed with cancer development history, suggesting that germline dysfunction of the MMR pathway could potentially pose hereditary risk to genetic predisposition of carcinogenesis in gliomas. Lastly, both TMZ-naïve and post-TMZ-treated hypermutated tumors exhibited a significant accumulation of neoantigen loads, suggesting immunotherapeutic alternatives. Our results present new and unique understanding of hypermutagenic process in adult gliomas and an important step towards clinical implication of immunotherapy in glioma treatment.

Fractionated stereotactic radiosurgery for malignant gliomas: comparison with single session stereotactic radiosurgery.

PURPOSE: Stereotactic radiosurgery (SRS) is feasible for malignant glioma; however, delivering the optimal radiation dose with sufficient large-volume coverage is a major concern. We aimed to investigate the clinical efficacy and safety of fractionated SRS (fSRS) versus single-session SRS (sSRS) for malignant gliomas. METHODS: We retrospectively reviewed 58 malignant glioma patients who underwent gamma knife SRS from January 2015 to December 2018. Forty-one underwent sSRS, and 17 underwent fSRS. Median dose for fSRS was 28 Gy (range 24-35 Gy), with a median dose of 6 Gy per fraction (range 5-7 Gy). Patients received 4 or 5 fractions on consecutive days. Median dose for sSRS was 18 Gy (range 11-25 Gy), with a median isodose of 50% (range 50-65%). Mean target volumes were 5.9 and 19.3 cc for sSRS and fSRS, respectively (p < 0.001, two-sided t test). RESULTS: After SRS, median progression-free survival (PFS) was 4.5 and 4.6 months (p = 0.58), and median overall survival (OS) was 12.7 and 12.6 months for sSRS and fSRS (p = 0.41), respectively (log-rank test). The incidence of clinically significant radiation necrosis was 20.5% (8/39) and 18.8% (3/16) for sSRS and fSRS, respectively (p = 1, Fisher's exact test). CONCLUSION: fSRS for malignant glioma conferred local control and survival comparable with conventional sSRS. The radiation necrosis incidence was comparable between groups when a parallel biological effective dose was administered to the larger target volumes in the fSRS group. fSRS can be a better alternative to sSRS if re-irradiation is considered for large malignant gliomas.

Outcome of three-fraction gamma knife radiosurgery for brain metastases according to fractionation scheme: preliminary results.

PURPOSE: The optimal interfraction intervals for fractionated radiosurgery has yet to be established. We investigated the outcome of fractionated gamma knife radiosurgery (FGKRS) for large brain metastases (BMs) according to different interfraction intervals. METHODS: Between September 2016 and May 2018, a total of 45 patients who underwent FGKRS for BMs were enrolled in this study. They were divided into two groups (standard fractionation over 3 consecutive days with a 24-h interfraction interval versus prolonged fractionation over 4 or 5 days with an interfraction interval of at least 48-h). BMs with ≥ 2 cm in maximum diameter or ≥ 5 cm3 in volume were included in analysis. RESULTS: Among 52 BMs treated with 3-fraction GKRS, 25 (48.1%) were treated with standard fractionation scheme, and 27 (51.9%) with prolonged fractionation scheme. The median follow-up period was 10.5 months (range 5-25). Local tumor control rates of the standard group were 88.9% at 6 months and 77.8% at 12 months, whereas those of the prolonged group were 100% at 6 and 12 months (p = 0.023, log-rank test). In multivariate analysis, fractionation scheme (hazard ratio [HR] 0.294, 95% CI 0.099-0.873; p = 0.027) and tumor volume (HR 0.200, 95% CI 0.051-0.781; p = 0.021) were revealed as the only significant factors affecting the local tumor control after 3-fraction GKRS. CONCLUSIONS: Our preliminary tumor control results suggest a promising role of 3-fraction GKRS with an interfraction interval of at least 48-h. This fractionation regimen could be an effective and safe treatment option in the management of large BMs.

Multi-institutional study of treatment patterns in Korean patients with WHO grade II gliomas: KNOG 15-02 and KROG 16-04 intergroup study.

INTRODUCTION: We performed this study to identify the treatment patterns of patients with low-grade gliomas (LGG) in Korea. METHODS: A total of 555 patients diagnosed as WHO grade II gliomas between 2000 and 2010 at 14 Korean institutions were included. The patients were divided into four adjuvant treatment groups: adjuvant fractionated radiotherapy (RT, N = 204), adjuvant chemotherapy (N = 20), adjuvant fractionated RT and chemotherapy (N = 65), and non-adjuvant treatment (N = 266) groups. We examined differences among the groups and validated patient/tumor characteristics associated with the adjuvant treatments. RESULTS: Astrocytoma was diagnosed in 210 patients (38%), oligoastrocytoma in 85 patients (15%), and oligodendroglioma in 260 patients (47%). Gross total resection was performed in 200 patients (36%), subtotal resection in 153 (28%), partial resection in 71 patients (13%), and biopsy in 131 patients (24%). RT was most commonly applied as an adjuvant treatment. The use of chemotherapy with or without RT decreased after 2008 (from 38 to 4%). The major chemotherapeutic regimen was procarbazine, lomustine, and vincristine (PCV); however, the proportion of temozolomide increased since 2005 (up to 69%). Patient/tumor characteristics related with RT were male gender, non-seizure, multiple lobes involvement, and non-gross total resection. Chemotherapy was associated with non-gross total resection and non-astrocytoma. CONCLUSIONS: A preference for RT and increased use of temozolomide was evident in the treatment pattern of LGG. The extent of resection was associated with a decision to perform RT and chemotherapy. To establish a robust guideline for LGG, further studies including molecular information are needed.

Impact of adjuvant treatments on survival in Korean patients with WHO grade II gliomas: KNOG 15-02 and KROG 16-04 intergroup study.

INTRODUCTION: Optimal treatment strategies for low-grade glioma (LGG) remain controversial. We analyzed treatment outcomes and evaluated prognostic factors of adult LGG patients in Korea. METHODS: We reviewed the medical records of 555 patients diagnosed with WHO grade II LGG (astrocytoma 37.8%, oligoastrocytoma 15.3%, and oligodendroglioma 46.8%) at 14 institutions between 2000 and 2010. Primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS). Propensity-score matching (PSM) analyses were performed to correct imbalances in patient/tumor characteristics among adjuvant treatment groups. RESULTS: The median follow-up time was 83.4 months, and the 5-year PFS and OS rates were 52.2% and 83.0%, respectively. Male, older age, poorer performance status, multiple lobe involvement, and astrocytoma histology were associated with poorer survival. Among the treatment factors, gross total resection (GTR) was associated with better PFS and OS, and adjuvant chemotherapy with improved PFS. Interestingly, adjuvant radiotherapy (RT) did not improve PFS; rather, it was related with poorer OS. Regarding patient/tumor characteristics, the RT group had poorer characteristics than the non-RT group. After PSM, we detected a tendency for improved PFS in the matched RT group, and no significant difference in OS compared with the matched non-RT group. CONCLUSIONS: The achievement of GTR is important to improve survival in LGG patients. Adjuvant chemotherapy may enhance PFS, but adjuvant RT did not improve survival outcomes. After PSM, we observed potential impacts of adjuvant RT on PFS. Our results may reflect real-world practice and consequently may help to optimize treatment strategies for LGG.

The influence of histology on the response of brain metastases to gamma knife radiosurgery: a propensity score-matched study.

BACKGROUND: In terms of response to fractionated radiotherapy, metastatic brain tumors of certain origins are considered radioresistant. OBJECTIVE: To determine the influence of "radioresistant" histology on outcomes of brain metastases treated with radiosurgery. METHODS: Between 2001 and 2017, 121 patients with brain metastases from renal cell carcinoma (RCC) and 2151 from non-small cell lung cancer (NSCLC) were reviewed. Eighty-seven pairs were derived using propensity score matching. Local progression-free survival (PFS), progression patterns, distant PFS, and overall survival were investigated. RESULTS: The median follow-up period was 13.7 months (range, 1.6-78.4 months). A total of 536 lesions were treated using gamma knife radiosurgery (GKS), with a median dose of 20 Gy (range, 12-28 Gy). The actuarial local PFS rates in the RCC group were 91% and 89% at 6 and 12 months, respectively, and did not differ from the NSCLC group (97% and 83% at 6 and 12 months, respectively). Continuous progression, without response to GKS, was noted in seven of the eight progressed RCCs. However, six of the seven progressed NSCLCs showed transient shrinkage before progression. The median distant PFS was 9.3 months (95% CI, 6.3-12.2) in the RCC group and 8.0 months (95% CI, 5.5-10.4) in the NSCLC group. The median overall survival was 16.1 months (95% CI, 11.3-20.8) and 14.9 months (95% CI, 11.9-17.8) in RCC and NSCLC groups, respectively. CONCLUSION: Histological differences had no effect on local control in the single high-dose range used for radiosurgery. However, changes in tumor volume during progression varied across tumor histology.

MGMT promoter methylation status as a prognostic factor for the outcome of gamma knife radiosurgery for recurrent glioblastoma.

We conducted this study to determine whether the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter was a prognostic marker for positive outcomes of gamma knife radiosurgery (GKS) for recurrent glioblastoma (GBM). We retrospectively examined 61 patients, who underwent GKS for local recurrent GBM between 2004 and 2015; in all patients, the methylation status of the MGMT promoter was identified via methylation-specific quantitative real-time polymerase chain reaction. All patients underwent surgical resection and were diagnosed histopathologically with GBM. Prognostic factors associated with progression-free survival (PFS) and overall survival (OS) were identified in univariate and multivariate analyses. Twenty-five (41%) had a methylated MGMT promoter, and 36 (59%) had an unmethylated MGMT promoter. The median age at GKS was 58 years. The median tumor volume at GKS was 7.0 cm3, and the median marginal dose was 16 Gy. The median follow-up period after GKS was 7.5 months. The median PFS time after GKS was 8.9 months (95% CI 4.3-13.5 months) in the methylated and 4.6 months (95% CI 3.7-5.5 months) in the unmethylated group (P = 0.016). The median OS time after GKS was 14.0 months (95% CI 9.3-18.7 months) in the methylated group and 9.0 months (95% CI 6.5-11.5 months) in the unmethylated group (P = 0.026). Methylation of the MGMT promoter correlated with better PFS and OS after GKS for recurrent GBM. Prospective comparative studies are required to determine whether MGMT methylation directly affects the efficiency of GKS.

Optimal treatment of jugular foramen schwannomas: long-term outcome of a multidisciplinary approach for a series of 29 cases in a single institute.

BACKGROUND: The goal of treatment for jugular foramen schwannomas (JFSs) is to achieve complete tumor removal with cranial nerve preservation. However, achieving this goal remains a challenge despite the advances in microsurgical techniques. The aim of this study was to determine optimal treatment strategies for JFSs based on a review of a series of 29 surgical cases in our institute. MATERIALS AND METHODS: Between 1997 and 2013, 29 patients with JFSs underwent surgical treatment by multidisciplinary otoneurosurgical approaches. We retrospectively evaluated various clinical outcomes including the extent of tumor resection, postoperative cranial nerve deficits, and the recurrence rate. Tumor extension was classified using the Kaye and Pellet classification (KPC) system, and the extent of tumor resection was graded as gross total resection (GTR), near total resection (NTR), and subtotal resection (STR). We utilized the House-Brackmann facial nerve grading system (HBFNGS), the average pure-tone audiometry and speech audiometry (PTA/SA) tests, and the American Speech-Language-Hearing Association National Outcome Measurement System (ASHA NOMS) swallowing scale (ASHA level) for assessment of functional outcomes. RESULTS: The extent of tumor resection was not related to the degree of immediate postoperative cranial nerve deficits. However, the surgical approach was significantly related to postoperative hearing status and immediate postoperative facial function. Also, among the ten patients who were below the level of acceptable facial function immediately postoperatively, nine patients (90%) recovered to acceptable facial function by the last follow-up. Concerning postoperative swallowing status, all 21 patients recovered swallowing function by the last follow-up. Postoperative Gamma Knife stereotactic radiosurgery (GKRS) was performed for three recurrent and seven residual tumors, and recurrence was not observed in the mean 36-month follow-up period. CONCLUSIONS: A surgical strategy should be tailored to the individual case, and clinicians should consider the possibility of recurrence and further adjuvant treatment.

Gamma knife radiosurgery for trigeminal neuralgia secondary to benign lesions.

BACKGROUND: Investigate the clinical outcomes of gamma knife radiosurgery (GKS) in patients with benign intracranial lesions and accompanying trigeminal neuralgia (TN). METHODS: From February 2002 to November 2011, 50 patients (11 males, 39 females) underwent GKS for intracranial lesions accompanied by TN. Pathological diagnoses included meningioma in 30 patients, vestibular schwannoma in 11, trigeminal schwannoma in 7, epidermoid cyst in 1, and arteriovenous malformation in 1. Twenty-two (44%) had a lesion dominantly located in the middle fossa and 26 patients (52%) in the posterior fossa. Twenty-five (50%) patients complained of type I pain, and 18 patients (36%) suffered from type II pain. The other 7 patients (14%) presented with facial pain that could not be determined. Pain was assessed retrospectively by subjective descriptions and with the Barrow Neurological Institute pain intensity score before and after GKS. RESULTS: Tumor control was evaluated with magnetic resonance imaging in 44 (95.7%) of 46 patients over a median follow-up period of 54.8 months (range, 13-142 months). Initial improvement in pain after GKS was observed in 46 (92%) patients. The percentage of patients with improved Barrow Neurological Institute score was 73.5% at 1 year, 70.7% at 2 years, and 76.5% at 3 years. Complete pain relief at the final follow-up was achieved in 18 patients (36%). Pain recurred in 13 patients (28.3%) after initial improvement. Pathological diagnosis, location of the lesion, and type of facial pain did not influence the initial pain response after GKS. Pain recurred more frequently in patients with meningioma than in those with schwannoma (P = .045). Type II pain showed better response to the treatment (P = .006). CONCLUSION: The majority of patients with facial pain secondary to a benign intracranial lesion showed improvement after GKS. However, a substantial proportion of the patients experienced incomplete pain relief and recurrence. GKS needs to be combined with an additional modality or the technique must be modified to achieve complete and durable pain control.

Clinical outcome of neurofibromatosis type 2-related vestibular schwannoma: treatment strategies and challenges.

To discuss the appropriate treatment strategy for NF2-related vestibular schwannoma (VS) according to our experiences, we analyzed long-term clinical and radiological data focusing on NF2-related VS patients. Seventeen NF2-related VS patients were included. Based on their first management modality for VS, we classified these patients into the following four groups: microsurgery (MS), fractionated gamma knife radiosurgery (f-GKS), single session gamma knife radiosurgery (s-GKS), and conservative management (CM). Each patient was assessed for each separate ear. Changes of tumor volume and hearing status for 32 ears in 17 patients according to their first treatment modality were evaluated. The mean follow-up duration and tumor volume of the MS (4 ears, 4 patients), f-GKS (12 ears, 10 patients), s-GKS (8 ears, 7 patients), and CM (8 ears, 7 patients) groups were 3.9 years and 1.6 mL; 5.1 years and 11.1 mL; 8.4 years and 5.6 mL; and 6.1 years and 1.6 mL, respectively. Relatively lower local control rates were observed in the MS and the CM group (0 and 12.5 %, respectively). On the other hand, better local control rates for follow-up periods of 5.1 and 8.4 years were achieved in the f-GKS and the s-GKS groups (75 and 50 %, respectively). However, hearing preservation in all treatment modalities could not be achieved effectively. Long-term preservation of hearing in at least one serviceable ear as well as tumor control should be considered for each patient. Therefore, a proper treatment option should be selected at the appropriate time according to clinical characteristics of individual patients.