Corrigendum: Vestibular schwannoma associated with neurofibromatosis type 2: Clinical course following stereotactic radiosurgery.

[This corrects the article DOI: 10.3389/fonc.2022.996186.].

Vestibular schwannoma associated with neurofibromatosis type 2: Clinical course following stereotactic radiosurgery.

Objective: A lack of understanding of the clinical course of neurofibromatosis type 2 (NF2)-associated vestibular schwannoma (VS) often complicates the decision-making in terms of optimal timing and mode of treatment. We investigated the outcomes of stereotactic radiosurgery (SRS) in this population. Methods: We retrospectively analyzed NF2 patients treated with Gamma-Knife SRS for VS in our tertiary referral center. A total of 41 treated lesions from 33 patients were collected with a follow-up period of 69.1 (45.0-104.8) months. We reviewed the treatment history, hearing function, and other treatment-related morbidities in individual cases. We also analyzed pre- and post-treatment tumor volumes via imaging studies. Longitudinal volumetric analyses were conducted for the tumor volume response of the 41 treated lesions following SRS. The growth pattern of 22 unirradiated lesions during an observation period of 83.4 (61.1-120.4) months was separately evaluated. Results: Most treated lesions showed effective tumor control up to 85% at 60 months after SRS, whereas unirradiated lesions progressed with a relative volume increase of 14.0% (7.8-27.0) per year during the observation period. Twelve (29%) cases showed pseudoprogression with significant volume expansion in the early follow-up period, which practically reduced the rate of tumor control to 57% at 24 months. Among the patients with serviceable hearing, two (20%) cases lost the hearing function on the treated side during the early follow-up period within 24 months. Conclusions: Progressive NF2-associated VS can be adequately controlled by SRS but the short-term effects of this treatment are not highly advantageous in terms of preserving hearing function. SRS treatment candidates should therefore be carefully selected.

Thirty-year clinical experience in gamma knife radiosurgery for trigeminal schwannomas.

We aimed to evaluate the radiographic and clinical outcomes after gamma knife radiosurgery (GKRS) for trigeminal schwannomas (TSs). A total of 87 patients who underwent GKRS for TSs between 1990 and 2020 were enrolled. The mean tumor volume was 4.3 cm3. The median prescribed dose for the margins of the tumor was 13 Gy. The median follow-up duration was 64.3 months (range 12.0-311.5 months). The overall local tumor control rate was 90%, and the symptom response rate was 93%. The response rate for each symptom was 88% for facial pain, 97% for facial sensory change, and 86% for cranial nerve deficits. Nineteen (22%) patients showed transient swelling, which had regressed at the time of the last follow-up. Cystic tumors were associated with transient swelling (p = 0.04). A tumor volume of < 2.7 cm3 was associated with local tumor control in univariable analysis. Transient swelling was associated with symptom control failure in both univariable and multivariable analyses (p = 0.04, odds ratio 14.538). GKRS is an effective treatment for TSs, both for local control and symptom control.

Radiosurgery for Cerebral Arteriovenous Malformation (AVM) : Current Treatment Strategy and Radiosurgical Technique for Large Cerebral AVM.

Arteriovenous malformations (AVMs) are congenital anomalies of the cerebrovascular system. AVM harbors 2.2% annual hemorrhage risk in unruptured cases and 4.5% annual hemorrhage risk of previously ruptured cases. Stereotactic radiosurgery (SRS) have been shown excellent treatment outcomes for patients with small- to moderated sized AVM which can be achieved in 80-90% complete obliteration rate with a 2-3 years latency period. The most important factors are associated with obliteration after SRS is the radiation dose to the AVM. In our institutional clinical practice, now 22 Gy (50% isodose line) dose of radiation has been used for treatment of cerebral AVM in single-session radiosurgery. However, dose-volume relationship can be unfavorable for large AVMs when treated in a single-session radiosurgery, resulting high complication rates for effective dose. Thus, various strategies should be considered to treat large AVM. The role of pre-SRS embolization is permanent volume reduction of the nidus and treat high-risk lesion such as AVM-related aneurysm and high-flow arteriovenous shunt. Various staging technique of radiosurgery including volume-staged radiosurgery, hypofractionated radiotherapy and dose-staged radiosurgery are possible option for large AVM. The incidence of post-radiosurgery complication is varied, the incidence rate of radiological post-radiosurgical complication has been reported 30-40% and symptomatic complication rate was reported from 8.1% to 11.8%. In the future, novel therapy which incorporate endovascular treatment using liquid embolic material and new radiosurgical technique such as gene or cytokine-targeted radio-sensitization should be needed.

Long-Term Outcome of Gamma Knife Radiosurgery for Brain Cavernoma: Factors Associated with Subsequent De Novo Cavernoma Formation.

BACKGROUND: We aimed to evaluate the factors associated with de novo brain cavernoma formations after patients underwent gamma knife radiosurgery (GKRS) and confirmed whether developmental venous anomaly (DVA) presented with a cavernoma and whether the cavernoma was included in the GKRS target location. METHODS: From January 2003 to December 2008, 95 patients underwent radiosurgery for brain cavernoma at our institution. Of these, 15 with multiple cavernomas related to familial cavernoma or with a history of surgical treatment for cavernoma were excluded. A total of 80 patients (44 men and 36 women; average age, 39.4 years) with sporadic cavernoma were retrospectively analyzed by considering the patient characteristics, including sex, age, target volume, radiation dose, clinical symptoms, cavernoma location, radiosurgery complications, and morphology of DVA. RESULTS: The average target volume, mean radiation dose, and mean target percentage were 1019.2 mm3, 13.7 Gy, and 51.1%, respectively. Nineteen patients showed cavernomas associated with DVA; of these, de novo cavernoma formations were noticed in 4 patients at a median of 49.5 months after undergoing GKRS. All de novo cavernomas were related to the presence of DVA and were located near the brainstem or cerebral peduncle. De novo cavernomas occurred when DVAs were not included in the GKRS-target location. CONCLUSIONS: All de novo cavernomas were located near the brainstem or cerebral peduncle, and they occurred in the presence of DVAs. The presence of DVA in the radiosurgery target location might be potentially an important factor associated with de novo cavernoma formation.

Factors affecting hearing deterioration in vestibular schwannoma patients treated with gamma knife radiosurgery: the Asan Medical Center experience.

OBJECTIVES: To investigate the changes in hearing and to determine factors predicting hearing deterioration in patients with vestibular schwannoma (VS) who undergo gamma knife radiosurgery (GKRS). DESIGN: A retrospective review of medical records in patients diagnosed with VS and initially treated with GKRS at a tertiary care medical center between 1995 and 2015 was performed. Tumor factors (location, volume), parameters related to irradiation to the tumor and cochlea, and distance between the tumor and cochlea were reviewed. RESULTS: Fifty-six patients were included in the final analysis with a mean observation period following GKRS as 24.4 ± 27.8 months. Prior to GKRS, the average pure tone threshold at 500, 1k, 2k, and 4k Hz (PTA4) was 51.0 ± 29.7 dB HL. After GKRS, the mean PTA4 was 71.6 ± 33.3 dB HL. Significant independent odds ratios for hearing deterioration were 8.5 for extracanalicular tumors, 18.8 for more than 10 shots in GKRS, and 12.2 for a distance between the tumor center and cochlea modiolus less than 20 mm. CONCLUSIONS: A significant hearing deterioration was shown in 2 years after GKRS. Tumor location, number of radiation shots, and distance between the tumor and cochlea affected hearing level after GKRS.

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 mm(3) (range 10-19500 mm(3)), 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.

Gamma Knife radiosurgery for recurrent or residual seizures after anterior temporal lobectomy in mesial temporal lobe epilepsy patients with hippocampal sclerosis: long-term follow-up results of more than 4 years.

OBJECT: Gamma Knife radiosurgery (GKRS) has proven efficacy in the treatment of drug-resistant mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and is comparable to conventional resective surgery. It may be effective as an alternative treatment to reoperation after failed temporal lobe surgery in patients with MTLE-HS. The purpose of this study was to investigate the efficacy of GKRS in patients with unilateral MTLE-HS who did not achieve seizure control or had recurrent seizures after anterior temporal lobectomy (ATL). METHODS: Twelve patients (8 males; mean age 35.50 ± 9.90 years) with MTLE-HS who underwent GKRS after failed ATL (Engel Classes III-IV) were included. GKRS targets included the remnant tissue or adjacent regions of the previously performed ATL with a marginal dose of 24-25 Gy at the 50% isodose line in all patients. Final seizure outcome was assessed using Engel's modified criteria during the final 2 years preceding data analysis. A comparison between signal changes on follow-up MRI and clinical outcome was performed. RESULTS: All patients were followed up for at least 4 years with a mean duration of 6.18 ± 1.77 years (range 4-8.8 years) after GKRS. At the final assessment, 6 of 12 patients were classified as seizure free (Engel Class Ia, n = 3; Ic, n = 2; and Id, n = 1) and 6 patients were classified as not seizure free (Engel Class II, n = 1; III, n = 2; and IV, n = 3). Neither initial nor late MRI signal changes after GKRS statistically correlated with surgical outcome. Clinical seizure outcome did not differ significantly with initial or late MRI changes after GKRS. CONCLUSIONS: GKRS can be considered an alternative option when the patients with MTLE-HS who had recurrent or residual seizures after ATL refuse a second operation.

New nidus formation adjacent to the target site of an arteriovenous malformation treated by Gamma Knife surgery.

New nidi are rarely found adjacent to the resection margin following treatment for an arteriovenous malformation (AVM), especially in adults. In addition, there are no reports in adults of new nidus formation adjacent to the targeted site of an AVM that angiography has verified to be completely obliterated by radiosurgery. The authors present their experience with recurrent AVMs following AVM radiosurgery in 3 patients whose ages were 9 years, 10 years, and 33 years. None of the patients had been treated with embolization before radiosurgery. Two patients had a history of intracerebral hemorrhage before radiosurgery. New lesions developed around the obliterated nidi in all 3 cases. Angiography performed after the first radiosurgery confirmed complete removal of the nidus in all 3 patients, and new nidus formation was detected 31, 132, and 36 months after the initial GKS. The new lesions were also treated by GKS. Occasionally, in patients with recurrent AVMs, such as those described in this paper, long-term clinical and angiographic follow-up may be required, even if complete occlusion is originally shown on angiograms.

Application of the gamma evaluation method in Gamma Knife film dosimetry.

PURPOSE: Gamma Knife (GK) radiosurgery is a minimally invasive surgical technique for the treatment of intracranial lesions. To minimize neurological deficits, submillimeter accuracy is required during treatment delivery. In this paper, the delivery accuracy of GK radiosurgery was assessed with the gamma evaluation method using planning dose distribution and film measurement data. METHODS: Single 4, 8, and 16 mm and composite shot plans were developed for evaluation using the GK Perfexion (PFX) treatment planning system (TPS). The planning dose distributions were exported as digital image communications in medicine - radiation therapy (DICOM RT) files using a new function of GK TPS. A maximum dose of 8 Gy was prescribed for four test plans. Irradiation was performed onto a spherical solid water phantom using Gafchromic EBT2 films in the axial and coronal planes. The exposed films were converted to absolute dose based on a 4th-order polynomial calibration curve determined using ten calibration films. The film measurement results and planning dose distributions were registered for further analysis in the same Leksell coordinate using in-house software. The gamma evaluation method was applied to two dose distributions with varying spatial tolerance (0.3-2.0 mm) and dosimetric tolerance (0.3-2.0%), to verify the accuracy of GK radiosurgery. The result of gamma evaluation was assessed using pass rate, dose gamma index histogram (DGH), and dose pass rate histogram (DPH). RESULTS: The 20, 50, and 80% isodose lines found in film measurements were in close agreement with the planning isodose lines, for all dose levels. The comparison of diagonal line profiles across the axial plane yielded similar results. The gamma evaluation method resulted in high pass rates of >95% within the 50% isodose line for 0.5 mm∕0.5% tolerance criteria, in both the axial and coronal planes. They satisfied 1.0 mm∕1.0% criteria within the 20% isodose line. Our DGH and DPH also showed that low isodose lines exhibited inferior gamma indexes and pass rates compared with higher isodose lines. CONCLUSIONS: The gamma evaluation method was applicable to GK radiosurgery. For all test plans, planning dose distribution and film measurement met the tolerance criteria of 0.5 mm∕0.5% within the 50% isodose line which are used for marginal dose prescription.