A Potential Risk of Radiation-Induced Cavernous Malformations Following Adjuvant Gamma Knife Radiosurgery for Mesial Temporal Lobe Epilepsy.

Objective: Several clinical studies have explored the feasibility and efficacy of radiosurgical treatment for mesial temporal lobe epilepsy, but the long-term safety of this treatment has not been fully characterized. This study aims to report and describe radiation-induced cavernous malformation as a delayed complication of radiosurgery in epilepsy patients. Methods: The series includes 20 patients with mesial temporal lobe epilepsy who underwent Gamma Knife radiosurgery (GKRS). The majority received a prescribed isodose of 24 Gy as an adjuvant treatment after anterior temporal lobectomy. Results: In this series, we identified radiation-induced cavernous malformation in three patients, resulting in a cumulative incidence of 18.4% (95% CI, 6.3 to 47.0%) at an eight-year follow-up. These late sequelae of vascular malformation occurred between 6.9 and 7.6 years after GKRS, manifesting later than other delayed radiation-induced changes, such as radiation necrosis. Neurological symptoms attributed to intracranial hypertension were present in those three cases involving cavernous malformation. Of these, two cases, which initially exhibited an insufficient response to radiosurgery, ultimately demonstrated seizure remission following the successful microsurgical resection of the cavernous malformation. Conclusion: All things considered, the development of radiation-induced cavernous malformation is not uncommon in this population and should be acknowledged as a potential long-term complication. Microsurgical resection of cavernous malformation can be preferentially considered in cases where the initial seizure outcome after GKRS is unsatisfactory.

Avoiding a Collision in Gamma Knife Radiosurgery : A Modified Mask Fixation Method.

OBJECTIVE: The latest version of the Leksell Gamma Knife IconTM allows for mask- and frame-based fixation. Although mask fixation provides fractionated treatment and immobilization using a noninvasive method, it is not free from collision. The authors investigated the collision problem with a modified mask fixation method. METHODS: This study presents a case of two meningiomas in the frontal area, where a collision occurs in the occipital area. A modified mask fixation method was introduced to avoid the collision : first, the edges of the head cushion were cut off and polystyrene beads with a diameter of approximately 5 cm were removed. Next, the head cushion was sealed using a stapler. Finally, the head cushion was flattened in the adapter. We compared the shot coordinates, 3-dimensional (3D) error, clearance distance, and vertical depth of the head cushion between the initial and modified mask fixations. RESULTS: When comparing the initial and modified mask fixations, the difference in the shot coordinates was +10.5 mm along the y-axis, the difference in the 3D error was approximately 18 mm, and the difference in clearance was -10.2 mm. The head cushion was approximately 8 mm deeper in the modified mask fixation. CONCLUSION: Based on these findings, we recommend a modified mask fixation method for gamma knife radiosurgery using ICON with a collision.

Hypofractionated stereotactic radiosurgery for large-sized skull base meningiomas.

PURPOSE: Although stereotactic radiosurgery (SRS) has been proven to be effective and safe for treating intracranial meningiomas, concerns have been raised about the use of SRS for large-sized tumors involving the skull base that frequently encroach onto adjacent critical neural structures. The purpose of this study was to investigate the role of hypofractionated SRS as a therapeutic option for large-sized skull base meningiomas. METHODS: Thirty-one consecutive patients (median age: 55 years, 9 men and 22 women) who had been treated with hypofractionated SRS using CyberKnife for large-sized skull base meningiomas (> 10 cm3 in volume, median of 18.9 cm3, range 11.6-58.2 cm3) were enrolled. All patients harbored middle or posterior skull base tumors, most frequently of cavernous sinus (n = 7, 22.6%), petroclival (n = 6, 19.4%), or tentorial edge (n = 6, 19.4%) locations. SRS was delivered in five daily fractions (range 3-5 fractions) with a median cumulative dose of 27.8 Gy (range 22.6-27.8 Gy). RESULTS: With a median follow-up of 57 months (range 9-98 months), tumor control was achieved for 28 (90.3%) of 31 patients. Treatment response on MRI included partial response (volume decrease > 20%) in 17 (54.8%) patients, stable in 11 (35.5%), and progression (volume increase > 20%) in 3 (9.7%). Of 21 patients with cranial neuropathy, 20 (95.2%) showed improved neurological status. CONCLUSIONS: Our current results suggest a promising role of hypofractionated SRS for large-sized skull base megningiomas in terms of tumor control and neurological outcomes. It is a reasonable therapeutic option for select patients.

Single-fraction versus hypofractionated stereotactic radiosurgery for medium-sized brain metastases of 2.5 to 3 cm.

PURPOSE: Given recently suggested utility of hypofractionated stereotactic radiosurgery (SRS) in treating large brain metastases (BMs) > 3 cm, we sought to prospectively control tumor size variable to investigate the efficacy and safety of hypofractionated SRS for medium-sized BMs (2.5 to 3 cm) compared with single-fraction SRS. METHODS: Between 2011 and 2015, a total of 100 patients with newly diagnosed BMs (n = 105) of 2.5 to 3 cm had been treated with either single-fraction (n = 67; median dose 20 Gy) or hypofractionated SRS (n = 38; median cumulative dose 35 Gy in 5 daily fractions). No patients received any prior or upfront whole brain radiotherapy. In each patient, treatment outcome was measured by local tumor control (LTC), overall and progression-free survival (OS and PFS), and the occurrence of radiation necrosis (RN). RESULTS: With a median follow-up of 14 months, significant differences were observed between the single-fraction versus hypofractionated SRS groups in the incidence of RN (29.9% vs. 5.3%, P < 0.001) and LTC (1-year LTC rates 66.6% vs. 92.4%, P = 0.028). There were no differences in PFS (median 6 months vs. 6 months, P = 0.381) and OS (median 13 months vs. 18 months, P = 0.239). Treatment-related adverse events ( ≥ grade 2 toxicity by CTCAE ver. 4.0) occurred more frequently in single-fraction group, although the difference did not reach statistical significance (56.3% vs. 36.1%, P = 0.084). CONCLUSIONS: Our results suggest a better safety and efficacy profile of hypofractionated SRS for medium-sized BMs compared with single-fraction SRS. Further prospective studies are needed to confirm these results.

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.

Experiences on two different stereotactic radiosurgery modalities of Gamma Knife and Cyberknife in treating brain metastases.

BACKGROUND: In this study, we compared the dosimetric properties between Gamma Knife (GK) and Cyberknife (CK), and investigated the clinical implications in treating brain metastases (BMs). METHODS: Between 2011 and 2013, 77 patients treated with either single-fraction GK for small BMs (n = 40) or fractionated CK for large BMs >3 cm (n = 37) were analyzed. Among a total of 160 lesions, 81 were treated with GK (median, 22 Gy) and 38 (large lesions) with three- or five-fraction CK (median, 35 Gy). The median tumor volume was 1.0 cc (IQR, 0.12-4.4 cc) for GK and 17.6 cc (IQR, 12.8-23.7 cc) for fractionated CK. A lesion-to-lesion dosimetric comparison was performed using the identical contour set in both systems. RESULTS: The mean dose to tumor was significantly higher in GK by 1.25-fold (P < 0.001), whereas normal tissue volume receiving 90-10 % of prescription dose was significantly larger in CK by 1.26-fold (P < 0.001). Nevertheless, no differences were observed in local tumor control (rates at 1 year, 89.7 % vs 87.0 %; P = 0.594) and overall survival (median, 14 vs 16 months; P = 0.493) between GK and fractionated CK groups. The incidences of radiation necrosis were also not different (12.3 % vs 15.8 %; P = 0.443). CONCLUSIONS: Despite slightly inferior dosimetric properties of CK, fractionated CK for large BMs appears to be as effective and safe as single-fraction GK for small BMs, representing fractionation as an effective strategy for enhancing efficacy and moderating toxicity in stereotactic radiosurgery for BMs.

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.