Fractionated Gamma Knife Radiosurgery Research Articles

Single Versus Fractionated Gamma Knife Radiosurgery for Nonfunctioning Pituitary Adenomas Close to the Optic Pathway: A Multicenter Propensity Score Matched Study.

Gamma Knife radiosurgery (GKRS), typically administered in a single session (S-GKRS), is an effective treatment for nonfunctioning pituitary adenoma (NFPA). For lesions close to the optic pathway, the use of hypofractionated radiosurgery is growing. This study seeks to compare the results of S-GKRS vs fractionated-GKRS (F-GKRS) for NFPAs adjacent to the optic pathway. Two cohorts of patients with residual or recurrent NFPAs in contact to the optic pathway were retrospectively included in this study: (1) a group of patients who underwent a 3-day course of F-GKRS in Europe and (2) a group of patients treated with S-GKRS in the United States. A propensity score matching (ratio 1:1) was carried out to obtain and compare 2 homogeneous groups of patients with NFPA. A total of 84 patients were included for analysis (42 in the S-GKRS cohort and 42 in the F-GKRS group). The 2 cohorts did not differ for age, sex, number of previous surgical procedure, tumor volume, and follow-up. The mean follow-up was 60.2 ± 37.0 months and 62.4 ± 37.4 months for F-GKRS and S-GKRS cohort, respectively (P = .38). The overall tumor control at last follow-up was achieved in 95.2% and 92.9% of patients in F-GKRS and S-GKRS, respectively (P = .64). The 1-year, 3-year, 5-year, and 7-year progression-free survival rate after F-GKRS was 100%, 97.1%, 97.1%, and 91%, respectively. In the S-GKRS sample, progression-free survival rates were 100%, 100%, 92.5%, and 92.5% at 1, 3, 5, and 7 years after treatment, respectively. Two patients (4.7%) from the F-GKRS cohort and 2 (4.7%) from the S-GKRS cohort sustained visual worsening after radiosurgery (P = 1.0). In the management of NFPAs adjacent to the optic pathway both F-GKRS and S-GKRS had comparable outcomes and risks at 7 years. Future prospective studies including larger cohorts with longer follow-up are needed to confirm our results.

Promising outcome of patients with recurrent glioblastoma after Gamma Knife-based hypofractionated radiotherapy

BackgroundThe role of Gamma Knife radiosurgery (GKRS) in recurrent glioblastoma remains unclear. The purpose of this study is to evaluate the effects of GKRS in a group of patients with recurrent glioblastoma, focusing on survival and safety. MethodsPatients undergoing GKRS for recurrent glioblastoma between September 2014 and April 2019 were included in this study. Relevant clinical and radiosurgical data, including GKRS-related complications, were recorded and analyzed. Overall survival (OS), local progression free survival (LPFS) and prognostic factors for outcome were thoroughly evaluated. ResultsFifty-three patients were analyzed (24 female, 29 male). The median age was 50 years (range, 19–78 years). The median GKRS treatment volume was 35.01 cm3 (range, 2.38-115.57 cm3). Twenty patients (38%) were treated with single fraction GKRS, while 33 (62%) were treated with GKRS-based hypofractionated stereotactic radiotherapy (HSRT). The median prescription dose for single fraction GKRS, 3-fractions HSRT and 5-fractions HSRT were 16 Gy (range, 10−20 Gy), 27 Gy (range, 18−33 Gy) and 25 Gy (range, 25−30 Gy), respectively. The median LPFS and OS times were 8.1 months and 11.4 months after GKRS, respectively. HSRT and Bevacizumab were associated with improved LPFS, while HSRT alone was associated with longer OS. ConclusionOur findings suggested that HRST would likely improve LPFS and OS in definite settings; the addition of Bevacizumab to GKRS was associated with increased rates of local control. No major complications were reported. Further prospective studies are warranted to confirm our findings.

Two-Day Fraction Gamma Knife Radiosurgery for Large Brain Metastasis.

We investigated how treating large brain metastasis (LBM) using two-day fraction gamma knife radiosurgery (GKRS) affects tumor control and patient survival. A prescription dose of 10.3 Gy was applied for two consecutive days, with a biologically effective dose (BED) equivalent to a tumor single-fraction dose of 16.05 Gy and a brain single-fraction dose of 15.12 Gy. Between November 2017 and December 2021, 42 patients (mean age: 68.3 years, range: 50-84 years, male: 29 [69.1%], female: 13 [30.9%]) with 44 tumors underwent two-day fraction GKRS to treat large volume brain metastasis. The main cancer types were non-small cell lung cancer (NSCLC, N=16), small cell lung cancer (SCLC, N=7), colorectal cancer (N=7), breast cancer (N=3), gastric cancer (N=2), and other cancers (N=7). Twenty-one (50.0%) patients had a single LBM, nineteen (46.3%) had a single LBM and other metastasi(e)s, and two had two (4.7%) large brain metastases. At the time of the two-day fraction GKRS, the tumors had a mean volume of 23.1 cc (range: 12.5-67.4). on each day, radiation was administered at a dose of 10.3 Gy, mainly using a 50% isodose-line. We obtained clinical and magnetic resonance imaging (MRI) follow-up data for 34 patients (81%) with 35 tumors, who had undergone two-day fraction GKRS. These patients did not experience acute or late radiation-induced complications during follow-up. The median and mean progression-free survival (PFS) periods were 188 and 194 days, respectively. The local control rates at 6, 9, and 12 months were 77%, 40%, and 34%, respectively. The prognostic factors related to PFS were prior radiotherapy (P = 0.019) and lung cancer origin (P = 0.041). Other factors such as tumor volumes, each isodose volumes, and peri-GKRS systemic treatment were not significantly related to PFS. The overall survival period of the 44 patients following repeat SRS ranged from 15-878 days (median: 263±38 days, mean: 174±43) after the two-day fraction GKRS. Eight patients (18.2%) were still alive. Considering the unsatisfactory tumor control, a higher prescription dose should be needed in this procedure as a salvage management. Moreover, in the treatment for LBM with fractionated SRS, using different isodoses and prescription doses at the treatment planning for LBMs should be important. However, this report might be a basic reference with the same fraction number and prescription dose in the treatment for LBMs with frame-based SRS.

Development of an RPA for Prediction of Radiation Necrosis Following Single Fraction Gamma Knife Radiosurgery for Brain Metastases

Radiation necrosis (RN) is a potential complication following treatment of brain metastases with stereotactic radiosurgery (SRS). Several risk factors for RN have been reported, but to our knowledge there are no recursive partitioning analysis (RPA) models to identify patients at highest risk for RN. We therefore sought to develop a predictive tool to identify patients at highest risk for the development of RN following single fraction SRS. Patients who underwent single fraction SRS for brain metastases from 2017-2021 were identified from a single institutional IRB-approved database. Patients with concern for RN were discussed in a multi-disciplinary setting and a diagnosis of RN was made based on pathologic or radiographic findings. Cox proportional hazards regression was done to identify factors associated with RN. RPA was performed to categorize patients into distinct risk groups for RN. Variables with p<0.1 on univariate analysis from the Cox regression analysis were included in the RPA. Patients with staged SRS, incomplete treatment records, or < 3 months radiographic follow-up were excluded from the analysis. The study population comprised 1,011 lesions from 283 patients with a median follow-up of 9.7 months. The majority of lesions had non-small cell lung cancer (NSCLC) (49%) as the primary site followed by breast (12%) and melanoma (11%). The median prescription dose was 24 Gy (range: 12-24 Gy). RN was diagnosed in 12.2% of lesions, of which 28% (35/123) were symptomatic RN. The median time to RN was 4.9 months. Variables identified for inclusion in the RPA included primary tumor site, use of targeted therapy, tumor location, pre-SRS hemorrhage, post-SRS hemorrhage, prior SRS to other lesions, number of SRS targets, maximum dose, maximum lesion diameter, 70% isodose line, heterogeneity index, conformality index, and gradient index. RPA identified four distinct groups. Group 1 was defined as maximum lesion diameter (MLD) <0.8 cm with primary tumor site other than breast, colorectal (CRC) or NSCLC (n = 174); group 2 was MLD <0.8 cm with breast, CRC, or NSCLC (n = 372). Group 3 was defined as MLD ≥ 0.8 cm without post-SRS hemorrhage (n = 336) and group 4 was MLD ≥0.8 cm with post-SRS hemorrhage (n = 129). Two-year RN free survival for all lesions was 82%, 100% for group 1, 89% for group 2, 76% for group 3, and 58% for group 4. We created the first RPA predictive model for RN following single fraction SRS and identified a subgroup of patients at highest risk. This RPA can help guide clinicians when educating patients on RN risk for brain metastases.

Fractionated versus staged gamma knife radiosurgery for mid-to-large brain metastases: a propensity score-matched analysis.

To compare treatment results between fractionated gamma knife radiosurgery (f-GKRS) and staged gamma knife radiosurgery (s-GKRS) for mid-to-large brain metastases (BMs). We retrospectively analyzed data of patients with medium (4-10 mL) to large (> 10 mL) BMs who underwent s-GKRS or f-GKRS between March 2008 and September 2022. Patients were treated with (i) s-GKRS before May 2018 and (ii) f-GKRS after May 2018. Patients who underwent follow-up magnetic resonance imaging at least once were enrolled. Case-matched studies were conducted by applying propensity score matching to minimize treatment selection bias and potential confounding. Local control (LC) was set as the primary endpoint and overall survival (OS) as the secondary endpoint. This study included 129 patients with 136 lesions and 70 patients with 78 lesions who underwent s-GKRS and f-GKRS, respectively. Overall, 124 lesions (62 lesions in each group) were selected in the case-matched group. No differences were observed in the 6-month and 1-year cumulative incidences of LC failure between the s-GKRS and f-GKRS groups (15.6% vs. 15.9% at 6 months and 25.6% vs. 25.6% at 1 year; p = 0.617). One-year OS rates were 62.6% (95% confidence interval [CI]: 45.4-75.7%) and 73.9% (95% CI: 58.8-84.2%) in the s-GKRS and f-GKRS groups, respectively. The post-GKRS median survival time was shorter in the s-GKRS group than in the f-GKRS group (17 vs. 36 months), without significance (p = 0.202). This is the first study to compare f-GKRS and s-GKRS in large BMs. Fractionation is as effective as staged GKRS for treating mid-to-large BMs.

Comparing Fractionated and Single-Fraction Gamma Knife Radiosurgery for Brain Metastases From Non-Small-Cell Lung Cancer With a Focus on Driver Alterations.

Background As the overall survival in non-small-cell lung cancer has increased, safer, long-term treatments for brain metastases are increasingly needed. This study aimed to analyze the outcomes of fractionated and single-fraction gamma knife radiosurgery for brain metastases from non-small-cell lung cancer, focusing on driver alteration status. Methodology Patients who underwent gamma knife radiosurgery as their first local treatment for brain metastases from non-small-cell lung cancer between May 2018 and December 2021 at our institution were retrospectively enrolled. Results Among the 98 patients (287 lesions), 45 (130 lesions) harbored driver alterations, includingepidermal growth factor receptor mutations in 35 patients and anaplastic lymphoma kinase or ROS1 rearrangement in 10 patients. Overall, 64 and 34 patients underwent single-fraction and fractionated radiosurgery (3-15 fractions), respectively. Large tumor size was a risk factor for recurrence, while fractionated radiosurgery (subdistribution hazard ratio (sHR) = 16.47; confidence interval (CI) = 3.58-75.77; p < 0.001) and small tumor size (sHR = 1.15; CI = 1.04-1.28; p = 0.008) independently protected against radiation necrosis. In the case-matched analyses, the cumulative radiation necrosis rates were significantly lower in the fractionated group than in the single-fraction group among all lesions (p = 0.017) and among those with driver alterations (p = 0.046),whereas no significant difference was confirmed among wild-type lesions (p = 0.382). Conclusions Fractionated gamma knife radiosurgery may be an alternative therapeutic approach for reducing the risk of radiation necrosis, particularly for patients with driver alterations, even when the tumors are small. Further research is necessary to determine the optimal indications for fractionated gamma knife radiosurgery and fractionation methods.

The role of single fraction Gamma Knife radiosurgery for intraventricular central neurocytomas and the utility of F-18 fluroethyltyrosine: two case reports

BackgroundPrimary treatment of central neurocytomas is surgical resection. Gamma Knife surgery is considered a valuable therapeutic option in case of residual (after subtotal resection) or recurrent central neurocytomas. Here, we focused on the role of F-18 fluroethyltyrosine as a marker to document tumor progression after initial resection, in the context of an atypical central neurocytoma. We also describe MIB-1’s role in evaluating therapeutic decision-making.Case presentationTwo patients with central neurocytomas were treated by Gamma Knife surgery in our center. The first case (31-year-old Caucasian male) had atypical central neurocytoma. Four and a half years after surgical resection, magnetic resonance imaging and F-18 fluroethyltyrosine documented clear progression of residual central neurocytoma, further treated by Gamma Knife surgery (18 Gy at 50%, target volume 1.4 cc, and prescription isodose volume 1.8 cc). The initial post-Gamma Knife surgery clinical course was uneventful, with progressive volumetric reduction of residual tumor up to 4.5 years, when out-of-field recurrence was suspected and confirmed by local F-18 fluroethyltyrosine hyperactivity. Second single-fraction Gamma Knife surgery was performed (18 Gy at 50%, target volume 0.49 cc, prescription isodose volume 0.72 cc). The second (32-year-old Caucasian female) had previous subtotal resection and typical central neurocytoma. Seven years later, she had residual tumor progression. Single-fraction Gamma Knife surgery was performed (16 Gy at 50% isodose line, target volume 1.7 cc, and prescription isodose volume 2.5 cc). Last follow-up showed tumor volume reduction. Follow-up magnetic resonance imaging showed important volumetric reduction of both treated lesions.ConclusionsIn atypical central neurocytomas, F-18 fluroethyltyrosine could be used as postoperative examination to detect small tumor remnants, follow-up evaluation following the Gamma Knife surgery or, in select cases, following surgical resection. The role of MIB-1 is important in therapeutic decision-making, as tumors with MIB-1 exceeding 2% are characterized by more aggressive clinical course. Single-fraction Gamma Knife surgery remains a valuable therapeutic option for postoperative residual atypical central neurocytomas and central neurocytoma recurrences.

Feasibility of fractionated gamma knife radiosurgery in the management of newly diagnosed Glioblastoma

BackgroundGlioblastoma (GBM) is the most common primary malignant brain tumor in adults, with overall survival remaining poor despite ongoing efforts to explore new treatment paradigms. Given these outcomes, efforts have been made to shorten treatment time. Recent data report on the safety of CyberKnife (CK) fractionated stereotactic radiosurgery (SRS) in the management of GBM using a five-fraction regimen. The latest Gamma Knife (GK) model also supports frameless SRS, and outcomes using GK SRS in the management of primary GBM have not yet been reported.ObjectiveTo report on the feasibility of five-fraction SRS with the GammaKnife ICON in the management of newly diagnosed GBM.MethodsIn this single institutional study, we retrospectively reviewed all patients from our medical center from January 2017 through December 2021 who received fractionated SRS with Gamma Knife ICON for newly diagnosed GBM. Patient demographics, upfront surgical margins, molecular subtyping, radiation treatment volumes, systemic therapies, and follow-up imaging findings were extracted to report on oncologic outcomes.ResultsWe identified six patients treated within the above time frame. Median age at diagnosis was 73.5 years, 66% were male, and had a median Karnofsky Performance Status (KPS) of 70. All tumors were IDH wild-type, and all but one were MGMT methylated and received concurrent temozolomide (TMZ). Within this group, progression free survival was comparable to that of historical data without significant radiation-induced toxicities.ConclusionGamma Knife ICON may be discussed as a potential treatment option for select GBM patients and warrants further investigation in the prospective setting.

Fractionated Gamma Knife radiosurgery after cyst aspiration for large cystic brain metastases: case series and literature review.

Tumor cyst aspiration followed by Gamma Knife radiosurgery (GKRS) for large cystic brain metastases is a reasonable and effective management strategy. However, even with aspiration, the target lesion tends to exceed the dimensions of an ideal target for stereotactic radiosurgery. In this case, the local tumor control rate and the risk of complication might be a critical challenge. This study is aimed to investigate whether fractionated GKRS (f-GKRS) could solve these problems. Between May 2018 and April 2021, eight consecutive patients with nine lesions were treated with f-GKRS in five or ten sessions after cyst aspiration. The aspiration was repeated as needed throughout the treatment course to maintain the cyst size and shape. The patient characteristics, radiologic tumor response, and clinical course were reviewed using medical records. The mean follow-up duration was 10.2 (2-28) months. The mean pre-GKRS volume and maximum diameter were 16.7 (5-55.8) mL and 39.0 (31-79) mm, respectively. The mean tumor volume reduction achieved by aspiration was 55.4%. The tumor volume decreased for all lesions, and symptoms were alleviated in all patients. The median overall survival was 10.0months, and the estimated 1-year survival rate was 41.7% (95% CI: 10.9-70.8%). The local tumor control rate was 100%. No irradiation-related adverse events were observed. f-GKRS for aspirated cystic brain metastasis is a safe, effective, and less invasive management option for large cystic brain metastases.

The effect of fractionated gamma knife radiosurgery on visual acuity in patients with optic nerve tumor.

BackgroundStereotactic radiosurgery (SRS) method has been considered the first-line treatment option to treat patients involved with pre-optic nerve tumors. However, studies have shown that using fractionated SRS, normal tissue sparing and tumor dose can be strongly increased simultaneously. Our main goal was to illustrate the effects of fractionated SRS approach in optic nerve tumor treatment and its adjacent sensitive structures.Materials and methods19 patients involved in optic nerve tumor with clinical symptoms of vision loss were treated with Gamma Knife radiosurgery in three sessions with 12 hours intervals between them. The prescribed dose was about 6.0 ± 1.2 Gy. Patient-related parameters including pre-treatment and after-treatment tumor size, visual acuity and visual field were evaluated using the Snell chart and MRI imaging. Patients were followed for about 14 months.ResultThe overall result showed vision improvement for patients with low and moderate visual loss. However, there was no significant improvement in patients with severe visual loss. Relative improvement was observed in blind patients, although poorly. There was no evidence of growth, recurrence, or new tumor after treatment in patients.ConclusionFractionated gamma knife radiosurgery offers a safe and effective alternative for benign lesions adjacent to the optic nerve.

Exponential growth of an asymptomatic meningioma responsive to fractionated Gamma Knife radiosurgery

Exponential growth of an asymptomatic meningioma responsive to fractionated Gamma Knife radiosurgery

Long-term results of gamma knife radiosurgery for foramen magnum meningiomas.

Outcomes of 37 patients of foramen magnum meningioma (FMM) were evaluated, and the related literature was reviewed to determine the efficacy of Gamma Knife radiosurgery (GKRS) for treating patients with FMM. We present the largest series reported from a single institution with the longest follow-up to date. The database of patients who underwent GKRS for FMM between 2007 and 2019 was evaluated retrospectively. A total of 37 patients with radiological and pathological features consistent with FMM were included in this series. Thirty-three patients were female, and 4 were male. The median age was 58years (range, 23-74years). The most common symptom at diagnosis was headache (64.9%). Twelve patients had a history of microsurgical resection. The median duration from the initial onset of symptoms to GKRS was 12months (range 1-140months). Among the 37 tumors, eight (21.6%) were located ventrally, 24 (64.9%) laterally, and five (13.5%) dorsally. The median target volume was 3.30cm3 (range, 0.6-17.6cm3). Thirty-five patients (95%) were treated with single fraction GKRS, and two patients (5%) were treated with hypofractionated GKRS. The median clinical follow-up was 80months (range, 18-151months), while the median radiological follow-up was 84months (range, 18-144months). At the last clinical follow-up after GKRS, 27 patients (73%) had improved symptoms, and none had worsened pre-GKRS symptoms. At the last radiological follow-up after GKRS, 23 tumors (62.2%) remained stable, 13 (35.1%) decreased in size, and 1 (2.7%) increased in size. Tumor control, including stable and regressed tumors, was achieved in 97.3% of patients. Our cohort demonstrates that GKRS is an effective and safe treatment for patients with either primary or recurrent/residual FMM.

Clinical and radiographic adverse events after Gamma Knife radiosurgery for brainstem lesions: A dosimetric analysis

ObjectivesTo analyze the association between dosvolume relationships and adverse events in brainstem lesions treated with Gamma Knife radiosurgery (GKRS). MethodsTreatment plans were generated on BrainLab Elements and GammaPlan software. Dosimetric data were analyzed as continuous variables for patients who received GKRS to brain metastases or arteriovenous malformations (AVM) within or abutting the brainstem. Adverse events were classified as clinical and/or radiographic. Logistic and cox regression were used to assess the relationship between dosimetric variables and adverse events. ResultsSixty-one patients who underwent single fraction GKRS for brain metastases or AVM were retrospectively analyzed. Median age was 62 years (range: 12–92 years) and the median prescription dose was 18 Gy (range: 13–25 Gy). Median follow-up was 6months. Clinical and radiographic complications were seen in ten (16.4%) and 17 (27.9%) patients, respectively. On logistic regression, increasing D05% was found to be associated with an increased probability of developing a clinical complication post-GKRS (OR: 1.18; 95% CI: 1.01–1.39; p = 0.04). Furthermore, mean brainstem dose (HR: 1.43; 95% CI: 1.05–1.94; p < 0.02), D05% (HR: 1.09; 95% CI: 1.01–1.18; p = 0.03), and D95% (HR: 2.37; 95% CI: 0.99–5.67; p = 0.05) were associated with an increased hazard of experiencing post-GKRS complications over time. ConclusionsIncreasing D05% to the brainstem is associated with an increased risk of developing clinical complications. Clinicians may consider this parameter in addition to fractionated stereotactic radiation therapy when well-established dose constraints are not met in this patient population. Additional data are needed to further validate these findings.

RTHP-13. EFFICACY OF FRACTIONATED GAMMA KNIFE RADIOSURGERY FOR ORBITAL CAVERNOUS HEMANGIOMA: 10-YEAR EXPERIENCE AT A SINGLE INSTITUTION

Abstract This study aimed to evaluate the efficacy and safety of fractionated gamma knife radiosurgery (GKS) for the treatment of orbital cavernous hemangioma (OCH). METHODS From January 2007 to June 2018, 34 patients who underwent fractionated GKS (median 20 Gy in 4 fractions) for OCH at a single tertiary institution were reviewed. Ophthalmic evaluations including exophthalmometry, best corrected visual acuity with the Snellen chart and Humphrey visual field were investigated. Changes in lesion volume were also analyzed. RESULTS The median age was 43 years (range, 10–67 years) and 18 patients were male (53%). The median clinical follow-up time was 42 months (range, 12–132 months). The most common presenting symptom was proptosis followed by visual impairment. Proptosis improved in all 27 patients. The mean value of proptosis was reduced from 2.9 mm to 1.1 mm (P &lt; 0.001). Of 15 patients who showed decreased visual acuity preoperatively, 12 patients (80%) had improved in vision. Preoperative visual field defects were evident in 17 patients and resolved in 15 patients (88%) after treatment. The median tumor volume at the time of GKS was 2.2 cm3 (range, 0.2–8.5 cm3). Tumor shrinkage was observed in all patients and the mean volume reduction rate was 64%. No patient experienced GKS-related ocular morbidity, though two transient GKS-related adverse events (6%) were observed. CONCLUSION Fractionated GKS is an effective and safe option for the treatment of OCH, with significant reduction in tumor volume and improvement of ophthalmic outcomes.

One-Day Two-Fraction Radiosurgery for Brain Metastases Using Gamma Knife.

Objective: We aimed to evaluate the feasibility of a one-day two-fraction Gamma Knife radiosurgery (GKRS) for brain metastases.Cases and methods: Ten cases with ten brain metastases (four cases of lung adenocarcinoma, one small cell lung carcinoma (SCLC), two renal cell carcinoma, one breast cancer, one esophageal carcinoma, and one bile duct carcinoma) were treated by one-day two-fraction (with an interval of more than six hours) GKRS under rigid skull frame fixation. Of the ten brain metastases, five lesions were in the frontal lobe, one in temporal, one in occipital, and three in the cerebellar hemisphere. The mean planning target volume (PTV) of the ten brain tumors was 7.8 ml (median, 8.0; range, 3.8 - 11.8). The ten targets of the mean prescription isodose volume (PIV) of 10.1 ml (median, 10.1; range, 4.4 - 15.9) were treated with a mean margin dose of 20.4 Gy (median, 20.5; range, 16.4 - 22) in two fractions. In five cases, other small brain metastases (one to seven tumors) were also treated simultaneously in a single fraction GKRS. The indication of two-fraction radiosurgery was large lesion size in eight, retreatment in three, the proximity of the motor area in three, and pre-existing perifocal edema symptom of dysarthria in two, nausea and vomiting in one, and dementia in one.Results: Eight cases were alive at the end of the follow-up period of one to nine months (median, 6). One patient with SCLC died four and a half months after GKRS, from aggressive regrowth of the treated frontal lesion after transient marked shrinkage. Another patient died four months after GKRS due to the progression of other brain tumors treated by single fraction GKRS at the same time. In nine of 10 cases, the size of the treated tumors was controlled until the end of the follow-up period or the patient’s death. In two cases, an additional GKRS was performed for newly developed brain metastases at distant locations at six months and five months after one-day two-fraction GKRS, respectively, and controlled at the end of the follow-up period.Conclusions: A relatively high dose may be safely delivered to large lesions, to those close to the important structures, or those with perifocal edema by one-day two-fraction radiosurgery. Local control was good except for a relapsed SCLC metastasis case. Evaluation in more cases with a longer follow-up period is necessary to determine definite indications and optimal prescription doses.

In Reply to the Letter to the Editor Regarding “Safety and Efficacy of Primary Mulitsession Dose Fractionated Gamma Knife Radiosurgery for Jugular Paragangliomas”

In Reply to the Letter to the Editor Regarding “Safety and Efficacy of Primary Mulitsession Dose Fractionated Gamma Knife Radiosurgery for Jugular Paragangliomas”

Letter to the Editor “Regarding Safety and Efficacy of Primary Multisession Dose Fractionated Gamma Knife Radiosurgery for Jugular Paragangliomas”

Letter to the Editor “Regarding Safety and Efficacy of Primary Multisession Dose Fractionated Gamma Knife Radiosurgery for Jugular Paragangliomas”

Outcome evaluation of patients treated with fractionated Gamma Knife radiosurgery for large (> 3 cm) brain metastases: a dose-escalation study.

Fractionated Gamma Knife radiosurgery (GKS) represents a feasible option for patients with large brain metastases (BM). However, the dose-fractionation scheme balanced between local control and radiation-induced toxicity remains unclear. Therefore, the authors conducted a dose-escalation study using fractionated GKS as the primary treatment for large (> 3 cm) BM. The exclusion criteria were more than 3 lesions, evidence of leptomeningeal disease, metastatic melanoma, poor general condition, and previously treated lesions. Patients were randomized to receive 24, 27, or 30 Gy in 3 fractions (8, 9, or 10 Gy per fraction, respectively). The primary endpoint was the development of radiation necrosis assessed by a neuroradiologist blinded to the study. The secondary endpoints included the local progression-free survival (PFS) rate, change in tumor volume, development of distant intracranial progression, and overall survival. Between September 2016 and April 2018, 60 patients were eligible for the study, with 46 patients (15, 17, and 14 patients in the 8-, 9-, and 10-Gy groups, respectively) available for analysis. The median follow-up duration was 9.6 months (range 2.5-25.1 months). The 6-month estimated cumulative incidence of radiation necrosis was 0% in the 8-Gy group, 13% (95% confidence interval [CI] 0%-29%) in the 9-Gy group, and 37% (95% CI 1%-58%) in the 10-Gy group. Being in the 10-Gy group was a significant risk factor for the development of radiation necrosis (p = 0.047; hazard ratio [HR] 7.2, 95% CI 1.1-51.4). The 12-month local PFS rates were 65%, 80%, and 75% in the 8-, 9-, and 10-Gy groups, respectively. Being in the 8-Gy group was a risk factor for local treatment failure (p = 0.037; HR 2.5, 95% CI 1.1-29.6). The mean volume change from baseline was a 47.5% decrease in this cohort. Distant intracranial progression and overall survival did not differ among the 3 groups. In this dose-escalation study, 27 Gy in 3 fractions appeared to be a relevant regimen of fractionated GKS for large BM because 30 Gy in 3 fractions resulted in unacceptable toxicities and 24 Gy in 3 fractions was associated with local treatment failure.

Safety and Efficacy of Primary Multisession Dose Fractionated Gamma Knife Radiosurgery for Jugular Paragangliomas

While multisession dose fractionated Gamma Knife radiosurgery (DFGKS) is common, its use has never been described for jugular paragangliomas (JP), which are notoriously difficult to treat. To define efficacy, safety, and complication profile of DFGKS in 2 or 3 consecutive sessions for the treatment of a cohort of 10 cases of JP. Between 2012 and 2017, 10 patients with JP were treated with DFGKS in 2 or 3 sessions, because it was not safe to treat the lesion in a single session because of the large volume or proximity to organs at risk. The small to medium-sized JP are treated with 16-22 Gy radiation, but the large-volume JP were treated with 23-25 Gy radiation dose. The Leksell G frame was kept in situ during the whole procedure. The tumor volumes on pretreatment and posttreatment imaging were compared, using the Leksell Gamma Plan treatment plan software to assess tumor progression. The patients were regularly evaluated for their clinical outcome with radiologic correlation. The mean radiologic follow-up was 39 months (range, 12-78 months). The mean marginal dose for 3 fractions and 2 fractions was 7.64 Gy at 50% and 11.2 Gy at 50%, respectively. The mean tumor size was 29.9 cm3 (range, 9.95-47.63 cm3) at treatment and 21.9 cm3 (range, 8.83-37.5 cm3) at follow-up (suggestive of 26.7% reduction). Tumor control was achieved in all patients (100%). Of 110 potential neurologic problems (signs/symptoms) evaluated (11 in each patient), 56 (50.9%) were present preoperatively. Of them, 27 (48.2%) improved and 29 (51.8%) stabilized after treatment. There were 2 new-onset neurologic problems (of 110, 1.8%) attributable to treatment (new-onset headache and spinal accessory paresis). No patient had any permanent neurologic deterioration. DFGKS for large-volume JP leads to acceptable progression-free survival, tumor control rate, and symptomatic improvement. It may be preferred to surgery or fractionated radiotherapy given its better safety, efficacy, and complication profile.

Fractionated Gamma Knife radiosurgery for skull base meningiomas: a single-institution experience

OBJECTIVEGamma Knife radiosurgery (GKRS) has been successfully used for the treatment of intracranial meningiomas given its steep dose gradients and high-dose conformality. However, treatment of skull base meningiomas (SBMs) may pose significant risk to adjacent radiation-sensitive structures such as the cranial nerves. Fractionated GKRS (fGKRS) may decrease this risk, but until recently it has not been practical with traditional pin-based systems. This study reports the authors' experience in treating SBMs with fGKRS, using a relocatable, noninvasive immobilization system.METHODSThe authors performed a retrospective review of all patients who underwent fGKRS for SBMs between 2013 and 2018 delivered using the Extend relocatable frame system or the Icon system. Patient demographics, pre- and post-GKRS tumor characteristics, perilesional edema, prior treatment details, and clinical symptoms were evaluated. Volumetric analysis of pre-GKRS, post-GKRS, and subsequent follow-up visits was performed.RESULTSTwenty-five patients met inclusion criteria. Nineteen patients were treated with the Icon system, and 6 patients were treated with the Extend system. The mean pre-fGKRS tumor volume was 7.62 cm3 (range 4.57-13.07 cm3). The median margin dose was 25 Gy delivered in 4 (8%) or 5 (92%) fractions. The median follow-up time was 12.4 months (range 4.7-17.4 months). Two patients (9%) experienced new-onset cranial neuropathy at the first follow-up. The mean postoperative tumor volume reduction was 15.9% with 6 patients (27%) experiencing improvement of cranial neuropathy at the first follow-up. Median first follow-up scans were obtained at 3.4 months (range 2.8-4.3 months). Three patients (12%) developed asymptomatic, mild perilesional edema by the first follow-up, which remained stable subsequently.CONCLUSIONSfGKRS with relocatable, noninvasive immobilization systems is well tolerated in patients with SBMs and demonstrated satisfactory tumor control as well as limited radiation toxicity. Future prospective studies with long-term follow-up and comparison to single-session GKRS or fractionated stereotactic radiotherapy are necessary to validate these findings and determine the efficacy of this approach in the management of SBMs.