Median Margin Dose Research Articles

Treatment of Asymptomatic Meningioma With Gamma Knife Radiosurgery: Long-Term Follow-up With Volumetric Assessment and Clinical Outcome.

Some patients are diagnosed with asymptomatic meningioma(s) after undergoing a screening CT and MRI for minor ailments or postresection. To help clinicians in decision making for treatment of asymptomatic meningiomas. A single center retrospective cohort study of 117 patients with 122 tumors treated with Gamma Knife radiosurgery (GKRS; Elekta AB, Stockholm, Sweden). Patients were followed with longitudinal imaging and clinical evaluations. Tumor volumetry and developments of new signs or symptoms after GKRS were the end points in the study. Median patient age at GKRS was 60 yr (range 21-86 yr) with a median clinical follow-up of 53 mo (range 20-252 mo). The median pre-GKRS tumor volume was 3.6±3.8 cc (±standard deviation). Tumors were treated with a median margin dose of 14±2 Gy. At last follow-up, median tumor volume was 2.5±3.6 cc. Radiological progression-free survival (PFS) rates were 97% and 94.4% at 5 yr and 10 yr, respectively. Clinical PFS rates were 86% and 70% at 5 yr and 10 yr, respectively. Development of neurological complications was seen in 21 (18%) patients, and 11 (52%) of them had undergone surgical resection prior to GKRS. GKRS is a reasonable treatment strategy for asymptomatic meningiomas and compares favorably to natural history studies in terms of tumor control and neurological preservation. It results in relatively low morbidity in previously untreated meningiomas and serves as an appealing alternative treatment modality for recurrent meningiomas in asymptomatic patients.

Repeat stereotactic radiosurgery for the management of locally recurrent brain metastases.

Stereotactic radiosurgery (SRS) is a well-established treatment option for brain metastases (BM). Repeat SRS for progressive BM is an increasingly used paradigm, although little data is available to support this practice. The goal of this study was to assess the safety and efficacy of a second SRS procedure on a previously treated BM. We performed a retrospective metastasis-level analysis of patients who underwent two SRS procedures on the same lesion and for whom at least 6months of radiological follow-up was available. The data collected included patient characteristics, clinical symptoms at time of treatment, SRS parameters, radiological response per RANO-BM criteria, clinical evolution and survival. Seventy-five BM in 56 patients were included in the analysis. Most frequent primary histologies were non-small-cell lung cancer (59%) and breast cancer (19%). At the second SRS, median treatment volume was 1.19cc (range 0.07-20.6) treated with a median margin dose of 18Gy (range 12-20) at the 50% isodose line (range 30-80%). Median follow-up was 11months. Progression per RANO-BM criteria occurred in 31%, yielding actuarial local control at 1, 2, and 5years of 68%, 54% and 54% respectively. At last follow-up, 10 patients (18%) had improved relative to the initial presentation, while 21 (38%) were stable and 25 (44%) were deteriorated. Radiation-induced edema and radionecrosis occurred in 8.3% and 5% respectively. The median survival from the diagnosis of BM was 30months. Repeat SRS is a safe and effective novel therapeutic approach to consider in carefully selected patients.

Gamma Knife Radiosurgery for Anterior Clinoid Process Meningiomas: A Series of 61 Consecutive Patients

Gamma Knife radiosurgery (GKRS) outcomes for anterior clinoid process (ACP) meningiomas have not been specifically reported within any meningioma series. We present the initial and largest series in the literature that describes the presenting features, radiosurgery parameters, and radiologic and long-term clinical outcomes for 61 patients with ACP meningiomas treated with GKRS. Medical records were reviewed for 61 consecutive patients at a single center who underwent GKRS for ACP meningioma between 2008 and2016. Of 61 patients with ACP meningiomas, 49 (80%) were treated with GKRS as primary treatment, and 12 (20%) were treated with GKRS as an adjuvant therapy. Before GKRS, 29 patients presented with visual impairment and 50 patients presented with headache. Median patient age was 54.9 years. Median tumor volume was 3.2 cm3, and median margin dose was 12.0 Gy. The median radiologic follow-up time after GKRS was 75 months. During follow-up, tumor volume regressed in 37 cases (61%) and remained unchanged in 24 cases (39%). None of the patients experienced tumor volume progression. Tumor volume <3 cm3 was an independent predictor of tumor volume regression after GKRS (univariate analysis, P= 0.047; multivariate analysis, P= 0.049). Of 29 patients who presented with visual impairment, 16 (55%) improved after GKRS. None of the 61 patients developed new neurologic deficits after GKRS. GKRS provides a high rate of tumor volume control for ACP meningiomas as well as a low complication rate. Excellent tumor volume control was associated with smaller tumor size only.

Long term results of primary radiosurgery for vestibular schwannomas.

Stereotactic radiosurgery (SRS) has become a primary option for management for both newly diagnosed vestibular schwannomas (VS), as well as VS that enlarge after initial observation. A retrospective review of our prospectively maintained data base found 871 patients who underwent Gamma knife® SRS as their initial (primary) management between 1987 and 2008. Follow-up ranged from 1-25years (median = 5.2years) Median tumor volume was 0.9cc (0.02-36) and median margin dose was 13Gy (12-25). Progression free survival (PFS) after SRS was 97% at 3years, 95% at 5years, and 94% at 10years. Freedom from delayed surgical resection was found in 98.7% of patients. Smaller tumor volume was significantly associated with improved PFS. There were 326 patients with serviceable hearing (Gardner-Robertson 1 or 2) at the time of SRS with audiological follow-up of ≥ 1year. Serviceable hearing preservation rates after SRS were 89.8% at 1year, 76.9% at 3years, 68.4% at 5years, 62.5% at 7years, and 51.4% at 10years. Factors associated with improved serviceable hearing preservation included younger age, Gardner-Robertson grade 1 at SRS, and absence of subjective complaints of dysequilibrium or vertigo (vestibulopathy). Fifty-one patients (5.8%) developed trigeminal neuropathy. Fourteen (1.6%) developed a transient House-Brackmann grade 2 or 3 facial neuropathy. In this report with extended follow-up, primary SRS achieved tumor growth control in 94% of patients. Optimization of long- term cranial nerve outcomes remains an important achievement of this management strategy for VS.

The Impact of Insulin-like Growth Factor Index and Biological Effective Dose on Outcomes After Stereotactic Radiosurgery for Acromegaly

Abstract INTRODUCTION Stereotactic radiosurgery (SRS) is a safe and effective adjuvant treatment for acromegaly. Clinical and dosimetric factors predicting biochemical remission are incompletely understood. METHODS A single-institution cohort study of non-syndromic, radiation-naïve patients with growth hormone producing pituitary adenomas (GHA) having single-fraction SRS between 1990 and 2017. Patients were excluded if they were receiving pituitary suppressive medications at the time of SRS or if they had &lt; 24 mo of follow-up. The primary outcome was biochemical remission defined as normalization of insulin-like growth factor-1 index (IGF-1i) off suppressive medications. Biochemical remission was assessed using Cox proportional hazards. RESULTS A total of 102 patients met study criteria. Forty-six (45%) were female, median age was 49 yr (IQR = 37–59), median follow-up was 63 mo (IQR = 29–100). Median pre-SRS IGF-1i was 1.66 (IQR = 1.37–3.22). Median margin dose was 25 Gy (IQR = 21–25); median estimated biological effective dose (BED) was 169.49 Gy (IQR = 124.95–196.00). Biochemical remission was achieved in 58 (57%) patients, whereas 22 patients (22%) had medication-controlled disease. IGF-1i was the strongest independent predictor of remission, with an unadjusted hazard ratio (HR) of 0.53 (95% CI = 0.36–0.75, P &lt; .0001). Number of isocenters, margin dose, and BED predicted remission on univariate analysis, but after adjusting for sex and baseline IGF-1i, only BED remained independently associated with outcome in both continuous (HR = 1.01, 95% CI = 1.00–1.01, P = .02) and binary models (HR = 2.27, 95% CI = 1.39–5.22, P = .002). Twenty-four (29%) developed new post-SRS hypopituitarism. CONCLUSION IGF-1i is a better predictor of biochemical remission after SRS than IGF-1 level. BED appears to predict biochemical outcome more reliably than radiation dose, but confirmatory study is needed.

MLTI-15. A CASE SERIES OF PRE-OPERATIVE GAMMA-KNIFE RADIOSURGERY FOR RESECTABLE BRAIN METASTASES

Recent advances in the systemic treatment of various cancers have resulted in longer survival and higher incidence of brain metastases. Phase 3 trials in north America and in Japan have demonstrated that stereotactic radiosurgery will be a standard adjuvant modality following surgery for resectable brain metastases. However, we don’t know the optimal sequence of this combination therapy. We hypothesized that pre-operative stereotactic radiosurgery for resectable brain metastases provides favorable rates of local control, overall survival, leptomeningeal dissemination and symptomatic radiation necrosis. We have experienced 4 cases of resected brain metastases within 1–7 days after Gamma-knife surgery (median margin dose:22Gy) and have been following their clinical course. We will show the repressive cases.

RADI-33. DISTRIBUTED FRAMELESS GAMMA KNIFE RADIOSURGERY: A NEW TREATMENT PARADIGM FOR PATIENTS WITH BRAIN METASTASES

INTRODUCTION: Stereotactic radiosurgery (SRS) has excellent efficacy for patients with limited intracranial disease. Its use in patients with >10 brain metastases remains controversial. Nonetheless, cancer patients are living longer due to advancements in systemic therapeutics and avoiding the neurocognitive toxicities of whole brain radiation therapy is critical. Recent reports suggest that SRS may be effective in patients with ≥10 metastases. Treating large numbers of brain metastases in a single Gamma Knife radiosurgery (GKRS) treatment session poses several challenges. Treatment of metastases in close proximity to one another leads to an increased dose to normal brain, potentially increasing the risk of necrosis. Furthermore, single session treatment of multiple metastases may last several hours, causing significant patient discomfort. Here, we describe a novel treatment paradigm to address these issues: distributed frameless GKRS. Patients with ≥6 brain metastases undergo multi-session frameless GKRS with both temporal and spatial distribution over 2–5 sessions, decreasing treatment time per day and not treating adjacent metastases simultaneously. METHODS: We evaluated all patients with brain metastases who underwent distributed frameless SRS, using the Gamma Knife ICON, between January 2017 and November 2018. Fifty-one patients with 1097 unique lesions were included in this analysis. RESULTS: Mean patient age was 58.8 (range 29–89) years. Median follow-up was 4.1 (range: 0–20.4) months. The median number of metastases treated was 5 (range: 1–19) per treatment session and 11.5 (range: 3–82) per treatment course. The median number of treatment sessions per treatment course was 3 (range: 2–10). The median number of treatment courses, per patient, was 1 (range: 1–4). The median margin dose was 15 Gy. The median overall survival was 5.9 (range: 0.2–20.9) months. CONCLUSIONS: Distributed frameless Gamma Knife radiosurgery is technically feasible and should be considered in lieu of single session GKRS for patients with ≥6 brain metastases.

RADI-36. FRAME-BASED VERSUS FRAMELESS GAMMA KNIFE RADIOSURGERY FOR BRAIN METASTASES

INTRODUCTION: Brain metastases occur in 10 to 40% of cancer patients. In an effort to avoid the neurocognitive toxicities of whole brain radiation therapy, stereotactic radiosurgery (SRS) has become the preferred treatment option for most brain metastases. Many cancer patients will require several rounds of SRS during the course of their disease. Frame-based radiosurgery causes physical discomfort with each treatment session. We present our experience with frameless Gamma Knife radiosurgery (GKRS) and compare the clinical outcomes to frame-based treatments in the same patient cohort. METHODS: We evaluated all patients with brain metastases who underwent both frame-based and frameless SRS, using the Gamma Knife ICON, between January 2017 and November 2018. 11 patients with 110 unique lesions were included in this analysis. Clinical outcomes, including local control, were compared between the two treatment modalities. RESULTS: Mean patient age was 60.0 (range: 41 – 76) years. Median follow-up was 7.9 (range: 0 – 22.1) months. Median number of metastases treated was 4 (range: 1 – 9) per frame-based treatment and 3 (range: 1 – 10) per frameless treatment. Median number of frame-based and frameless procedures, per patient, was 1 (range: 1 – 3) and 1 (range: 1 – 2), respectively. Median tumor volume was 0.06 (range: 0.01 – 11.49) cm3 in the frame-based treatments and 0.14 (range: 0.01 – 4.22) cm3 in the frameless treatments. Median margin dose was 18 Gy for both the frame-based and frameless treatments. Local control was 86.5 and 91.5% at 6 and 9 months post-treatment, respectively in the frame-based treatments and 82.8 and 87.5% at 6 and 9 months post-treatment, respectively in the frameless treatments. CONCLUSIONS: Frameless GKRS results in similar rates of local control compared to frame-based GKRS. This treatment option should be considered in patients undergoing GKRS, as it balances clinical outcomes with patient comfort.

RADI-28. UP-FRONT SINGLE SESSION RADIOSURGERY FOR LARGE BRAIN METASTASES - VOLUMETRIC RESPONSES AND OUTCOMES

OBJECTIVE: Patients presenting with large brain metastases (LBM), described in the literature as ≥2.5 cm in maximum diameter or ≥10cm3in volume, pose a management challenge. For patients not compromised by mass effect, corticosteroid therapy followed by SRS allows for efficient, minimal access care that facilitates immediate institution of systemic therapy. METHODS: We performed a volumetric-based analysis in order to determine the efficacy of single-session SRS in the treatment of LBM in comparison to other treatment modalities. Thirty patients over the age of 18 with systemic cancer and brain metastases (≥2.7cm in greatest diameter or ≥10cm3in volume) who underwent single session SRS were included. Serial tumor volumes, clinical outcomes, and medication requirements were studied. RESULTS: Among 30 patients, 70% of patients had either lung, melanoma, or breast cancer. Median initial tumor size (maximum diameter) was 32mm (range 28–43) and median initial tumor volume was 9.32cm3 (range 1.09–25.31). Median marginal dose was 16Gy (range 12–18). Average percent decrease in tumor volume was 50% on imaging at 4–8 weeks, 60% at 4–6 months, 48% at 6–8 months, and 67% at >8 months compared to initial imaging. Only one patient required a subsequent craniotomy 4 years after SRS for an enlarging cyst which was granulation tissue consistent with radiation effects on pathology. There were no adverse events immediately following SRS. Median corticosteroid use after SRS was 21 days. There was no statistically significant difference in KPS score between treatment day and last follow up, suggesting relative safety and maintenance of function. CONCLUSION: Initial high dose corticosteroid therapy followed by prompt single session SRS is a safe and efficacious method of managing patients with large brain metastases (defined in our study as ≥2.7cm or ≥10cm3), if the clinical condition of the patient is acceptable at presentation.

RADI-27. ROLE OF STEREOTACTIC RADIOSURGERY IN THE CARE OF PATIENTS WITH &amp;gt;/= 25 CUMULATIVE BRAIN METASTASES

INTRODUCTION: Stereotactic radiosurgery (SRS) is an accepted treatment for multiple brain metastases. However, the upper limit of the number of brain metastases over the course of care suitable for this approach is controversial. METHODS: From a review of our prospective registry, 48 patients treated with SRS for ≥ 25 brain metastases in either single or multiple sessions between 2013 and 2019 were identified. Patient, tumor, and treatments characteristics were evaluated. Clinical outcomes and overall survival (OS) were analyzed. RESULTS: Thirty-one females (64.6%) and 17 males (35.4%) with a median age of 56 years (25–91) were included. Primary diagnoses included lung (n=23, 47.9%), breast (n=13, 27.1%), melanoma (n=8, 16.7%), and other (n=4, 8.33%). Initial median GPA index was 2 (0.5–3). Nine patients (18.8%) had received whole brain radiation therapy (WBRT) prior to first SRS treatment, with a median dose of 35Gy (30–40.5Gy). Ten patients (20.8%) received WBRT after initial SRS, with a median dose of 30Gy (20-30Gy). Thus, only 19 patients (40%) ever received WBRT. Median number of radiosurgeries per patient was 3 (1–12). Median number of cumulative tumors irradiated was 31 (25–110). Median number of tumors irradiated at first SRS was 10 (1–35). Median marginal dose for the largest tumor per session was 16Gy (10-21Gy). Median SRS total tumor volume was 6.8cc (0.8–23.4). Median follow-up since initial SRS was 16 months (1–71). At present, 21 (43.7%) are alive. Median OS from the diagnosis of brain metastases was 31 months (2–97), and OS from the time of first SRS, 22 months (1–70). Median KPS at first SRS and last follow-up was the same (90). Sixty-three percent did not require a corticosteroid course. CONCLUSION: In selected patients with a large number of cumulative brain metastases (≥ 25), SRS is effective and safe. Therefore, WBRT may not be required in this population.

Upfront Gamma Knife radiosurgery for Cushing's disease and acromegaly: a multicenter, international study.

Gamma Knife radiosurgery (GKS) is typically used after failed resection in patients with Cushing's disease (CD) and acromegaly. Little is known about the upfront role of GKS for patients with CD and acromegaly. In this study, the authors examine the outcome of upfront GKS for patients with these functioning adenomas. An international group of 7 Gamma Knife centers sent pooled data from 46 patients (21 with CD and 25 with acromegaly) undergoing upfront GKS to the coordinating center of the study for analysis. Diagnosis was established on the basis of clinical, endocrine, and radiological studies. All patients were treated on a common radiosurgical platform and longitudinally followed for tumor control, endocrine remission, and hypopituitarism. Patients received a tumor median margin dose of 25 Gy (range 12-40.0 Gy) at a median isodose of 50%. The median endocrine follow-up was 69.5 months (range 9-246 months). Endocrine remission was achieved in 51% of the entire cohort, with 28% remission in acromegaly and 81% remission for those with CD at the 5-year interval. Patients with CD achieved remission earlier as compared to those with acromegaly (p = 0.0005). In patients post-GKS, the pituitary adenoma remained stable (39%) or reduced (61%) in size. Hypopituitarism occurred in 9 patients (19.6%), and 1 (2.2%) developed third cranial nerve (CN III) palsy. Eight patients needed further intervention, including repeat GKS in 6 and transsphenoidal surgery in 2. Upfront GKS resulted in good tumor control as well as a low rate of adverse radiation effects in the whole group. Patients with CD achieved a faster and far better remission rate after upfront GKS in comparison to patients with acromegaly. GKS can be considered as an upfront treatment in carefully selected patients with CD who are unwilling or unable to undergo resection, but it has a more limited role in acromegaly.

Gamma Knife radiosurgery for the treatment of Nelson's syndrome: a multicenter, international study.

Nelson's syndrome is a rare and challenging neuroendocrine disorder, and it is associated with elevated adrenocorticotrophic hormone (ACTH) level, skin hyperpigmentation, and pituitary adenoma growth. Management options including resection and medical therapy are traditional approaches. Ionizing radiation in the form of Gamma Knife radiosurgery (GKRS) is also being utilized to treat Nelson's syndrome. In the current study the authors sought to better define the therapeutic role of stereotactic radiosurgery (SRS) in Nelson's syndrome. Study patients with Nelson's syndrome were treated with single-fraction GKRS (median margin dose of 25 Gy) at 6 different centers as part of an International Radiosurgery Research Foundation (IRRF) investigation. Data including neurological function, endocrine response, and radiological tumor response were collected and sent to the study-coordinating center for review. Fifty-one patients with median endocrine and radiological follow-ups of 91 and 80.5 months from GKRS, respectively, were analyzed for endocrine remission, tumor control, and neurological outcome. Statistical methods were used to identify prognostic factors for these endpoints. At last follow-up, radiological tumor control was achieved in 92.15% of patients. Endocrine remission off medical management and reduction in pre-SRS ACTH level were achieved in 29.4% and 62.7% of patients, respectively. Improved remission rates were associated with a shorter time interval between resection and GKRS (p = 0.039). Hypopituitarism was seen in 21.6% and new visual deficits were demonstrated in 15.7% of patients. GKRS affords a high rate of pituitary adenoma control and improvement in ACTH level for the majority of Nelson's syndrome patients. Hypopituitarism is the most common adverse effect from GKRS in Nelson's syndrome patients and warrants longitudinal follow-up for detection and endocrine replacement.

Low-Dose Gamma Knife Radiosurgery for Acromegaly.

Remission rate is associated with higher dose of Gamma Knife Radiosurgery (GKRS; Gamma Knife: Elekta AB, Stockholm, Sweden) for acromegaly, but the dose ≥25 Gy is not always feasible when the functioning adenoma is close to optic apparatus. To evaluate the efficacy and safety of low-dose (<25 Gy) GKRS in the treatment of patients with acromegaly. Single-center retrospective review of acromegaly cases treated with GKRS between June 1994 and December 2016. A total of 76 patients with the diagnosis of acromegaly who were treated with low-dose GKRS were selected for inclusion. Patients were treated with a median margin dose, isodose line, and treatment volume of 15.8 Gy, 57.5%, and 4.8 mL, respectively. Any identifiable portion of the optic apparatus was limited to a radiation dose of 10 Gy. All patients underwent full endocrine, ophthalmological, and imaging evaluation prior to and after GKRS treatments, and results of these were analyzed. Biochemical remission was achieved in 33 (43.4%) patients. Actuarial remission rates were 20.3%, 49.9%, and 76.3% at 4, 8, and 12 yr, respectively. Absence of cavernous sinus invasion (P=.042) and lower baseline insulin-like growth factor-1 levels (P=.019) were significant predictors of remission. New hormone deficiencies were found in 9 (11.8%) patients. Actuarial hormone deficiency rates were 3%, 14%, and 22.2% at 4, 8, and 10 yr, respectively. Two (2.6%) patients who achieved initial remission experienced recurrence. No optic complications were encountered. Reasonable remission and new hormone deficiency rates can be achieved with low-dose GKRS for acromegaly. These rates may be comparable to those with standard GKRS margin doses.

Abstract 4867: Radiosurgery consultation to treatment interval, additional brain metastases during the interim and outcomes after therapy

Abstract Background: Expediting the process of diagnosis and treatment should theoretically improve outcome. Delays in beginning therapy can cause anxiety to the patients and physicians who may be concerned about tumor progression before treatment is initiated. Treatment delays can be characterized as patient-generated or logistical medical infrastructure prolongations. Objective: The goal of the present study was to determine the impact of stereotactic radiosurgery (RS) consultation to treatment interval (CTI) and the development of additional brain metastases (BRM) during the interim on outcomes after RS. Methods: Between October 2014 and April 2018, 15 individuals developed more contrast-enhancing BRMs during the CTI. These patients were treated with gamma knife RS (including the six patients who underwent gross resection of metastatic intracranial neoplasm). The median duration of CTI was 19 days (range 5-61 days). A comparison of the ≤19 days CTI (eight patients) to the &amp;gt;19 days CTI (seven patients) was performed to assess the effects of the extent of delay to RS. The total number of BRM for RS was 68. The median target volume was 0.48 cm3, and the median margin dose was 24 Gy. Results: Most (67%) of the subjects exhibited good performance status. The overall crude survival rate at two years was 27%; acute or late toxicity after RS was not observed. Comparison of the CTI groups revealed: i) A longer CTI was not associated with a poorer prognosis; ii) BRM recurrence after RS was less common in this patient subgroup; iii) Quality of life (QOL) was satisfactory even though the CTI was prolonged. Conclusion: Acceptable longevity with minimal morbidity satisfying the QOL consideration was found in this audit of cases about CTI and the occurrence of more BRMs during the interim. Decreasing CTI in patients with BRM remains an important goal of quality improvement. Citation Format: Federico Ampil, Gloria Caldito, Troy Richards. Radiosurgery consultation to treatment interval, additional brain metastases during the interim and outcomes after therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4867.

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.

Gamma Knife radiosurgery for intracranial benign meningiomas: follow-up outcome in 130 patients.

OBJECTIVEThe authors retrospectively analyzed the follow-up data in 130 patients with intracranial benign meningiomas after Gamma Knife radiosurgery (GKRS), evaluated the tumor progression-free survival (PFS) rate and neurological function preservation rate, and determined the predictors by univariate and multivariate survival analysis.METHODSThis cohort of 130 patients with intracranial benign meningiomas underwent GKRS between May 2012 and May 2015 at the Second Hospital of Tianjin Medical University. The median age was 54.5 years (range 25-81 years), and women outnumbered men at a ratio of 4.65:1. All clinical and radiological data were obtained for analysis. No patient had undergone prior traditional radiotherapy or chemotherapy. The median tumor volume was 3.68 cm3 (range 0.23-45.78 cm3). A median margin dose of 12.0 Gy (range 10.0-16.0 Gy) was delivered to the tumor with a median isodose line of 50% (range 50%-60%).RESULTSDuring a median follow-up of 36.5 months (range 12-80 months), tumor volume regressed in 37 patients (28.5%), was unchanged in 86 patients (66.2%), and increased in 7 patients (5.4%). The actuarial tumor progression-free survival (PFS) rate was 98%, 94%, and 87% at 1, 3, and 5 years, respectively, after GKRS. Tumor recurred in 7 patients at a median follow-up of 32 months (range 12-56 months). Tumor volume ≥ 10 cm3 (p = 0.012, hazard ratio [HR] 8.25, 95% CI 1.60-42.65) and pre-GKRS Karnofsky Performance Scale score < 90 (p = 0.006, HR 9.31, 95% CI 1.88-46.22) were independent unfavorable predictors of PFS rate after GKRS. Of the 130 patients, 101 (77.7%) presented with one or more neurological symptoms or signs before GKRS. Neurological symptoms or signs improved in 40 (30.8%) patients, remained stable in 83 (63.8%), and deteriorated in 7 (5.4%) after GKRS. Two (1.5%) patients developed new cranial nerve (CN) deficit. Tumor volume ≥ 10 cm3 (p = 0.042, HR = 4.73, 95% CI 1.06-21.17) and pre-GKRS CN deficit (p = 0.045, HR = 4.35, 95% CI 0.84-22.48) were independent unfavorable predictors for improvement in neurological symptoms or signs. Six (4.6%) patients developed new or worsening peritumoral edema with a median follow-up of 4.5 months (range 2-7 months).CONCLUSIONSGKRS provided good local tumor control and high neurological function preservation in patients with intracranial benign meningiomas. Patients with tumor volume < 10 cm3, pre-GKRS Karnofsky Performance Scale score ≥ 90, and no pre-GKRS CN deficit (I-VIII) can benefit from stereotactic radiosurgery. It can be considered as the primary or adjuvant management of intracranial benign meningiomas.

Gamma knife radiosurgery for the treatment of cavernous sinus meningiomas: post-treatment long-term clinical outcomes, complications, and volume changes.

To evaluate the outcomes of patients who underwent Gamma Knife radiosurgery (GKRS) for the treatment of cavernous sinus (CS) meningiomas. We retrospectively reviewed the clinical and radiological outcomes of 95 patients with CS meningiomas at Taipei Veterans General Hospital between 1993 and 2011. The study cohort comprised 27 men and 68 women with a median age of 50years (range 29-79years). The median pre-GKRS tumor volume was 6.6ml (range 0.9-35.7ml). The median margin dose was 12Gy (range 11-21Gy). The clinical factors related to favorable outcomes were assessed. The median follow-up period was 59 (range 12-209) months. At the final follow-up, the tumor volume regressed in 70 patients (74%) and progressed in eight (8%). Kaplan-Meier analysis revealed that the progression-free survival rates at 5 and 10years were 92.7% and 81.2%, respectively. Three patients (3.2%) experienced exacerbated cranial nerve dysfunction following radiosurgery. Confined tumors were found to be an independent prognostic factor for tumor control and shorter times to regression in the multivariable analyses. No risk factor for tumor progression was identified in either the univariate or multivariate analyses. GKRS provides good long-term tumor control and is associated with low cranial nerve-related morbidity development rates in patients with small- to medium-sized CS meningiomas. Confined tumor could be an independent prognostic factor for tumor control and shorter times to regression in multivariate analysis. Life-long follow-up is mandatory in such settings, even for outpatients with shrunken or stabilized tumors.

Long-Term Outcomes for Pediatric Patients with Brain Arteriovenous Malformations Treated with Gamma Knife Radiosurgery, Part 2: The Incidence of Cyst Formation, Encapsulated Hematoma, and Radiation-Induced Tumor

Long-term data about the incidence of late adverse radiation effects (AREs) in pediatric brain arteriovenous malformations (AVMs) treated with Gamma Knife radiosurgery (GKRS) are lacking. This study addresses the incidence of late AREs, including cyst formation (CF), chronic encapsulated hematoma (CEH), and radiation-induced tumor, in pediatric patients with AVM treated with GKRS. This is a single-institutional study involving pediatric patients with AVM who underwent GKRS between 1991 and 2014. Among 201 pediatric patients with AVM (age ≤15 years), 189 who had at least 12 months of follow-up were assessed in this study. The median treatment volume was 2.2 cm3, and the median marginal dose was 20 Gy. The mean follow-up period was 136 months. During the follow-up period, symptomatic radiation-induced perilesional edema was found in 5 patients (3%), CFs in 7 patients (4%), CEHs in 7 patients (4%), and radiation-induced tumors in 2 patients (1%). The cumulative incidences of late AREs including CF, CEH, and radiation-induced tumor were 1.2% at 5 years, 5.2% at 8 years, 6.1% at 10 years, 7.2% at 15 years, and 17.0% at 20 years. In the multivariate analysis, treatment volume alone was a significant factor for late AREs (P < 0.001; hazard ratio, 1.111). GKRS is a reasonable treatment option for pediatric AVMs to prevent future intracranial hemorrhages, particularly in the eloquent regions. However, considerable attention should be paid to late AREs such as CFs, CEHs, and radiation-induced tumors because of longer life expectancy in pediatric patients.

Long-Term Outcomes for Pediatric Patients with Brain Arteriovenous Malformations Treated with Gamma Knife Radiosurgery, Part 1: Analysis of Nidus Obliteration Rates and Related Factors

Little is known about long-term outcomes for pediatric brain arteriovenous malformations (AVMs) treated with Gamma Knife radiosurgery (GKRS). This study investigated annual hemorrhage rates and nidus obliteration rates, and the factors affecting them, in pediatric AVMs treated with GKRS. We examined 189 pediatric AVM patients (age ≤15 years) who underwent GKRS and had at least 12 months of follow-up. The Spetzler-Martin (S-M) grade was I in 29 patients (15%), II in 57 (30%), III in 82 (43%), IV in 16 (9%), and V in 5 (3%). The median treatment volume was 2.2 cm3, and the median marginal dose was 20 Gy. The mean follow-up period was 136 months. During a cumulative latency period to nidus obliteration of 813 years, 23 hemorrhages occurred, resulting in an annual post-GKRS hemorrhage rate of 2.8%. The cumulative hemorrhage rates after GKRS were 3.3%, 8.5%, and 11.9% at 3, 5, and 10 years, respectively. Higher S-M grade was significantly associated with intracranial hemorrhages during the latency period (P < 0.001). The actuarial nidus obliteration rates with repeated GKRS were 64% and 81% at 5 and 10 years, respectively. Absence of pre-GKRS embolization (P= 0.023) and higher marginal dose (P= 0.029) were significant factors predicting nidus obliteration. GKRS is a reasonable treatment option in pediatric AVMs to prevent future hemorrhages. Because higher S-M grade AVMs are more likely to hemorrhage during the latency period, a combined therapy with endovascular embolization should be considered to prevent AVM rupture.

Tumor Control and Cranial Nerve Outcomes After Adjuvant Radiosurgery for Low-Grade Skull Base Meningiomas

We evaluated the tumor control and cranial nerve (CN) outcomes after adjuvant stereotactic radiosurgery (SRS) for petroclival, cavernous sinus, and cerebellopontine angle meningiomas. From our prospectively maintained database of 2022 patients with meningioma who had undergone Leksell SRS during a 30-year interval, we found 43 patients with petroclival, 94 with cavernous sinus, and 13 patients with cerebellopontine angle meningiomas who had undergone adjuvant SRS after surgical resection of the meningioma. The patients included in the present report had had ≥1 CN deficit at the initial presentation and a minimum follow-up period of 12 months. The median age at SRS was 54 years (range, 22-81). SRS was performed for residual tumor in 104 patients (69%) and recurrent tumor in 46 patients (31%). The median tumor volume treated with SRS was 8.1 cm3 (range, 0.3-42), and the median margin dose was 13 Gy (range, 10-20). Tumor control was achieved in 135 patients (90%) at a median follow-up point of 75 months. The progression-free survival rate after SRS was 99.5% at 1 year, 98% at 3 years, 95% at 5 years, and 90% at 10 years. Overall, 29 of the 150 patients (19%) reported improvement in CN function. Deterioration in CN function after SRS developed in 15 patients (10%). The rate of deterioration was 3.5% at 1 year, 5.5% at 3 years, and 7% at 5 years. Adjuvant SRS provides effective tumor control and a low rate of new or worsening CN deficits.