Stereotactic radiosurgery for secretory pituitary adenomas: systematic review and International Stereotactic Radiosurgery Society practice recommendations

OBJECTIVE A systematic review was performed to provide objective evidence on the use of stereotactic radiosurgery (SRS) in the management of secretory pituitary adenomas and develop consensus recommendations. METHODS The authors performed a systematic review of the English-language literature up until June 2018 using the PRISMA guidelines. The PubMed (Medline), Embase, and Cochrane databases were searched. A total of 45 articles reporting single-institution outcomes of SRS for acromegaly, Cushing’s disease, and prolactinomas were selected and included in the analysis. RESULTS For acromegaly, random effects meta-analysis estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rates were 97.0% (95% CI 96.0%–98.0%), 44.0% (95% CI 35.0%–53.0%), and 17.0% (95% CI 13.0%–23.0%), respectively. For Cushing’s disease, random effects estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rate were 92.0% (95% CI 87.0%–95.0%), 48.0% (95% CI 35.0%–61.0%), and 21.0% (95% CI 13.0%–31.0%), respectively. For prolactinomas, random effects estimates for crude tumor control rate, crude endocrine remission rate, and any new hypopituitarism rate were 93.0% (95% CI 90.0%–95.0%), 28.0% (95% CI 19.0%–39.0%), and 12.0% (95% CI 6.0%–24.0%), respectively. Meta-regression analysis did not show a statistically significant association between mean margin dose with crude endocrine remission rate or mean margin dose with development of any new hypopituitarism rate for any of the secretory subtypes. CONCLUSIONS SRS offers effective tumor control of hormone-producing pituitary adenomas in the majority of patients but a lower rate of endocrine improvement or remission.

RADI-06. Gamma knife surgery for brain stem metastases

Introduction Gamma Knife Surgery (GKS) is widely used for treatment of brainstem metastases (BSMs) with or without whole bran radiation therapy (WBRT). We hypothesized that BSMs treated with GKS using lower doses and omitting WBRT result in acceptable tumor control rates and low complication rates. Methods A retrospective single center study was performed to investigate the outcome following GKS of BSMs. All 33 patients with follow-up information treated with GKS for 39 metastases located in the cerebral peduncle, midbrain, pons or medulla oblongata were included in the study. The median treatment dose, defined as the lowest dose to 95% of the tumor volume, was 18 Gy. The tumor control rate as well as the survival time were related to a number of patients, tumor and treatment parameters. Results The local tumor control rate was 100% at one year and 89% at five years, and the overall median survival was 17 months. A good performance status and a treatable extracranial disease were favorably related to survival time. Two complications were observed, one lethal hemorrhage at the day of the treatment and one transient complication three months following GKS, resulting in a 6% complication rate at five years. Four of the 10 patient with symptomatic BSM improved clinically after GKS, while six remained unchanged. Conclusions High local control and a low complication rates can be achieved using GKS for BSMs using lower doses as compared to brain metastases in other locations.

Intensity-modulated Radiotherapy for Pituitary Somatotroph Adenomas

Objective To summarize our experience in the treatment of pituitary somatotroph adenomas by fractionated intensity-modulated radiotherapy (IMRT), describe the treatment outcomes, and determine predictors. Methods and Materials Patients with pituitary somatotroph adenoma treated by IMRT in our institution from August 2009 to January 2019 were reviewed. A total of 113 patients (37 male) were included in this study. The median age was 33 years (range 12-67 years). A total of 112 patients had not achieved complete remission after surgery, and 1 patient was treated by radiotherapy (RT) alone because she refused to surgery. The median growth hormone level was 8.6 ng/mL (range 2-186 ng/mL) and the median insulin-like growth factor (IGF)-1 level was 732 ng/mL (range 314-1485 ng/mL) pre-RT. The radiation doses to clinical target volume were usually 50-56 Gy in 25 to 30 fractions and to gross tumor volume were 60.2 Gy in 28 fractions while simultaneous integrated boost-IMRT used. After RT, the patients were followed up with endocrine testing every 6 to 12 months and magnetic resonance imaging annually. Endocrine complete remission was defined as a normal sex- and age-adjusted IGF-1 level without any pituitary suppressive medications. The outcomes including endocrine remission and new hypopituitarism after RT were recorded. The median follow-up time was 36 months (range 6-105.5 months). Results The endocrine complete remission rates of IGF-1 at 1, 2, 3, and 5 years were 6%, 22.8%, 48.6%, and 74.3%, respectively. The median time to complete remission was 36.2 ± 3.8 months. The tumor control rate was 99% during the follow-up. The overall incidence of RT-induced hypopituitarism was 28.3% at the last follow-up. Univariate and multivariate analysis demonstrated that tumor sizes before RT, pre-RT IGF-1 level, and age significant predicted the endocrine remission. Conclusions IMRT is a highly effective treatment for pituitary somatotroph adenoma. Endocrine remission rate, tumor control rate, the median time to remission and hypopituitarism incidence are similar to stereotactic radiosurgery. Age and IGF-1 level before RT were significant predictive factors in endocrine remission.

Tumor Control Rates in Patients Undergoing Stereotactic Radiosurgery for Cystic Vestibular Schwannomas: A Systematic Review and Meta-Analysis

INTRODUCTION Cystic vestibular schwannomas (VS) represent a subtype that grows more rapidly due to expansion of cystic contents and are important candidates for stereotactic radiosurgery (SRS) intervention due to their tendency to adhere to the neurovasculature. However, the paucity of comprehensive outcomes data is currently a limiting factor to understanding the potential of using SRS to treat cystic VS. METHODS This study was conducted in accordance with the PRISMA guidelines. A search was conducted in October 2018 through the PubMed, Scopus, Embase, Web of Science, and Cochrane databases. Data on tumor control rates were extracted and analyzed using meta-analysis and tests for heterogeneity between articles, with the t2, Cochran's Q, and I2 statistics reported. Publication bias was assessed using funnel plots and Egger's testing. RESULTS A total of 246 patients underwent SRS for cystic VS, with reported mean or median follow-up of 49.7 to 150 mo. Following SRS treatment for cystic VS across all studies, 92% of patients had tumor control at follow up, (95%-CI: 88%-95%). In studies that specifically reported tumor control rate at 5 yr, control rate was also 92% (95%-CI: 87%-95%). Tumor control rate specifically for patients who underwent GammaKnife was 93% (95%-CI: 88%-95%). CONCLUSION Results of our meta-analysis suggest that SRS is a viable treatment option for cystic VS, exhibiting effective tumor control rates. Despite the paucity of pertinent data, our conclusions provide evidence in contrast to the initial impressions of SRS treatment for cystic VS within the neurosurgical community.

Volumetric changes and clinical outcome for petroclival meningiomas after primary treatment with Gamma Knife radiosurgery

OBJECTIVEPetroclival meningiomas (PCMs) can cause devastating clinical symptoms due to mass effect on cranial nerves (CNs); thus, patients harboring these tumors need treatment. Many neurosurgeons advocate for microsurgery because removal of the tumor can provide relief or result in symptom disappearance. Gamma Knife radiosurgery (GKRS) is often an alternative for surgery because it can cause tumor shrinkage with improvement of symptoms. This study evaluates qualitative volumetric changes of PCM after primary GKRS and its impact on clinical symptoms.METHODSThe authors performed a retrospective study of patients with PCM who underwent primary GKRS between 2003 and 2015 at the Gamma Knife Center of the Elisabeth-Tweesteden Hospital in Tilburg, the Netherlands. This study yields 53 patients. In this study the authors concentrate on qualitative volumetric tumor changes, local tumor control rate, and the effect of the treatment on trigeminal neuralgia (TN).RESULTSLocal tumor control was 98% at 5 years and 93% at 7 years (Kaplan-Meier estimates). More than 90% of the tumors showed regression in volume during the first 5 years. The mean volumetric tumor decrease was 21.2%, 27.1%, and 31% at 1, 3, and 6 years of follow-up, respectively. Improvement in TN was achieved in 61%, 67%, and 70% of the cases at 1, 2, and 3 years of follow-up, respectively. This was associated with a mean volumetric tumor decrease of 25% at the 1-year follow-up to 32% at the 3-year follow-up.CONCLUSIONSGKRS for PCMs yields a high tumor control rate with a low incidence of neurological deficits. Many patients with TN due to PCM experienced improvement in TN after radiosurgery. GKRS achieves significant volumetric tumor decrease in the first years of follow-up and thereafter.

Long-Term Outcomes After Gamma Knife Radiosurgery for Benign Meningioma: A Single Institution's Experience With 424 Patients

BACKGROUND Gamma knife radiosurgery (GKRS) is recognized as an important treatment modality for meningioma. OBJECTIVE To analyze the long-term outcomes in meningioma patients treated with GKRS to determine the risk factors related to treatment failure and peritumoral edema (PTE) development. METHODS Between 1998 and 2010, 770 consecutive patients were treated with GKRS for intracranial meningioma. After the exclusion of patients with follow-up periods of less than 5 yr and those with neurofibromatosis, multiple meningiomas, nonbenign meningioma, or radiotherapy, a total of 424 patients were enrolled in this study. The median follow-up duration was 92 mo. The median tumor volume was 4.35 cm3, and the median marginal dose was 14 Gy. RESULTS The overall local tumor control rate was 84%. The actuarial tumor control rates were 91.7% and 78.9% at 5 and 10 yr, respectively. The tumor control rate of a radiologically diagnosed tumor was higher than that of a grade I tumor (82% vs 70.1% at 10 yr, P = .001). In multivariate analysis, factors associated with tumor progression were female sex (hazard ratio: 0.5, P = .025) and a previous history of craniotomy (hazard ratio: 1.9, P = .009). Symptomatic PTE was identified in 36 (8.5%) patients, and the factor associated with poor PTE was the presence of PTE before GKRS (odds ratio: 4.6, P < .001). Permanent complication rate was 4%. CONCLUSION GKRS appears to be an effective treatment modality for meningioma with long-term follow-up. However, the identification of delayed tumor progression in our study suggests that extended follow-up data should be collected after GKRS.

Single hepatocellular carcinoma (HCC) ineligible for surgical resection (SR): High tumor control rate with conformal radiotherapy + transarterial chemoembolization (CRT + TACE).

433 Background: SR is a curative therapy of single HCC. CRT is efficient for small HCC (≤ 5 cm), whereas its combination to TACE (CRT+TACE) is needed for large ( > 5 cm) HCC. However, SR remains the gold-standard in guidelines for large HCC. This work aims to compare these approaches. Methods: Retrospective analysis of prospectively collected data, on patients (pts) included at Lyon North Hepatobiliary Centre, Child-Pugh-A, single HCC. CRT+TACE was decided at the HCC board by ineligibility for SR, radiofrequency or liver transplantation. Outcome of pts was compared between CRT+TACE and SR. Continuous variables were assessed by the t-Student test, and survival analysis by the Cox proportional-hazards regression. Results: 178 pts (68 CRT+TACE, 110 SR), males 78%, cirrhosis 52%, etiology (alcohol 46%, HCV 17%, HBV 13%, NASH 30%), 103 small, 75 large HCC, median age 66 ys, tumor size 50 mm, AFP 8 ng/mL, albuminemia (ALB) 39 g/L, platelets (PLAT) 166 Giga/L, follow-up 33 months. CRT+TACE complete response rate: 92% small / 80% large HCC. Small HCC comparison: CRT+TACE vs SR: age (67 vs 64, P= NS), cirrhosis (94% vs 47%, P< 0.0001), ALB (36 vs 40, P= 0.0001), PLAT (150 vs 201, P= 0.02), AFP (381 vs 300, P= NS). CRT-TACE was a poor outcome factor in univariate analysis for overall survival (OS) (HR 2.32; P= 0.01), progression-free survival (PFS) (HR 1.90; P= 0.007), but did not remain independent in multivariate analysis due to combined factors: age > 70, cirrhosis, ALB < 35, PLAT < 100. Large HCC comparison: CRT+TACE vs SR: age (73 vs 62, P= 0.0008), cirrhosis (70% vs 25%, P= 0.0004), ALB (38 vs 39, P= NS), PLAT (173 vs 240, P= 0.01), AFP (5616 vs 3456, P= NS). CRT-TACE was a poor outcome factor only for OS (HR 3.01; P= 0.0007) in univariate analysis. After adjustment to other factors (age > 70, cirrhosis, PLAT < 100), CRT-TACE was not independent in multivariate analysis for OS ( P= 0.19). Conclusions: CRT+TACE induced an encouraging tumor control rate in a population of older pts, more deteriorated chronic hepatopathy than pts treated by SR. Especially for large HCC, SR was not better than CRT+TACE on the outcome. Prospective randomized trials are warranted to confirm these data.

Gamma Knife radiosurgery for glomus jugulare tumors: a single-center series of 75 cases

OBJECTIVEGlomus jugulare tumors are rare indolent tumors that frequently involve the lower cranial nerves (CNs). Complete resection can be difficult and associated with lower CN injury. Gamma Knife radiosurgery (GKRS) has established its role as a noninvasive alternative treatment option for these often formidable lesions. The authors aimed to review their experience at the National Centre for Stereotactic Radiosurgery, Sheffield, United Kingdom, specifically the long-term tumor control rate and complications of GKRS for these lesions.METHODSClinical and radiological data were retrospectively reviewed for patients treated between March 1994 and December 2010. Data were available for 75 patients harboring 76 tumors. The tumors in 3 patients were treated in 2 stages. Familial and/or hereditary history was noted in 12 patients, 2 of whom had catecholamine-secreting and/or active tumors. Gamma Knife radiosurgery was the primary treatment modality in 47 patients (63%). The median age at the time of treatment was 55 years. The median tumor volume was 7 cm3, and the median radiosurgical dose to the tumor margin was 18 Gy (range 12–25 Gy). The median duration of radiological follow-up was 51.5 months (range 12–230 months), and the median clinical follow-up was 38.5 months (range 6–223 months).RESULTSThe overall tumor control rate was 93.4% with low CN morbidity. Improvement of preexisting deficits was noted in 15 patients (20%). A stationary clinical course and no progression of symptoms were noted in 48 patients (64%). Twelve patients (16%) had new symptoms or progression of their preexisting symptoms. The Kaplan-Meier actuarial tumor control rate was 92.2% at 5 years and 86.3% at 10 years.CONCLUSIONSGamma Knife radiosurgery offers a risk-versus-benefit treatment option with very low CN morbidity and stable long-term results.

Gamma Knife radiosurgery for vestibular schwannomas: evaluation of tumor control and its predictors in a large patient cohort in The Netherlands

OBJECT The authors of this study sought to assess tumor control and complication rates in a large cohort of patients who underwent Gamma Knife radiosurgery (GKRS) for vestibular schwannoma (VS) and to identify predictors of tumor control. METHODS The records of 420 patients treated with GKRS for VS with a median marginal dose of 11 Gy were retrospectively analyzed. Patients with neurofibromatosis Type 2 or who had undergone treatment for VS previously were excluded. The authors assessed tumor control and complication rates with chart review and used the Cox proportional hazards model to identify predictors of tumor control. Preservation of serviceable hearing, defined as Gardner-Robertson Class I–II, was evaluated in a subgroup of 71 patients with serviceable hearing at baseline and with available follow-up audiograms. RESULTS The median VS tumor volume was 1.4 cm3, and the median length of follow-up was 5.1 years. Actuarial 5-and 10-year tumor control rates were 91.3% and 84.8%, respectively. Only tumor volume was a statistically significant predictor of tumor control rate. The tumor control rate decreased from 94.1% for tumors smaller than 0.5 cm3 to 80.7% for tumors larger than 6 cm3. Thirteen patients (3.1%) had new or increased permanent trigeminal nerve neuropathy, 4 (1.0%) had new or increased permanent facial weakness, and 5 (1.2%) exhibited new or increased hydrocephalus requiring a shunting procedure. Actuarial 3-year and 5-year hearing preservation rates were 65% and 42%, respectively. CONCLUSIONS The 5-year actuarial tumor control rate of 91.3% in this cohort of patients with VS compared slightly unfavorably with the rates reported in other large studies, but the complication and hearing preservation rates in this study were similar to those reported previously. Various factors may contribute to the observed differences in reported outcomes. These factors include variations in treatment indication and in the definition of treatment failure, as well as a lack of standardization of terminology and of evaluation of complications. Last, differences in dosimetric variables may also be an explanatory factor.