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PURPOSE: The aims of this study were to evaluate long-term multidimensional fatigue in patients with brain metastases (BM) up to 21 months after Gamma Knife radiosurgery (GKRS) and (change in) fatigue as predictor of survival. METHODS: Patients with 1 to 10 BM, expected survival > 3 months, and Karnofsky Performance Status ≥ 70, and Dutch non-cancer controls were included. Fatigue was measured with the Multidimensional Fatigue Inventory. Levels of fatigue between patients and controls were compared using independent-samples t-tests. Linear mixed models were used to evaluate fatigue within the patient group up to 21 months after GKRS. Pre-GKRS fatigue and minimal clinically important (MCI) changes in fatigue in the first three months (defined as a 2-point difference) after GKRS were evaluated as predictors of survival time. RESULTS: Prior to GKRS, patients with BM (n = 92) experienced significantly higher fatigue on all subscales than controls (n = 104). Over 21 months, physical fatigue increased, and mental fatigue decreased significantly. More specifically, general, and physical fatigue increased significantly between pre-GKRS and 3 months, followed by stable scores between 3 (n = 67) and 6 (n = 53), 6 and 12 (n = 34) and 12 and 21 (n = 21) months. An MCI increase in general or physical fatigue over the first 3 months after GKRS was a significant predictor of shorter survival time. CONCLUSION: Except for mental fatigue, all aspects of fatigue remained elevated or further increased up to 21 months after treatment. Furthermore, an increase in general or physical fatigue within three months after GKRS may be a prognostic indicator for poorer survival. GOV IDENTIFIER: NCT02953756, November 3, 2016.
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Neoplasias Encefálicas , Radiocirurgia , Humanos , Neoplasias Encefálicas/secundário , Seguimentos , Avaliação de Estado de Karnofsky , Prognóstico , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
WHO grade I meningiomas occasionally show regrowth after radiosurgical treatment, which cannot be predicted by clinical features. There is increasing evidence that certain biomarkers are associated with regrowth of meningiomas. The aim of this retrospective study was to asses if these biomarkers could be of value to predict regrowth of WHO grade I meningiomas after additive radiosurgery. Forty-four patients with WHO grade I meningiomas who underwent additive radiosurgical treatment between 2002 and 2015 after Simpson IV resection were included in this study, of which 8 showed regrowth. Median follow-up time was 64 months (range 24-137 months). Tumors were analyzed for the proliferation marker Ki-67 by immunohistochemistry and for deletion of 1p36 by fluorescence in situ hybridization (FISH). Furthermore, genomic DNA was analyzed for promoter hypermethylation of the genes NDRG1-4, SFRP1, HOXA9 and MGMT. Comparison of meningiomas with and without regrowth after radiosurgery revealed that loss of 1p36 (p = 0.001) and hypermethylation of NDRG1 (p = 0.046) were correlated with regrowth free survival. Loss of 1p36 was the only parameter that was significantly associated with meningioma regrowth after multivariate analysis (p = 0.01). Assessment of 1p36 loss in tumor tissue prior to radiosurgery might be considered an indicator of prognosis/regrowth. However, this finding has to be validated in an independent larger set of tumors.
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Deleção Cromossômica , Cromossomos Humanos Par 1 , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/radioterapia , Meningioma/patologia , Meningioma/radioterapia , Recidiva Local de Neoplasia/patologia , Radiocirurgia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Organização Mundial da SaúdeRESUMO
INTRODUCTION: Prognosis of patients with brain metastasis (BM) from renal cell carcinoma (RCC) is relevant for treatment decisions and can be estimated with the Renal Graded Prognostic Assessment (GPA). The aim of this study is to validate the updated version of this instrument in a cohort treated with Gamma Knife radiosurgery (GKRS) without prior local intracerebral therapy. METHODS: Between 2007 and 2018, 106 RCC patients with BM were treated with GKRS. They were categorized according to the updated Renal GPA. Overall survival (OS), distant intracranial failure and local failure were estimated using the Kaplan-Meier method and risk factors were identified with Cox proportional hazard regressions. RESULTS: Median OS was 8.6 months. Median OS for GPA categories 0.0-1.0 (15%), 1.5-2.0 (12%), 2.5-3.0 (35%) and 3.5-4.0 (29%) was 2.9, 5.5, 8.1 and 20.4 months, respectively. Karnofsky performance status < 90, serum hemoglobin ≤ 12.5 g/dL, age > 65 years and time from primary diagnosis to brain metastasis < 1 year were significantly related with shorter survival, while presence of extracranial disease, the volume and total number of BM had no significant impact on OS. A total count of > 4 BM was the only predictive factor for distant intracranial failure, while none of the investigated factors predicted local failure. CONCLUSIONS: This study confirms the updated Renal GPA in an independent cohort as a valuable instrument to estimate survival in patients with BM from RCC treated with GKRS.
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Neoplasias Encefálicas , Carcinoma de Células Renais , Neoplasias Renais , Radiocirurgia , Idoso , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Renais/cirurgia , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Survival rates have improved in the past years for patients with brain metastases (BMs). OBJECTIVE: To evaluate cognitive functioning and health-related quality of life (HRQoL) after Gamma Knife radiosurgery (GKRS) in a relatively large sample of long-term survivors. METHODS: Data from 38 long-term survivors (assessments available ≥ 12 mo post-GKRS) with, at time of enrollment, 1 to 10 newly diagnosed BMs, expected survival > 3 mo, and Karnofsky Performance Status ≥ 70 were analyzed. Cognitive functioning and HRQoL were assessed pre-GKRS (n = 38) and at 3 (n = 38), 6 (n = 37), 9 (n = 37), 12 (n = 34), 15 (n = 28), and 21 (n = 21) mo post-GKRS. The course of cognitive test performance and of HRQoL over time was analyzed using linear mixed models. Individual changes in cognitive performance and HRQoL from pre-GKRS to 21 mo were determined using reliable change indexes (RCIs) and clinical meaningful cutoffs, respectively. RESULTS: Cognitive performances and HRQoL of long-term survivors remained stable or improved up to 21 mo after GKRS. Improvements were found for immediate and delayed verbal memory, working memory, information processing speed, and emotional well-being. On the individual level, most patients had stable or improved test performances or HRQoL. For physical well-being only, most patients (47.6%) showed a decline (vs 28.6% improvement or 23.8% no change) from pre-GKRS until 21 mo post-GKRS. CONCLUSION: Up to 21 mo after GKRS, cognitive functioning and overall HRQoL improved or remained stable in long-term survivors. In long-term survivors with 1 to 10 BMs, GKRS did not cause (additional) cognitive deteriorations or declines in HRQoL at longer-term follow-up.
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Neoplasias Encefálicas , Cognição/fisiologia , Qualidade de Vida , Radiocirurgia , Sobreviventes/estatística & dados numéricos , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/cirurgia , HumanosRESUMO
BACKGROUND: Gamma Knife radiosurgery (GKRS) has been proven to be a successful primary treatment for metastatic brain tumors (BM). BM can come in cystic lesions and are often too large for GKRS. An alternative approach to treat cystic BM is stereotactic cyst aspiration (SCA) for volume reduction, making it suitable for GKRS afterwards. OBJECTIVE: Our objective is evaluation of volumetric reduction after SCA, tumor control, and complications after SCA directly followed by GKRS. METHODS: We performed a retrospective analysis of all patients who underwent SCA directly followed by GKRS at the Gamma Knife Center of the Elisabeth-Tweesteden Hospital in Tilburg between 2002 and 2015. In total, 54 patients had undergone this combined approach. Two patients were excluded because of prior intracranial treatment. The other 52 patients were included for analysis. RESULTS: SCA resulted in a mean volumetric reduction of 56.5% (range 5.50-87.00%). In 83.6% of the tumors (46 tumors), SCA led to sufficient volumetric reduction making GKRS possible. The overall local tumor control (OLTC) of the aspirated lesions post-GKRS was 60.9% (28 out of 46 tumors). Median progression-free survival (PFS) and overall survival (OS) for all patients were 3 (range 5 days-14 months) and 12 months (range 5 days-58 months), respectively. Leptomeningeal disease was reported in 5 (9.6%) cases. CONCLUSION: SCA directly followed by GKRS is an effective and time-efficient treatment for large cystic BM in selected patients in which surgery is contraindicated and those with deeply located lesions.
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Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Cistos/mortalidade , Cistos/cirurgia , Feminino , Humanos , Masculino , Neoplasias Meníngeas/cirurgia , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Radiocirurgia/métodos , Estudos Retrospectivos , Sucção , Resultado do TratamentoRESUMO
PURPOSE: Increasingly more patients with multiple (> 4) brain metastases (BM) are being treated with stereotactic radiosurgery (SRS). Preserving patients' health-related quality of life (HRQoL) is an important treatment goal. The aim of this study was to assess (individual) changes in HRQoL in patients with 1-10 BM over time. METHODS: A total of 92 patients were assessed before (n = 92) and at 3 (n = 66), 6 (n = 53), and 9 (n = 41) months after Gamma Knife radiosurgery (GKRS), using the Functional Assessment of Cancer Therapy-Brain (FACT-Br). The course of HRQoL was analyzed using linear mixed models. Clinical minimally important differences were used to evaluate individual changes. RESULTS: At group level, patients' physical well-being worsened, whereas emotional well-being improved over 9 months. Scores on other HRQoL subscales did not change significantly. Number (1-3 versus 4-10) and volume (small, medium, and large) of BM did not influence HRQoL over time, except for the subscale additional concerns; medium intracranial tumor volume was associated with less additional concerns. On the individual level as well, physical well-being declined while emotional well-being improved in most patients over 9 months after GKRS. At patient level, however, most patients had both declines as well as improvements in the different HRQoL aspects. CONCLUSION: Our results indicate that even in patients with up to 10 BM, both at group and individual subscale level, aspects of HRQoL remained stable over nine months after GKRS, except for an improvement in emotional well-being and a decline in physical well-being. Nevertheless, HRQoL scores varied considerably at the individual patient level. TRAIL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02953756, November 3, 2016.
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Neoplasias Encefálicas/cirurgia , Neoplasias/cirurgia , Qualidade de Vida , Radiocirurgia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/secundário , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Prognóstico , Estudos Prospectivos , Taxa de SobrevidaRESUMO
OBJECTIVE: Stereotactic radiosurgery (SRS) is one of the treatment modalities for vestibular schwannomas (VSs). However, tumor progression can still occur after treatment. Currently, it remains unknown how to predict long-term SRS treatment outcome. This study investigates possible magnetic resonance imaging (MRI)-based predictors of long-term tumor control following SRS. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: Analysis was performed on a database containing 735 patients with unilateral VS, treated with SRS between June 2002 and December 2014. Using strict volumetric criteria for long-term tumor control and tumor progression, a total of 85 patients were included for tumor texture analysis. INTERVENTION(S): All patients underwent SRS and had at least 2 years of follow-up. MAIN OUTCOME MEASURE(S): Quantitative tumor texture features were extracted from conventional MRI scans. These features were supplied to a machine learning stage to train prediction models. Prediction accuracy, sensitivity, specificity, and area under the receiver operating curve (AUC) are evaluated. RESULTS: Gray-level co-occurrence matrices, which capture statistics from specific MRI tumor texture features, obtained the best prediction scores: 0.77 accuracy, 0.71 sensitivity, 0.83 specificity, and 0.93 AUC. These prediction scores further improved to 0.83, 0.83, 0.82, and 0.99, respectively, for tumors larger than 5âcm. CONCLUSIONS: Results of this study show the feasibility of predicting the long-term SRS treatment response of VS tumors on an individual basis, using MRI-based tumor texture features. These results can be exploited for further research into creating a clinical decision support system, facilitating physicians, and patients to select a personalized optimal treatment strategy.
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Neuroma Acústico , Radiocirurgia , Humanos , Imageamento por Ressonância Magnética , Neuroma Acústico/diagnóstico por imagem , Neuroma Acústico/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: A growing number of patients with brain metastases (BM) are being treated with stereotactic radiosurgery (SRS), and the importance of evaluating the impact of SRS on the health-related quality of life (HRQoL) in these patients has been increasingly acknowledged. This systematic review summarizes the current knowledge about the HRQoL of patients with BM after SRS. METHODS: We searched EMBASE, Medline Ovid, Web-of-Science, the Cochrane Database, PsycINFO Ovid, and Google Scholar up to November 15, 2018. Studies in patients with BM in which HRQoL was assessed before and after SRS and analyzed over time were included. Studies including populations of several types of brain cancer and/or several types of treatments were included if the results for patients with BM and treatment with SRS alone were described separately. RESULTS: Out of 3638 published articles, 9 studies met the eligibility criteria and were included. In 4 out of 7 studies on group results, overall HRQoL of patients with BM remained stable after SRS. In small study samples of longer-term survivors, overall HRQoL remained stable up to 12 months post-SRS. Contradictory results were reported for physical and general/global HRQoL, which might be explained by the different questionnaires that were used. CONCLUSIONS: In general, SRS does not have significant negative effects on patients' overall HRQoL over time. Future research is needed to analyze different aspects of HRQoL, differences in individual changes in HRQoL after SRS, and factors that influence these changes. These studies should take into account several methodological issues as discussed in this review.
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Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Nível de Saúde , Qualidade de Vida/psicologia , Radiocirurgia/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , SobreviventesRESUMO
PURPOSE: Information on predictive factors of cognitive functioning in patients with (multiple) brain metastases (BM) selected for radiosurgery may allow for more individual care and may play a role in predicting cognitive outcome after radiosurgery. The aim of this study was to evaluate cognitive performance, and predictors thereof, in patients with 1-10 BM before radiosurgery. METHODS: Cognition was measured before radiosurgery using a standardized neuropsychological test battery in patients with 1-10 BM (expected survival > 3 months; KPS ≥ 70; no prior BM treatment). Regression formulae were constructed to calculate sociodemographically corrected z scores. Group and individual cognitive functioning was analyzed. Multivariable regression was used to explore potential predictors. RESULTS: Patients (N = 92) performed significantly worse than controls (N = 104) on all 11 test variables (medium-large effect sizes for 8 variables). Percentages of impairment were highest for information processing (55.3%), dexterity (43.2%) and cognitive flexibility (28.7%). 62% and 46% of patients had impairments in at least two, or three test variables, respectively. Models including combinations of clinical and psychological variables were predictive of verbal memory, psychomotor speed, information processing and dexterity. Neither number nor volume of metastases predicted patients' test performance. CONCLUSIONS: Already before radiosurgery, almost half of the patients suffered from severe cognitive deficits in at least three test variables. At group and individual level, information processing, cognitive flexibility, and dexterity were most affected. These cognitive impairments may impair daily functioning and patients' ability to make (shared) treatment decisions. Both clinical (symptomatic BM; timing of BM diagnosis) and psychological (mental fatigue) characteristics influenced cognitive performance. CLINICAL TRIAL INFORMATION: Cognition and Radiation Study A (CAR-Study A; ClinicalTrials.gov Identifier: NCT02953756; Medical Ethics Committee file number: NL53472.028.15/P1515).
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Neoplasias Encefálicas/psicologia , Neoplasias Encefálicas/radioterapia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Radiocirurgia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/secundário , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Prognóstico , Estudos ProspectivosRESUMO
We report on ultrasmall zinc oxide single-crystalline nanoparticles of narrow size distribution and long-term colloidal stability. These oleate-stabilized nanoparticles were synthesized using microwave-assisted synthesis for 5 min, corresponding to a 99% decrease in synthesis time, when compared to the conventional synthesis method. It was observed that the average particle radius increases from 2.6 ± 0.1 to 3.8 ± 0.1 nm upon increasing synthesis temperature from 125 to 200 °C. This change also corresponded to observed changes in the optical band gap and the fluorescence energy of the particles, from 3.44 ± 0.01 to 3.36 ± 0.01 eV and from 2.20 ± 0.01 to 2.04 ± 0.01 eV, respectively. Small-angle X-ray scattering, dynamic light scattering, and UV-vis and fluorescence spectroscopy were employed for particle characterization. Debye-Scherrer analysis of the X-ray diffraction (XRD) pattern reveals a linear increase of the crystallite size with synthesis temperature. The consideration of the convolution of a Lorentz function with a Gaussian function for data correction of the instrumental peak broadening has a considerable influence on the values for the crystallite size. Williamson-Hall XRD analyses in the form of the uniform deformation model, uniform stress deformation model, and uniform deformation energy density model revealed a substantial increase of strain, stress, and deformation energy density of the crystallites with decreasing size. Exponential and power law models were utilized for quantification of strain, stress, and deformation energy density.
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PURPOSE: Fatigue is a common and distressing symptom in cancer patients which negatively affects patients' daily functioning and health-related quality of life. The aim of this study was to assess multidimensional fatigue in patients with brain metastases (BM) before, and after Gamma Knife radiosurgery (GKRS). METHODS: Patients with BM, an expected survival > 3 months, and a Karnofsky Performance Status ≥ 70 and 104 Dutch non-cancer controls were recruited. The Multidimensional Fatigue Inventory (MFI), measuring general fatigue, physical fatigue, mental fatigue, reduced activity and reduced motivation, was used. Baseline levels of fatigue between patients and controls were compared using independent-samples t-tests. The course of fatigue over time, and clinical and psychological predictors thereof, were analyzed using linear mixed models (within-group analyses). RESULTS: Ninety-two, 67 and 53 patients completed the MFI at baseline, and 3 and 6 months after GKRS. Before GKRS, patients with BM experienced significantly higher levels of fatigue on all subscales compared to controls (medium to large effect sizes). Over 6 months, general and physical fatigue increased significantly (p = .009 and p < .001), and levels of mental fatigue decreased significantly (p = .027). No significant predictors of the course of fatigue over time could be identified. CONCLUSIONS: Fatigue is a major problem for patients with BM. Different patterns over time were observed for the various aspects of fatigue in patients with BM. Information on the various aspects of fatigue is important because fatigue may negatively affect patients' functional independence, health-related quality of life, and adherence to therapy.
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Neoplasias Encefálicas/cirurgia , Fadiga/diagnóstico , Neoplasias/cirurgia , Qualidade de Vida , Radiocirurgia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/secundário , Fadiga/etiologia , Feminino , Seguimentos , Humanos , Avaliação de Estado de Karnofsky , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Prognóstico , Estudos ProspectivosRESUMO
PURPOSE: Information on health-related quality of life (HRQoL) of patients with brain metastases (BM) before stereotactic radiosurgery (SRS) is very relevant to improve communication between patients and clinicians and to be able to interpret changes in HRQoL after SRS. The aim of this study was to evaluate the prevalence and severity of complaints on different aspects of pre-SRS HRQoL among patients with BM and to identify predictors thereof. METHODS: Patients with 1-10 newly diagnosed BM, expected survival > 3 months, Karnofsky Performance Status ≥ 70, and scheduled to undergo SRS were included. HRQoL was measured with the Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire. One-sample z-tests were conducted to analyze differences between patients with BM and published normative data of a general adult sample and of an adult cancer sample. Multiple regression analyses were run to identify predictors of pre-SRS HRQoL. RESULTS: On the individual level, most patients with BM (57.6% of 92 included patients) reported complaints regarding emotional well-being. As a group, patients with BM reported significantly lower emotional well-being compared to both control groups and significantly higher social well-being compared to the general population. Worse psychological factors, e.g. physical fatigue, depression, mental fatigue and anxiety, predicted aspects of pre-SRS HRQoL. CONCLUSIONS: An increased understanding of pre-SRS HRQoL and predictors hereof, provides us with more insight into the well-being of our patients with BM and is necessary for the interpretation of (changes in) HRQoL after SRS.
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Neoplasias Encefálicas/psicologia , Neoplasias Encefálicas/secundário , Neoplasias/patologia , Seleção de Pacientes , Qualidade de Vida , Radiocirurgia/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade , Neoplasias Encefálicas/cirurgia , Estudos de Casos e Controles , Depressão , Fadiga , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Prognóstico , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Gynecological brain metastases (BM) are rare and usually develop as part of widespread disseminated disease. Despite treatment, the majority of these patients do not survive > 1 year due to advanced extracranial disease. The use of Gamma Knife Radiosurgery (GKRS) for gynecological BM is not well known. The goal of this study is to evaluate the efficacy of GKRS for gynecological BM. METHODS: We performed a retrospective study of patients with gynecological BM who underwent GKRS between 2002 and 2015. A total of 41 patients were included. Outcome measures were local tumor control (LC), development of new BM and/or leptomeningeal disease, overall intracranial progression free survival (PFS) and survival. RESULTS: LC was 100%, 92%, 80%, 75% and 67% at 3, 6, 9, 12 and 15 months, respectively. PFS was 90%, 61%, 41%, 23% and 13% at 3, 6, 9, 12 and 15 months, respectively. During follow-up (FU), 18 (44%) patients had intracranial progression. Distant BM occurred in 29% of the patients. Local recurrence and distant recurrence occurred after a mean FU time of 15.5 (2.6-71.9) and 11.4 (2-40) months, respectively. Thirty-one (76%) patients died due to extracranial tumor progression and only 2 (5%) patients died due to progressive intracranial disease. The overall mean survival from time of GKRS was 19 months (1-109). The 6-month, 1-year, and 2-year survival rate from the time of GKRS were 71%, 46%, and 22%, respectively. CONCLUSION: GKRS is a good treatment option for controlling gynecological BM. As most patients die due to extracranial tumor progression, their survival might improve with better systemic treatment options in addition to GKRS.
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Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Neoplasias dos Genitais Femininos/patologia , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/secundário , Radiocirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/epidemiologia , Feminino , Seguimentos , Neoplasias dos Genitais Femininos/epidemiologia , Neoplasias dos Genitais Femininos/radioterapia , Humanos , Neoplasias Meníngeas/epidemiologia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
OBJECTIVEThe aim of this study was to gain insight into the influence of the pretreatment growth rate on the volumetric tumor response and tumor control rates after Gamma Knife radiosurgery (GKRS) for incidental vestibular schwannoma (VS).METHODSAll patients treated with GKRS at the Gamma Knife Center, ETZ Hospital, who exhibited a confirmed radiological progression of their VS after an initial observation period were included. Pre- and posttreatment MRI scans were volumetrically evaluated, and the volume doubling times (VDTs) prior to treatment were calculated. Posttreatment volumes were used to create an objective mathematical failure definition: 2 consecutive significant increases in tumor volume among 3 consecutive follow-up MRI scans. Spearman correlation, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis were used to determine the influence of the VDT on the volumetric treatment response.RESULTSThe resulting patient cohort contained 311 patients in whom the VDT was calculated. This cohort had a median follow-up time of 60 months after GKRS. Of these 311 patients, 35 experienced loss of tumor control after GKRS. The pretreatment growth rate and the relative volume changes, calculated at 6 months and 1, 2, and 3 years following treatment, showed no statistically significant correlation. Kaplan-Meier analysis revealed that slow-growing tumors, with a VDT equal to or longer than the median VDT of 15 months, had calculated 5- and 10-year control rates of 97.3% and 86.0%, respectively, whereas fast-growing tumors, with a VDT less than the median growth rate, had control rates of 85.5% and 67.6%, respectively (log-rank, p = 0.001). The influence of the VDT on tumor control was also determined by employing the Cox regression analysis. The resulting model presented a significant (p = 0.045) effect of the VDT on the hazard rates of loss of tumor control.CONCLUSIONSBy employing a unique, large database with long follow-up times, the authors were able to accurately investigate the influence of the pretreatment VS growth rate on the volumetric GKRS treatment response. The authors have found a predictive model that illustrates the negative influence of the pretreatment VS growth rate on the efficacy of radiosurgery treatment. The resulting tumor control rates confirm the high efficacy of GKRS for slow-growing VS. However, fast-growing tumors showed significantly lower control rates. For these cases, different treatment strategies may be considered.
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PURPOSE: Stereotactic radiation surgery (SRS) is increasingly applied in patients with brain metastases (BM) and is expected to have fewer adverse effects on cognitive functioning than whole brain radiation therapy (WBRT). Patients with BM are often confronted with a relatively short life expectancy, and the prevention or delay of cognitive decline to maintain quality of life is a clinically and highly relevant treatment goal. This review systematically and specifically evaluates the current literature on the cognitive effects of SRS in patients with BM. METHODS AND MATERIALS: Published trials on SRS alone or in combination with WBRT, including objective assessment of cognitive functioning, were identified through a systematic search of the PubMed database up to March 2018. RESULTS: Of the 241 records screened, 14 studies matched the selection criteria: 2 pilot studies, 7 single-group/observational trials (1 study update), and 5 randomized trials (1 secondary analysis). CONCLUSIONS: In general, the results show little to no objective cognitive decline up to 4 months after SRS compared with WBRT. However, most trials suffered from methodologic limitations that hindered reliable conclusions. Most importantly, few studies investigated the specific cognitive effects of SRS alone or versus WBRT. Furthermore, disentangling the cognitive effects of SRS from the effects of the disease itself and from the effects of other treatments remains very difficult. By presenting this comprehensive review, we aim to encourage researchers to probe deeper into this area and to do so in a standardized and methodologically optimal manner. The ultimate objective of this line of research is to inform both doctors and patients more precisely about the cognitive effects they can expect from treatment. This study is expected to improve the quality of decision-making and maximize clinical outcomes for each individual patient.
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OBJECTIVE: In recent years, gamma knife radiosurgery (GKRS) has become increasingly more popular as a salvage treatment modality for patients diagnosed with recurrent gliomas. The goal of GKRS for recurrent glioma patients is to improve survival rates with minimal burden for these patients. The emphasis of this report is on local tumor control (TC), clinical outcome and survival analysis. METHODS: We performed a retrospective analysis of prospectively collected data of all patients who underwent GKRS for gliomas at the Gamma Knife Center Tilburg between 23-09-2002 and 21-05-2015. In total, 94 patients with glioma were treated with GKRS. Two patients were excluded because GKRS was used as a first stage treatment. The other 92 patients were included for analysis. RESULTS: TC was 37% for all tumors (TC was 50% in LGGs and 27% in HGGs). Local progression (LP) was 46% for all tumors (LP was 31% in LGGs and 58% in HGGs). New distant lesions were seen in 18% of all patients (in 5% of LGG patients and 31% of HGG patients). Median progression-free and overall survival (PFS and OS) for all patients were 10.5 and 34.4 months, respectively. Median PFS was 50.1 and 5.7 months for low and high grade tumors, respectively. Median OS was 86.6 and 12.8 months for low and high grade tumors, respectively. No serious adverse events were noted post-GKRS. CONCLUSION: GKRS can safely be used as salvage treatment for recurrent glioma and seems to improve survival rates in (high grade) glioma patients with minimal burden.
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Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Recidiva Local de Neoplasia/radioterapia , Radiocirurgia , Terapia de Salvação , Adolescente , Adulto , Idoso , Criança , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Adulto JovemRESUMO
We report on etching of polyacrylic acid-stabilised silver nanoparticles in the presence of glutathione (GSH). The initial particles with a radius of 3.2 nm and consisting of â¼8100 silver atoms dissolve in a two-step reaction mechanism while in parallel smaller silver particles with a radius of 0.65 nm and consisting of 60 to 70 silver atoms were formed. The kinetics of the etching of the initial particles, accompanied by formation of smaller silver particles was interpreted based on in situ, time-resolved small-angle X-ray scattering (SAXS) experiments.
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BACKGROUND: Gamma Knife radiosurgery (GKRS) is increasingly applied in patients with multiple brain metastases and is expected to have less adverse effects in cognitive functioning than whole brain radiation therapy (WBRT). Effective treatment with the least negative cognitive side effects is increasingly becoming important, as more patients with brain metastases live longer due to more and better systemic treatment options. There are no published randomized trials yet directly comparing GKRS to WBRT in patients with multiple brain metastases that include objective neuropsychological testing. METHODS: CAR-Study B is a prospective randomised trial comparing cognitive outcome after GKRS or WBRT in adult patients with 11-20 newly diagnosed brain metastases on a contrast-enhanced MRI-scan, KPS ≥70 and life expectancy of at least 3 months. Randomisation by the method of minimization, is stratified by the cumulative tumour volume in the brain, systemic treatment, KPS, histology, baseline cognitive functioning and age. The primary endpoint is the between-group difference in the percentage of patients with significant memory decline at 3 months. Secondary endpoints include overall survival, local control, development of new brain metastases, cognitive functioning over time, quality of life, depression, anxiety and fatigue. Cognitive functioning is assessed by a standardised neuropsychological test battery. Assessments (cognitive testing, questionnaires and MRI-scans) are scheduled at baseline and at 3, 6, 9, 12 and 15 months after treatment. DISCUSSION: Knowledge gained from this trial may be used to inform individual patients with BM more precisely about the cognitive effects they can expect from treatment, and to assist both doctors and patients in making (shared) individual treatment decisions. This trial is currently recruiting. Target accrual: 23 patients at 3-months follow-up in both groups. TRIAL REGISTRATION: The Netherlands Trials Register number NTR5463. ClinicalTrials.gov registration number NCT02953717 , first received October 27, 2016, 8 patients were enrolled in this study on 31 July 2017.
Assuntos
Protocolos Antineoplásicos , Neoplasias Encefálicas/radioterapia , Radiocirurgia , Adulto , Cognição , Humanos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos , Qualidade de Vida , Radioterapia , Resultado do Tratamento , Adulto JovemRESUMO
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.
Assuntos
Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Radiocirurgia/instrumentação , Neoplasias da Base do Crânio/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Neoplasias Meníngeas/patologia , Meningioma/patologia , Microcirurgia , Pessoa de Meia-Idade , Países Baixos , Neoplasias da Base do Crânio/patologia , Resultado do Tratamento , Carga TumoralRESUMO
OBJECTIVE Neurofibromatosis Type 2 (NF2) is a tumor syndrome characterized by an autosomal dominant pattern of inheritance. The hallmark of NF2 is the development of bilateral vestibular schwannomas (VSs), generally by 30 years of age. One of the first-line treatment options for small to medium-large VSs is radiosurgery. Although radiosurgery shows excellent results in sporadic VS, its use in NF2-related VS is still a topic of dispute. The aim of this study was to evaluate long-term tumor control, hearing preservation rates, and factors influencing outcome of optimally dosed, contemporary Gamma Knife radiosurgery (GKRS) for growing VSs in patients with NF2 and compare the findings to data obtained in patients with sporadic VS also treated by means of GKRS. METHODS The authors performed a retrospective analysis of 47 growing VSs in 34 NF2 patients who underwent GKRS treatment performed with either the Model C or Perfexion Leksell Gamma Knife, with a median margin dose of 11 Gy. Actuarial tumor control rates were estimated using the Kaplan-Meier method. For patient- and treatment-related factors, a Cox proportional hazards model was used to identify predictors of outcome. Trigeminal, facial, and vestibulocochlear nerve function were assessed before and after treatment. NF2-related VS patients were matched 1:1 with sporadic VS patients who were treated in the same institute, and the same indications for treatment, definitions, and dosimetry were used in order to compare outcomes. RESULTS Actuarial tumor control rates in NF2 patients after 1, 3, 5, and 8 years were 98%, 89%, 87%, and 87%, respectively. Phenotype and tumor volume had significant hazard rates of 0.086 and 22.99, respectively, showing that Feiling-Gardner phenotype and a tumor volume not exceeding 6 cm3 both were associated with significantly better outcome. Actuarial rates of serviceable hearing preservation after 1, 3, 5, and 7 years were 95%, 82%, 59%, and 33%, respectively. None of the patients experienced worsening of trigeminal nerve function. Facial nerve function worsened in 1 patient (2.5%). No significant differences in tumor control, hearing preservation, or complications were found in comparing the results of GKRS for NF2-related VS versus GKRS for sporadic VS. CONCLUSIONS With modern GKRS, the use of low margin doses for treating growing VSs in patients with NF2 demonstrates good long-term tumor control rates. Feiling-Gardner phenotype and tumor volume smaller than 6 cm3 seem to be independently associated with prolonged progression-free survival, highlighting the clinical importance of phenotype assessment before GKRS treatment. In addition, no significant differences in tumor control rates or complications were found in the matched-control cohort analysis comparing GKRS for VS in patients with NF2 and GKRS for sporadic VS. These results show that GKRS is a valid treatment option for NF2-related VS, in addition to being a good option for sporadic VS, particularly in patients with the Feiling-Gardner phenotype and/or tumors that are small to medium in size. Larger tumors in patients with the Wishart phenotype appear to respond poorly to radiosurgery, and other treatment modalities should therefore be considered in such cases.