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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. 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. 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 65 years and time from primary diagnosis to brain metastasis 4 BM was the only predictive factor for distant intracranial failure, while none of the investigated factors predicted local failure. 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.

BackgroundSurvival rates have improved in the past years for patients with brain metastases (BMs).ObjectiveTo evaluate cognitive functioning and health-related quality of life (HRQoL) after Gamma Knife radiosurgery (GKRS) in a relatively large sample of long-term survivors.MethodsData 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.ResultsCognitive 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.ConclusionUp 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.

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.

PurposeA 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.MethodsWe 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.ResultsOut 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.ConclusionsIn 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.

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

Aims: Stereotactic radiosurgery is increasingly used to treat multiple (four or more) brain metastases. Preserving cognitive functions is a highly relevant treatment goal because cognitive deteriorations may negatively affect a patient's quality of life. The aim of this study was to assess cognitive change, at the group and individual level, in patients with 1 to 10 brain metastases up to 9 months after Gamma Knife radiosurgery (GKRS).Materials and methods: Ninety-two patients with 1 to 10 newly diagnosed brain metastases, expected survival >3 months and Karnofsky Performance Status (KPS) ≥70 and 104 non-cancer controls were included. A neuropsychological test battery was administered before GKRS (n = 92) and at 3 (n = 66), 6 (n = 52) and 9 (n = 41) months after GKRS. The course of test performances, while taking into account practice effects, was analysed using linear mixed models. Pre-GKRS predictors of cognitive trajectories were analysed. To determine proportions of individuals with cognitive changes, reliable change indices, with correction for practice effects, were calculated.Results: At the group level, immediate memory, working memory and information processing speed significantly improved over 9 months after GKRS. There were no cognitive declines. Neither number nor volume of brain metastases influenced cognitive change over time. At the individual level, proportions of patients with stable, improved or declined performances were comparable with controls, except for information processing speed (more individuals with improvements in patients) and motor dexterity (more improvements and declines in patients).Conclusions: Cognitive functioning in patients with 1 to 10 brain metastases was preserved, or improved, up to 9 months after GKRS. Neither number nor volume of brain metastases influenced cognitive performance.

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.

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 5 cm3.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.

OBJECTIVEGamma Knife radiosurgery (GKRS) has become an accepted treatment for vestibular schwannoma, with a high rate of tumor control and good clinical outcome. In a small number of cases, additional treatment is needed. This retrospective study examines the clinical outcome, reproducibility of volumetric response patterns, and tumor control rate after administering a second GKRS to treat vestibular schwannomas.METHODSA total of 38 patients were included: 28 patients underwent a radiosurgical procedure as the initial treatment (Group 1), and 10 patients underwent microsurgical resection with adjuvant radiosurgery on the tumor remnant as the initial treatment (Group 2). The indication for a second GKRS treatment was growth observed on follow-up imaging. The median margin dose was 11.0 Gy for the first procedure and 11.5 Gy for the second procedure. Tumor control after retreatment was assessed through volumetric analysis. Clinical outcome was assessed through medical chart review.RESULTSMedian tumor volume at retreatment was 3.6 cm3, with a median treatment interval of 49 months. All patients showed tumor control in a median follow-up period of 75 months after the second radiosurgical procedure. Volumetric tumor response after the second procedure did not correspond to response after the first procedure. After retreatment, persisting House-Brackmann Grade II facial nerve dysfunction was observed in 3 patients (7.9%), facial spasms in 5 patients (13%), and trigeminal nerve hypesthesia in 3 patients (7.9%). Hearing preservation was not evaluated because of the small number of patients with serviceable hearing at the second procedure.CONCLUSIONSRepeat GKRS after a failed first treatment appears to be an effective strategy in terms of tumor control. The volumetric response after a repeat procedure could not be predicted by the volumetric response observed after first treatment. This justifies considering repeat GKRS even for tumors that do not show any volumetric response and show continuous growth after first treatment. An increased risk of mild facial and trigeminal nerve dysfunction was observed after the second treatment compared with the first treatment.

Melanoma brain metastases (MBM) are common in patients with stage IV disease. For Gamma Knife radiosurgery (GKRS) on MBM, risk scores such as RPA and melanoma-GPA aid to identify prognostic subgroups. This study aimed to validate the overall survival (OS) risk score developed by Chowdhury et al. in our center’s patient cohort. A total of 104 MBM patients were treated with GKRS between 1/1/2002 and 31/12/2014 in our institution. Patients were categorized according to RPA, melanoma-GPA and Chowdhury OS score. The Kaplan–Meier method was used to estimate overall survival, and predicted survival probabilities were calculated for calibration. Cox proportional hazards regressions were performed to identify additional risk factors. Overall, median follow-up time was 80 months, while median OS (mOS) after GKRS was 6 months. Stratified according to the Chowdhury OS score, mOS in the high, medium and low risk group was 3.4, 7.1, and 10.0 months, respectively. The addition of other patient or disease characteristics to the Chowdhury OS model did not improve its performance. The C-index of the melanoma-GPA was 0.46 while the Chowdhury OS had an index of 0.67. In comparison with the RPA and melanoma-GPA, the Chowdhury OS score more accurately distinguished between separate risk groups among patients with MBM treated with GKRS. Contrary to the original study by Chowdhury, follow-up time was sufficient here for the low-risk group to reach the mOS time of 10 months.

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.

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.

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.Our objective is evaluation of volumetric reduction after SCA, tumor control, and complications after SCA directly followed by GKRS.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.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.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.

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. 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. 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. 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.

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. Electronic supplementary material The online version of this article (10.1007/s11060-019-03186-z) contains supplementary material, which is available to authorized users.

Little understanding exists of referral patterns for patients with brain metastasis from non-small cell lung cancer (NSCLC) towards treatment with Gamma Knife radiosurgery (GKRS). Therefore, we explored current clinical daily practice and prognosis.In total, 1129 patients with synchronously diagnosed brain metastasis from NSCLC diagnosed between 2008 and 2014 were selected from the population-based Netherlands Cancer Registry; 242 patients were treated with GKRS.Patients receiving GKRS were younger (62 years versus 64 years) and had lower tumour burden: the presence of T2 was higher and T4 was lower (43% versus 33%; P = 0.0158, 19% versus 28%; P = 0.0044, respectively). They more frequently had cN0 (32% versus 19%; P ≤ 0.0001), less frequently had N3 disease (18% versus 29%; P = 0.0004) and there were fewer metastatic sites. In multivariable logistic regression analysis, only age ≤60 years (odds ratio 1.4; 95% confidence interval 1.0-2.0) and patients with N0 stage, compared with those with N2, N3 and NX (odds ratio 0.6 [0.4-0.9], 0.3 [0.2-0.6], 0.3 [0.1-0.6], respectively), were more likely to receive GKRS. Gender, T-stage, histology, number of comorbidities, country of birth as proxy for ethnicity and socioeconomic status were not associated. The median survival was 9.6 months after GKRS versus 4.0 months in the noGKRS group (Log-rank: P ≤ 0.0001). Multivariably, GKRS, female, lower T-/N-stage,2 comorbidities, adenocarcinoma and higher socioeconomic status were associated with a significantly reduced hazard of death. For the patients with at least one follow-up magnetic resonance image (80%), local intracranial tumour control was achieved in 93% at the last follow-up.Patients presenting with synchronic brain metastasis from NSCLC who are referred to a third-line treatment centre for GKRS are younger and have a lower tumour load. Due to a high level of local control, GKRS is able to provide a significant window of opportunity for additional treatment of the primary tumour.

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. 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. 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. 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.

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.

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.

OBJECTIVENeurofibromatosis 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.METHODSThe 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.RESULTSActuarial 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.CONCLUSIONSWith 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.

Objective It is still not clear whether Gamma Knife radiosurgery (GKRS) for nonfunctional pituitary adenomas should be used as a standard adjuvant postoperative therapy or applied when there is documented progression of the remnant on follow-up magnetic resonance imaging. Methods We performed a retrospective study of patients with nonfunctional pituitary adenomas who underwent primary surgery and GKRS between 2002 and 2015. Patients were divided into 2 groups on the basis of the GKRS indication: adjuvant treatment (GKRS ≤6 months postoperatively) or delayed treatment (GKRS if documented progression occurred on the follow-up magnetic resonance imaging). Results Fifty patients were included and grouped based on adjuvant ( n = 13) or delayed ( n = 37) GKRS following primary surgery. The adjuvant and delayed groups had 10-year actuarial tumor control rates of 92% and 96% ( P = 0.408), respectively. The 10-year actuarial endocrinologic control rate was 82% for the adjuvant group and 49% for the delayed group ( P = 0.597). None of the patients developed any new neurologic deficit post-GKRS. GKRS-induced complications (intratumoral bleeding and tumoral tissue inflammation) occurred in 6% of the patients, of whom 4% were in the delayed group and 2% in the adjuvant group. Conclusion Adjuvant treatment with GKRS yields the same high long-term tumor control as delayed GKRS. Neither adjuvant nor delayed GKRS induced additional neurologic complications. There is a trend that adjuvant GKRS induces less additional endocrinologic deficits compared with delayed GKRS.

Objective To assess if modern management of extracranial malignant diseases has prolonged the survival times for patients with more than 2 brain metastases (BM). Methods Data from 2385 patients treated with Gamma Knife surgery (GKS) for ≥3 BM between 1982 and 2011 were retrospectively analyzed. The patients were divided into 6 groups based on the treatment year and the median and 10% survival times were compared with the median and mean treatment dates in each group. Results The later the treatment date, the longer the median as well as the 10% survival times. The relation between the median treatment date and both the 10% and median survival times could be accurately expressed by a linear as well as an exponential curve fit. The median and 10% survival times increased by around 80% and 150%, respectively, between 1990 and 2010. Conclusions Both the median and 10% survival times have increased in recent years among patients with more than 2 BM treated with GKS. Both linear and exponential regressions accurately expressed the increase in both median and 10% survival times during the years 1990–2010. Findings from other published data support the observation of longer survival times among patients treated more recently, independent of the patients being treated with GKS or with whole-brain radiation therapy with or without radiosurgery. Thus, earlier findings of short survival times for patients with multiple BM are no longer valid, at least not for patients deemed suitable for radiosurgery. Aggressive management is thus warranted for these patients.

Object In large vestibular schwannoma (VS), microsurgery is the main treatment option, and complete resection is considered the primary goal. However, previous studies have documented suboptimal facial nerve outcomes in patients who undergo complete resection of large VSs. Subtotal resection is likely to reduce the risk of facial nerve injury but increases the risk of lesion regrowth. Gamma Knife surgery (GKS) can be performed to achieve long-term growth control of residual VS after incomplete resection. In this study the authors report on the results in patients treated using planned subtotal resection followed by GKS with special attention to volumetric growth, control rate, and symptoms. Methods Fifty consecutive patients who underwent the combined treatment strategy of subtotal microsurgical removal and GKS for large VSs between 2002 and 2009 were retrospectively analyzed. Patients with neurofibromatosis Type 2 were excluded. Patient charts were reviewed for clinical symptoms. Audiograms were evaluated to classify hearing pre- and postoperatively. Preoperative and follow-up contrast-enhanced T1-weighted MR images were analyzed using volume-measuring software. Results Surgery was performed via a translabyrinthine (25 patients) or retrosigmoid (25 patients) approach. The median follow-up was 33.8 months. Clinical control was achieved in 92% of the cases and radiological control in 90%. One year after radiosurgery, facial nerve function was good (House-Brackmann Grade I or II) in 94% of the patients. One of the two patients who underwent surgery to preserve hearing maintained serviceable hearing after resection followed by GKS. Conclusions Considering the good tumor growth control and facial nerve function preservation as well as the possibility of preserving serviceable hearing and the low number of complications, subtotal resection followed by GKS can be the treatment option of choice for large VSs.

Object In large vestibular schwannomas (VSs), microsurgery is the main treatment option. A wait-and-scan policy or radiosurgery are generally not recommended given concerns of further lesion growth or increased mass effect due to transient swelling. Note, however, that some patients do not present with symptomatic mass effect or may still have serviceable hearing. Moreover, others may be old, suffer from severe comorbidity, or refuse any surgery. In this study the authors report the results in patients with large, growing VSs primarily treated with Gamma Knife surgery (GKS), with special attention to volumetric growth, control rate, and symptoms. Methods The authors retrospectively analyzed 33 consecutive patients who underwent GKS for large, growing VSs, which were defined as > 6 cm3 and at least indenting the brainstem. Patients with neurofibromatosis Type 2 were excluded from analysis, as were patients who had undergone previous treatment. Volume measurements were performed on contrast-enhanced T1-weighted MR images at the time of GKS and during follow-up. Medical charts were analyzed for clinical symptoms. Results Radiological growth control was achieved in 88% of cases, clinical control (that is, no need for further treatment) in 79% of cases. The median follow-up was 30 months, and the mean VS volume was 8.8 cm3 (range 6.1–17.7 cm3). No major complications occurred, although ventriculoperitoneal shunts were placed in 2 patients. The preservation of serviceable hearing and facial and trigeminal nerve function was achieved in 58%, 91%, and 86% of patients, respectively, with any facial and trigeminal neuropathy being transient. In 92% of the patients presenting with trigeminal hypesthesia before GKS, the condition resolved during follow-up. No patient- or VS-related feature was correlated with growth. Conclusions Primary GKS for large VSs leads to acceptable radiological growth rates and clinical control rates, with the chance of hearing preservation. Although a higher incidence of clinical control failure and postradiosurgical morbidity is noted, as compared with that for smaller VSs, primary radiosurgery is suitable for a selected group of patients. The absence of symptomatology due to mass effect on the brainstem or cerebellum is essential, as are close clinical and radiological follow-ups, because there is little reserve for growth or swelling.

OBJECTIVES/HYPOTHESIS: Gamma knife radiosurgery (GKRS) has become an important treatment modality for vestibular schwannomas. The primary aim of this study was to investigate whether tumor growth at the moment of GKRS has any correlation with the outcome. The secondary aim was to identify clinical predictors of radioresistance in vestibular schwannoma patients treated with GKRS. STUDY DESIGN: One hundred vestibular schwannoma patients, treated with GKRS, were divided into two groups: 1) proven tumor growth preceding GKRS; and 2) previous history of growth unknown. GKRS outcome was defined in two ways. According to the first definition, GKRS was said to have failed when additional treatment had taken place. According to the second one, a volume decrease >20% after 2 years marked successful treatment. METHODS: Correlations between outcome and growth status were determined with SPSS software. Furthermore, the study assessed how different variables (patient data, history, tumor characteristics, imaging, and audiovestibular examinations) correlated with the outcome of GKRS. RESULTS: No significant difference regarding success and failure of GKRS was found between the two patient groups. The mean reduction in tumor volume after GKRS was less pronounced in patients in whom tumor growth was demonstrated before treatment, but this finding was not significant. No significant predictors (P < .05) could be identified in this data set. CONCLUSIONS: This study found no indication that growth at the moment of GKRS influences therapeutic outcome, nor did it identify any predictors of the outcome after GKRS in vestibular schwannoma patients.

Item does not contain fulltext OBJECTIVES/HYPOTHESIS: A prospective long-term follow-up study was conducted to evaluate the results of gamma knife radiosurgery (GKRS) for vestibular schwannoma (VS) patients. Both axial and volumetric measurements are used to determine tumor size during follow-up. STUDY DESIGN: Individual prospective cohort study. METHODS: A total of 110 VS patients were referred for radiosurgery between 2002 and 2007. All patients were treated with a Leksell 4C gamma knife. There were 12.5 to 13 Gy prescribed to the isodose covering 90% of the tumor volume. The resulting marginal dose was on average 11.0 Gy (range, 9.3-12.5 Gy). Tumor size and tumor volume were determined before and after gamma knife treatment at regular intervals. The minimal follow-up period was 2 years. RESULTS: There were 100 patients included in the study. Eight patients needed additional treatment after a mean follow-up period of 38 months. One patient experienced a temporary facial nerve deficit. No growth pattern could be recognized for tumor growth after GKRS. Based on the measurements of the largest extrameatal diameter, the tumor size would have decreased or remained stable in 94%. Based on volumetric measurement, the tumor size was decreased or remained stable in 79%. CONCLUSIONS: High tumor control and low complication rates make GKRS a good therapy for VS. If tumor growth occurs after GKRS, a conservative management can be considered because continued tumor growth is uncertain. The extrameatal diameter on axial magnetic resonance imaging seems to be a reliable parameter of the size of a VS. Volumetry is the preferred method to assess the dimensions of a VS, although the consequences of strong volumetric increase, especially in small tumors, can be different depending on individual differences in tumor size.

Object The success rates and side effects of Gamma Knife surgery (GKS) in patients with trigeminal neuralgia (TN) are not fully clear. A comparison of data across previous reports is hampered by differences in treatment protocols, lengths of follow-up, and outcome criteria. The purpose of this paper is to contribute to knowledge of the efficacy of GKS in TN by reviewing data in a large group of patients with this disorder, who were treated with a uniform treatment protocol and evaluated using a well-established pain scale and Kaplan-Meier analysis. Methods The authors reviewed 450 treatments in 365 patents with medically refractory TN who were treated between June 2002 and October 2009 at the Gamma Knife Center Tilburg. In all patients 80 Gy was prescribed, with a single 4-mm isocenter located at the root entry zone (REZ). In 79 patients repeated GKS was performed using a uniform dose of 80 Gy, which was delivered, in a highly standardized manner, to a spot anterior to the position of the first treatment. Follow-up was obtained by reviewing the patients' medical records and conducting telephone interviews. Outcome was assessed using the Barrow Neurological Institute (BNI) pain scale and the BNI facial numbness scale. Results The median follow-up period was 28 months. In the idiopathic TN group, rates of adequate pain relief, defined as BNI Pain Scores I–IIIB, were 75%, 60%, and 58% at 1, 3, and 5 years, respectively. In the multiple sclerosis (MS)–related TN group the rates of adequate pain relief were 56%, 30%, and 20% at 1, 3, and 5 years, respectively. Repeated GKS was as successful as the first. An analysis of our treatment strategy of repeated GKS showed rates of adequate pain relief of 75% at 5 years in the idiopathic TN and 46% in the MS-related TN group. Somewhat bothersome numbness was reported by 6% of patients after the first treatment and by 24% after repeated GKS. Very bothersome numbness was reported in 0.5% after the first GKS and in 2% after the second treatment. Conclusions In this study the authors analyzed outcomes of GKS in a large cohort of patients with TN; uniform treatment consisted of 80 Gy delivered to the REZ. The initial and long-term outcomes of pain relief and sensory dysfunction are comparable to recently published results at other institutions, where similar outcome criteria were used. These data should prove helpful to assist patients and clinicians in their TN management decisions.

Contains fulltext : 89525timmer.pdf (Publisher’s version ) (Closed access) This study evaluates the impact of gamma knife radiosurgery (GKRS) on the quality of life (QOL) of patients with a sporadic vestibular schwannoma (VS). This study pertains to 108 VS patients who had GKRS in the years 2003 through 2007. Two different QOL questionnaires were used: medical outcome study short form 36 (SF36) and Glasgow benefit inventory (GBI). Radiosurgery was performed using a Leksell 4C gamma knife. The results of the QOL questionnaires in relation to prospectively and retrospectively gathered data of the VS patients treated by GKRS. Eventually, 97 patients could be included in the study. Their mean tumor size was 17 mm (range 6-39 mm); the mean maximum dose on the tumor was 19.9 Gy (range 16-25.5 Gy) and the mean marginal dose on the tumor was 11.1 (range 9.3-12.5 Gy). SF36 scores showed results comparable to those for a normal Dutch population. GBI showed a marginal decline in QOL. No correlation was found between QOL and gender, age, tumor size, or radiation dose. Increased audiovestibular symptoms after GKRS were correlated with a decreased GBI score, and decreased symptoms were correlated with a higher QOL post-GKRS. In this study shows that GKRS for VS has little impact on the general QOL of the VS patient. However, there is a wide range in individual QOL results. Individual QOL was influenced by the audiovestibular symptoms. No predictive patient, tumor, or treatment factors for QOL outcome after GKRS could be determined. Comparison with microsurgery is difficult because of intra group variability. 01 juni 2010

Object The aim of this study was to analyze factors influencing survival time and patterns of distant recurrences after Gamma Knife surgery (GKS) for metastases to the brain. Methods Information was available for 1855 of 1921 patients who underwent GKS for single or multiple cerebral metastases at 4 different institutions during different time periods between 1975 and 2007. The total number of Gamma Knife treatments administered was 2448, an average of 1.32 treatments per patient. The median survival time was analyzed, related to patient and treatment parameters, and compared with published data following conventional fractionated whole-brain irradiation. Results Twenty-five patients survived for longer than 10 years after GKS, and 23 are still alive. Age and primary tumor control were strongly related to survival time. Patients with single metastases had a longer survival than those with multiple metastases, but there was no difference in survival between patients with single and multiple metastases who had controlled primary disease. There were no significant differences in median survival time between patients with 2, 3–4, 5–8, or > 8 metastases. The 5-year survival rate was 6% for the whole patient population, and 9% for patients with controlled primary disease. New hematogenous spread was a more significant problem than micrometastases in patients with longer survival. Conclusions Patient age and primary tumor control are more important factors in predicting median survival time than number of metastases to the brain. Long-term survivors are more common than previously assumed.

OBJECTIVES/HYPOTHESIS: This study was designed to evaluate hearing preservation after gamma knife radiosurgery (GKRS) and to determine the relation between hearing preservation and cochlear radiation dose in patients with a sporadic vestibular schwannoma (VS). METHODS: Prospective study involving patients suffering from VS who received GKRS from June 2003 until November 2007. Pure tone and speech audiometry were conducted before and after GKRS. The thresholds at pure tone audiometry were taken as a measure of hearing. Pure tone average (PTA) was defined as the mean threshold at 0.5 kHz, 1.0 kHz, 2.0 kHz, and 4.0 kHz. Hearing was classified according to the 2003 consensus meeting in Tokyo. Stereotactic surgery was performed using a Leksell 4C Gamma Knife (Elekta, Stockholm, Sweden). RESULTS: A total of 69 patients were included in the study. Mean tumor size was 17 mm. Mean marginal dose at the tumor was 11.0 Gy (range, 9.3 Gy-12.3 Gy), mean maximal dose was 19.7 Gy (range, 16 Gy-25.5 Gy). Mean maximal dose at the cochlea was 10.27 Gy (range, 3.1 Gy-16.1 Gy), and mean minimal dose at the cochlea was 2.6 Gy (range, 0.9 Gy-7.4 Gy). Mean PTA before GKRS was 43 dB (standard deviation [SD] 20 dB), mean PTA after GKRS was 63 dB (SD 30 dB). Mean interval between pre-GKRS audiometry and GKRS was 8.0 months. Between GKRS and post-GKRS audiometry, mean interval was 14.2 months. Hearing was considered to be preserved (max +1 class, Tokyo classification) in 52 (75%) of 69 patients. However, only 32 patients had class A, B, or C (serviceable hearing) before GKRS. Within this group, only 13 patients (41%) had a hearing class A, B, or C after GKRS. A significant relation was found between the maximal cochlear dose and the difference in PTA before and after GKRS. CONCLUSIONS: Hearing preservation is correlated to the maximal radiation dose at the cochlea. The purpose of developing GKRS techniques was to avoid collateral damage in healthy tissues. This study emphasizes the need for exact radiation planning to reduce the cochlear radiation dose if the hearing is to be preserved. Laryngoscope, 2009.

The aim of this study was to assess the outcome in patients with cerebellar glioblastoma (GBM) treated in 15 institutions of the Rare Cancer Network.Data from a series of 45 adult patients with cerebellar GBM were collected in a retrospective multicenter study. Median age was 50.3 years. Brainstem invasion was observed in 9 (20%) patients. Radiotherapy (RT) was administered to 36 patients (with concomitant chemotherapy, 7 patients). Adjuvant chemotherapy after RT was administered in 8 patients. Median RT dose was 59.4 Gy. Median follow-up was 7.2 months (range, 3.4-39.0).The 1-year and 2-year actuarial overall survival rate was 37.8% and 14.7%, respectively, and was significantly influenced by salvage treatment (p = 0.048), tumor volume (p = 0.044), extent of neurosurgical resection (p = 0.019), brainstem invasion (p = 0.0013), additional treatment after surgery (p0.001), and completion of the initial treatment (p0.001) on univariate analysis. All patients experienced local progression: 8 and 22 had progression with and without a distant failure, respectively. The 1- and 2-year actuarial progression free survival was 25% and 10.7%, respectively, and was significantly influenced by brainstem invasion (p = 0.002), additional treatment after surgery (p = 0.0016), and completion of the initial treatment (p0.001). On multivariate analysis, survival was negatively influenced by the extent of surgery (p = 0.03) and brainstem invasion (p = 0.02).In this multicenter retrospective study, the observed pattern of failure was local in all cases, but approximately 1 patient of 4 presented with an extracerebellar component. Brainstem invasion was observed in a substantial number of patients and was an adverse prognostic factor.

BACKGROUND. The objective of this study was to evaluate the palliative effect of reirradiation and hyperthermia in patients with unresectable, recurrent colorectal carcinoma. METHODS. The medical records of 54 patients with unresectable, recurrent colorectal carcinoma that caused pain and who were treated with reirradiation and hyperthermia, were evaluated retrospectively. Previous radiotherapy was given up to a total dose ranging from 25-70 grays (Gy). The median interval between prior radiotherapy and reirradiation was 22 months (range, 4-97 months). The total reirradiation dose varied from 24 Gy to 32 Gy given in fractions of 4 Gy twice weekly. Three or four hyperthermia treatments were given once weekly. Toxicity was registered. The influence of World Health Organization (WHO) performance status, maximum tumor dimension, and time between first radiotherapy and reirradiation on therapeutic outcome was evaluated. The results of this study were compared with published results on patients who received radiotherapy with or without hyperthermia. RESULTS. Forty-seven patients (87%) completed the planned treatment schedule. The maximum toxicity was Grade 2. All patients were evaluated for palliative effect. The median follow-up was 10 months. A good or complete palliative effect was achieved in 72% of patients for a median duration of 6 months. Patients who had a better WHO performance status, smaller tumors, and a longer interval between first radiotherapy and reirradiation had slightly better outcomes, although none of those parameters reached statistical significance. CONCLUSIONS. The described combined treatment was feasible and well tolerated. Comparison of results from radiotherapy plus hyperthermia with results after radiotherapy alone suggested that additional hyperthermia prolonged the duration of palliation. Firm proof of the contribution of hyperthermia will require performing a Phase III study.

Since the time of its inception within neurosurgery, the practice of radiosurgery has grown and evolved with the introduction of new technologies and the involvement of other disciplines. Currently, radiosurgery practices involve neurosurgery, radiation oncology, medical physics and, in many centers, neuroradiology. Various commercially available radiosurgical devices are used, including the conventional linear accelerator, CyberKnife, Gamma Knife, and even particle therapy units. The historical roots of each radiosurgery practice affect the terminology and procedures applied for treatment planning and delivery, resulting in wide variability in image acquisition, planning, and verification practices across the community. This organic development has led to a “confusion of tongues,” challenging our ability to interpret the published scientific literature in a meaningful way and hindering the radiosurgery community’s ability to collaborate effectively to advance the science and practice of radiosurgery. The broader radiation therapy literature contains a growing body of evidence that the quality of radiation delivery has a significant impact on clinical outcomes. This was highlighted in a secondary report of a large multicenter phase 3 trial of head and neck cancer, which showed

BACKGROUND: The dural tail (DT) has been described as a common feature in meningiomas. There is a great variation of tumor invasion and extent of tumor cells in the DT. Therefore, the necessity to include the whole DT in Gamma Knife radiosurgery is not clear, since inclusion increases the target volume and therefore increases the risk of complications. In this analysis, we evaluated whether the complete tail should be included as part of the target in Gamma Knife radiosurgery for meningiomas.METHODS: Between June 2002 and December 2010, Gamma Knife radiosurgery was performed in 160 patients with 203 meningiomas with a DT. In 105 tumors, the diagnosis was based on magnetic resonance imaging (MRI) characteristics, and in 98 tumors, the diagnosis was confirmed by histopathologic examination after surgery. The median volume of the tumors was 3.55 cc. All tumors were treated with Gamma Knife radiosurgery with a median prescribed dose of 13 Gy (range 11-15), resulting in a median marginal dose of 11 Gy (range 10-15). Only the part of the DT closely related to the tumor mass was included in the target. The median follow-up period was 41 months (range 12-123).RESULTS: In image-based meningiomas, the overall local control rate was 96.2% with 2- and 5-year control rates of 98.0% and 95.1%, respectively. In WHO grade I tumors, the overall local control rate was 85.9% with 2- and 5-year control rates of 94.5% and 88.0%, respectively. The overall local control rate in World Health Organization (WHO) grade II tumors was 70.6% with control rates of 83.4% and 64.4% after 2 and 5 years, respectively. The growth of all new tumors was found in the radiation target area. No tumor growth was observed in the part of the DT that had been excluded from the target volume.CONCLUSION: We found in this study that routinely excluding the DT from the target does not lead to out-of-field tumor progression. Given the possibility that the DT is infiltrated with tumor cells, regular follow-up is needed.

PURPOSE: The purpose of this study was to present a technique of abdominosacral resection and its results in patients with locally advanced primary or locally recurrent rectal cancer with dorsolateral fixation. METHODS: Between 1994 and 1999, 13 patients with locally advanced primary rectal cancer and 37 patients with locally recurrent rectal cancer underwent abdominosacral resection as part of a multimodality treatment,i.e., preoperative irradiation, surgery, and intraoperative irradiation. After the abdominal phase, the patient was turned from supine to prone position to perform the transsacral phase of the resection. RESULTS: Margins were microscopically negative in 26 patients (52 percent), microscopically positive in 18 (36 percent), and positive with gross residual disease in 6 patients. Operation time ranged from 210 to 590 (median, 390) minutes, and blood loss ranged from 400 to 10,000 (median, 3,500) ml. No operative or hospital deaths occurred. Postoperative complications occurred in 41 patients (82 percent); most notable were perineal wound infections or dehiscence (n=24, 48 percent). Other complications were postoperative urinary retention or incontinence (n=9, 18 percent), peritonitis (n=4), grade II neuropathy (n=1), and fistula formation (n=3). Kaplan-Meier 3-year overall survival, disease-free survival, and local control rates were, respectively, 41 percent, 31 percent, and 61 percent. Completeness of the resection (negativevs. positive margins) was a significant factor influencing survival (P=0.04), diseasefree survival (P=0.0006), and local control (P=0.0002). CONCLUSION: The abdominosacral resection provides wide access and may be the therapeutic solution for the accomplishment of a radical resection for distally situated, dorsally or dorsolaterally fixed primary or locally recurrent rectal cancers.

Neoplastic meningosis can be a complication of a tumor originating in the brain or the meninges, or it can be a complication of a solid tumor elsewhere that has metastasized to the leptomeninges. The therapeutic dilemma for a radiation oncologist is that neoplastic meningosis involves the entire neuraxis and, as a consequence, ideally, the entire neuraxis should be radiated. However, delivering the necessary radiation dose to the entire neuraxis may be associated with considerable neurologic or bone marrow toxicity. Radiotherapy of neoplastic meningosis can be performed by external beam radiation or by intrathecal injection of radioactive nuclides or radiolabeled monoclonal antibodies. Intrathecal radiation has the theoretical advantage that treatment is directed towards the entire neuraxis with limited irradiation outside the neuraxis. In practice, intrathecal radiation is still under investigation and subject to some limitations and toxicities. Indications and techniques for external beam radiation may range from either therapeutic or elective cranial or craniospinal radiation to palliative involved-field radiation. Patients with neoplastic meningosis are frequently treated with a combination of radiation and chemotherapy, and/or may have been irradiated to the nervous system in the past. Both are well known risk factors for radiation damage to the nervous system. In general, current treatment protocols focus on the development of combination chemotherapy programs and reduction of the radiation dose to minimize toxicity and/or to improve tumor control.

Purpose: To evaluate the results of transurethral resection (TUR), external beam radiotherapy (EBRT), and interstitial radiation (IRT) with iridium-192, using the afterloading technique in patients with muscle invasive bladder cancer. Methods and Materials: From May 1989 until September 1995, 66 patients with primary, solitary muscle invasive bladder cancer were treated with TUR, EBRT, and IRT, aiming at bladder preservation. According to the protocol, in three patients low-dose EBRT was applied, whereas 63 patients received high-dose EBRT. Immediately prior to IRT, 42 patients underwent a lymphnode dissection, and in 16 cases a partial cystectomy was performed. For IRT, two to five catheters were used and IRT was started within 24 h after surgery. The majority of patients received 30 Gy of IRT, with a mean dose rate of.58 Gy/h. In three patients, additional EBRT was applied following IRT. Follow-up consisted of regular cystoscopies, mostly done during joint clinics of urologist and radiation oncologist, with urine cytology routinely performed. The median follow-up period was 26 months. The Kaplan-Meier method was used for the determination of survival rates. Results: In seven patients, a bladder relapse developed. The probability of remaining bladder relapse free at 5 years was 88%. The bladder was preserved in 98% of the surviving patients. Metastases developed in 16 patients, and the probability of remaining metastasis free at 5 years was 66%. The cumulative 5-year overall and bladder and distant relapse free survival were 48% and 69%, respectively. Acute toxicity was not serious in the majority of cases; surgical correction of a persisting vesicocutaneous fistula was necessary in two patients, whereas a wound toilet had to be performed in another patient. Serious late toxicity (bladder, RTOG Grade 3) was experienced by only one patient. Conclusions: Interstitial radiation preceded by TUR and EBRT, in a selected group of patients with muscle invasive bladder cancer, yields an excellent bladder tumor control rate with a high probability of bladder preservation. Survival was mainly dependent on the development of distant metastases. Serious acute and late toxicity was rare.

The aim of the study was to analyze the results following salvage Gamma Knife® surgery (GKS) for distant recurrent brain metastases in patients previously treated with GKS for brain metastases.Survival time and freedom from new distant recurrences (DR) were studied in 251 patients treated with salvage GKS for brain metastases that had developed following a first GKS. The patients were followed prospectively and the results related to a number of patient parameters as well as the results following the first GKS.The median survival time was 9.6 months, and the median time of freedom from developing DR was 7.5 months after salvage GKS. The survival time was unrelated to age, gender, prior WBRT, and primary disease. It was significantly longer in patients with a single DR at salvage GKS as compared to those with multiple ones (16 versus 8.3 months). Patients with 2-4 DRs lived longer than those with4 lesions, 10 versus 5.8 months. The survival was significantly longer following salvage GKS as compared to following the first GKS. The prognosis of a patient with DR may therefore be less ominous than previously assumed. A classification system for DRs based on their clinical impact and treatability is therefore suggested.The longer survival time following salvage GKS as compared to following the first GKS suggests that many patients benefit from salvage GKS. A classification system of DR is suggested to estimate its clinical impact.

Object The aim of this study was to assess the order of micrometastases that can be detected with high-resolution MR imaging at the time of Gamma Knife surgery (GKS), and to estimate the impact this has on the time until and incidence of distant recurrences. Methods A consecutive series of 835 patients with brain metastases treated with GKS in a 7-year period, excluding patients in whom earlier brain metastases were treated with other modalities, were retrospectively analyzed. In all patients GKS was based on high Gd–dose (0.3 mmol/kg), high-resolution stereotactic MR imaging. These images were compared with the standard pretreatment MR images, and the difference in number of metastases found was analyzed. The distant recurrence rate following GKS was compared with that found in a prospective randomized study (Aoyama et al.) comparing radiosurgery to radiosurgery plus prophylactic whole-brain radiation therapy. Results New tumors were diagnosed in 40% (95% CI 36%–43%) of all patients as well as in the majority of patients with multiple lesions found on the diagnostic scan. The more tumors there were on the diagnostic scan, the higher the likelihood of detecting additional lesions with high-resolution imaging. It was calculated that approximately 50% of the micrometastases present at the time of GKS could be diagnosed with high-resolution imaging, which decreased the incidence of and delayed the time for the development of distant recurrences. Conclusions Additional brain metastases can be diagnosed in 40% of patients by using high-resolution imaging. Thus, radiosurgical treatments based on high-resolution stereotactic MR imaging decrease the incidence of and lengthen the time to distant recurrences.

Gamma knife radiosurgery (GKRS) has become an important treatment modality for vestibular schwannomas. The primary aim of this study was to investigate whether tumor growth at the moment of GKRS has any correlation with the outcome. The secondary aim was to identify clinical predictors of radioresistance in vestibular schwannoma patients treated with GKRS.One hundred vestibular schwannoma patients, treated with GKRS, were divided into two groups: 1) proven tumor growth preceding GKRS; and 2) previous history of growth unknown. GKRS outcome was defined in two ways. According to the first definition, GKRS was said to have failed when additional treatment had taken place. According to the second one, a volume decrease20% after 2 years marked successful treatment.Correlations between outcome and growth status were determined with SPSS software. Furthermore, the study assessed how different variables (patient data, history, tumor characteristics, imaging, and audiovestibular examinations) correlated with the outcome of GKRS.No significant difference regarding success and failure of GKRS was found between the two patient groups. The mean reduction in tumor volume after GKRS was less pronounced in patients in whom tumor growth was demonstrated before treatment, but this finding was not significant. No significant predictors (P.05) could be identified in this data set.This study found no indication that growth at the moment of GKRS influences therapeutic outcome, nor did it identify any predictors of the outcome after GKRS in vestibular schwannoma patients.

Item does not contain fulltext Different planning and treatment systems for intracranial stereotactic radiosurgery available in the Netherlands are compared. The systems for intracranial radiosurgery include: Gamma Knife, Cyberknife, Novalis, and Tomotherapy. Electronic data of 5 patients was transferred to all participating centres and treatment plans were generated according to 2 different prescription protocols. For this study, plans were also generated for a conventional linac. Even systems with a high resolution (Gammaknife and Novalis) have conformity indices in violation with RTOG guidelines (CI > 2.5) when target volumes of 1 cc), all systems perform well. The workload of the different techniques was comparable although the treatment times were usually longer for Gamma Knife radiosurgery. We conclude that small targets should be treated by dedicated systems, larger volumes (> 0.5-1 cc) can also be treated using conventional treatment systems equipped with a MLC. 01 juni 2010

This study was designed to evaluate hearing preservation after gamma knife radiosurgery (GKRS) and to determine the relation between hearing preservation and cochlear radiation dose in patients with a sporadic vestibular schwannoma (VS).Prospective study involving patients suffering from VS who received GKRS from June 2003 until November 2007. Pure tone and speech audiometry were conducted before and after GKRS. The thresholds at pure tone audiometry were taken as a measure of hearing. Pure tone average (PTA) was defined as the mean threshold at 0.5 kHz, 1.0 kHz, 2.0 kHz, and 4.0 kHz. Hearing was classified according to the 2003 consensus meeting in Tokyo. Stereotactic surgery was performed using a Leksell 4C Gamma Knife (Elekta, Stockholm, Sweden).A total of 69 patients were included in the study. Mean tumor size was 17 mm. Mean marginal dose at the tumor was 11.0 Gy (range, 9.3 Gy-12.3 Gy), mean maximal dose was 19.7 Gy (range, 16 Gy-25.5 Gy). Mean maximal dose at the cochlea was 10.27 Gy (range, 3.1 Gy-16.1 Gy), and mean minimal dose at the cochlea was 2.6 Gy (range, 0.9 Gy-7.4 Gy). Mean PTA before GKRS was 43 dB (standard deviation [SD] 20 dB), mean PTA after GKRS was 63 dB (SD 30 dB). Mean interval between pre-GKRS audiometry and GKRS was 8.0 months. Between GKRS and post-GKRS audiometry, mean interval was 14.2 months. Hearing was considered to be preserved (max +1 class, Tokyo classification) in 52 (75%) of 69 patients. However, only 32 patients had class A, B, or C (serviceable hearing) before GKRS. Within this group, only 13 patients (41%) had a hearing class A, B, or C after GKRS. A significant relation was found between the maximal cochlear dose and the difference in PTA before and after GKRS.Hearing preservation is correlated to the maximal radiation dose at the cochlea. The purpose of developing GKRS techniques was to avoid collateral damage in healthy tissues. This study emphasizes the need for exact radiation planning to reduce the cochlear radiation dose if the hearing is to be preserved. Laryngoscope, 2009.