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Background EORTC study 22033–26033 showed no difference in progression-free survival between high-risk low-grade glioma receiving either radiotherapy (RT) or temozolomide (TMZ) chemotherapy alone as primary treatment. Considering the potential long-term deleterious impact of RT on memory functioning, this study aims to determine whether TMZ is associated with less impaired memory functioning. Methods Using the Visual Verbal Learning Test (VVLT), memory functioning was evaluated at baseline and subsequently every 6 months. Minimal compliance for statistical analyses was set at 60%. Conventional indices of memory performance (VVLT Immediate Recall, Total Recall, Learning Capacity, and Delayed Recall) were used as outcome measures. Using a mixed linear model, memory functioning was compared between treatment arms and over time. Results Neuropsychological assessment was performed in 98 patients (53 RT, 46 TMZ). At 12 months, compliance had dropped to 66%, restricting analyses to baseline, 6 months, and 12 months. At baseline, patients in either treatment arm did not differ in memory functioning, sex, age, or educational level. Over time, patients in both arms showed improvement in Immediate Recall (P = 0.017) and total number of words recalled (Total Recall; P < 0.001, albeit with delayed improvement in RT patients (group by time; P = 0.011). Memory functioning was not associated with RT gross, clinical, or planned target volumes. Conclusion In patients with high-risk low-grade glioma there is no indication that in the first year after treatment, RT has a deleterious effect on memory function compared with TMZ chemotherapy.

Conventional magnetic resonance imaging (MRI) is unable to differentiate tumor/nontumor enhancing tissues. We have applied delayed-contrast MRI for calculating high resolution treatment response assessment maps (TRAMs) clearly differentiating tumor/nontumor tissues in brain tumor patients.One hundred and fifty patients with primary/metastatic tumors were recruited and scanned by delayed-contrast MRI and perfusion MRI. Of those, 47 patients underwent resection during their participation in the study. Region of interest/threshold analysis was performed on the TRAMs and on relative cerebral blood volume maps, and correlation with histology was studied. Relative cerebral blood volume was also assessed by the study neuroradiologist.Histological validation confirmed that regions of contrast agent clearance in the TRAMs1 h post contrast injection represent active tumor, while regions of contrast accumulation represent nontumor tissues with 100% sensitivity and 92% positive predictive value to active tumor. Significant correlation was found between tumor burden in the TRAMs and histology in a subgroup of lesions resected en bloc (r(2) = 0.90, P.0001). Relative cerebral blood volume yielded sensitivity/positive predictive values of 51%/96% and there was no correlation with tumor burden. The feasibility of applying the TRAMs for differentiating progression from treatment effects, depicting tumor within hemorrhages, and detecting residual tumor postsurgery is demonstrated.The TRAMs present a novel model-independent approach providing efficient separation between tumor/nontumor tissues by adding a short MRI scan1 h post contrast injection. The methodology uses robust acquisition sequences, providing high resolution and easy to interpret maps with minimal sensitivity to susceptibility artifacts. The presented results provide histological validation of the TRAMs and demonstrate their potential contribution to the management of brain tumor patients.

BACKGROUND: It is currently unknown whether increasing radiotherapy volumes have a negative impact on the health-related quality of life (HRQoL) of low-grade glioma (LGG) patients on the short-term. The aim of this study was to examine if the size of the target volume is independently associated with HRQoL. MATERIAL AND METHODS: Patients treated with radiotherapy in the European Organisation for Research and Treatment of Cancer (EORTC) 22033–26033 study, and who completed a baseline HRQoL form, were included. This phase 3 trial of radiotherapy vs. temozolomide chemotherapy in high-risk LGG requiring treatment did not show a progression free survival difference. HRQoL was measured at baseline and every 3 months thereafter until progression, using the EORTC QLQ-C30 core questionnaire and QLQ-BN20 brain module. Associations between radiation volumes and (changes in) four preselected HRQoL scales (global health status, cognitive and social functioning, and fatigue) were determined. Also, it was determined if radiation volumes were independently associated with a change in HRQoL over time. RESULTS: A total of 195 out of the 240 patients randomized to radiotherapy (81.3%) were included in this analysis. The brain volume receiving radiotherapy was not associated with (changes in) HRQoL during the first 24 months after radiotherapy. Over time, radiation volumes were also not independently associated with HRQoL. Although treatment with radiotherapy resulted in worse functioning, and more fatigue three months after treatment, pre-treatment levels were reached thereafter and maintained during further follow-up. Particularly the occurrence of tumour progression was found to be associated with clinically relevant worse social functioning (Beta: -13.7, 95% CI:-19.5 to -7.9), and more fatigue (Beta: 13.2, 95% CI:7.8–18.5) during 24 months follow-up. CONCLUSION: The volume of brain receiving focal radiotherapy does not seem to be an important determinant for the level of HRQoL in high-risk LGG patients on the short-term. From this point of view, safety margins do not need to be reconsidered. However, the impact of radiation volumes on long-term HRQoL, as well as neurocognitive functioning, remains to be investigated.

BACKGROUND: TTFields are low intensity, intermediate frequency alternating electric fields, delivered through a portable, non-invasive device (Optune, Novocure(TM)). The EF-14 phase III trial showed significant prolongation of both progression-free and overall survival in newly diagnosed glioblastoma (GBM) patients. This is the first report on clinical experience with 110 patients treated with TTFields in Israel, focusing on safety and patient acceptance in our country. METHODS: Patients received Optune-prescription in 6 neuro-oncology centers in Israel and used the device for at least one month. The cohort included both newly diagnosed (n=53) and recurrent GBM (rGBM, n=57) patients. The male/female ratio was 74/36 with a median age of 58.0 (18–82) years at start of treatment. Of patients with rGBM, 51% were treated at first progression. RESULTS: Our data shows a high acceptance, with a compliance rate (monthly usage of the device) within the first 3 months of 80% for newly diagnosed GBM and 66% for rGBM. Median treatment compliance was independent of age, sex and stage of disease. In addition, our data indicates that the compliance is not negatively correlated with time on treatment, as the median compliance for newly diagnosed GBM patients was still at 79% within the first 6 months. With regards to device-related side effects, data shows that in total 30 patients (27%) experienced mild-moderate skin irritations that were usually manageable with local steroid creams and did not cause significant treatment breaks despite the warm climate in Israel. Other side effects related to the device were heat sensation in 10 patients (9%) and electric sensation in 9 patients (8%) that did not cause significant treatment interruption. CONCLUSIONS: The accumulating clinical experience shows that TTFields are well-tolerated by patients in Israel without any major deviation from reported treatment-related side effects. Treatment compliance remains stable during a 6-month period.

BACKGROUND: TTFields are low intensity, intermediate frequency alternating electric fields, delivered through a portable, non-invasive device (Optune, Novocure(TM)). The EF-14 phase III trial showed significant prolongation of both progression-free and overall survival in newly diagnosed glioblastoma (GBM) patients. This is the first report on clinical experience with 110 patients treated with TTFields in Israel, focusing on safety and patient acceptance in our country. MATERIAL AND METHODS: Patients received Optune-prescription in 6 neuro-oncology centers in Israel and used the device for at least one month. The cohort included both newly diagnosed (n=53) and recurrent GBM (n=57) patients. The male/female ratio was 74/36 with a median age of 58.0 (18–82) years at start of treatment. Of patients with recurrent GBM, 51% were treated at first progression. RESULTS: Our data shows a high acceptance, with a compliance rate (monthly usage of the device) within the first 3 months of 80% for newly diagnosed GBM and 66% for recurrent GBM. Median treatment compliance was independent of age, sex and stage of disease. In addition, our data indicates that the compliance is not negatively correlated with time on treatment, as the median compliance for newly diagnosed GBM patients was still at 79% within the first 6 months. With regards to device-related side effects, data shows that in total 30 patients (27%) experienced mild-moderate skin irritations that were usually manageable with local steroid creams and did not cause significant treatment breaks despite the warm climate in Israel. Other side effects related to the device were heat sensation in 10 patients (9%) and electric sensation in 9 patients (8%) that did not cause significant treatment interruption. CONCLUSION: The accumulating clinical experience shows that TTFields are well-tolerated by patients in Israel without any major deviation from reported treatment-related side effects. Treatment compliance remains stable during a 6-month period.

INTRODUCTION: Data from trials suggest that GBMs adjacent to the subventricular zone and associated with ependymal enhancement on MRI, have a more aggressive and multifocal phenotype which render the patient to a shorter overall survival (OS). The aim of the current study was to re-assess whether ependymal enhancement is associated with a worse outcome. METHODS: After institutional review board approval, a retrospective review of all patients who were treated for GBM in our institution from 2005 to 2011 was conducted. Only patients in whom the pretreatment MRI was available were included in our study. Data extracted from the medical records included age, date of diagnosis, co-morbidities, performance status at time of the first visit prior to initiating treatment, treatment regimen and time of death. All MRI imaging were blindly reviewed by one of the investigators, and were evaluated for distance from the subventricular zone, ependymal enhancement and pial enhancement. The groups were divided according to ependymal enhancement and data extracted was evaluated for association with survival. RESULTS: Between 2005 and 2011, 230 patients were treated at our center. Sixty five patients were excluded from the study due to insufficient data. Sixty seven patients (40.6%) had evidence of ependymal enhancement on MRI (group A). Seventy patients (42.4%) did not have evidence of enhancement (group B). In 28 patients (17%) the imaging was inconclusive, due to involvement of the temporal horn, therefore defined as group C. Median survival of all groups was 15.3 months (range 13.6 to 16.95). Median survival according to ependymal enhancement was 14 months for group A (range 12 to 16), 15.9 months group B (range 14.28 to 17.65) and 11.7 months for group C (range 6.47 to 16.92 ) (P > 0.05). Age