An ageing population brings new challenges for oncologists in the management of older cancer patients. There is increasing use of a geriatric assessment (GA) to evaluate fitness for treatment and identify geriatric syndromes. GAs can predict for chemotherapy toxicity and overall survival however there is a paucity of data within the neuro oncology cohort. A criticism of GAs is that they are time and resource consuming. We conducted a feasibility study to assess whether a GA could be performed by members of the usual clinical staff in a UK NHS neuro oncology outpatient setting. Patients aged ≥ 65 with a new diagnosis of GBM were prospectively recruited from neuro-oncology outpatient clinics across 3 UK centres. A modified GA was performed by the clinical nurse specialists and demographic, imaging and toxicity data collected. Feasibility was assessed primarily by recruitment rate. Secondary outcomes of completion rate, acceptability to staff and patients and overall survival were measured. After completion of the study, face to face semi-structured interviews with the nurses were performed; these were interpreted qualitatively using thematic analysis. Recruitment to the study completed within the 1 year study time. 22 women and 28 men were enrolled with a mean age of 71 (65–86). Median overall survival was 8.2 months. 41 patients received active treatment (17 palliative radiotherapy, 19 chemo radiation and 5 temozolomide alone). Of the 35 patients who were tested, 31% showed MGMT promoter methylation; no IDH mutations were detected. All centres achieved recruitment rates above the target of 80% (mean 92%, 95% CI 86%-96%). Mean assessment completion rate was 94% (95% CI 92–95%). The nurses reported that completing the assessment was manageable and that, in some cases, underlying patient factors were identified that led to changes in treatment plans. Univariable regression analysis showed the MoCA (HR 2.78, p=0.02), IADLs (HR 2.88, p=0.03), baseline mobility (HR 12.1 p=0.002), ECOG PS (HR 29.2 p=0.003) and level of anxiety (HR 3.5 p=0.001) were related to overall survival, alongside treatment received. Multivariate Cox regression modelling confirmed the MoCA score to be a significant independent predictive factor for overall survival. ASCO and SIOG promote the use of a GA in the management of older cancer patients and it is becoming widely used within other tumour groups. However, to the authors’ knowledge, this is the first study of a GA within the neuro oncology patient cohort, a group with its own particular symptom burden. We have shown that performing a GA is feasible within the confines of a busy UK outpatient clinic and that, within the accepted limits of the study size, the results can help predict overall survival irrespective of treatment received. Wider use of a neurologically focussed GA should now be explored with greater patient numbers.

INTRODUCTION: Based on imaging features, glioblastoma (GBM) can be classified as solitary, multifocal or multicentric. The incidence of multifocal/multicentric GBM has been reported to range from 0.5 to 35% and some studies have reported poorer survival in patients with multiple lesions. Two potential reasons have been proposed: (1) intrinsic differences in tumour biology; (2) failure to encompass the entire tumour within the radiotherapy planning tumour volume. To address this question we investigated clinical, imaging and genetic features in a cohort of GBM patients. METHODS: Imaging, clinical, treatment, MGMT methylation and outcome data were collected retrospectively from consecutive GBM patients treated in a single cancer centre between January 2011 and June 2012. Tumours were categorised as solitary, multifocal or multicentric by a consultant neuroradiologist. RESULTS: 122 patents with GBM were identified. Median age was 60 and male:female ratio was 2.1:1. MGMT promoter status was unmethylated in 48% of tumours, methylated in 37% and unknown in 15%. Preoperative imaging modality was CT in 70% and MRI in 30% of patients. Overall, the proportion of patients with solitary, multifocal and multicentric tumours was 78%, 15.5% and 6.5 % respectively, but in patients undergoing MR imaging these proportions were 60%, 26.5% and 13.5%. Gross total resection was performed in 65% of solitary compared with 42% of multifocal and 25% of multicentric cases, and radical chemoradiation was delivered to 50% of solitary, 58% of multifocal and 12% of multicentric cases. Overall, median survival was increased in solitary compared with multifocal/multicentric patients (9.9 vs. 6.7 months, p = 0.046). In patients receiving radical chemoradiation, however, there was no difference in overall survival between solitary and multifocal/multicentric patients (18.5 vs. 16.8 months, p=0.57). MGMT promoter methylation was associated with increased survival in patients with solitary tumours (14.6 vs. 8.5 months, p= 0.014) but not multifocal/multicentric tumours (3.8 vs. 6.9 months, p= 0.3). CONCLUSION: In this retrospective study the incidence of multifocal/multicentric GBM was in line with previous studies. Pre-operative CT imaging may underestimate the incidence of multifocal/multicentric disease. Our main finding was that multifocality or multicentricity did not affect survival in patients to whom radical chemo-radiotherapy could be delivered.

OBJECTIVE: To evaluate the impact of re-irradiation on performance status and survival in patients with recurrent glioma. METHOD: A retrospective analysis was performed on 14 patients who received re-irradiation for recurrent glioma from Dec 2013 to Feb 2015. The GTV was defined as the contrast-enhancing lesion on T1-weighted MRI. No CTV was defined. Median GTV- PTV margin was 1.25cm (range 0.7 - 2.1). All patients received VMAT, 2 non co-planar arcs. The dose delivered was 30Gy in 5 fractions. Performance status and corticosteroid dosages had been recorded prospectively for all patients. A cohort of 22 recurrent glioma patients were identified in the 5 months prior to Dec 2013. This group did not receive reirradiation. Overall survival from initial diagnosis was calculated using the Kaplan-Meier method using SPSS. RESULTS: REIRRRADIATION COHORT: Median age was 49 (range 22-59). At initial diagnosis, 5 patients had glioblastoma (GBM), 2 WHO grade II astrocytoma and 7 WHO Grade II oligodendroglioma. All low grade (LGG) patients had radiological evidence of transformation to higher grade. All patients initially had surgical debulking followed by radiation to a median dose of 60Gy (range 54Gy-60Gy). At time of re-irradiation, patients had a mean KPS of 70% (range 60-90) and had progressed through at least one line of chemotherapy. Re-irradiation volumes overlapped previously irradiated fields in 14 patients. 1 week post XRT median KPS was 70% (range 60-90). 1 month post XRT median KPS was 90% (range 70-90). Median dexamethasone dose prescribed was 2mg pre-XRT (range 0-12), 4mg 1 week post XRT (range 0-8) and 4 mg 1 month post XRT (range 0-10). All patients completed treatment and no severe acute or late complications were observed. Progression free survival from the time of irradiation was 4.2 months (range 1-7) for GBM, 6.1 months (range 1 - 8) for LGG. Median survival from date of reirradiation was 8 months for GBM (range 5-11) and 11 months for LGG (range 5-18). Median overall survival from date of diagnosis for GBM was 34 months (range 26 - 46), and 126 months (range 49-192) for LGG. As a comparison, a similar cohort of patients aged <65, KPS >70% who had progressed through at least one line of chemotherapy after primary radiotherapy were identified from July 2013- Dec 2013. 12 were GBM patients: median survival from date of 2nd line treatment was 11 months (4-29) and median overall survival was 31 months (14-46). 10 LGG patients were identified with a median survival from date of 2nd line treatment of 12 months and median overall survival was 61.5 months (19-101). CONCLUSION: Re-irradiation is a safe and feasible treatment for recurrent glioma and the majority of patients experienced an improvement in performance status after treatment. However in this small, retrospective study there was no signal that reirradiation was associated with improved survival when compared with similar cohorts managed without reirradiation.

The Beatson West of Scotland Cancer Center (BWOSCC) has been treating brain metastasis using LINAC based stereotactic radiosurgery with micromultileaf collimator (Brain lab M3) since 2008. Patients are immobilised using Brainlab fixation and treated with static fixed fields (6MV photon), delivered at conventional dose rates of 400-600 monitor units per minute (MU/min). In August 2012 a TrueBeam STX (Varian Medical Systems) was installed. Patients with localised CNS lesions are now treated with 10MV FFF VMAT. METHOD: Treatment records for 10 for conformal static field patients and 10 VMAT FFF patients were reviewed on Varian Eclipse and Offline Review. Beam on time (BOT), time in room (TIR), and clinical dose rate (CDR) were compared. BOT (minutes:seconds) is the aggregate “beam-on” time for all fields or arcs in a given plan. TIR (minutes:seconds) is measured from the first alignment image to last beam off, inclusive of all pre-treatment imaging studies and/or shifts. CDR (MU/min) is the number of MU divided by the BOT.Static field patients had MV imaging only. VMAT patients had kV imaging and pre-treatment cone beam CT (CBCT). 18 patients had single metastasis, 2 patients had 2 mets. 11 patients were treated with 20Gy, 7: 18Gy and 2: 15Gy. RESULTS: Median Planning Target Volume was 5.41cm3 (min 0.98cm3 max 18.88cm3). 10 patients were treated with 6MV static fields (between 4 and 6 fields). 10 patients with 10MV FFF (All 10 Patients had 2 co-planar) arcs. Beam on time: 6X Static 5.85 (range 4.55-6.6), VMAT FFF 2.60 (range 2.01-3.9). Time In Room: 6X Static 34.17 (range 20.42-58.13) VMAT FFF 17.12 (range 12.42-28.28). Monitor Units: 6X Static 2726 (range 2119-3168) VMAT FFF 6216.5 (range 4472-9340). Clinical Dose Rate: 6X Static 600MU/Min VMAT FFF 2385.5MU/Min. CONCLUSION: VMAT FFF has dramatically reduced the TIR: shorter BOT reduces the likelihood of intrafraction motion. It is envisaged that VMAT FFF treatment times will be reduced further as Radiographer competency and skill increases. This is essential in busy RT departments where treatment slots are at a premium.

INTRODUCTION: The translocator protein (TSPO) is a 18 kDa mitochondrial molecule associated with neuroinflammation and over-expressed in several brain diseases. 11C-(R)PK11195 is a specific ligand of TSPO for PET studies. We investigated the in vivo TSPO expression in high- and low-grade gliomas using 11C-(R)PK11195 PET, and applied it in guiding tumour biopsies. METHOD: 24 patients underwent volumetric MRI and dynamic 11C-(R)PK11195 PET scans. Reference tissue input function was obtained from the grey matter of cerebellum to determine the 11C-(R)PK11195 uptake in the tumours and the mirrored regions of interest (ROIs) in the contralateral hemispheres. Co-registered MR/PET images were used to guide tumour biopsies prior to surgical debulking, with high and/or low 11C-(R)PK11195 uptake foci defined as biopsy targets. Biopsy specimens were assessed for TSPO expression by immunohistochemical staining. RESULTS: In low-grade gliomas (14 cases), 11C-(R)PK11195 uptake within the tumours was lower than the contralateral ROIs (p = 0.001); sporadic high uptake foci were found in 8 tumours. In high-grade gliomas, 7 out of the 10 tumours showed higher uptake than the contralateral ROIs (p = 0.016), 4 of which displayed intensive 11C-(R)PK11195 signal despite only minor contrast enhancement on the MRI. There was low 11C-(R)PK11195 uptake and no contrast enhancement in 3 anaplastic asctrocytomas. Immunostains on tissue sections confirmed variable TSPO expression in neoplastic cells and activated microglia/macrophages. CONCLUSION: TSPO expression is decreased in low-grade gliomas and increased in most high-grade gliomas. TSPO expression within gliomas is inhomogeneous as detected by 11C-(R)PK11195 PET and confirmed by immunohistochemistry.

Purpose There is a need for high-quality evidence regarding the frequency, independent clinical associations, and longitudinal course of depression in patients with cerebral glioma. Patients and Methods This was a twin-center, prospective, observational cohort study with 6-month follow-up. Consenting adults with a new diagnosis of cerebral glioma received the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition to diagnose major depressive disorder (MDD). Interviews occurred shortly after the start of radiotherapy (T1), with follow-up interviews 3 months later (T2) and 6 months later (T3). Independent associations between MDD and clinical variables were analyzed using logistic regression. Results One hundred fifty-five patients participated. The frequency of MDD was 13.5% ± 5.4% at T1 (n = 155); 14.8% ± 6.7% at T2 (n = 108); and 6.8% ± 5.3% at T3 (n = 88). Overall, 32 individuals were diagnosed with MDD during the study period (20.6% ± 6.4%). Inter-rater diagnostic agreement for MDD was good (κ = 0.81; 95% CI, 0.60 to 1.00). Independent predictors of MDD were functional impairment (odds ratio, 3.9; 95% CI, 1.5 to 10.8) and a previous history of depression (odds ratio, 2.7; 95% CI, 0.99 to 7.3). MDD persisted for at least 3 months in half of the patients with adequate follow-up, but many depressed patients also dropped out of the study as a result of clinical deterioration. Conclusion In this longitudinal study, one in five patients with glioma developed clinical depression in the 6 months after starting radiotherapy. Patients with functional impairment or previous depression were at higher risk. MDD often persisted for at least 3 months. Clinicians should seek and treat depression in adults with glioma.

INTRODUCTION: Substituted indoles and related structures have been shown to exhibit potent anticancer activity against breast cancer cell lines. Here, the effects of structurally similar substituted indoles against the human glial cancer cell lines, 1321N1 and U87MG, have been investigated by comparing the effects of these compounds to conventional anti cancer drugs. METHODS: Cell viability in the presence of the test compounds was measured using an MTS assay and corroborated by an ATP cell proliferation assay as well as a Trypan blue exclusion test. The significance of reactive oxygen species (ROS) in the process was determined using an Image-iT® LIVE ROS kit from Invitrogen. RESULTS: Both cell lines were treated with four commercial anticancer drugs and IC50 values were only reached at concentrations of 20 µM for cisplatin and 50 µM for gemcitabine over 48hrs on the 1321N1 cell line. However, the more malignant U87MG cell line was resistant to all the drugs, except for cisplatin where the IC50 value was reached at 300 µM after treatment for 48hrs. Similar studies were carried out with various substituted indoles and the cytotoxicity results on both cell lines showed that the IC50 value was reached within 90 minutes for the most potent compound at a concentration of 600 µM (1321N1) and 800 µM (U87MG). The idea that the mechanism of action of these compounds may work through the generation of ROS was investigated and this was confirmed over a similar time course using a suitable fluorogenic marker. Moreover, it was shown that the addition of an antioxidant (ascorbic acid) abolished the potency of the most active compound. CONCLUSION: Here, it has been demonstrated that certain substituted indoles are able to have a rapid, deleterious effect on the viability of two glioma cell lines and indicated that ROS generation may induce cell death.