Interaction between the Neuroprotective and Hyperglycemia Mitigation Effects of Walnut-Derived Peptide LVRL via the Wnt3a/ß-Catenin/GSK-3ß Pathway in a Type 2 Diabetes Mellitus Model.

The term type 3 diabetes mellitus (T3DM) has been considered for Alzheimer's disease (AD) due to the common molecular and cellular characteristics found between type 2 diabetes mellitus (T2DM) and cognitive deficits. However, the specific mechanism of T3DM remains elusive, especially the neuroprotective effects of dietary components in hyperglycemic individuals. In this study, a peptide, Leu-Val-Arg-Leu (LVRL), found in walnuts significantly improved memory decline in streptozotocin (STZ)- and high-fat-diet (HFD)-stimulated T2DM mouse models (p < 0.05). The LVRL peptide also mitigated hyperglycemia, enhanced synaptic plasticity, and ameliorated mitochondrial dysfunction, as demonstrated by Morris water maze tests, immunoblotting, immunofluorescence, immunohistochemistry, transmission electron microscopy, and cellular staining. A Wnt3a inhibitor, DKK1, was subsequently used to verify the possible role of the Wnt3a/ß-Catenin/GSK-3ß pathway in glucose-induced insulin resistance in PC12 cells. In vitro LVRL treatment dramatically modulated the protein expression of p-Tau (Ser404), Synapsin-1, and PSD95, elevated the insulin level, increased glucose consumption, and relieved the mitochondrial membrane potential, and MitoSOX (p < 0.05). These data suggested that peptides like LVRL could modulate the relationship between brain insulin and altered cognition status via the Wnt3a/ß-Catenin/GSK-3ß pathway.

Correction: Therapeutic effects of a walnut-derived peptide on NLRP3 inflammasome activation, synaptic plasticity, and cognitive dysfunction in T2DM mice.

Correction for 'Therapeutic effects of a walnut-derived peptide on NLRP3 inflammasome activation, synaptic plasticity, and cognitive dysfunction in T2DM mice' by Yanru Li et al., Food Funct., 2024, 15, 2295-2313, https://doi.org/10.1039/D3FO05076A.

Therapeutic effects of a walnut-derived peptide on NLRP3 inflammasome activation, synaptic plasticity, and cognitive dysfunction in T2DM mice.

NLRP3 inflammasome activation plays a key role in the development of diabetes-induced cognitive impairment. However, strategies to inhibit NLRP3 inflammasome activation remain elusive. Herein, we evaluated the impact of a walnut-derived peptide, TWLPLPR (TW-7), on cognitive impairment in high-fat diet/streptozotocin-induced type 2 diabetes mellitus (T2DM) mice and explored its underlying mechanisms in high glucose-induced HT-22 cells. In the Morris water maze test, TW-7 alleviated cognitive deficits in mice; this was confirmed at the level of synaptic structure and dendritic spine density in the mouse hippocampus using transmission electron microscopy and Golgi staining. TW-7 increased the expression of synaptic plasticity-related proteins and suppressed the NEK7/NLRP3 inflammatory pathway, as determined by western blotting and immunofluorescence analysis. The mechanism of action of TW-7 was verified in an HT-22 cell model of high glucose-induced insulin resistance. Collectively, TW-7 could regulate T2DM neuroinflammation and synaptic function-induced cognitive impairment by inhibiting NLRP3 inflammasome activation and improving synaptic plasticity.

Novel strategy to the characterization and enhance the glycemic control properties of walnut-derived peptides via zinc chelation.

This study aimed to utilize zinc coordination to promote the hypoglycemic and antioxidant properties of walnut-derived peptides, such as walnut protein hydrolysate (WPH) and Leu-Pro-Leu-Leu-Arg (LPLLR, LP5), of which LP5 was previously identified from WPH. The optimal conditions for the chelation were a peptide-to-zinc ratio of 6:1, pH of 9, duration of 50 min, and temperature of 50 °C. The WPH-Zn and LP5-Zn complexes increased the α-glucosidase inhibition, α-amylase inhibition, and antioxidant activity more than WPH and LP5 (p < 0.05). In particular, the antioxidant activity of WPH-Zn was superior to LP5-Zn. This is attributable to the WPH containing more aromatic amino acids, carboxylate groups and the imidazole groups, which implies its capacity to potentially coordinate with Zn2+ to form the WPH-Zn complex. Moreover, particle size, zeta potential, and scanning electron microscope indicated that the chelation of Zn2+ by peptides led to intramolecular and intermolecular folding and aggregation.

Intrinsic Polarized Electric Field Induces a Storing Mechanism to Achieve Energy Storing Catalysis in V2 C MXene.

Efficient storage and separation of holes and electrons pose significant challenges for catalytic reactions, particularly in the context of single-phase catalysis. Herein, V2 C MXene, with its intrinsic polarized electric field, successfully overcomes this obstacle. To enhance hole storage, a multistep etching process is employed under reducing conditions to control the content of surface termination groups, thus exposing more defective active sites. The intrinsically polarized electric field confines holes to the surface of the layer and free electrons within the layer, leading to a lag in e- release compared to h+ . The quantities of stored holes and electrons are measured to be 18.13 µmol g-1 and 106.37 µmol g-1 , respectively. Under dark, V2 C demonstrates excellent and stable dark-catalytic performance, degrading 57.91% of tetracycline (TC 40 mg L-1 ) and removing 23% of total organic carbon (TOC) after 140 min. In simulated sunlight and near-infrared light, the corresponding degradation rates reach 72.24% and 79.54%, with corresponding TOC removal rates of 49% and 48%, respectively. The hole and electron induced localized surface plasmon resonance (LSPR) effects contribute to a long-lasting and enhanced broad-spectrum mineralization of V2 C MXene. This study provides valuable insights into the research and application of all-weather MXene energy storage catalytic materials.

Accurate Measurement of Defect Generation Rates in Silicon Carbide Irradiated with Energetic Ions.

In this work, we obtained the Si vacancy generation rates η in SiC nanowire samples irradiated with 1, 3 MeV protons, and 2.8 MeV helium ions using the electrical resistivity measurement, which further indicated an intuitive linear function correlation between η and the nuclear stopping power of the incident ions at a low dpa level with a coefficient of 2.15 × 10-3 eV-1. Prediction through this correlation is consistent with previous work. Besides, the measured value is about 1/2 of the simulation results with the popular SRIM code. Overall, our work provides a feasible way to get the generation rate of a certain irradiation-induced defect by electric measurements, and the correlation obtained is practically useful in various applications.

Leptomeningeal neuraxis relapse in glioblastoma is an uncommon but not rare event associated with poor outcome.

BACKGROUND: Spinal neuraxis leptomeningeal metastasis (LM) relapse in glioblastoma is an uncommon event that is challenging to manage. This study aims to determine the incidence, associated factors, and outcome of LM relapse in patients with glioblastoma managed with radical intent. METHODS: Patients managed for glioblastoma using the EORTC-NCIC (Stupp) Protocol from 2007 to 2019 were entered into a prospective ethics-approved database. Follow-up included routine cranial MRI surveillance with further imaging as clinically indicated. LM relapse was determined by MRI findings and/or cerebrospinal fluid analysis. The chi-square test of independence was used to evaluate clinico-pathologic factors associated with increased risk of subsequent LM relapse. Median survival post-LM relapse was calculated using Kaplan-Meier technique. RESULTS: Four-hundred-and-seven patients were eligible, with median follow-up of 60 months for surviving patients. Eleven (2.7%) had LM at first relapse and in total 21 (5.1%) experienced LM in the entire follow-up period. Sites of LM relapse were 8 (38%) focal spinal, 2 (10%) focal brainstem medulla and 11 (52%) diffuse spinal. Median overall survival from initial diagnosis for the entire cohort was 17.6 months (95% CI 16.7-19.0). Median survival from LM relapse to death was 39 days (95% CI: 19-107). Factors associated with LM relapse were age less than 50 years (p < 0.01), initial disease located in the temporal lobe (p < 0.01) and tumours lacking MGMT promoter methylation (p < 0.01). CONCLUSIONS: LM relapse is an uncommon but not rare event in patients managed radically for glioblastoma. It is associated with poor outcome with the majority of patients deceased within two months of recognition.

Decision Regret and Bother With the Addition of Androgen Deprivation Therapy to Definitive Radiation Treatment for Localized Prostate Cancer.

PURPOSE: Androgen deprivation therapy (ADT) combined with radiation treatment (RT) is recommended by the National Comprehensive Cancer Network guidelines for unfavorable intermediate and high-risk localized prostate cancer. Although there is a variable survival benefit conferred by ADT, there are potential side effects to consider for patient decision-making. We aimed to assess the side effects and bother of adding ADT to RT, the degree of regret, and what overall survival (OS) benefit men would want to justify adding or extending the duration of ADT, after their experience with this treatment. METHODS AND MATERIALS: Men receiving ADT with definitive RT completed a questionnaire asking about the side effects and degree of bother from ADT using a 4-point scale. They were also asked about regret, and what survival benefit would warrant ADT. RESULTS: In the study, 846 patients received definitive RT, of whom 356 received ADT and were asked about their experience with ADT. Of these, 234 responded (66%). In 54%, ADT caused some bother, most commonly hot flushes (32%), fatigue (29%), and sexual problems (29%). Five percent regretted receiving ADT "quite a lot" or "very much." Approximately one-third of men deemed a 1% OS benefit from ADT worthwhile, whereas one-third (34%) would want a >10% OS benefit enough to justify choosing ADT again. In addition, 49% of patients who received short-term ADT would accept longer duration ADT for a 6% OS benefit. CONCLUSIONS: Significant regret for ADT was low (5%). There was a clear dichotomy between those who deemed any OS benefit from ADT worthwhile versus those who needed a significant survival benefit to justify the side effects. Given that some men may change their opinion on the relative value of ADT after experiencing its effects, this study emphasizes the importance of revisiting patients after 6 months to given patients an opportunity to renegotiate their treatment.

Environment-Dependent Radiation Tolerance of Graphene Transistors under Proton Irradiation.

Electronic devices based on two-dimensional materials are promising for application in space instrumentation because of their small size and low power consumption, and irradiation tolerance of these devices is required because of the existence of energetic particles in aerospace conditions. We investigate the performance degradation of graphene field effect transistors (GFETs) with 3 MeV protons by using an in situ irradiation facility. Our results indicate that GFET performance degraded severely at the ion fluence of 8 × 1011 cm-2. Surprisingly, although the performance of the proton-irradiated GFETs is difficult to recover in vacuum, it can nearly completely recover within hours when the GFET is moved into an air environment, indicating that the performance change is due to the charge accumulation in SiO2 under proton irradiation rather than the lattice damage of graphene. Our results have great importance for the application of 2D devices in aerospace and other radiative environments.

Multifunctional graphene heterogeneous nanochannel with voltage-tunable ion selectivity.

Ion-selective nanoporous two-dimensional (2D) materials have shown extraordinary potential in energy conversion, ion separation, and nanofluidic devices; however, different applications require diverse nanochannel devices with different ion selectivity, which is limited by sample preparation and experimental techniques. Herein, we develop a heterogeneous graphene-based polyethylene terephthalate nanochannel (GPETNC) with controllable ion sieving to overcome those difficulties. Simply by adjusting the applied voltage, ion selectivity among K+, Na+, Li+, Ca2+, and Mg2+ of the GPETNC can be immediately tuned. At negative voltages, the GPETNC serves as a mono/divalent ion selective device by impeding most divalent cations to transport through; at positive voltages, it mimics a biological K+ nanochannel, which conducts K+ much more rapidly than the other ions with K+/ions selectivity up to about 4.6. Besides, the GPETNC also exhibits the promise as a cation-responsive nanofluidic diode with the ability to rectify ion currents. Theoretical calculations indicate that the voltage-dependent ion enrichment/depletion inside the GPETNC affects the effective surface charge density of the utilized graphene subnanopores and thus leads to the electrically controllable ion sieving. This work provides ways to develop heterogeneous nanochannels with tunable ion selectivity toward broad applications.

Circ_ANKIB1 stabilizes the regulation of miR-19b on SOCS3/STAT3 pathway to promote osteosarcoma cell growth and invasion.

Osteosarcoma is a highly malignant tumor. The molecular mechanism of its occurrence and development has not yet been clarified. Current studies have found that noncoding RNAs, such as circular RNAs (circRNAs) and microRNAs (miRNAs), play important regulatory roles in the progression of diseases. Our previous studies have shown that miR-19b is an oncogene in osteosarcoma. Further studies have shown that circ_ANKIB1 has binding sites for miR-19b, and both molecules were generally upregulated in osteosarcoma cells. RIP assay, RNA pull down, and dual-luciferase reporter gene assay showed that circ_ANKIB1 could directly bind to miR-19b and act as an miR-19b sponge in osteosarcoma cells. Circ_ANKIB1 promoted miR-19b expression, inhibited the expression of the downstream target gene SOCS3, and then activated the STAT3 pathway. When cotransfected with circ_ANKIB1 siRNA, and miR-19b mimics, the expression of SOCS3 and the phosphorylation level of STAT3 did not change significantly. Continuous detection of cell growth and invasion showed that the downregulation of circ_ANKIB1 or miR-19b significantly inhibited cell proliferation and invasion, but increased the apoptotic level. When cotransfected with circ_ANKIB1 siRNA and miR-19b mimics or SOCS3 siRNA, the cell proliferation, apoptosis, and invasion levels did not change significantly, suggesting that circ_ANKIB1 could affect the STAT3 pathway and osteosarcoma cell growth and invasion by enhancing the regulation of miR-19b on the downstream target gene SOCS3. These findings suggest that circRNAs stabilize miRNA functions, and further studies on this new function of circRNAs will provide a meaningful reference for the diagnosis and treatment of tumors and other diseases.

Validation of the 8th edition UICC/AJCC TNM staging system for HPV associated oropharyngeal cancer patients managed with contemporary chemo-radiotherapy.

BACKGROUND: To compare outcomes of high-risk human papilloma virus-related oropharyngeal squamous cell carcinoma (HPV OPSCC) treated with modern radiation treatment (RT) and daily image-guidance, staged with the 7th versus the 8th Edition (Ed) Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) TNM staging systems. METHODS: All eligible patients with HPV OPSCC treated definitively over a 10-year period (2007-2016) at a single institution were included. Protocols consisting of either RT or chemo-radiation (CRT) (weekly cisplatin or cetuximab) +/- neoadjuvant chemotherapy for those with bulky disease were used. All patients were Fluorine-18-deoxyglucose positron emission tomography (FDG-PET) staged at baseline and at intervals for up to 2 years post-treatment. Patients received parotid-sparing intensity modulated or volumetric modulated arc therapy with simultaneous integrated boost to either 70Gy in 35 fractions or 66Gy in 30 fractions. The overall survival (OS) was determined for each stage using the 7th Ed and subsequently with the updated 8th Ed staging system. RESULTS: One hundred fifty-three patients were analysed. Patient stage groupings varied between the 7th and 8th Eds respectively; Stage I (0.7% vs 64.7%), Stage II (8.5% vs 22.2%), stage III (21.6% vs 12.4%) and stage IV (69.3% vs 0.7%). In the 7th Ed, the 5 year probability of OS for stages I to III was 90%, versus stage IV 85.5%. There was no statistically significant difference between the staging groups (p = 0.85). In the 8th Ed there was a statistically significant difference in 5 year OS for stage I and stage II disease (96.9% vs 77.1% respectively; p < 0.0001), but not between stage II and III disease (p = 0.98). CONCLUSIONS: The new 8th Ed UICC/AJCC TNM staging system better discriminates between stage I and Stage II HPV OPSCC with respect to OS compared with the 7th Ed staging system. Further investigation is required for stage III or IV patients.

Role of delayed salvage bevacizumab at symptomatic progression of chemorefractory glioblastoma.

BACKGROUND: Assess benefit of salvage bevacizumab (BEV) at time of symptomatic progression in patients with refractory glioblastoma (GBM). METHODS: Patients managed with adjuvant long course chemo-radiation therapy for GBM were entered into a prospective database. At chemorefractory symptomatic progression, patients were offered BEV or best supportive care. Re-irradiation (ReRT) was used with BEV in selected patients. BEV continued indefinitely until deterioration limited hospital based infusion. The primary endpoint was median survival calculated from date of decision for BEV to proceed (BEVstart), or decision to decline BEV (BEVreject). RESULTS: Fifty-five patients were managed of which 48 patients have relapsed disease. The median survival post relapse was 6 months (95%CI: 4.6-7.4). At relapse, 28 patients received BEV with only 14% delivered at first relapse. The median number of BEV cycles was 8 (range 1-25). ReRT was subsequently used in 16 (33%) relapsed patients. BEV treated patients were associated with improved median survival post relapse with 9 months vs 3 months (p < 0.01). The median survival from BEV related decision-making at symptomatic refractory progression to death was 4 months (95%CI: 2.0-6.0). BEVstart was associated with improved survival from this date with median survival of 6 months vs 1 month with BEVreject (p < 0.01). Median survival with ReRT from this date was 8 months vs 3 months without ReRT (p = 0.01). In the BEV patients at eventual progression, death occurred at a median of 30 days post BEV cessation. CONCLUSION: In this clinic managing selected patients with chemorefractory progressive glioblastoma, delayed salvage bevacizumab, often in combination with re-irradiation, may provide an increase in survival duration compared with best supportive care.

Influence of molecular classification in anaplastic glioma for determining outcome and future approach to management.

INTRODUCTION: Assess survival of patients with anaplastic glioma (AG) and the relationship to molecular subtype. METHODS: Patients with AG managed with IMRT between 2008 and 2014 were entered into a prospective database assessing relapse-free survival (RFS) and overall survival (OS). Isocitrate dehydrogenase (IDH) mutations were assessed prospectively from 2011, and subsequent testing of historical patients allowing categorisation under WHO 2016 classification as anaplastic astrocytoma IDH wild type (AAwt), anaplastic astrocytoma IDH mutated (AAmut), anaplastic oligodendroglioma (AOD) or other glial tumour (OTH). Kaplan-Meier estimates of survival distribution were calculated for the primary endpoint of overall survival and Log-rank test used to determine associated factors. RESULTS: One hundred and fifty-six patients were included with median follow-up for survivors of 4.7 years. Fifty-six per cent were managed after initial diagnosis, whilst 18% received IMRT at second or later relapse. Seventy-three per cent had temozolomide as part of initial therapy. A total of 118 or 75% of patients had IDH mutated glioma, of which 61 were AOD and 57 AAmut. There were 68 relapses and 52 deaths for a 6yrRFS of 51.2% and 6yrOS of 62.5%. AAwt was associated with worse survival (P < 0.001); and delay of RT until second or later relapse (P = 0.03). Within the 118 patients with IDH mutated tumours, 6yrOS for AOD and AAmut were 90.0% and 62.5%, respectively (P = 0.003). Also two or more craniotomies (P < 0.001), delayed RT (P = 0.006) and age <40 years (P = 0.022) were associated with worse survival on univariate analysis but only AAmut subtype and number of craniotomies on multivariate analysis. CONCLUSION: Within AG, molecular classification predicts for survival, and should influence current decision-making.

Tumour volume reduction following PET guided intensity modulated radiation therapy and temozolomide in IDH mutated anaplastic glioma.

The role of maximal surgical debulking in isocitrate dehydrogenase (IDH) mutated anaplastic glioma prior to adjuvant radiation therapy remains uncertain. This study assessed the reduction in tumour volume following intensity modulated radiation therapy (IMRT) and temozolomide in this favourable and more responsive tumour pathology. 56 patients were managed from 2011 to 2014 and 53 had residual disease. To assess radiological response, tumour volumes were created on representative T1/T2Flair MRI sequences using identical slice-levels in three planes for pre-IMRT, month + 3 and month + 12 post-IMRT scans. Change in volumes was assessed between time periods. Progression-free survival (PFS) was calculated from start of radiotherapy. Median follow-up for survivors is 48.2 months. Pathology was anaplastic oligodendroglioma (AOD) and anaplastic astrocytoma IDH-mutated (AAmut) in 32 and 21 patients respectively. 93% received sequential chemotherapy. The median residual disease on T1 and T2Flair imaging was 9.7 cm3 and 20.6 cm3. 17 patients relapsed for projected 5 year PFS of 74.9%; with 8 isolated relapses within initial surgical site. On MRI at month + 3, the median volume for T1 and T2Flair reduced by 69.4% and 67.3% respectively; which further decreased to 82.4% and 81.3% at month + 12. By month + 12, 69.2% and 62.2% of patients had >75% volume reduction. Patients with AOD had superior reduction at month + 3 compared with AAmut (p = 0.02); but equivalent reduction at month + 12 (p = 0.14). Thus, in patients with anaplastic glioma harbouring an IDH mutation, where an attempt at near-total resection may be associated with unacceptable morbidity, this data suggests that the radiation therapy may provide effective cytoreduction of residual disease.

Optimising Outcomes for Glioblastoma through Subspecialisation in a Regional Cancer Centre.

Delivery of highly sophisticated, and subspecialised, management protocols for glioblastoma in low volume rural and regional areas creates potential issues for equivalent quality of care. This study aims to demonstrate the impact on clinical quality indicators through the development of a novel model of care delivering an outsourced subspecialised neuro-oncology service in a regional centre compared with the large volume metropolitan centre. Three hundred and fifty-two patients with glioblastoma were managed under the European Organisation for Research and Treatment of Cancer and National Cancer Institute of Canada Clinical Trials Group (EORTC-NCIC) Protocol, and survival outcome was assessed in relation to potential prognostic factors and the geographical site of treatment, before and after opening of a regional cancer centre. The median overall survival was 17 months (95% CI: 15.5⁻18.5), with more favourable outcome with age less than 50 years (p < 0.001), near-total resection (p < 0.001), Eastern Cooperative Oncology Group (ECOG) Performance status 0, 1 (p < 0.001), and presence of O-6 methylguanine DNA methyltransferase (MGMT) methylation (p = 0.001). There was no difference in survival outcome for patients managed at the regional centre, compared with metropolitan centre (p = 0.35). Similarly, no difference was seen with clinical quality process indicators of clinical trial involvement, rates of repeat craniotomy, use of bevacizumab and re-irradiation. This model of neuro-oncology subspecialisation allowed equivalent outcomes to be achieved within a regional cancer centre compared to large volume metropolitan centre.

Acute Epithelial Toxicity Is Prognostic for Improved Prostate Cancer Response to Radiation Therapy: A Retrospective, Multicenter, Cohort Study.

PURPOSE: To test the hypothesis that increased acute toxicity, measured using subdomains reflective of epithelial cell damage, will be associated with reduced late biochemical failure, as a surrogate for tumor radiosensitivity. METHODS AND MATERIALS: The study design was retrospective, with discovery and validation cohorts involving routinely collected data. Eligible patients had prostate cancer, underwent radiation therapy with curative intent, and had acute toxicity assessed prospectively. The discovery cohort was from a single institution. Genitourinary and gastrointestinal acute toxicity related to epithelial cell damage (hematuria, dysuria, proctitis, or mucus) were related to freedom from late biochemical failure (FFBF; nadir + 2). The validation cohort was from two separate institutions. RESULTS: In all, 503 patients were included in the discovery cohort and 658 patients in the validation cohort. In the validation cohort, patients with acute radiation toxicity reflecting epithelial damage had a longer FFBF on both univariate (hazard ratio [HR] 0.37; P = .004) and multivariate (HR 0.45; P = .035) analysis. The impact of acute toxicity on late FFBF seemed to be greater in patients treated with androgen deprivation (HR 0.19) than in those without (HR 0.48). CONCLUSION: Patients reporting acute radiation toxicity reflective of epithelial cell damage during definitive radiation therapy for prostate cancer have significantly longer FFBF, consistent with an underlying genetic link between normal tissue and tumor radiosensitivity.

Predicting patterns of failure in temporal lobe GBMs: possible implications on radiotherapy treatment portals.

BACKGROUND: Characterise patterns of failure of Temporal Lobe (TL) Glioblastoma (GBM) following treatment with relation to normal temporal lobe anatomy and neural pathways. METHODS: 335 GBM patients received radiotherapy between 03/2007 and 07/2014, 100 were located in TL. Site of initial tumour and subsequent relapse were subdivided into 5 local TL sites (anterior, lateral, medial, posterior and superior); 5 adjacent regional sites (occipital lobe, inferior frontal lobe, caudate/thalamus/internal/external capsules, fornix/ventricular trigone), and 5 distant failure sites (ventricles, contralateral hemisphere, brainstem, leptomeninges and spine). Extension along major neuroanatomical pathways at initial presentation and at first documented Magnetic Resonance Imaging (MRI) failure were categorised into anterior, superior, medial and posterior pathways. RESULTS: Of the 100 patients, 86 had radiological progress with a median survival of 17.3 months. At initial diagnosis, 74% of tumours were linked to one TL site and 94% were confined to the TL. 19% had neural pathway disease at initial pre-treatment MRI. At first recurrence locoregional site failure was 74%. 26% failed within distant sites and 53% patients were noted to have neural pathway involvement. Initial tumour location predicted for local site recurrence (p < 0.0001), regional site recurrence (p = 0.004) and neural pathway recurrence pattern (p = 0.005), but not for distant sites (p = 0.081). CONCLUSION: Most GBMs fail at local or adjacent regional sites. Many of the recurrences occurred in a predictable pattern within a local or regional site, unique to initial TL site with more than half involving neural pathways. Knowledge of tumour infiltration and failure may improve target definition and radiotherapy.

68 Ga-PSMA-PET/CT staging prior to definitive radiation treatment for prostate cancer.

AIM: To explore the utility of prostate specific membrane antigen (PSMA)-positron emission tomography (PET)/computed tomography (CT) in addition to conventional imaging prior to definitive external beam radiation treatment (EBRT) for prostate cancer. METHODS: All men undergoing PSMA-PET/CT prior to definitive EBRT for intermediate and high-risk prostate cancer were included in our ethics approved prospective database. For each patient, clinical and pathological results, in addition to scan results including site of PSMA positive disease and number of lesions, were recorded. Results of conventional imaging (bone scan, CT and multiparametric magnetic resonance imaging [MRI]) were reviewed and included. RESULTS: One hundred nine men underwent staging PSMA-PET/CT between May 2015 and June 2017; all patients had national comprehensive cancer network (NCCN) intermediate or high-risk prostate cancer and 87% had Gleason score (GS) 4 + 3 or higher. There was positive uptake corresponding to the primary in 108, equivocal in one. All patients with image detected nodal or bony lesions had GS 4 + 3 or more disease. Compared to conventional imaging with bone scan, CT and multiparametric MRI, PSMA-PET/CT upstaged an additional 7 patients (6.4%) from M0 to M1, 16 from N0M0 to N1M0 (14.7%) and downstaged 3 (2.8%) from M1 to M0 disease. CONCLUSION: PSMA-PET/CT identified the primary in 99% of patients, and altered staging in 21% of men with intermediate or high-risk prostate cancer referred for definitive EBRT compared to CT, bone scan and multiparametric MRI. Following this audit, we recommend the routine use of PSMA-PET/CT prior to EBRT in this patient group.

Survival improvements with adjuvant therapy in patients with glioblastoma.

BACKGROUND: Evaluate survival of patients diagnosed with glioblastoma multiforme (GBM) managed with adjuvant intensity modulated radiation therapy and temozolomide since the introduction of the European Organisation for Research and Treatment of Cancer and National Cancer Institute of Canada Clinical Trials Group (EORTC-NCIC) protocol. METHODS: All patients with GBM managed between May 2007 and December 2014 with EORTC-NCIC protocol were entered into a prospective database. The primary endpoint was the median survival. Univariate predictors of survival were evaluated with respect to tumour resection, age and Eastern Cooperative Oncology Group (ECOG) performance status using log-rank comparisons. RESULTS: Two hundred and thirty-three patients were managed under the protocol and analysed for outcome. The median age was 57 years; the rate of gross total resection, subtotal resection and biopsy were 47.2%, 35.2% and 17.6%, respectively. At progression, 49 patients had re-resection, and in addition to second-line chemotherapy, 86 patients had Bevacizumab including 26 with re-irradiation. Median survival was 17.0 months (95% CI: 15.4-18.6). On univariate evaluation, extent of resection (P = 0.001), age, ECOG performance status and recursive partitioning analysis class III were shown to significantly improve survival (P < 0.0001). The median survival for gross total resection, age <50 years, ECOG 0-1 and recursive partitioning analysis class III were 21, 27, 20 and 47 months, respectively. CONCLUSION: This study confirms the significant improvement in median survival in GBM that has occurred in recent years since introduction of the EORTC-NCIC protocol. Further improvements have occurred presumably related to subspecialized care, improved resection rates, sophisticated radiotherapy targeting and early systemic salvage therapies. However, the burden of the disease within the community remains high and the median survival improvements over time have plateaued.