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Glioblastoma (GBM) often exhibits distinct anatomical patterns of relapse after radiotherapy. Tumour cell migration along myelinated white matter tracts is a key driver of disease progression. The failure of conventional imaging to capture subclinical infiltration has driven interest in advanced imaging biomarkers capable of quantifying tumour–brain interactions. Diffusion tensor imaging (DTI), radiomics, and connectomics represent a triad of innovative, non-invasive approaches that map white matter architecture, predict recurrence risk, and inform biologically guided treatment strategies. This review examines the biological rationale and clinical applications of DTI-based metrics, radiomic signatures, and tractography-informed connectomics in GBM. We discuss the integration of these modalities into machine learning frameworks and radiotherapy/surgical planning, supported by landmark studies and multi-institutional data. The implications for personalised neuro-oncology are profound, marking a shift towards risk-adaptive, tract-aware treatment strategies that may improve local control and preserve neurocognitive function.

Background Numerous studies have reported that spending time in nature is associated with the improvement of various health outcomes and well-being. This review evaluated the physical and psychological benefits of a specific type of exposure to nature, forest therapy. Method A literature search was carried out using MEDLINE, PubMed, ScienceDirect, EMBASE, and ProQuest databases and manual searches from inception up to December 2016. Key words: “Forest” or “Shinrin -Yoku” or “Forest bath” AND “Health” or “Wellbeing”. The methodological quality of each randomized controlled trials (RCTs) was assessed according to the Cochrane risk of bias (ROB) tool. Results Six RCTs met the inclusion criteria. Participants’ ages ranged from 20 to 79 years. Sample size ranged from 18 to 99. Populations studied varied from young healthy university students to elderly people with chronic disease. Studies reported the positive impact of forest therapy on hypertension ( n  = 2), cardiac and pulmonary function ( n  = 1), immune function ( n  = 2), inflammation ( n  = 3), oxidative stress ( n  = 1), stress ( n  = 1), stress hormone ( n  = 1), anxiety ( n  = 1), depression ( n  = 2), and emotional response ( n  = 3). The quality of all studies included in this review had a high ROB. Conclusion Forest therapy may play an important role in health promotion and disease prevention. However, the lack of high-quality studies limits the strength of results, rendering the evidence insufficient to establish clinical practice guidelines for its use. More robust RCTs are warranted.

Additionally, these tumours present with varying neuroradiological appearance related to volume, morphology, and neuroanatomical site, which means interventions require individualisation based on these parameters. 2 The RANO resect group have collaboratively produced evidence-based guidelines for neurosurgical management of glioblastoma, and an associated prognostic classification for extent of resection and residual disease. 3 These guidelines have been practice changing for decision making at the time of initial surgery in patients with glioblastoma, where an early immediate survival advantage from minimising residual disease can be weighed against the risks of morbidity. Research might evolve further, as non-invasive techniques can assist in preoperative decision making, diagnosing of IDH mutation either through 2-hydroxyglutarate MRI spectroscopy or peripheral blood liquid biopsy. 9 The RANO resect group report provides an evidence base for high-volume neuro-oncology units that can offer the infrastructure for more aggressive resections with an emphasis on safe resection. [...]given the potential for long survival with IDH-mutated glioma, these recommendations around potential accreditation pathways might not only apply to neurosurgical units but to all neuro-oncology specialists delivering subspecialty interventions in this patient cohort.

Background Several studies have identified fatigue as one of the major symptoms experienced during and after cancer treatment. However, there are limited options to manage cancer related fatigue (CRF) with pharmacological interventions. Several acupuncture studies suggested that acupuncture has a positive impact on CRF. This review aims to assess the evidence of acupuncture for the treatment of CRF. Method Electronic database searches were conducted on 4 English databases (Medline, PubMed, Embase, and ScienceDirect). Search keywords were; “acupuncture” and “cancer,” or “cancer related fatigue.” Studies published as full text randomized controlled trials (RCTs) in English were included. Estimates of change in fatigue cores were pooled using a random effects meta-analysis where randomized comparisons were available for true acupuncture versus sham acupuncture and true acupuncture versus usual care. The quality of original papers were assessed using the Cochrane Collaboration’s tool for assessing risk of bias (ROB). Results Nine RCTs were selected for review with a total of 809 participants and a range of 13 to 302 participants within the studies. Six RCTs reported significant improvement of CRF for the acupuncture intervention compared to the control groups. Pooled estimates suggest Brief Fatigue Inventory scores are 0.93 points lower 95% CI (−1.65, −0.20) in true acupuncture versus sham acupuncture and 2.12 points lower 95% C (−3.21, −1.04) in true acupuncture versus usual care. Six studies had low risk of bias (ROB) and 3 studies had a moderate ROB predominantly in blinding of participants, blinding of assessors and incomplete data outcomes. Among the 9 RCTs, 2 studies have reported the occurrence of minor adverse effects (spot bleeding and bruising) related to acupuncture treatment. No serious adverse reactions related to acupuncture were reported. Conclusion The current literature review suggests that acupuncture has therapeutic potential in management of CRF for cancer survivors. Promotion of acupuncture in cancer care to manage CRF may improve the quality of life of cancer survivors.

Background: Glioblastomas are the most common and fatal primary brain malignancy in adults. There is a growing interest in identifying the molecular mechanisms of these tumors to develop novel treatments. Glioblastoma neo-angiogenesis is driven by VEGF, and another potential molecule linked to angiogenesis is PSMA. Our study suggests the potential for an association between PSMA and VEGF expression in glioblastoma neo-vasculature. Methods: Archived IDH1/2 wild-type glioblastomas were accessed; demographic and clinical outcomes were recorded. PSMA and VEGF expression by IHC were examined. Patients were dichotomized into PSMA expression high (3+) and low (0–2+) groups. The association between PSMA and VEGF expression was evaluated using Chi2 analysis. OS in PSMA high and low expression groups were compared using multi-linear regression. Results: In total, 247 patients with IDH1/2 wild-type glioblastoma with archival tumor samples (between 2009–2014) were examined. PSMA expression correlated positively with VEGF expression (p = 0.01). We detected a significant difference in median OS between PSMA vascular endothelial expression high and low groups—16.1 and 10.8 months, respectively (p = 0.02). Conclusion: We found a potential positive correlation between PSMA and VEGF expression. Secondly, we showed a potential positive correlation between PSMA expression and overall survival.

Purpose: Patients with glioblastoma (GBM) may demonstrate varying patterns of infiltration and relapse. Improving the ability to predict these patterns may influence the management strategies at the time of initial diagnosis. This study aims to examine the impact of the ratio (T2/T1) of the non-enhancing volume in T2-weighted images (T2) to the enhancing volume in MRI T1-weighted gadolinium-enhanced images (T1gad) on patient outcome. Methods and Materials: A retrospective audit was performed from established prospective databases in patients managed consecutively with radiation therapy (RT) for GBM between 2016 and 2019. Patient, tumour and treatment-related factors were assessed in relation to outcome. Volumetric data from the initial diagnostic MRI were obtained via the manual segmentation of the T1gd and T2 abnormalities. A T2/T1 ratio was calculated from these volumes. The initial relapse site was assessed on MRI in relation to the site of the original T1gad volume and surgical cavity. The major endpoints were median relapse-free survival (RFS) from the date of diagnosis and site of initial relapse (defined as either local at the initial surgical site or any distance more than 20 mm from initial T1gad abnormality). The analysis was performed for association between known prognostic factors as well as the radiological factors using log-rank tests for subgroup comparisons, with correction for multiple comparisons. Results: One hundred and seventy-seven patients with GBM were managed consecutively with RT between 2016 and 2019 and were eligible for the analysis. The median age was 62 years. Seventy-four percent were managed under a 60Gy (Stupp) protocol, whilst 26% were on a 40Gy (Elderly) protocol. Major neuroanatomical subsites were Lateral Temporal (18%), Anterior Temporal (13%) and Medial Frontal (10%). Median volumes on T1gd and T2 were 20 cm3 (q1–3:8–43) and 37 cm3 (q1–3: 17–70), respectively. The median T2/T1 ratio was 2.1. For the whole cohort, the median OS was 16.0 months (95%CI:14.1–18.0). One hundred and forty-eight patients have relapsed with a median RFS of 11.4 months (95%CI:10.4–12.5). A component of distant relapse was evident in 43.9% of relapses, with 23.6% isolated relapse. Better ECOG performance Status (p = 0.007), greater extent of resection (p = 0.020), MGMT methylation (p < 0.001) and RT60Gy Dose (p = 0.050) were associated with improved RFS. Although the continuous variable of initial T1gd volume (p = 0.39) and T2 volume (p = 0.23) were not associated with RFS, the lowest T2/T1 quartile (reflecting a relatively lower T2 volume compared to T1gd volume) was significantly associated with improved RFS (p = 0.016) compared with the highest quartile. The lowest T2/T1 ratio quartile was also associated with a lower risk of distant relapse (p = 0.031). Conclusion: In patients diagnosed with GBM, the volumetric parameters of the diagnostic MRI with a ratio of T2 and T1gad abnormality may assist in the prediction of relapse-free survival and patterns of relapse. A further understanding of these relationships has the potential to impact the design of future radiation therapy target volume delineation protocols.

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.

Background Currently there are very few biomarkers to identify head and neck squamous cell carcinoma (HNSCC) cancer patients at a greater risk of recurrence and shortened survival. This study aimed to investigate whether a marker of systemic inflammation, the neutrophil-to-lymphocyte ratio (NLR), was predictive of clinical outcomes in a heterogeneous cohort of HNSCC cancer patients. Methods We performed a retrospective analysis to identify associations between NLR and clinicopathological features to recurrence free survival (RFS) and overall survival (OS). Univariate analysis was used to identify associations and selected variables were included in multivariable Cox regression analysis to determine predictive value. Results A total of 145 patients with stage I-IV HNSCC that had undergone radiotherapy were analysed. Seventy-six of these patients had oropharyngeal cancer and 69 had non-oropharyngeal HNSCC and these populations were analysed separately. NLR was not associated to any clinicopathological variable. On univariate analysis, NLR showed associations with RFS and OS in both sub-populations. Multivariable analysis showed patients with NLR > 5 had shortened OS in both sub-populations but NLR > 5 only predicted RFS in oropharyngeal patients. Poor performance status predicted OS in both sub-populations and current smokers had shortened OS and RFS in non-oropharyngeal patients. Conclusions The results show patients with NLR > 5 predict for shorter overall survival. Further prospective validation studies in larger cohorts are required to determine the clinical applicability of NLR for prognostication in HNSCC patients.

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.