Survival In High-grade Glioma Research Articles

Sexually dimorphic computational histopathological signatures prognostic of overall survival in high-grade gliomas via deep learning.

High-grade glioma (HGG) is an aggressive brain tumor. Sex is an important factor that differentially affects survival outcomes in HGG. We used an end-to-end deep learning approach on hematoxylin and eosin (H&E) scans to (i) identify sex-specific histopathological attributes of the tumor microenvironment (TME), and (ii) create sex-specific risk profiles to prognosticate overall survival. Surgically resected H&E-stained tissue slides were analyzed in a two-stage approach using ResNet18 deep learning models, first, to segment the viable tumor regions and second, to build sex-specific prognostic models for prediction of overall survival. Our mResNet-Cox model yielded C-index (0.696, 0.736, 0.731, and 0.729) for the female cohort and C-index (0.729, 0.738, 0.724, and 0.696) for the male cohort across training and three independent validation cohorts, respectively. End-to-end deep learning approaches using routine H&E-stained slides, trained separately on male and female patients with HGG, may allow for identifying sex-specific histopathological attributes of the TME associated with survival and, ultimately, build patient-centric prognostic risk assessment models.

Anti-epileptic Therapy with Lamotrigine Associated with Improved Progression-free Survival in High-grade Glioma: A Large-series Analysis (S27.008)

Anti-epileptic Therapy with Lamotrigine Associated with Improved Progression-free Survival in High-grade Glioma: A Large-series Analysis (S27.008)

Metabolic habitat imaging with hemodynamic heterogeneity predicts individual progression-free survival in high-grade glioma

We design a feasibility study to obtain a set of metabolic-hemodynamic habitats for tackling tumor spatial metabolic patterns with hemodynamic information. Preoperative data from 69 high-grade gliomas (HGG) patients with subsequent histologic confirmation of HGG were prospectively collected (January 2016 to March 2020) after concurrent chemoradiotherapy (CCRT). Four vascular habitats were automatically segmented by multiparametric magnetic resonance imaging (MRI). The metabolic information, either at enhancing or edema tumor regions, was obtained by two neuroradiologists. The relative habitat volumes were used for weight estimation procedures for computing the coefficients of a linear regression model using weighted least squares (WLS) for metabolite semiquantifications (i.e. the Cho/NAA ratio and the Cho/Cr ratio) at vascular habitats. Multivariate Cox proportional hazard regression analyses are used to obtain the odds ratio (OR) and develop a nomogram using weighted estimators corresponding to each covariate derived from Cox regression coefficients. There was a strongly correlation between perfusion indexes and the Cho/Cr ratio (rCBV, r=0.71) or Cho/NAA ratio (rCBV, r=0.66) at high-angiogenic enhancing tumor habitats (HAT) habitat. Compared isocitrate dehydrogenase (IDH) mutation to their wild type, the IDH wild type had significantly decreased Cho/Cr ratio (IDH mutation: Cho/Cr ratio=2.44±0.33, IDH wildtype: Cho/Cr ratio=2.66±0.36, p=0.02) and Cho/NAA ratio (IDH mutation: Cho/Cr ratio=4.59±0.61, IDH wildtype: Cho/Cr ratio=4.99±0.66, p=0.022) at the HAT. The C-index for the median progression-free survival (PFS) prediction was 0.769 for the Cho/NAA nomogram and 0.747 for the Cho/Cr nomogram through 1000 bootstrapping validation. Our findings suggest that spatial metabolism combined with hemodynamic heterogeneity is associated with individual PFS to HGG patients post-CCRT.

NCOG-20. WEARABLE DEVICE DATA QUANTIFY DISEASE PROGRESSION IN HIGH GRADE GLIOMA AND MAY PROVIDE NOVEL OUTCOME MEASURES

Abstract BACKGROUND Functional status is a prognostic measure of survival in high grade glioma (HGG). Real-time monitoring between clinical encounters can extend the reach of care and provide actionable insights to drive more personalized and proactive care. We present data from the completed BrainWear Study, a highly novel study evaluating if data captured via a wrist-worn wearable device in patients with HGG can be used to explain, influence and/or predict cancer-related outcomes. Materials and METHODS All participants agreed to wear a wrist-worn Axivity AX3 triaxial accelerometer changed at 14-day intervals. Raw accelerometer data was processed using the UKBiobank Accelerometer analysis package v6.2.3 for Python and inclusion of high-quality wear time selected as ≥72 hours of data over 7-days. We analysed variation in activity by patient demographics and MRI result utilising the Response Assessment in Neuro-Oncology (RANO) criteria. Patient reported outcomes (PROs) were completed at planned study timepoints. Wilcoxin-signed rank test was used to compare participant activity at timepoints of stable or progressive disease (PD). Mixed-effects models were used to evaluate changes in activity. RESULTS 12512 days of accelerometer data were recorded from 56 patients (36 male; 20 female) with a median age of 60 years. 80% of the data were characterised as high-quality. Mean acceleration(mg) and time spent walking daily(h/day) correlated positively with the global health QOL and physical functioning scores and inversely with the fatigue score from PROs. In the 6-weeks surrounding an MRI scan, patients with PD walked on average 1856 steps less per day than those with stable disease, and spent 22 minutes less walking (p=0.0403). Several wearable data daily physical activity measures demonstrated statistically significant change at the time of PD. CONCLUSION Remote monitoring data can complement snapshots of health gathered during clinical visits. Collection of digital data hold promise for novel HGG trial outcome measure development.

Exploring the mechanism of 18F-fluorodopa uptake in recurrent high-grade gliomas: A comprehensive histomolecular-positron emission tomography analysis.

Dihydroxy-6-[18F]fluoro-L-phenylalanine (18F-FDOPA) positron emission tomography (PET) is a valuable tool for managing high-grade gliomas (HGGs), but there is a lack of literature on its relationship with glioma subtypes since the 2021 reclassification of brain tumors. There is also debate surrounding the mechanism of 18F-FDOPA uptake, particularly after chemoradiation therapy. This study aimed to investigate the correlation between 18F-FDOPA uptake and histomolecular characteristics, particularly L-amino acid transporter 1 (LAT1) expression, in recurrent gliomas, and examine their impact on survival in HGGs. Thirty-nine patients with recurrent HGGs (14 isocitrate dehydrogenase [IDH]-mutant, 25 IDH-wildtype) who underwent a brain 18F-FDOPA PET/computed tomography (CT) or PET/magnetic resonance imaging (MRI) followed by surgical resection of the 18F-FDOPA-avid lesion within 6 months, were retrospectively reviewed. PET results were compared with histological examination and for SCL7A5/LAT1 immunostaining. The study also examined the relationship between PET parameters, LAT1 expression, and survival outcomes. Astrocytoma IDH-mutant G4 had higher 18F-FDOPA uptake than glioblastoma IDH-wildtype G4 (maximum tumor-to-normal brain ratio [TBRmax] 5 [3.4-9] vs. 3.8 [2.8-5.9], p = 0.02). IDH-mutant gliomas had higher LAT1 expression than IDH-wildtype gliomas (100 [14-273] vs. 15.5 [0-137], p < 0.05) as well as higher TBRmax (5 [2.4-9] vs. 3.8 [2.8-6], p < 0.05). In survival analysis, LAT1 score >100 was a predictor for longer progression-free survival in IDH-mutant HGGs. To our knowledge, our study is the first to suggest a link between LAT1 expression and IDH mutation status. We showed that higher TBRmax was associated with higher LAT1 expression and IDH mutation status. Further studies are needed to better understand the mechanisms underlying amino acid PET tracers uptake, especially in the post-radiation and chemotherapy settings.

SDPS-35 TUMOR-RELATED EPILEPSY IN HIGH-GRADE GLIOMA: A LARGE SERIES SURVIVAL ANALYSIS

Abstract BACKGROUND Seizures are a common clinical occurrence throughout the disease course in glioblastoma (GBM). While many studies have explored the impact of surgical and medical treatment for GBM on seizure incidence and prevalence, limited study has been directed towards the prognostic effect of seizures occurring in the post-treatment setting. METHODS We retrospectively reviewed 238 patients with histologically-confirmed high grade glioma treated at our institution between 2018 and 2021. Seizure presentation was classified as early onset (occurring at the time of GBM presentation), or late onset (first seizure occurring after beginning standard surgical and medical treatment). Using a multivariate Cox proportional-hazards model, hazard ratios were assessed for timing of seizure presentation, as well as other clinical and tumor-associated variables. RESULTS Incidence of first seizure after the onset of treatment was found to be associated with improved overall survival (HR=0.66, p=0.03), while increasing age (HR 1.02, p=0.007) and deep/midline tumor location (HR 1.86, p=0.003) were associated with decreased overall survival. CONCLUSION While seizure at presentation may be associated with better survival in high-grade glioma, more analysis is underway to confirm the finding in a larger cohort and to evaluate the impact of molecular alterations in seizure incidence and management. Further study in this patient cohort utilizing detailed next-generation sequencing will evaluate the association of the patient-specific tumor profile on seizures and overall survival.

Adjuvant Vaccination with Allogenic Dendritic Cells Significantly Prolongs Overall Survival in High-Grade Gliomas: Results of a Phase II Trial

Immunotherapy for cancer treatment has gained increased attention in recent years. Recently, our group reported the case of a patient with glioblastoma who underwent vaccination based on dendritic cells and experienced a strong Th1 immune response together with near-complete tumor remission. Here we report the results of a phase I/II prospective, non-controlled clinical trial with 37 patients harboring glioblastoma or grade 4 astrocytomas. At the time of first recurrence after surgery, patients began receiving monthly intradermal injections of allogenic DC-autologous tumor cell hybridomas. Overall survival, quality of life, and immunological profiles were assessed prospectively. Compared with patients in the Genomic Data Commons data bank, overall survival for vaccinated patients with glioblastoma was 27.6 ± 2.4 months (vs. 16.3 ± 0.7, log-rank p < 0.001, hazard ratio 0.53, 95%CI 0.36-0.78, p < 0.01), and it was 59.5 ± 15.9 for vaccinated astrocytoma grade 4 patients (vs. 19.8 ± 2.5, log-rank p < 0.05, hazard ratio 0.18, 95%CI 0.05-0.62, p < 0.01). Furthermore, seven vaccinated patients (two IDH-1-mutated and five wild type) remain alive at the time of this report (overall survival 47.9 months, SD 21.1, range: 25.4-78.6 months since diagnosis; and 34.2 months since recurrence, range: 17.8 to 40.7, SD 21.3). We believe that the data reported here can foster the improvement of treatment protocols for high-grade gliomas based on cellular immunotherapy.

Perfusion MR prior to radiotherapy is a strong predictor of survival in high-grade gliomas after proton and carbon ion radiotherapy

To assess the survival predictability of perfusion magnetic resonance imaging (MRI) by the normalized cerebral blood volume (nCBV) prior to particle beam radiotherapy (PBRT) in high-grade glioma (HGG) patients underwent particle therapy. The study retrieved dynamic susceptibility contrast MRI acquired prior to PBRT between 6/2015 and 3/2019 in 45 patients with HGG. Maximum nCBV (nCBVmax) within or adjacent to surgical/tumor bed was measured using 'hot-spot' method. The predictive values of nCBVmax for progression-free survival (PFS) and overall survival (OS) were assessed in univariate Kaplan-Meier curve and multivariate Cox proportional hazards (CPH) models. Nomograms based on CPH results were constructed to individualize the predicted probability of OS and PFS. The Kaplan-Meier curves and all CPH models based on nCBVmax as continuous variable (nCBVmax-C), group by cut-off derived from median value and Youden-index method showed that nCBVmax prior to radiotherapy was a strong predictor for both PFS and OS in HGG patients who underwent PBRT. Nomograms built on CPH models showed similar excellent performance in both discrimination and calibration. Perfusion imaging prior to PBRT is a strong predictor of survival in HGG. Novel perfusion MR-based nomogram with prospective validation could potentially be formally used in future clinical practice to individualize survival probability.

A brain tumor reporting and data system to optimize imaging surveillance and prognostication in high-grade gliomas.

High-grade glioma (HGG), including glioblastoma, is the most common primary brain neoplasm and has a dismal prognosis. After initial treatment, follow-up decisions are guided by longitudinal MRI performed at routine intervals. The Brain Tumor Reporting and Data System (BT-RADS) is a proposed structured reporting system for posttreatment brain MRIs. The purpose of this study is to determine the relationship between BT-RADS scores and overall survival in HGG patients. Chart review of grade 4 glioma patients who had an MRI at a single institution from November 2018 to November 2019 was performed. BT-RADS scores, tumor characteristics, and overall survival were recorded. Likelihood of improvement, stability, or worsening on the subsequent study was calculated for each score. Survival analysis was performed using Kaplan-Meier method, log-rank test, and a time-dependent cox model. Significance level of .05 was used. The study identified 91 HGG patients who underwent a total of 538 MRIs. Mean age of patients was 57 years old. Score with the highest likelihood for worsening on the next follow-up was 3b. The risk of death was 53% higher with each incremental increase in BT-RADS scores (hazard ratio, 1.53; 95% confidence interval [CI], 1.07-2.19; p=.019). The risk of death was 167% higher in O-6-methylguanine-DNA-methyltransferase unmethylated tumors (hazard ratio, 2.67; 95% CI, 1.34-5.33; p=.005). BT-RADS scores can be used as a reference guide to anticipate whether patients' subsequent MRI will be improved, stable, or worsened. The scoring system can also be used to predict clinical outcomes and prognosis.

A Novel 5-Aminolevulinic Acid-Enabled Surgical Loupe System-A Consecutive Brain Tumor Series of 11 Cases.

The concept of maximally safe resection (MSR) has been shown to improve clinical outcomes in the treatment of high-grade gliomas (HGGs). To achieve MSR, surgical adjuncts such as functional imaging, neuronavigation, intraoperative mapping, ultrasound, and fluorescence-guided surgery are routinely used. 5-Aminolevulinic acid (5-ALA) is an oral agent that has been increasingly adopted in fluorescence-guided resection of HGG. In randomized clinical trials of 5-ALA, it has been shown to increase the extent of resection and progression-free survival in HGG. Current commercially available 5-ALA detection systems are all microscope-based and can sometimes be cumbersome to use. To present our experience using a novel 5-ALA-enabled surgical loupe system. 5-ALA-enabled loupes were used in 11 consecutive patients with either suspected HGG on magnetic resonance imaging or recurrence of known lesions. Lesion appearance was examined under white light, 5-ALA loupes, and a 5-ALA microscope. Tumor specimens were checked for fluorescence and sent for pathologic examination. In our experience, a 5-ALA-enabled surgical loupe system offers excellent visualization of 5-ALA in patients with HGG. In 10 of 11 patients, fluorescent tissue was confirmed to be high-grade glioma by pathology. In 1 patient, tissue was not fluorescent, and final pathology was World Health Organization grade I meningioma. A 5-ALA-enabled surgical loupe system offers excellent intraoperative visualization of 5-ALA fluorescence in HGG and can be a viable surgical adjunct for achieving MSR of HGG.

CTIM-05. A PHASE 1/2 STUDY OF THE COMBINATION OF INDOXIMOD AND TEMOZOLOMIDE FOR ADULT PATIENTS WITH TEMOZOLOMIDE-REFRACTORY PRIMARY HIGH-GRADE GLIOMAS

Abstract BACKGROUND Optimal management of progressive high-grade gliomas (HGG) is not fully defined and outcomes are poor. Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme which converts tryptophan to kynurenines, which contribute to the immunosuppresive tumor microenvironment (TME). Targeting the TME by inhibiting IDO1 is a strategy for potential improvement in survival in HGG. METHODS A phase 1/2 trial using the IDO1 inhibitor indoximod was conducted in progressive grade 3 and 4 gliomas. The phase 1 cmponent used a 3 + 3 design escalating indoximod from 600mg po BID to 1200mg po BID in conjunction with temozolomide (150 mg/m2, 5/28 days). The phase 2 component consisted of 3 cohorts: A) indoximod+temozolomide B) indoximod+temozolomide+bevacizumab (patients already on bevacizumab) C) indoximod+temozolomide+stereotactic radiosurgery (SRS). Patients were treated until progression or toxicity. RESULTS 33.3% of patients developed indoximod TEAEs. There were no dose limiting toxicities in the phase 1 component (n=12). 1200 mg BID was established as the phase 2 dose of indoximod. In the phase 2 component (n=148) PFS6 was 74% (A), 93% (B), 70% (C). Median OS was 289 days [10.3 months](A), 159 days [5.7 months](B), 285 days [10.2 months](C). Correlative study results will be available for meeting presentation. CONCLUSIONS The IDO1 inhibitor indoximod proved safe and tolerable in conjunction with temozolomide, bevacizumab, and SRS in patients with progressive HGG. There was a trend toward better survival outcomes when indoximod was combined with temozolomide alone or temozolomide+SRS.

OS09.6.A Cognition and health-related quality of life in long time survivors of high-grade glioma

Abstract BACKGROUND Although prognosis is poor in high-grade glioma (HGG) patients, some become a long-term survivor (LTS). Health-related quality of life (HRQOL) and cognition are seen as indicators for quality of survival in HGG but data in LTS and their caregivers are scarce. We aim to investigate cognition and HRQOL in LTS with evaluation by their proxies. MATERIAL AND METHODS We included LTS with initial HGG-diagnosis between 1999–2014. Cognition was assessed with: Boston Naming Test, shortened Token Test, verbal (Category and Letter) Fluency, Diagnostic Instrument of Mild Aphasia, Hopkins Verbal Learning Test and Trail Making Test (A, B, B/A) and HRQOL with: EORTC Quality of Life Questionnaire (C30) and Brain Cancer Module (BN20). 15 Proxies evaluated patients’ HRQOL with: C30, BN20 and they filled in a burden scale: Caregiver Strain Index (CSI). RESULTS 21 patients with grade III or IV glioma and 7 years (range 5–20 years) median survival after diagnosis participated. Compared to normative data patients deviated significantly on HVLT (direct recall, delayed recall, recognition true positives), TMT (A, B and B/A), BNT and CF (p&amp;lt;0.05) which was not affected by hemispheric localization (left/right) or tumor grade (III/IV). HVLT delayed recall was significantly worse in patients with &amp;gt;12 years survival compared to patients with &amp;lt;12 years survival. Average QoL rating in patients was 75%, proxy’s evaluation about patients’ QoL was similar. Moderate correlations (p&amp;lt;0.05) were found between impaired scores on TMT and CF and C30 cognition subscale and between impaired scores on CF, HVLT delayed recall and BNT and BN20 language subscale. At individual level only one patient had intact scores on all administered tests. Other patients had mild impairments on 1–5 subtests and severe impairment on 1–8 subtests. Five out of 14 (36%) proxies reported a great level of caregiver strain on CSI. CONCLUSION Most LTS suffer from cognitive impairments. Despite worse prognosis and cognitive impairments, at group level patients report relatively intact QoL, which is supported by their proxies. However, at the individual level severity of impairments is variable and high caregiver strain is reported in one-third of the proxies. Objective cognitive functioning was only modestly associated with subjective experience in patients. A patient-tailored approach is recommended to investigate individual impairments and needs for rehabilitation and support for patients and also for their carers.

Overexpression of Cell-Surface Marker SLC16A1 Shortened Survival in Human High-Grade Gliomas.

Solute carrier family 16 member 1 (SLC16A1) is a crucial transcription factor in modifying cancer progression and metastasis. However, its character in defining the clinical prognosis of human gliomas has not been illuminated. In our analysis from PREdiction of Clinical Outcomes from Genomic Profiles (PRECOG), The Cancer Genome Atlas (TCGA), and Chinese Glioma Genome Atlas (CGGA), we found that SLC16A1 mRNA expression level was significantly increased in high-grade gliomas in contrast to low-grade gliomas and non-tumor controls (P < 0.05). Kaplan-Meier analysis of four independent cohort studies from the Gene Expression Omnibus (GEO) profile, TCGA, and CGGA which consistently presented patients with high SLC16A1 mRNA expression displayed poor overall survival in high-grade glioma patients (P < 0.05 by log-rank test). Based on the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), the protein-protein interaction analysis of SLC16A1-regulated oncogenesis showed SLC16A1 as a potential hub protein. Immunohistochemical staining exhibited that SLC16A1 protein overexpressed in high-grade gliomas compared with low-grade clinical glioma samples. All these findings suggest that SLC16A1 expression has a positive correlation with WHO pathological grading and poor survival. SLC16A1 might be a potential biomarker of prognosis in human gliomas.

Prognostic factors and clinical nomogram predicting survival in high-grade glioma.

Genomic-based tools have been used to predict poor prognosis high-grade glioma (HGG). As genetic technologies are not generally available in countries with limited resources, clinical parameters may be still necessary to use in predicting the prognosis of the disease. This study aimed to identify prognostic factors associated with survival of patients with HGG. We also proposed a validated nomogram using clinical parameters to predict the survival of patients with HGG. A multicenter retrospective study was conducted in patients who were diagnosed with anaplastic astrocytoma (WHO III) or glioblastoma (WHO IV). Collected data included clinical characteristics, neuroimaging findings, treatment, and outcomes. Prognostic factor analysis was conducted using Cox proportional hazard regression analysis. Then, we used the significant prognostic factors to develop a nomogram. A split validation of nomogram was performed. Twenty percent of the dataset was used to test the performance of the developed nomogram. Data from 171 patients with HGG were analyzed. Overall median survival was 12 months (interquartile range: 5). Significant independent predictors included frontal HGG (hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.40-0.60), cerebellar HGG (HR: 4.67; 95% CI: 0.93-23.5), (HR: 1.55; 95% CI: 1.03-2.32; reference = total resection), and postoperative radiotherapy (HR: 0.18; 95% CI: 0.10-0.32). The proposed nomogram was validated using nomogram's predicted 1-year mortality rate. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the curve of our nomogram were 1.0, 0.50, 0.45, 1.0, 0.64, and 0.75, respectively. We developed a nomogram for individually predicting the prognosis of HGG. This nomogram had acceptable performances with high sensitivity for predicting 1-year mortality.

Deep Transfer Learning and Radiomics Feature Prediction of Survival of Patients with High-Grade Gliomas.

Patient survival in high-grade glioma remains poor, despite the recent developments in cancer treatment. As new chemo-, targeted molecular, and immune therapies emerge and show promising results in clinical trials, image-based methods for early prediction of treatment response are needed. Deep learning models that incorporate radiomics features promise to extract information from brain MR imaging that correlates with response and prognosis. We report initial production of a combined deep learning and radiomics model to predict overall survival in a clinically heterogeneous cohort of patients with high-grade gliomas. Fifty patients with high-grade gliomas from our hospital and 128 patients with high-grade glioma from The Cancer Genome Atlas were included. For each patient, we calculated 348 hand-crafted radiomics features and 8192 deep features generated by a pretrained convolutional neural network. We then applied feature selection and Elastic Net-Cox modeling to differentiate patients into long- and short-term survivors. In the 50 patients with high-grade gliomas from our institution, the combined feature analysis framework classified the patients into long- and short-term survivor groups with a log-rank test P value < .001. In the 128 patients from The Cancer Genome Atlas, the framework classified patients into long- and short-term survivors with a log-rank test P value of .014. For the mixed cohort of 50 patients from our institution and 58 patients from The Cancer Genome Atlas, it yielded a log-rank test P value of .035. A deep learning model combining deep and radiomics features can dichotomize patients with high-grade gliomas into long- and short-term survivors.

PATZ1 Is Overexpressed in Pediatric Glial Tumors and Correlates with Worse Event-Free Survival in High-grade Gliomas.

Glial tumors are the leading cause of cancer-related death and morbidity in children. Their diagnosis, mainly based on clinical and histopathological factors, is particularly challenging because of their high molecular heterogeneity. Thus, tumors with identical histotypes could result in variable biological behaviors and prognoses. The PATZ1 gene has been recently shown to be expressed in adult gliomas, including glioblastomas, where it correlates with the proneural subtype and with a better prognosis. Here, we analyzed the expression of PATZ1 in pediatric gliomas, first at mRNA level in a public database, and then at protein level, by immunohistochemistry, in a cohort of 52 glial brain tumors from young patients aged from 6 months to 16 years. As for adult tumors, we show that PATZ1 is enriched in glial tumors compared to the normal brain, where it correlates positively and negatively with a proneural and mesenchymal signature, respectively. Moreover, we show that PATZ1 is expressed at variable levels in our cohort of tumors. Higher expression was detected in high-grade than low-grade gliomas, suggesting a correlation with the malignancy. Among high-grade gliomas, higher levels of PATZ1 have consistently been found to correlate with worse event-free survival. Therefore, our study may imply new diagnostic opportunities for pediatric gliomas.

Patient Reported Outcome (PRO) Among High-Grade Glioma Patients Receiving TTFields Treatment: A Two Center Observational Study.

Study design: A two center, observational study.Introduction: Patient reported outcome (PRO) plays an increasingly important role in the evaluation of novel therapies for tumor patients. It has been shown that tumor treating fields (TTFields) in combination with standard therapy prolong survival in high-grade glioma (hgG) patients. But critics claim that TTFields significantly impacts patients' everyday life due to side effects and average daily time on therapy (18 h) in a patient population with very limited life expectancy and high symptom burden. However, very limited data exist on PRO for TTFields treatment.Methods: This two center, observational study describes PRO of 30 hgG patients receiving TTFields in combination with chemotherapy. We introduced a device-specific questionnaire (DSQ) addressing device-specific restrictions and impact on daily live after 2 months of therapy. Additionally following questionnaires were used: EORTC (European Organization for Research and Treatment of Cancer), QLQ-30 (Quality of life of cancer patients), QLQ BN20 (Quality of life brain cancer module), QLQ FA13 (Cancer-related fatigue), and SSUK-8 (social support).Results: Surveys have been completed by 91% of enrolled patients. EORTC QLQ-30 revealed better physical, emotional, and cognitive function than social and role function of study cohort. TTFields users reported frequently on positive social support and a low level of detrimental interactions. Seventy one percent of patients felt affected in daily life due to TTFields at least 2–3 times per week up to several times per day while maintaining high therapy compliance. Most frequent device-specific restrictions were duration of therapy (74%), size (66%), and weight (70%) of the device and changing time and bonding of the transducer arrays (66%, mean duration: 43.6 min). Restrictions on exercise of hobbies/work (63%/61%), body care (71%), and sexuality/relationship (64%) were most relevant. Seventy percent would recommend TTFields to others and 67% would reuse TTFields treatment again based on their current experience.Conclusion: The study shows that although TTFields treatment frequently affects everyday life in all aspects, therapy compliance was high and 67% of patients would reconsider TTFields for themselves. We propose that findings of PRO be taken into account for medical consultation about TTFields and in future device development to deliver high-value patient-centered care.

Neutrophil-to-Lymphocyte Ratio: Can It Be Used as an Adjunct Tool to Predict Histopathological Grade of Brain Tumor?

Background Since histopathology is available only after surgery, clinical condition and radiological characters of the tumor are important factors on which a clinician counsels the patient of brain tumor to take a decision regarding the management. Neutrophil lymphocyte ratio (NLR), a marker of inflammation can be used as a prognostic marker to predict the survival in high-grade gliomas and metastases. We evaluated the utility of NLR as an adjunct tool in predicting the histopathological grade of brain tumors. Materials and Methods One hundred sixteen patients with a diagnosis of brain tumors planned for surgical excision or biopsy were enrolled in the study. NLR was estimated in the preoperative blood sample. Patients were grouped into low- and highgrade brain tumors and their mean NLRs were analyzed. Similar evaluation was carried out between the intra- and extra-axial tumors. Results Mean age of the study group was 40.14 years with 61 males. Seventy-eight patients had low-grade tumor and 38 patients had high-grade tumor. Sixty patients had extra-axial tumors and 56 patients had intra-axial tumors. The mean NLR of low-grade tumors was 1.68 ± 0.53 and that of high-grade tumors was 3.12 ± 0.74. NLR > 2.4 can be used to identify high-grade brain tumors with a sensitivity of 80%, specificity of 92%, positive predictive value of 82.1%, negative predictive value of 91%, an excellent impact with likelihood ratio (+) of 10.1, and an odds ratio of 54.1. The mean NLR of extra-axial tumors was 1.68 + 0.62 and that of intra-axial tumors was 2.64 ± 0.91. These observations were statistically significant with p -value < 0.05. Conclusions NLR is an easily available and inexpensive marker of systemic inflammation, which varies across different histopathological grades of brain tumors. Mean NLR is higher in high-grade tumors and also intra-axial tumors with a cutoff value of NLR > 2.4 and > 2.0, respectively.

Neutrophil-Lymphocyte Ratio Dynamics Is Useful to Distinguish between Recurrence and Pseudoprogression in High-Grade Gliomas

Distinguishing recurrence and pseudoprogression is a major challenge in the clinical practice of treatment for high-grade gliomas (HGGs). Neutrophil–lymphocyte ratio (NLR) had been reported to be closely related with survival in HGGs. We aimed to assess the predictive value of NLR in the differential diagnosis of recurrence and pseudoprogression. 135 patients with histologically confirmed HGGs were studied. All patients underwent focal radiotherapy and concomitant temozolomide (TMZ), followed by 6 cycles of TMZ if MRI showed no progressive enlargement of contrast-enhancing lesion. MRI evaluation was taken 4 weeks after concurrent chemoradiotherapy and then every 2 months later. NLR was calculated at 4 time points of pretreatment, 1 month after operation, 4 weeks following completion of RT-TMZ and MRI showed lesion enlarged or treatment completed. Forty-seven (34.8%) in 135 patients were found to be pseudoprogression (PsPD) and 28 (20.7%) were early disease progression (ePD). The mean pretreatment and post-treatment NLR was 4.2±2.1 and 5.1±3.5 respectively. The median overall survival in PsPD group (25.2 months) was significantly longer than ePD (15.4 months) and no progression group (nPD) (21.6 months) (p<0.001). Overall survival was significantly shorter in NLR>=4 cohort compared with NLR<4 (p=0.03), but no significant difference was found between PsPD and ePD (p=0.197). Patients with decreased NLR showed significantly longer survival than no decreased group (p<0.001) and decreased NLR was found significant difference between PsPD and ePD (p=0.022). Univariate and multivariate logistic regression analyses suggested that decreased NLR was an independent prognosis factor (p=0.031). Decreased NLR is an independent prognostic factor and useful to distinguish between recurrence and pseudoprogression in HGGs.

High-grade Glioma - A decade of care in Christchurch.

High-grade glioma (HGG) is a devastating illness. Our study aimed to investigate outcomes for patients with HGG treated in Christchurch focussing particularly on those diagnosed with glioblastoma mulitforme (GBM); compare GBM survival with international standards; examine factors associated with better prognosis; and assess the involvement of various allied health disciplines. A 10-year retrospective study of patients who were diagnosed and treated for HGG at Christchurch Hospital. Kaplan-Meier method was used to estimate survival. Predefined multivariate analysis was performed to investigate potential prognostic and predictive factors. A total of 363 patients were diagnosed with HGG at a median age of 64years with a 5-year overall survival of 6.1%. Patients with grade IV tumours had a poorer outcome than grade III patients (P=0.0002, log-rank test). Eighty-two per cent of patients had a surgical resection or biopsy of the tumour. For those patients with GBM, gross tumour resection followed by radical chemoradiation was associated with better survival compared with needle biopsy (HR=1.93, P=0.018); increasing age was negatively associated with survival (HR=1.02 per additional age year, P=0.037); however, waiting time between neurosurgery and radiation did not affect survival. Six per cent of patients received formal psychological input. Our survival outcomes were comparable with internationally published series. More research is required to improve survival in HGG, including molecular guided treatment, and better define treatment paradigms, such as for the elderly and frail.