Diagnosis Of High-grade Glioma Research Articles

Tumor-related epilepsy in high-grade glioma: a large series survival analysis.

Seizures are a common clinical occurrence in high-grade glioma (HGG). While many studies have explored seizure incidence and prevalence in HGG, limited studies have examined the prognostic effect of seizures occurring in the post-diagnosis setting. This study aims to assess the impact of seizure presentation on HGG survival outcomes. Single-center retrospective review identified 950 patients with histologically-confirmed high-grade glioma. Seizure presentation was determined by clinical history and classified as early onset (occurring within 30 days of HGG presentation) or late onset (first seizure occurring after beginning HGG treatment). The primary outcome, hazard ratios for overall survival and progression-free survival, was assessed with multivariable Cox proportional-hazards models. IDH1 mutation status (assessed through immunohistochemistry) was only consistently available beginning in 2015; subgroup analyses were performed in the subset of patients with known IDH1 status. Epileptic activity before (HR = 0.81, 95% CI = 0.68-0.96, P = 0.017) or after (HR = 0.74, 95% CI = 0.60-0.91, P = 0.005) HGG diagnosis associated with improved overall survival. Additionally, late seizure onset significantly associated with lower odds of achieving partial (OR = 0.25, 95% CI = 0.12-0.53, P = < 0.001) or complete (OR = 0.30, 95% CI = 0.18-0.50, P < 0.001) seizure control than patients with early seizure onset. Clinical seizures both at the time of diagnosis and later during the HGG treatment course are associated with improved overall survival. This association potentially persists for both IDH1-wildtype and IDH1-mutant patients, but further study is required.

E.2 Proof of concept for liquid biopsy: positive correlation between extracellular vesicles shed by high grade gliomas and volume of hypervascular tumour tissue on MRI

Background: High grade gliomas (HGGs) shed extracellular vesicles (EVs) into the bloodstream. EV-derived RNA (EV-RNA) can be detected in plasma, making it a potential biomarker for HGG recurrence after treatment. We sought to establish a baseline relationship between EV-RNA in plasma and hypervascular HGG tissue on MRI. Methods: Eight patients with a new diagnosis of HGG had measurements of plasma EV-RNA and contemporaneous dynamic susceptibility contrast (DSC) MRI. Patient-specific median signal intensity of corpus callosum (mSI-CC) was determined from 10 measurements on the relative cerebral blood volume (rCBV) map. Tumour tissue with signal intensity &gt; mSI-CC and &gt; 2x, &gt; 3x, &gt; 4x and &gt; 5x mSI-CC was segmented on the rCBV map. EV-RNA plasma concentration was correlated with tissue volumes. Results: Pearson correlation showed a significant positive relationship between EV-RNA plasma concentration and tissue volume with signal intensity &gt; mSI-CC (r(6) = 0.899, p = 0.002). No significant relationship could be detected for progressively smaller tissue volumes with signal intensity &gt; 2x, &gt; 3x, &gt; 4x and &gt; 5x mSI-CC. Conclusions: EV-RNA plasma concentration correlates strongly with the total volume of hypervascular HGG tissue on DSC MRI at baseline and merits further evaluation as a biomarker of tumour behaviour in longitudinal imaging studies.

P.100 Plasma extracellular vesicle sampling from high grade gliomas demonstrates a small RNA signature indicative of disease and identifies lncRNA RPPH1 as a novel biomarker

Background: High grade gliomas (HGGs) and cells of the tumour microenvironment secrete extracellular vesicles (EVs) into the plasma that contain genetic and protein cargo which function in paracrine signalling. Isolation of these EVs and their cargo could lead to an important tool that can inform on diagnosis and disease-course of HGGs. Methods: EVs were isolated using Vn96 capture from plasma obtained longitudinally from HGG patients. sRNA was enriched from the EVs, followed by next-generation sequencing, multidimensional scaling, differential expression, and in silico functional enrichment analyses. Results: Over 750 differentially expressed sRNA were identified between HGG and controls. Pathway analysis revealed miRNA highly enriched in both EV and HGG pathways demonstrating the validity of results in capturing a signal from HGG. Other sRNA included several novel HGG plasma-EV biomarkers including lncRNA RPPH1, RNY4, and RNY5. Furthermore, in paired longitudinal patient sampling, RPPH1 informed on surgical resection (decreased on resection) and importantly increased again with clinically defined progression. TCGA analysis demonstrated increased expression of RPPH1 in HGG tissue and additionally, higher expression of RPPH1 was associated with a worse disease-specific prognosis. Conclusions: The present study supports the role of plasma-EV sRNA sampling (and particularly RPPH1) as part of a multi-pronged approach to HGG disease course surveillance.

Full kinetic modeling analysis of [18F]fluorocholine Positron Emission Tomography (PET) at initial diagnosis of high-grade glioma

PurposeThe main objective was to characterize the tracer uptake kinetics of [18F]fluoromethylcholine ([18F]F-CHO) in high-grade gliomas (HGG) through a full PET kinetic modeling approach. Secondarily, we aimed to explore the relationship between the PET uptake measures and the HGG molecular features. Materials and methodsTwenty-four patients with a suspected diagnosis of HGG were prospectively included. They underwent a dynamic brain [18F]F-CHO-PET/CT, from which a tumoral time-activity curve was extracted. The plasma input function was obtained through arterial blood sampling with metabolite correction. These data were fitted to 1- and 2-tissue-compartment models, the best of which was selected through the Akaike information criterion. We assessed the correlation between the kinetic parameters and the conventional static PET metrics (SUVmax, SUVmean and tumor-to-background ratio TBR). We explored the association between the [18F]F-CHO-PET quantitative parameters and relevant molecular biomarkers in HGG. ResultsTumoral time-activity curves in all patients showed a rapid rise of [18F]F-CHO uptake followed by a plateau-like shape. Best fits were obtained with near-irreversible 2-tissue-compartment models. The perfusion-transport constant K1 and the net influx rate Ki showed strong correlation with SUVmax (r = 0.808–0.861), SUVmean (r = 0.794–0.851) and TBR (r = 0.643–0.784), p < 0.002. HGG was confirmed in 21 patients, of which those with methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) gene promoter showed higher mean Ki (p = 0.020), K1 (p = 0.025) and TBR (p = 0.001) than the unmethylated ones. Conclusion[18F]F-CHO uptake kinetics in HGG is best explained by a 2-tissue-compartment model. The conventional static [18F]F-CHO-PET measures have been validated against the perfusion-transport constant (K1) and the net influx rate (Ki) derived from kinetic modeling. A relationship between [18F]F-CHO uptake rate and MGMT methylation is suggested but needs further confirmation.

QLTI-11. TIMELINE FROM INITIAL MRI TO INTERVENTION IN NEWLY DIAGNOSED HIGH GRADE GLIOMA

Abstract OBJECTIVE Prompt treatment of high-grade glioma is crucial for prolonging life. In an attempt to identify factors that lead to delays in treatment, we evaluated the amount of time between initial MRI and treatment start date for our patients with newly diagnosed high grade glioma. METHODS This was a retrospective chart review study. Adults over the age of 18 years of age with newly diagnosed high grade glioma were included if they were seen by the neuro-oncology department at Loma Linda University Medical Center. Reviewed charts were dated from November 2020 to August 2022. We evaluated the amount of time between initial MRI and several important milestones in the diagnosis and treatment of high grade glioma, including resection; biopsy results; neuro-oncology consult; radiation-oncology consult; date that chemotherapy was ordered, received by the patient, and initiated; and radiation therapy start date. RESULTS Twenty-two patients with new diagnosis of high-grade glioma were identified. Six patients were excluded due to complicated treatment courses involving outside facilities. Sixteen patients were included in the study. Thirteen patients (81%) had a diagnosis of glioblastoma, 2 (12%) had a diagnosis of diffuse midline glioma, and 1 (6%) had a diagnosis of anaplastic astrocytoma. The mean number of days between initial MRI and chemotherapy start date was 88. Prolonged timelines were seen in all analyzed metrics. CONCLUSIONS There is a significant delay in chemotherapy initiation for patients with high grade glioma at our facility. We also provide a framework for other institutions to evaluate their system processes in order to improve care delivery.

NCOG-17. RETROSPECTIVE REVIEW OF THE TREATMENT OF VENOUS THROMBOEMBOLISM IN GLIOBLASTOMA PATIENTS RECEIVING BEVACIZUMAB

Abstract Patients with malignant gliomas have an inherently high risk of venous thromboembolism (VTE).1 Bevacizumab is an anti-vascular endothelial growth factor (VEGF) monoclonal antibody commonly used in the treatment of recurrent high-grade gliomas and is known to increase the risk of VTE as well as intracranial hemorrhage.2 Anticoagulation (AC) for VTE also increases the risk intracranial hemorrhage in patients with malignant brain tumors.3 This makes the treatment of VTE in patients with GBM receiving bevacizumab therapy particularly challenging. Here we completed a single center retrospective chart review of patients with glioblastoma (GBM) treated concurrently with anticoagulation for VTE and bevacizumab therapy. The purpose of this review was to assess the safety of concurrent use of these therapies and to note any statistically significant difference in the incidence of hemorrhagic complications between patients treated with anticoagulation at therapeutic versus prophylactic dosing. METHODS: 144 patients with a diagnosis of high-grade glioma and were treated at UCI from 1/1/2019 through 1/1/2022 were screened for the study. 13 GBM patients on treatment with bevacizumab and concurrent anticoagulation were included. Clinical records of these patients were reviewed for the incidence of intracranial hemorrhage or any clinically significant bleeding. RESULTS: The incidence of ICH in GBM patients on concurrent therapy with bevacizumab and anticoagulation was 7.7% and the incidence of other minor bleeding complications was 7.7%. ICH and other minor bleeding was exclusively seen in patients on therapeutic anticoagulant dosing. No bleeding complications were noted in patients on prophylactic AC dosing. CONCLUSION: There is a risk of ICH in patients receiving both bevacizumab and anticoagulation, however compared to historical data, the incidence reported in our study is less than the incidence of ICH in GBM patients on anticoagulation alone. Our study suggests that it is relatively safe to treat patients with these therapies simultaneously.

DISP-05. UNDERSTANDING THE INDIVIDUAL CHALLENGES AND EXPERIENCES OF YOUNG ADULTS WITH A DIAGNOSIS OF GLIOBLASTOMA AND HIGH-GRADE ASTROCYTOMA

Abstract High-grade gliomas are highly aggressive and fatal primary malignant brain tumors in adults with ineffective existing treatment methods. Older adults are greatly impacted by high-grade gliomas as they are more common among this population. Young adults (individuals aged 18-39) are uniquely impacted by high-grade glioma. However, there are few resources and information available to address these unique needs. The purpose of this study is to explore the lived experience of this population to inform the development of resources to help address their specific needs. A qualitative descriptive design drawing on thematic analysis was chosen to conduct and analyze interviews with young adult high-grade glioma patients at the Princess Margaret Cancer Center. Interviews focused on patient experiences as a high-grade glioma patient at Princess Margaret Cancer Center, the challenges they face and changes they would like implemented. A coding framework was created to determine emerging themes using qualitative data analysis software NVivo 10. To date, 5 interviews (1 men; 4 women; age range 19-37) have been completed. Interviews described the challenges living with high-grade glioma as a young adult and the changes in resources and support services patients would like implemented. Experiences highlighted 1) difficulty accepting this change in life and disruptions brought upon life goals and plans at the young adult age; 2) an overall lack of young adult high-grade glioma specific education, advocacy and support resources 3) A call for more community building and connecting so patients do not feel alone through this diagnosis. These patient interviews highlight a connection between the young adult age and high-grade glioma diagnosis and the challenges experienced and the services required. These results will serve as the foundation to advocate for the creation of tools that cater to patient needs of young adult high-grade glioma patients.

BIOM-19. PLASMA EXTRACELLULAR VESICLE SAMPLING FROM HIGH GRADE GLIOMA PATIENTS DEMONSTRATES A SMALL RNA SIGNATURE INDICATIVE OF DISEASE AND IDENTIFIES LNCRNA RPPH1 AS A HIGH GRADE GLIOMA BIOMARKER

Abstract High grade gliomas (HGGs) and cells of the tumour microenvironment (TME) secrete extracellular vesicles (EVs) into the plasma that contain genetic and protein cargo which function in paracrine signaling. Isolation of these EVs and their cargo from plasma could lead to a simplistic tool that can inform on diagnosis and disease course of HGG. In the present study, plasma extracellular vesicles (EVs) were captured utilizing a peptide affinity method (Vn96 peptide) from high grade glioma (HGG) patients and normal controls followed by next generation sequencing (NovaSeq6000) to define a small RNA (sRNA) signature unique to HGG. Over 750 differentially expressed sRNA (miRNA, snoRNA, lncRNA, tRNA, mRNA fragments and non-annotated regions) were identified between HGG and controls. MiEAA 2.0 pathway analysis of the miRNA in the sRNA signature revealed miRNA highly enriched in both EV and HGG pathways demonstrating the validity of results in capturing a signal from the TME. Also revealed were several novel HGG plasma EV sRNA biomarkers including lncRNA RPPH1 (Ribonuclease P Component H1), RNY4 (Ro60-Associated Y4) and RNY5 (Ro60-Associated Y5). Furthermore, in paired longitudinal patient plasma sampling, RPPH1 informed on surgical resection (decreased on resection) and importantly RPPH1 increased again on clinically defined progression. The present study supports the role of plasma EV sRNA sampling (and particularly RPPH1) as part of a multi-pronged approach to HGG disease course surveillance.

Multi-Institutional Report of Re-Irradiation for Recurrent High-Grade Glioma

Significant heterogeneity exists with regards to prior published reports of re-irradiation (re-RT) in patients with recurrent high grade glioma (HGG). A multi-institutional database of 10 academic centers across the United States was created to analyze prognostic outcomes for re-RT for recurrent HGG, which included WHO Grade III and Grade IV tumors. Patients with HGG who had initially received standard radiotherapy (RT) and were subsequently treated with a course of re-RT at recurrence were included in the study. Factors assessed to delineate a significant association with overall survival (OS) and toxicity included age, KPS, number of relapses, dose, use of bevacizumab (BEV) or temozolomide (TMZ), time from prior RT, histology, RT target, re-RT target> 5cm and extent of resection, and MGMT methylation status. The Kaplan-Meier Method was used to estimate OS. Cox proportional hazards regression models were used to identify factors associated with OS. Toxicity outcomes were assessed using logistic regression. Significance was assumed if p<0.05. Data management and decision management software were used for all analyses. Between 2001 and 2022, 280 patients from 10 academic institutions were treated with re-RT for diagnosis of recurrent HGG. 133 patients (71.1%) had a histologic glioblastoma (GBM) at the time of re-RT, with the remainder having Grade 3 gliomas. Median dose delivered at re-RT was 47 Gy BED10 (IQR 47 - 53 Gy BED10), with the most common regimen being 35 Gy in 10 fractions. 83 patients (56%) had GTV greater than 5 cm treated with re-RT. 183 patients (79%) received concurrent systemic therapy, including 95 (41%) who received concurrent TMZ and 86 (45%) who received concurrent BEV. Median OS for the entire cohort was 10 months. Increasing dose at re-RT was associated with improved OS (OR 0.80 95% CI 0.67-0.95, p = 0.10 per 10 Gy BED10), as was dose greater than 47 Gy BED10, which is equivalent to 35 Gy in 10 fractions (OR 0.70, 95% CI 0.54-0.91). Concurrent TMZ was also associated with improved OS (OR 0.68, 95% CI 0.46-0.83, p < 0.01). 32/143 (22%) patients evaluable for toxicity experienced Grade 2 or greater adverse radiation effect (ARE). Use of BEV was associated with decreased toxicity (OR 0.45, 95% CI 0.21-0.98, p = 0.05). Dose at re-RT (OR 1.07 per 10 Gy BED10, p = 0.78), a GTV > 5cm (OR 1.39, p = 0.44), and the use of concurrent TMZ (OR 1.90, p = 0.10) were not associated with Grade 2 or greater ARE. Higher dose of re-RT and use of concurrent TMZ led to improved OS in recurrent HGG patients without an associated increased rate of ARE. Use of BEV decreased the likelihood of Grade 2 or greater ARE in the re-RT setting for these recurrent HGG patients.

Evaluation of the Diagnostic Performance of F18-Fluorodeoxyglucose-Positron Emission Tomography, Dynamic Susceptibility Contrast Perfusion, and Apparent Diffusion Coefficient in Differentiation between Recurrence of a High-grade Glioma and Radiation Necrosis.

Differentiation between recurrence of brain tumor and radiation necrosis remains a challenge in current neuro-oncology practice despite recent advances in both radiological and nuclear medicine techniques. The purpose of this study was to compare the diagnostic performance of dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging (MRI), apparent diffusion coefficient (ADC) derived from diffusion-weighted imaging, and F18-fluorodeoxyglucose-positron emission tomography (F18-FDG-PET) in the differentiation between the recurrence of a high-grade glioma and radiation necrosis. Patients with a diagnosis of high-grade glioma (WHO Grades III and IV) who had undergone surgical resection of the tumor followed by radiotherapy with or without chemotherapy were included in the study. DSC perfusion, diffusion-weighted MRI, and PET scan were acquired on a hybrid PET/MRI scanner. For each lesion, early and delayed tumor-to-brain ratio (TBR), early and delayed maximum standardized uptake value (SUVmax), normalized ADC ratio, and normalized relative cerebral blood volume (rCBV) ratio were calculated and the pattern of lesional enhancement was noted. The diagnosis was finalized with either histopathological examination or the characteristics on follow-up imaging. The statistical analysis using the receiver operator characteristic curves was done to determine the diagnostic performance of DSC perfusion, 18-F FDG-PET, and ADC in differentiation between tumor recurrence and radiation necrosis. Fifty patients were included in the final analysis, 32 of them being men (64%). A cutoff value of early TBR >0.8 (sensitivity of 100% and specificity of 80%), delayed TBR >0.93 (sensitivity of 92.3% and specificity of 80%), early SUVmax >10.2 (sensitivity of 76.9% and specificity of 80%), delayed SUVmax >13.2 (sensitivity of 61.54% and specificity of 100%), normalized rCBV ratio >1.21 (sensitivity of 100% and specificity of 60%), normalized ADC ratio >1.66 (sensitivity of 38.5% and specificity of 80%), and Grade 3 enhancement (sensitivity of 100% and specificity of 60%) were found to differentiate recurrence from radiation necrosis. Early TBR had the highest accuracy (94.44%), while ADC ratio had the lowest accuracy (50%). A combination of early TBR (cutoff value of 0.8), late TBR (cutoff value of 0.93), and rCBV ratio (cutoff value of 1.21) showed a sensitivity of 100%, specificity of 92.3%, positive predictive value of 88.9%, negative predictive value of 93.7%, and an accuracy of 96.6% in discrimination between radiation necrosis and recurrence of tumor. F18-FDG-PET and DSC perfusion can reliably differentiate tumor recurrence from radiation necrosis, with early TBR showing the highest accuracy. ADC demonstrates a low sensitivity, specificity, and accuracy in differentiating radiation necrosis from recurrence. A combination of early TBR, delayed TBR, and rCBV may be more useful in discrimination between radiation necrosis and recurrence of glioma, with this combination showing a better diagnostic performance than individual parameters or any other combination of parameters.

Diffusion basis spectrum imaging as an adjunct to conventional MRI leads to earlier diagnosis of high-grade glioma tumor progression versus treatment effect.

Following chemoradiotherapy for high-grade glioma (HGG), it is often challenging to distinguish treatment changes from true tumor progression using conventional MRI. The diffusion basis spectrum imaging (DBSI) hindered fraction is associated with tissue edema or necrosis, which are common treatment-related changes. We hypothesized that DBSI hindered fraction may augment conventional imaging for earlier diagnosis of progression versus treatment effect. Adult patients were prospectively recruited if they had a known histologic diagnosis of HGG and completed standard-of-care chemoradiotherapy. DBSI and conventional MRI data were acquired longitudinally beginning 4 weeks post-radiation. Conventional MRI and DBSI metrics were compared with respect to their ability to diagnose progression versus treatment effect. Twelve HGG patients were enrolled between August 2019 and February 2020, and 9 were ultimately analyzed (5 progression, 4 treatment effect). Within new or enlarging contrast-enhancing regions, DBSI hindered fraction was significantly higher in the treatment effect group compared to progression group (P = .0004). Compared to serial conventional MRI alone, inclusion of DBSI would have led to earlier diagnosis of either progression or treatment effect in 6 (66.7%) patients by a median of 7.7 (interquartile range = 0-20.1) weeks. In the first longitudinal prospective study of DBSI in adult HGG patients, we found that in new or enlarging contrast-enhancing regions following therapy, DBSI hindered fraction is elevated in cases of treatment effect compared to those with progression. Hindered fraction map may be a valuable adjunct to conventional MRI to distinguish tumor progression from treatment effect.

PATH-22. CLINICAL FEATURES AND MOLECULAR CHARACTERIZATION OF LEPTOMENINGEAL DISEASE IN PATIENTS WITH HIGH GRADE GLIOMA

Abstract INTRODUCTION Leptomeningeal disease (LMD) is a challenging complication of high grade glioma (HGG) and critical questions remain unanswered regarding clinicopathologic risk factors, molecular associations, and optimal treatment. METHODS Patients with molecularly-profiled HGG (Caris Life Sciences; Phoenix, AZ) with LMD at two institutions were included. Medical records were reviewed for clinicopathological characteristics, treatment, and outcome. Kaplan-Meier estimates of patient survival were performed on censored data using Cox’s proportional hazard model. RESULTS 43 patients (male: 33, female: 10; median age: 56 years) were identified, comprising 41 grade 4 (glioblastoma: 38; gliosarcoma: 2; H3K27M diffuse midline glioma: 1) and 2 grade 3 tumors (astrocytoma: 1; pleomorphic xanthoastrocytoma: 1). LMD diagnosed at HGG diagnosis (n=18) versus recurrence (n=22) was associated with longer post-LMD survival [pLMD-OS: 15.3m vs. 4.8m, HR: 0.07, 95% CI: 0.02-0.29, p=0.0004] but similar overall survival [mOS: 15.3m vs. 12.3m; HR: 0.82; 95% CI: 0.36-1.85; p=0.63]. Pathology-diagnosed LMD (n=15) versus MRI-diagnosed LMD (n=26) was associated with longer post-LMD survival [pLMD-OS: 15.4m vs. 5.2m, HR: 14.9, 95% CI: 0.01-0.30, p=0.0004] but similar overall survival [mOS: 17.1m vs. 12.3m; HR: 0.66; 95% CI: 0.3-1.58; p=0.38]. Post-LMD survival was significantly prolonged for supratentorial (n=28) versus infratentorial/spinal (n=4) locations regardless of the diagnostic modality [pLMD-OS: 2.6m vs. 11.3m, HR: 14.4, 95% CI: 2.73-75.7, p=0.0017], and did not significantly differ between symptomatic (n=20) and asymptomatic (n=23) patients [pLMD-OS: 4.8m vs. 11.2m, HR: 1.75, 95% CI: 0.82-3.77, p=0.15). pTERT mutation (81%), EGFR amplification (43%), and MGMT methylation (33%) were prevalent but IDH1 mutation was rare (2.8%). Comparison with a separate glioblastoma cohort (n=1400) suggested more frequent amplification of CHIC2, MDM4, and KDR, higher mutation rates of RUNX1, APC, and RAD51C, colder tumor microenvironment (TME), and lower expression of immune checkpoint-related genes. CONCLUSIONS Clinicopathological characteristics affect post-LMD survival, and cohort comparison suggests molecular and TME differences in LMD-HGG tumors.

QOL-09. NAVIGATING DISABILITY INSURANCE FOR PATIENTS DIAGNOSED WITH LOW-GRADE GLIOMA

Abstract Central nervous system tumors and their treatments can cause neurologic, cognitive, and psychiatric symptoms that restrict a patient’s ability to work. In the United States, a diagnosis of high-grade glioma (grade 3 or 4) medically qualifies a patient for disability benefits through Social Security. Low-grade gliomas can be similarly debilitating, with at least 50% of patients presenting with one or more cognitive deficits and 80% of patients with tumor-related epilepsy. In light of these serious symptoms, it is unsurprising at least half of patients with low-grade glioma do not return to work within one year of diagnosis. Yet a diagnosis of low-grade glioma does not in and of itself qualify patients for disability benefits; the burden of proof is substantially higher. Thus, patients with low-grade glioma require special attention as they seek disability benefits. Here, we outline the process of medical documentation to support disability benefits, Security Disability Insurance (SSDI) and Supplemental Security Income (SSI). We provide a template to assist providers in facilitating the application process for patients with low-grade glioma seeking disability benefits. The provider’s role is not to simply “declare” a patient disabled, but rather to provide comprehensive documentation regarding the patient’s diagnosis, treatment, response to treatment, symptoms, and functional status in the medical record. As cognitive symptoms and seizures are two key sources of disability in low-grade glioma patients, referrals to neuropsychology and epileptology, among other sub-specialties, are key to improve patient care and bolster documentation of the patient’s symptoms in these domains. Likewise, connecting patients with social workers and disability claims representatives can assist them in navigating the complicated application process. Providers are better able to help their patients navigate the disability application process when they understand how disability evaluations work and what key information evaluators seek.

A Randomized Trial of Comparative Dosimetric Study of Radiotherapy in High Grade Gliomas Based on the Guidelines of 2019-NRG and EORTC Target Delineation

<h3>Purpose/Objective(s)</h3> Postoperative radiotherapy is important for high-grade glioma (WHO Grade 3-4), but the optimal way for contouring the target area for radiotherapy is still unclear. The purpose of this randomized trial was to compare the dosimetric differences in radiation treatment plans (TPS) generated based on the European Organization for Research and Treatment of Cancer (EORTC) and NRG consensus (NRG-2019) guidelines to provide evidence for optimal target delineation for high-grade glioma. <h3>Materials/Methods</h3> Patients with diagnosis of high-grade glioma were randomly assigned (1:1) to receive postoperative radiotherapy based on either EORTC guideline or NRG-2019 guideline. We report the result of dosimetric comparison first. In 13 high grade glioma patients, both EORTC and NRG-2019 radiation treatment plans were generated for dosimetric comparison. For EORTC group, the prescription dose was 95% PTV 60 Gy in 30 fractions. The gross tumor volume (GTV) including resection cavity and residual tumor encompassed the T1-weighted images (T1WI) and T2 FLAIR contrast-enhancing lesion. For NRG-2019group, GTV involved the T1-weighted images (T1WI) and T2 FLAIR contrast-enhancing foci and peritumoral edema on the preoperative CT or MRI. The prescription dose of PTV1 was 46 Gy in 23 fractions. The areas were then diminished to contain merely the contrast enhancing foci with a 2.5 cm margin as CTV2, and PTV2 was equal the CTV2 plus 0.3 cm margin for additional prescription dose was 14 Gy in 7 fractions. It should be noted that CTV1 and CTV2 were trimmed according to the anatomical barriers, falx, ventricles, etc. This trial is registered with chictr.org.cn, number ChiCTR2100046667. <h3>Results</h3> The median volume for PTV of EORTC plans, PTV1 of NRG-2019 plans, PTV2 of NRG-2019 plans were 336.6 cm³ (range 161.1-511.5 cm³), 365.3 cm³ (range 123.4-535.0 cm³), and 263.2 cm³ (range 116.8-497.7 cm³), respectively. Both treatment plans were found to have similar efficiency and evaluated as acceptable for patient treatment. Both treatment plans showed well conformal index and homogeneity index and were not statistically significantly different. There was no significant difference in the volume percent of brain irradiated to 30 Gy, 46 Gy, and 60 Gy according to different target delineations (P = 0.397, P = 0.590 and P = 0.739, respectively). These two plans also showed no significant differences in the doses to the brainstem, optic chiasm, optic nerve, lens, eyes, pituitary, and temporal lobes (P = 0.858, P = 0.858, 0.701, P = 0.794, P = 0.701, P = 0.427, P = 0.489, P = 0.898, P = 0.626, P = 0.942 and P = 0.161, respectively). <h3>Conclusion</h3> Compared with EORTC guidelines for postoperative radiotherapy for high-grade glioma, the NRG-2019 target area delineation guidelines were able to include peritumor edema in the CTV without increasing the radiation dose to organs at risk (OARs). This study further provides a foundation for the application of the NRG-2019 consensus in radiotherapy for patients with high-grade gliomas.

Treatment Patterns and Outcomes of Patients with High-Grade Glioma during the COVID-19 Pandemic

Purpose/Objective(s)During the first year of the COVID-19 pandemic there was global disruption in the provision of healthcare, causing significant pressure on hospital resources. High-grade gliomas (HGG) are rapidly progressive tumors, so patients with delays in diagnosis or treatment due to COVID-19-related disruptions might have poor outcomes. Therefore, we retrospectively evaluated the impact of the COVID-19 pandemic on treatment patterns and outcomes of patients with HGG in British Columbia (BC).Materials/MethodsA case cohort with a pathologic diagnosis of HGG (grade 4 astrocytoma and glioblastoma) treated at BC Cancer centers with radiotherapy between March 1, 2020 – March 1, 2021 (“COVID era”), and a control cohort treated between March 1, 2018 – March 1, 2019 (“pre-COVID era”) were identified. Patient demographics, tumor characteristics, treatment details, and dates of radiographic progression and death were included in the chart review. Analyses were performed with one-way ANOVA and Chi-squared tests for comparisons between eras. The Kaplan-Meier method was used to assess progression-free survival (PFS) and overall survival (OS) and differences in outcome between eras were investigated using the log-rank test.Results164 patients were identified: 85 in the pre-COVID era and 79 in the COVID era. There was no statistically significant baseline difference in age, sex, comorbidities, ECOG, tumor diameter, IDH mutation status, or MGMT methylation status between eras. There was also no statistically significant difference between time from symptom onset to first imaging, time from first imaging to surgery, time from surgery to oncologic consultation between eras, and time from surgery to radiotherapy. Significantly more patients were managed with biopsy relative to partial or gross total resection during the COVID era 22% (17/79) than the pre-COVID era 13% (11/85) (p = 0.04). However, radiation treatment (RT) did not differ between eras, with similar rates of conventionally fractionated RT in the pre-COVID era (87%, 74/85) and the COVID era (82%, 65/79) (p = 0.23). Use of concurrent and/or adjuvant temozolomide also was not significantly different between eras (p = 0.27 and p = 0.19, respectively). Median PFS was 7.0 months in both eras (CI95 = 5.5 – 8.5 months for pre-COVID era, CI95 = 5.8 – 8.2 months for COVID era, p = 0.3), and median OS was 13 months in the pre-COVID era (CI95 = 10.3 – 15.7 months) and 16 months in the COVID era (CI95 =11.5 – 20.5 months), though this difference was not significant (p = 0.09).ConclusionTo our knowledge, this is the first study to assess outcomes of patients treated for HGG during the COVID-19 pandemic. We found that, despite less use of surgery in the COVID era, the outcomes of patients with HGG were not affected.

Low Grade Glioma - A COVID Low Surgical Priority?

Abstract AIMS During the COVID pandemic (March 2020) SBNS published guidance advising that low grade gliomas (LGG) should be categorised as “low surgical priority”, therefore surgery could be delayed by six months. Aims: (1) Examine the effect of the COVID pandemic on the time taken from neuro-oncology MDT discussion to surgery in presumed LGG. (2) Investigate the proportion of presumed LGG receiving an integrated diagnosis of high grade glioma (HGG) before and during the COVID pandemic. METHOD Retrospective case note analysis of patients with presumed LGG including radiological and histopathological reports. Population split into two groups – Group A pre-pandemic (March 2019-2020) and Group B mid-pandemic (March-December 2020). RESULTS Forty-three patients (30M, 13F) with presumed LGG were identified – 23/43 in Group A and 20/43 in Group B. Mean age was 45 years (26-77y). Twenty-two patients (Group A 12/23 (52%) &amp; Group B 10/20 (50%)) had no radiological features of transformation. Mean number of days between discussion and surgery was 32 (2-96 days, SD=28) for group A and 98 (6-286 days, SD=92) for group B (p=.006: [95% CI: 21-110]). Fifteen patients in each group (65% v 75%) had an integrated diagnosis of HGG (p=.486). Of the patients with no radiological features of transformation 6 (50%) had a HGG in Group A and 7 (70%) in Group B (p=.342). CONCLUSION During the COVID pandemic patients with presumed LGG had their surgical management significantly delayed, with an increase in the proportion who were diagnosed with HGG. Presumed LGG patients should have higher surgical priority even when resources are constrained.

JS09.7.A Reirradiation for recurrent high grade glioma (HGG) patients: results of a single arm prospective phase 2 study

Abstract Background Standard of care for recurrent high grade glioma (HGG) is missing. Several treatment options have been investigated including re-irradiation (re-RT). Results are promising but provided by retrospective studies. We designed a single arm prospective phase II study aiming to evaluate efficacy, and toxicity of re-irradiation. Material and Methods Adults patients with good performance status, HGG diagnosis reclassified according to the new 2021 fifth edition WHO CNS classification, an interval time (IT) from previous RT ≥ 6 months were included. Outcome was evaluated by MRI imaging at 1 month, and every 3 months thereafter. Toxicities were evaluated in terms of radionecrosis occurrence, and neurocognitive status. Results Ninety recurrent HGG patients were treated, 11 oligodendroglioma grade 3, 18 astrocytoma grade 3 and 4, and 61 glioblastoma grade 4. The median age was 54 years, and majority had KPS 90-100. The median IT between first-RT and re-RT was 24 months. Re-surgery has been performed in 56.6%, and chemotherapy in 53.3%. The median follow up time was 64 months; median overall survival (OS) time,1,2,3-year OS rates were 17 months (95%CI 14-19), 66.7%±4.9, 32.6%±5.0, and 22.2 ± 4.7. Prognostic factors impacting on survival were age (p = 0.0154), IT between first RT and re-RT (p = 0.0051), glioma grade (p = 0.0090), and IDH status (p = 0.0001). Radionecrosis grade 2-3 occurred in 9 (10%) patients; neurocognitive functions remained stable until disease progression. Conclusion Re-RT proved to be a safe and feasible treatment option with low toxicity. Younger patients with grade 3 IDH mutated gliomas, and a longer IT had the better outcome.

312TiP Impact of early palliative care integration on quality of life and symptom burden in patients with high-grade glioma

High-grade gliomas (HGG) have a poor prognosis despite improvements using a multimodal approach. The progressive decline in neurological function and quality of life can have a devastating impact on patients, and caregivers. Palliative Care (PC) follow-up has proven benefits in terms of quality of life and cost savings for health care services. Guidelines recommend integrating PC as early as possible in the cancer management plan. However it’s often done at a later stage of disease progression. MATERIALS AND METHODS: Prospective, unblinded, randomized, controlled study, assigning eligible patients according to a 1:1 distribution without stratification, in control and intervention arms. TARGET POPULATION: Patients with an initial diagnosis of HGG, referred to a Medical Oncology consultation. PRIMARY ENDPOINTS Quality of life and symptom burden. SECONDARY ENDPOINT Overall survival, number and time of hospitalizations, number of visits to the ER. RECRUITING TIME: 6 months (March-August 2022). FOLLOW-UP: 2 years INTERVENTION: After referral by multidisciplinary meeting, at the first Medical Oncology consultation, a proposal for integration in the project will be made and informed consents will be obtained. Patients included will be distributed in a 1:1 ratio between the control arm (CA) (standard of care at the institution) and the intervention arm (IA) (standard of care + early follow-up in PC consultation). The QLQ-C30 and FACT-L questionnaires will be applied and clinical and socio-demographic data will be collected. Patients in the IA will be called for PC consultation within 2 weeks. The frequency of PC follow-up will be individualized. In both arms, questionnaires and updated clinical data will be collected at baseline, one month later, and then every 2 months in the first year and every 4 months in the second year. The authors.

Radiosurgery and Stereotactic Brain Radiotherapy with Systemic Therapy in Recurrent High-Grade Gliomas: Is It Feasible? Therapeutic Strategies in Recurrent High-Grade Gliomas.

Purpose. For recurrent high-grade gliomas (HGG), no standard therapeutic approach has been reported; thus, surgery, chemotherapy, and re-irradiation (re-RT) may all be proposed. The aim of the study was to evaluate safety and efficacy of re-RT by radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) in association to chemotherapy in patients with recurrent HGG. Material/Methods: All patients with histological diagnosis of HGG that suffered by recurrent disease diagnosed by magnetic resonance imaging (MRI), according to Response Assessment in Neuro-Oncology (RANO) criteria, after primary/adjuvant chemo-radiotherapy treatment and underwent to re-RT by SRS/FSRT were included in the analysis. Second-line chemotherapy was administered. Outcomes were evaluated by neurological examination and brain MRI performed 1 month after re-RT and then every 2–3 months. Results: From November 2019 to September 2021, 30 patients presenting recurrent HGG underwent re-RT. Median dose was 24 Gy (range 15–36 Gy), and median fractions was 5 (range 1–6). Twenty-one patients (70%) had RPA class ≤ IV. One patient had a histological diagnosis of anaplastic oligodendroglioma, 24 patients (80%) were affected by glioblastoma (GBM) including 3 cases of multifocal form, and 5 patients (17%) by anaplastic astrocytoma. Median time between primary/adjuvant RT and disease recurrence was 8 months. In six cases (20%) re-operation was performed, and in most cases (87%), a second line of systemic therapy was administrated. At a median follow-up time from recurrence of 13 months (range 6–56 months), 10 patients (33%) were alive: 2 patients with partial response disease, 7 patients with stable disease, and 1 patient with out-field progression disease. Of the 20 patients who died (67%), 15 (75%) died for progression disease and 5 (25%) for other causes (3 due to septic event, 1 due to thrombo-embolic event, and 1 due to car accident). Median OS and PFS after recurrence were 12.1 and 11.2 months. Six-month and one-year OS were, respectively, 81% and 51%. No acute or late neurological side effects grade ≥ 2 and no case of radio-necrosis were reported. One patient experienced, after reintervention and during Regorafenib treatment (administered 40 days after surgery), dehiscence of the surgical wound. In three cases, grade 2 distal paresthesia was reported. Grade 3–4 hematologic toxicity occurred in seven cases. Three case of grade 5 toxicities during chemotherapy were reported: three septic events and one thrombo-embolic event. Conclusion. Re-RT with SRT/FSRT in association with second-line systemic therapy is a safe and feasible treatment for patients with HGG recurrence. Validation of these results by prospective studies is needed.

Diagnostic Accuracy of PET/CT or PET/MRI Using PSMA-Targeting Radiopharmaceuticals in High-Grade Gliomas: A Systematic Review and a Bivariate Meta-Analysis.

Background: Several studies proposed the use of positron emission tomography (PET) with Prostate Specific Membrane Antigen (PSMA)-targeting radiopharmaceuticals in brain tumors. Our aim is to calculate the diagnostic accuracy of these methods in high-grade gliomas (HGG) with a bivariate meta-analysis. Methods: A comprehensive literature search of studies on the diagnostic accuracy of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals in HGG was performed. Original articles evaluating these imaging methods both in the differential diagnosis between HGG and low-grade gliomas (LGG) and in the assessment of suspicious HGG recurrence were included. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and diagnostic odds ratio (DOR) including 95% confidence intervals (95% CI) were calculated. Statistical heterogeneity was also assessed using the I2 test. Results: The meta-analysis of six selected studies (157 patients) provided the following results about PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals in the diagnosis of HGG: sensitivity 98.2% (95% CI: 75.3–99.9%), specificity 91.2% (95% CI: 68.4–98.1%), LR+ 4.5 (95% CI: 2.2–9.3), LR− 0.07 (95% CI: 0.04–0.15), and DOR 70.1 (95% CI: 19.6–250.9). No significant statistical heterogeneity among the included studies was found (I2 = 0%). Conclusions: the quantitative data provided demonstrate the high diagnostic accuracy of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals for HGG detection. However, more studies are needed to confirm the promising role of PSMA-targeted PET in this clinical setting.