Search

PURPOSE To compare clinical outcomes in a cohort of patients with advanced non–small-cell lung cancer (NSCLC) with targetable genomic alterations detected using plasma-based circulating tumor DNA (ctDNA) or tumor-based next-generation sequencing (NGS) assays treated with US Food and Drug Administration–approved therapies at a large academic research cancer center. METHODS A retrospective review from our MD Anderson GEMINI database identified 2,224 blood samples sent for ctDNA NGS testing from 1971 consecutive patients with a diagnosis of advanced NSCLC. Clinical, treatment, and outcome information were collected, reviewed, and analyzed. RESULTS Overall, 27% of the ctDNA tests identified at least one targetable mutation and 73% of targetable mutations were EGFR-sensitizing mutations. Among patients treated with first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapies, there were no significant differences in progression-free survival of 379 days and 352 days ( P value = .41) with treatment based on tissue (n = 40) or ctDNA (n = 40), respectively. Additionally, there were no differences in progression-free survival or objective response rate among those with low (n = 8, 0.01%-0.99%) versus high (n = 16, ≥ 1%) levels of ctDNA of the targetable mutation as measured by variant allele frequency (VAF). Overall, there was excellent testing concordance (n = 217 tests) of > 97%, sensitivity of 91.7%, and specificity of 99.7% between blood-based ctDNA NGS and tissue-based NGS assays. CONCLUSION There were no significant differences in clinical outcomes among patients treated with approved EGFR-TKIs whose mutations were identified using either tumor- or plasma-based comprehensive profiling and those with very low VAF as compared with high VAF, supporting the use of plasma-based profiling to guide initial TKI use in patients with metastatic EGFR-mutant NSCLC.

Purpose: Lower grade gliomas (LGGs) are malignant brain tumors. Current therapy is associated with short- and long-term toxicity. Progression to higher tumor grade is associated with contrast enhancement on MRI. The majority of LGGs harbor mutations in the genes encoding isocitrate dehydrogenase 1 or 2 (IDH1/IDH2). Vorasidenib (AG-881) is a first-in-class, brain-penetrant, dual inhibitor of the mutant IDH1 and mutant IDH2 enzymes. Patients and Methods: We conducted a multicenter, open-label, phase I, dose-escalation study of vorasidenib in 93 patients with mutant IDH1/2 (mIDH1/2) solid tumors, including 52 patients with glioma that had recurred or progressed following standard therapy. Vorasidenib was administered orally, once daily, in 28-day cycles until progression or unacceptable toxicity. Enrollment is complete; this trial is registered with ClinicalTrials.gov, NCT02481154. Results: Vorasidenib showed a favorable safety profile in the glioma cohort. Dose-limiting toxicities of elevated transaminases occurred at doses ≥100 mg and were reversible. The protocol-defined objective response rate per Response Assessment in Neuro-Oncology criteria for LGG in patients with nonenhancing glioma was 18% (one partial response, three minor responses). The median progression-free survival was 36.8 months [95% confidence interval (CI), 11.2–40.8] for patients with nonenhancing glioma and 3.6 months (95% CI, 1.8–6.5) for patients with enhancing glioma. Exploratory evaluation of tumor volumes in patients with nonenhancing glioma showed sustained tumor shrinkage in multiple patients. Conclusions: Vorasidenib was well tolerated and showed preliminary antitumor activity in patients with recurrent or progressive nonenhancing mIDH LGG.

Background Since IDH-mutant (mIDH) low-grade gliomas (LGGs) progress slowly and have a relatively long survival, there is a significant need for earlier measurements of clinical benefit. Guidance using the LGG RANO criteria recommends serial bidirectional (2D) measurements on a single slice; however, questions remain as to whether volumetric (3D) measurements are better, since they would allow for more accurate measurements in irregular shaped lesions and allow readers to better assess areas of subtle change. Methods Twenty-one (out of 24) non-enhancing, recurrent mIDH1 LGGs were enrolled in a phase I, multicenter, open-label study of oral ivosidenib (NCT02073994), and with imaging pre- and post-treatment as part of this exploratory ad hoc analysis. 2D and 3D measurements on T2-weighted FLAIR images were centrally evaluated at an imaging contract research organization using a paired read and forced adjudication paradigm. The effects of 2D vs 3D measurements on progression-free survival (PFS), growth rate measurement variability, and reader concordance and adjudication rates were quantified. Results 3D volumetric measurements showed significantly longer estimated PFS (P = .0181), more stable (P = .0063) and considerably slower measures of tumor growth rate (P = .0037), the highest inter-reader agreement (weighted kappa = 0.7057), and significantly lower reader discordance rates (P = .0002) with 2D LGG RANO. Conclusion 3D volumetric measurements are better for determining response assessment in LGGs due to more stable measures of tumor growth rates (ie, less “yo-yo-ing” of measurements over time), highest inter-reader agreement, and lowest reader discordance rates. Continued evaluation in future studies is warranted to determine whether these measurements reflect clinical benefit.

Background: The primary outcome was to evaluate whether goal-directed fluid therapy (GDFT) protocol, established on stroke volume variation (SVV) and oxygen delivery index (DO2I) using electrical c...

Background To date, there is limited data on evaluation of the cordotomy lesion and predicting clinical outcome. Objective To evaluate the utility of magnetic resonance (MR)-based radiomic analysis to quantify microstructural changes created by the cordotomy lesion and predict outcome in patients undergoing percutaneous cordotomy for medically refractory cancer pain. Methods This is a retrospective interpretation of prospectively acquired data in 10 patients (5 males, age range 43-76 yr) who underwent percutaneous computed tomography-guided high cervical cordotomy for medically refractory cancer pain between 2015 and 2016. All patients underwent magnetic resonance imaging (MRI) of the cordotomy lesion on postoperative day 1. After segmentation of T2-weighted images, 310 radiomic features were extracted. Pain outcomes were recorded on postoperative day 1 and day 7 using the visual analog scale. R software was used to build statistical models based on MRI radiomic features for prediction of pain outcomes. Results A total of 20 relevant radiomic features were identified using the maximum relevance minimum redundanc method. Radiomics predicted postoperative day 1 pain scores with an accuracy of 90% (P = .046), 100% sensitivity, 75% specificity, 85.7% positive predictive value, and 100% negative predictive value. The radiomics model also predicted if the postoperative day 1 pain score was sustained on postoperative day 7 with an accuracy of 100% (P = .028), 100% sensitivity, 100% specificity, and 100% positive and negative predictive value. Conclusion MR-based radiomic analysis of the cordotomy lesion was predictive of pain outcomes at 1 wk after percutaneous cordotomy for intractable cancer pain.

On July 24, 2020, a workshop sponsored by the National Brain Tumor Society was held on innovating brain tumor clinical trials based on lessons learned from the COVID-19 experience. Various stakeholders from the brain tumor community participated including the US Food and Drug Administration (FDA), academic and community clinicians, researchers, industry, clinical research organizations, patients and patient advocates, and representatives from the Society for Neuro-Oncology and the National Cancer Institute. This report summarizes the workshop and proposes ways to incorporate lessons learned from COVID-19 to brain tumor clinical trials including the increased use of telemedicine and decentralized trial models as opportunities for practical innovation with potential long-term impact on clinical trial design and implementation.

Pseudoprogression (PsP) is a diagnostic clinical dilemma in cancer. In this study, we retrospectively analyse glioblastoma patients, and using their dynamic susceptibility contrast and dynamic contrast-enhanced perfusion MRI images we build a classifier using radiomic features obtained from both Ktrans and rCBV maps coupled with support vector machines. We achieve an accuracy of 90.82% (area under the curve (AUC) = 89.10%, sensitivity = 91.36%, 67 specificity = 88.24%, p = 0.017) in differentiating between pseudoprogression (PsP) and progressive disease (PD). The diagnostic performances of the models built using radiomic features from Ktrans and rCBV separately were equally high (Ktrans: AUC = 94%, 69 p = 0.012; rCBV: AUC = 89.8%, p = 0.004). Thus, this MR perfusion-based radiomic model demonstrates high accuracy, sensitivity and specificity in discriminating PsP from PD, thus provides a reliable alternative for noninvasive identification of PsP versus PD at the time of clinical/radiologic question. This study also illustrates the successful application of radiomic analysis as an advanced processing step on different MR perfusion maps., MRI scans of glioblastoma patients can be misleading and some patients appear to show features of progressive disease although they respond to treatment. Here, the authors use MRI images of progressive disease or pseudoprogression and build a classifier using machine learning to distinguish the two.

Seizures are commonly thought to occur in a spontaneous, unpredictable manner. However, it is well-established that a subset of patients with epilepsy can experience reflex seizures that are consistently elicited by a specific stimulus. While various forms of reflex epilepsy have been documented in the literature, acute affective states have not been commonly described as a potential reflex seizure trigger. We performed a systematic literature review to determine if acute emotional states can trigger reflex seizures. We included any case in which reflex seizures repeatedly occurred in response to a patient-specific stimulus that was reported as emotionally relevant by the authors. This yielded our case series of ten patients who have been described to have reflex seizures in response to emotional stimuli. We characterized features of these cases including the following: age, gender, developmental and psychiatric history, seizure semiology and duration, emotional triggers, other reflex triggers, relationship between reflex triggers and seizures, investigations, localization, final diagnosis, treatment, and outcome. Considerable variability was found between cases. A trend toward limbic seizure semiology with psychic aura originating in networks involved in emotional processing was noted, with temporal lobe epilepsy being the most common, although without clear laterality or gender predominance. In addition, the report of a significant life stressor occurring at epilepsy onset in three of ten patients as well as the initial suspicion that reflex epileptic seizures were psychogenic in three cases both emphasize the role of electroencephalography in assessment of such presentations to avoid missing a diagnosis of epilepsy. Findings from these ten cases suggest that a patient-specific affective stimulus may trigger reflex seizures in a subset of patients, and that this could be underrecognized or mislabeled as nonepileptic. We encourage future studies with larger numbers to further characterize this phenomenon. Insights gained may enhance our understanding of seizure localization and bear potential treatment implications.

The effect of different concentrations of NaCl (6, 8 and 10 dS/m) on growth and alkaloids production in 21 days-old callus of Egyptian henbane (Hyoscyamu muticus L.) was studied. Results showed that 10 dS/m of NaCl increased fresh and dry weight by 4.1 and 2.8 fold more than control, respectively. Two fold Total alkaloids increased by 2 fold at 10 dS/m compared to control or wild leaves. In contrary, wild leaves had the highest amount of hyosyamine (2.8 mg/g DW) followed by 6 dS/m stressed-callus (1.14 mg/g DW) as detected by HPTLC. Peroxidase and superoxide dismutase activity were increased by 2.6 and 2.3 fold, respectively in highly salt stressed callus than control while catalase activity (CAT) was decreased. Anthocyanin concentration was increased 3 fold in 10 dS/m of NaCl stressed callus compared to control. Glutathione content was increased by 33.8% under low level of NaCl more than control. Reduction of photosynthetic pigments under all NaCl levels led to decrease the total carbohydrate and protein content. Protein band with molecular weight 109 KDa was a unique band in 10dS/m of NaCl treated callus with high expression of protein bands with MW 44, 38 and 32. Histologically, callus cells under high level of NaCl had amoeboid shape and start in senescence with formation of lysiogenous intercellular spaces.

OBJECTIVEDexamethasone, a known regulator of mesenchymal programming in glioblastoma (GBM), is routinely used to manage edema in GBM patients. Dexamethasone also activates the expression of genes, such as CEBPB, in GBM stem cells (GSCs). However, the drug’s impact on invasion, proliferation, and angiogenesis in GBM remains unclear. To determine whether dexamethasone induces invasion, proliferation, and angiogenesis in GBM, the authors investigated the drug’s impact in vitro, in vivo, and in clinical information derived from The Cancer Genome Atlas (TCGA) cohort.METHODSExpression profiles of patients from the TCGA cohort with mesenchymal GBM (n = 155) were compared with patients with proneural GBM by comparative marker selection. To obtain robust data, GSCs with IDH1 wild-type (GSC3) and with IDH1 mutant (GSC6) status were exposed to dexamethasone in vitro and in vivo and analyzed for invasion (Boyden chamber, human-specific nucleolin), proliferation (Ki-67), and angiogenesis (CD31). Ex vivo tumor cells from dexamethasone-treated and control mice were isolated by fluorescence activated cell sorting and profiled using Affymetrix chips for mRNA (HTA 2.0) and microRNAs (miRNA 4.0). A pathway analysis was performed to identify a dexamethasone-regulated gene signature, and its relationship with overall survival (OS) was assessed using Kaplan-Meier analysis in the entire GBM TCGA cohort (n = 520).RESULTSThe mesenchymal subgroup, when compared with the proneural subgroup, had significant upregulation of a dexamethasone-regulated gene network, as well as canonical pathways of proliferation, invasion, and angiogenesis. Dexamethasone-treated GSC3 demonstrated a significant increase in invasion, both in vitro and in vivo, whereas GSC6 demonstrated a modest increase. Furthermore, dexamethasone treatment of both GSC3 and GSC6 lines resulted in significantly elevated cell proliferation and angiogenesis in vivo. Patients with mesenchymal GBM had significant upregulation of dexamethasone-regulated pathways when compared with patients with proneural GBM. A prognostic (p = 0.0007) 33-gene signature was derived from the ex vivo expression profile analyses and used to dichotomize the entire TCGA cohort by high (median OS 12.65 months) or low (median OS 14.91 months) dexamethasone signature.CONCLUSIONSThe authors present evidence that furthers the understanding of the complex effects of dexamethasone on biological characteristics of GBM. The results suggest that the drug increases invasion, proliferation, and angiogenesis in human GSC-derived orthotopic tumors, potentially worsening GBM patients’ prognoses. The authors believe that careful investigation is needed to determine how to minimize these deleterious dexamethasone-associated side effects in GBM.

Purpose Psychogenic nonepileptic seizures (PNES) are one of the most common differential diagnoses of epilepsy. Our objective is to describe current medical care in Canada and identify patterns of practice and service gaps. Methods In 2015, a 36-question survey was sent via email to the 131 members of the Canadian League Against Epilepsy. The questions were designed after literature review and discussion with the ILAE PNES Task Force. Questions were separated into 5 sections: 1) the role of the respondent and their exposure to PNES, 2) diagnostic methods, 3) management of PNES, 4) etiological factors, and 5) problems accessing health care. Results Sixty-two questionnaires were analyzed (response rate: 47%). Most respondents were epileptologists (76%). The majority of respondents personally diagnosed PNES and communicated the diagnosis to the patient, but only 55% provided follow-up within their practice and only 50% recommended or arranged treatment. Many (35%) were either unfamiliar with the diagnosis of PNES or inexperienced in arranging or offering treatment. Most (79%) provided follow-up to patients with concomitant epilepsy, but when PNES was the sole diagnosis follow-up rates were low. Although 84% of respondents felt that individualized psychological therapy was the most effective treatment, 40% of patients were not referred to psychotherapy and in most cases availability such therapy was low (30–60%). Conclusions Canadian health professionals' understanding of PNES mostly reflects current international expert opinion. Once diagnosis is made however, the majority of patients are discharged from neurological services without appropriate psychological care.

BACKGROUND Ivosidenib (AG-120, IVO) is a first-in-class oral inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1), and vorasidenib (AG-881, VOR) is an oral, potent, brain-penetrant inhibitor of mIDH1/2. Both have been evaluated in glioma patients in ongoing phase 1 studies. In orthotopic glioma models, IVO and VOR reduced 2-hydroxyglutarate (2-HG) levels by 85% and 98%, respectively, despite different brain-to-plasma ratios (< 0.04 vs 1.33). METHODS Patients with recurrent, nonenhancing, WHO-2016 grade 2/3, mIDH1-R132H oligodendroglioma or astrocytoma undergoing craniotomy were randomized 2:2:1 to IVO 500mg QD, VOR 50mg QD, or no treatment (cohort 1), or 1:1 to IVO 250mg BID or VOR 10mg QD (cohort 2), for 4 weeks preoperatively. Postoperatively, patients continued receiving IVO or VOR (control patients were randomized 1:1 to IVO or VOR). Tumors were assessed for mIDH1 status, cellularity, and 2-HG and drug concentrations. Treated subjects were compared with controls and mIDH1/wild-type banked reference samples. Primary endpoint: tumor 2-HG concentration following IVO or VOR. RESULTS As of March 1, 2019, 27 patients (18 men; 25/2 grade 2/3) were randomized preoperatively in cohort 1 (IVO 10, VOR 12, untreated 5): 27 received drug (IVO 13, VOR 14); 1 discontinued VOR postoperatively due to disease progression. Of 26 tumors analyzed, 22 were evaluable. Mean brain-to-plasma ratios: 0.13 IVO, 1.59 VOR. Relative to untreated samples, IVO and VOR reduced tumor 2-HG by 92.0% (95% CI 73.2, 97.4) and 92.5% (95% CI 78.1, 97.7), respectively. Common (≥ 4 patients) TEAEs (all cohort 1 patients, all grades): diarrhea (37.0%), constipation, hypocalcemia, and nausea (each 18.5%), anemia, hyperglycemia, pruritus, headache, and fatigue (each 14.8%). Cohort 2 has completed accrual, with analyses ongoing. CONCLUSIONS In cohort 1 of this phase 1 perioperative study, IVO and VOR demonstrated brain penetrance and lowered 2-HG compared with controls. Updated data from both cohorts will be presented.

PURPOSE Presurgical fMRI is an important tool for surgery navigation in achieving maximum resection of a brain tumor. However, the functional localization accuracy may be compromised by spatial transformation from echo-planar images to high-resolution structural images. We evaluated functional localization errors associated with the spatial transformation process using three algorithms commonly applied to the presurgical fMRI in the clinic. METHODS MR images of 20 brain tumor patients for presurgical evaluation of eloquent areas near motor cortices were analyzed. All fMRI data were spatially transferred to 3D T1-weighted images using three algorithms: (a) coordinate matching (CM), (b) automated registration (AR), and (c) AR plus manual adjustment (ARadj ). Activation clusters overlaid on original echo-planar images were manually delineated on slice-matched 2D T1- weighted images and then transferred to the 3D T1-weighted image volume, and served as the reference localization. Functional localization errors were estimated by measuring the distance between the reference localization and the activation cluster after spatial transformation and then compared for the three algorithms. RESULTS The 3D Euclidean distance for AR (10.2 ± 4.9 mm) was found to be significantly larger (P < 0.05) than those for CM (5.6 ± 2.6 mm) and ARadj (5.8 ± 3.0 mm) algorithms. The difference between the localization errors in CM and ARadj was not statistically significant. CONCLUSIONS A procedure was proposed to evaluate functional localization errors associated with spatial transformation in presurgical fMRI. Our results highlighted the necessity of routine quality control for the AR processing in the clinic.

Background : Bleeding from oesophageal varices is a severe complication of portal hypertension. Endoscopic variceal ligation (EVL) is the treatment of choice for acute variceal bleeding. It is also performed for primary and secondary prophylaxis of bleeding from oesophageal varices. After Endoscopic Band Ligation (EBL), patients are at risk of post-interventional bleeding; the risk factors for this complication are poorly evaluated . The aim of this work : was to evaluate the risk factors for predicting variceal bleeding after elective endoscopic variceal ligation (EVL). Patients and Methods: This study will be carried out in Zagazig University Hospital and El-Galaa Family Military Hospital. The patients was subjected to different demographic, clinical, biochemical, ultrasonographic and endoscopic findings. Results : The incidence of bleeding after elective EVL was 6%. The results showed significant differences between the bleeders and non bleeders regards the severity of liver disease measured by Child-Pugh score , the platelets count, hemoglobin level, prothrombin time , the liver regards its ( size, echogenicity, irregularity of the surface, presence of HFL and Portosystemic collaterals ) , the size and extension of varices. Conclusion: For prediction of variceal bleeding after elective EVL; We can rely on many characteristics, such as age, gender, liver function, severity of varices, number of rubber bands, and so forth. But as demonstrated by the multivariate analysis, there were only four independent risk factors among these, namely moderate to excessive ascites, PT > 18, number of rubber bands placed, size and extent of varices. These four risk factors may therefore be more meaningful than the others for predicting the occurrence of bleeding following elective EVL.

Bio-inspired technologies have remarkable potential for energy harvesting from clean and sustainable energy sources. Inspired by the hummingbird-wing structure, we propose a shape-adaptive, lightweight triboelectric nanogenerator (TENG) designed to exploit the unique flutter mechanics of the hummingbird for small-scale wind energy harvesting. The flutter is confined between two surfaces for contact electrification upon oscillation. We investigate the flutter mechanics on multiple contact surfaces with several free-standing and lightweight electrification designs. The flutter driven-TENGs are deposited on simplified wing designs to match the electrical performance with variations in wind speed. The hummingbird TENG (H-TENG) device weighed 10 g, making it one of the lightest TENG harvesters in the literature. With a six TENG network, the hybrid design attained a 1.5 W m−2 peak electrical output at 7.5 m/s wind speed with an approximately linear increase in charge rate with the increased number of TENG harvesters. We demonstrate the ability of the H-TENG networks to operate Internet of Things (IoT) devices from sustainable and renewable energy sources.

2008 Background: Somatic mutations in IDH1 and IDH2 occur in ̃80% and ̃4% of LGGs, respectively, promoting tumorigenesis via increased levels of the oncometabolite D-2-hydroxyglutarate (2-HG). Vorasidenib (VOR; AG-881) is an oral, brain-penetrant, dual inhibitor of mIDH1/2; ivosidenib (IVO; AG-120) is a first-in-class oral inhibitor of mIDH1. In this ongoing perioperative study, treatment with IVO/VOR reduced 2-HG levels in resected tumors vs untreated control tumors in patients (pts) with LGG (NCT03343197; Mellinghoff SNO 2019). We assessed the biological impact of 2-HG suppression on tumors and TIME. Methods: Pts (n = 49) with recurrent, non-enhancing, mIDH1-R132H LGG eligible for resection were randomized to IVO (500 mg QD/250 mg BID), VOR (10/50 mg QD), or no treatment, for 4 weeks preoperatively. Tumor tissue samples collected at surgery were assessed in genomic (n = 42), transcriptomic (n = 42), and immunohistochemistry (IHC; n = 43) analyses. Unpaired t-test was used for statistical comparisons. Results: Optimal 2-HG suppression (post-treatment 2-HG below the upper limit of 2-HG levels in a reference set of 15 wild-type [wt] IDH samples) was observed in 23 of 40 pts, including 9 (90%) pts receiving VOR 50 mg QD and 6 (50%) receiving IVO 500 mg QD. Of samples with valid biomarker data, those with optimal 2-HG suppression (n = 21) showed upregulation of neural differentiation-related gene expression, but downregulation of stemness-related gene expression, vs those with suboptimal 2-HG suppression (post-treatment 2-HG above upper limit of wt IDH 2-HG levels; n = 17; p < 0.01). IHC analysis of the proliferation marker Ki-67 showed a ̃2-fold decrease in Ki-67–positive cells in samples with optimal 2-HG suppression (mean 2.7%; n = 22) vs those with suboptimal suppression (5.8%; n = 16; p < 0.05). Epigenetic analysis revealed a ̃2-fold increase in mean 5-hydroxymethylcytosine (5hmC) levels in samples with optimal (0.36%; n = 17) vs suboptimal 2-HG suppression (0.2%; n = 15; p < 0.05), suggesting reversal of TET2 inhibition. IHC analysis of TIME revealed increases in mean CD3+ and CD8+ tumor-infiltrating lymphocyte levels in samples with optimal (1.05% [CD3]/0.22% [CD8]; n = 22) vs suboptimal 2-HG suppression (0.44% [CD3]/0.07% [CD8]; n = 16; p < 0.05). Optimal 2-HG suppression was associated with upregulation of gene expression related to type I interferon signaling and antigen presentation (p < 0.01). Conclusions: These data suggest that both tumor-intrinsic and -extrinsic mechanisms underlie 2-HG suppression by VOR and IVO. VOR, and IVO to a lesser extent, increased 5hmC, promoted cellular differentiation, and inhibited tumor cell proliferation; both also increased T-cell infiltration, activated interferon signaling, and increased antigen presentation capability. These data support development of VOR in combination with immunotherapy. Clinical trial information: NCT03343197.

Preoperative mapping of language areas using fMRI greatly depends on the paradigms used, as different tasks harness distinct capabilities to activate speech processing areas. In this study, we compared the ability of 3 covert speech paradigms: Silent Sentence Completion (SSC), category naming (CAT) and verbal fluency (FAS), in localizing the Wernicke’s area and studied the association between genomic markers and functional activation. Fifteen right-handed healthy volunteers and 35 mixed-handed patients were included. We focused on the anatomical areas of posterosuperior, middle temporal and angular gyri corresponding to Wernicke’s area. Activity was deemed significant in a region of interest if P

Radiogenomics is a relatively new and exciting field within radiology that links different imaging features with diverse genomic events. Genomics advances provided by the Cancer Genome Atlas and the Human Genome Project have enabled us to harness and integrate this information with noninvasive imaging phenotypes to create a better 3-dimensional understanding of tumor behavior and biology. Beyond imaging-histopathology, imaging genomic linkages provide an important layer of complexity that can help in evaluating and stratifying patients into clinical trials, monitoring treatment response, and enhancing patient outcomes. This article reviews some of the important radiogenomic literatures in brain tumors.

The new World Health Organization classification of brain tumors depends on combining the histologic light microscopy features of central nervous system (CNS) tumors with canonical genetic alterations. This integrated diagnosis is redrawing the pedigree chart of brain tumors with rearrangement of tumor groups on the basis of geno-phenotypical behaviors into meaningful groups. Multiple radiogenomic studies provide a bridge between imaging features and tumor microenvironment. An overlap that can be integrated within the genophenotypical classification of CNS tumors for a better understanding of different clinically relevant entities.

Objective: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder characterized by prominent neuropsychiatric symptoms. Given the nature of its pathophysiology, psychiatrists tend to be one of the first clinicians encountering patients with the disease. Methods: In the present review of patients described in the literature with psychiatric symptoms, the authors aimed to characterize the psychiatric symptoms of the disease and its management in adults and adolescents as well as children (≤12 years old). A total of 544 patients fulfilled the inclusion criteria. Results: The authors found that 77% of patients with NMDAR encephalitis presented initially with psychiatric symptoms. These were mostly agitation (59%) and psychotic symptoms (in 54%, especially disorganized behavior and visual-auditory hallucinations), with agitation even more commonly being the presenting symptom in children (66%). Where psychotic symptoms were detailed, visual (64%) and auditory (59%) hallucinations were the most common, as well as persecutory delusions (73%). However, delusions were not clearly characterized in most cases. Catatonia was described in 42% of adult patients and 35% of children. Of the patients with documented exposure to antipsychotics, 33% were suspected to have an adverse drug reaction (notably, neuroleptic malignant syndrome in 22% of the cases). Conclusions: On the basis of these findings, it is important to consider anti-NMDAR encephalitis in the differential diagnosis of patients with an acute onset psychosis, especially in association with agitation, catatonia, or adverse response to antipsychotics. Furthermore, it is important to use antipsychotics with caution in patients with suspected or confirmed anti-NMDAR encephalitis.

BACKGROUND Low-grade gliomas (LGGs; WHO grade II) are incurable and ultimately progress to high-grade gliomas. The current treatment options are surgery followed by observation (“watch and wait”) for patients with lower risk for disease progression or postoperative chemoradiotherapy (high-risk population). There are no approved targeted therapies. IDH1 and IDH2 mutations (mIDH1/2) occur in approximately 80% and 4% of LGGs, respectively, and promote tumorigenesis via neomorphic production of D-2-hydroxyglutarate. Vorasidenib, an oral, potent, reversible, brain-penetrant pan-inhibitor of mIDH1/2, was evaluated in 76 patients with glioma in two phase 1 studies (dose escalation and perioperative) and was associated with a favorable safety profile at daily doses below 100 mg. Preliminary clinical activity was observed in non-enhancing glioma patients in both studies, with an objective response rate (ORR) of 18.2% and median progression-free survival of 31.4 months in the dose escalation study. METHODS Approximately 366 patients will be randomized 1:1 to vorasidenib (50 mg QD) or matched placebo and stratified by 1p19q status (intact vs co-deleted). Key eligibility criteria: age ≥ 12 years; grade II oligodendroglioma or astrocytoma (per WHO 2016 criteria) not in need of immediate treatment and without high-risk features; centrally confirmed mIDH1/2 status; ≥ 1 surgery for glioma with most recent ≥ 1 year but ≤ 5 years before randomization, and no other anticancer therapy; Karnofsky performance status ≥ 80%; and centrally confirmed measurable, non-enhancing disease evaluable by magnetic resonance imaging. Crossover from placebo to the vorasidenib arm is permitted upon centrally confirmed radiographic progression per RANO-LGG criteria. Primary endpoint: progression-free survival assessed by independent review. Secondary endpoints: safety and tolerability, tumor growth rate assessed by volume, ORR, overall survival, and quality of life. Clinical data will be reviewed regularly by an independent data monitoring committee. The study is currently enrolling patients in the US, with additional countries planned (NCT04164901).

Objective: The aim of this study was to compare two different surgical techniques for treating mild to moderate cases of hallux valgus. Methods: Forty-one patients (58 feet) with mild to moderate hallux valgus were treated by either percutaneous technique (n = 24) patients (33 feet) or by distal chevron osteotomy (n = 17) (25 feet). Results: In the percutaneous group, after a mean follow up of 49.36 months, the mean correction of hallux valgus angle (HV) was 26.69°; in the intermetatarsal angle, average correction was 9.45°. The mean improvement of American Orthopedic Foot and Ankle Score (AOFAS) was 46.45 points. In the chevron osteotomy group, the mean follow up of 51.56 months, the mean correction of hallux valgus angle was 26.78°; in the intermetatarsal angle, average correction was 9°. The mean improvement of AOFAS was 44.76 points. Conclusion: Both techniques gave satisfactory results. However, the percutaneous technique is safer than the distal chevron osteotomy.

Background Resistant plantar fasciopathy is a common orthopedic problem. Aim Comparing two different methods of treatment. Methods Fifty patients with chronic resistant plantar fasciopathy were divided into two groups. The first included 23 patients treated by endoscopic release of plantar fascia (EPF) and the second included 27 patients treated by injection of platelet-rich plasma (PRP). Results In the EPF group, the average VAS improved from 8.28 to 2.35. The average AOFAS improved from 65 to 94. In the PRP group, average VAS improved from 8.22 to 2.9 and the average AOFAS improved from 66 to 92. Conclusion Both methods gave comparable results at late follow-up.

Somatic mutations in the genes encoding the metabolic enzymes isocitrate dehydrogenase (IDH) 1 and 2 occur in many cancers, including glioma, cholangiocarcinoma, and acute myeloid leukemia. Mutant IDH (mIDH) proteins have a gain-of-function enzyme activity, catalyzing the reduction of alpha-ketoglutarate (α-KG) to the oncometabolite D-2-hydroxyglutarate (2-HG). 2-HG competitively inhibits α-KG-dependent enzymes, leading to epigenetic dysregulation and tumorigenesis. TET2 is an α-KG-dependent enzyme mediating the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which leads to DNA demethylation. In mIDH tumors, TET2 activity is inhibited by 2-HG, leading to DNA hypermethylation. In addition, IDH mutations are associated with immune evasion in gliomas. IDH mutations are common in low-grade gliomas (LGG; WHO grade 2/3) and include mutations in IDH1 (~80%) and IDH2 (~4%). Ivosidenib (AG-120, IVO) is a first-in-class, oral inhibitor of mIDH1, and vorasidenib (AG-881, VOR) is an oral, potent, brain-penetrant inhibitor of both mIDH1 and mIDH2. In an ongoing perioperative study (NCT03343197), IVO and VOR demonstrated brain penetrance and >90% suppression of 2-HG in resected mIDH1 gliomas after pre-operative treatment for approximately 4 weeks. In this analysis, we examined the cellular mechanisms underlying mIDH inhibition in LGG using resected tumor tissues collected following treatment with IVO and VOR. Optimal 2-HG suppression (defined by post-treatment 2-HG levels equal to or lower than the upper range of IDH wild-type tumor 2-HG levels) in IVO- or VOR-treated samples (n=17) led to a ~2-fold increase in 5hmC compared with untreated controls and banked reference samples (n=35; P=0.04). Furthermore, immunohistochemistry (IHC) analysis of the proliferation marker Ki-67 showed a ~3-fold decrease in the percentage of Ki-67-positive cells in IVO- or VOR-treated samples with optimal 2-HG suppression (n=21) compared with untreated controls (n=5; P=0.02). Tumor immune microenvironment analyses were also conducted. Comparing IVO- or VOR-treated samples (n=21) with untreated controls and banked reference samples (n=33), RNAseq analysis showed a ~2-fold decrease in the expression of tumor-associated macrophage markers CD68 (P=0.01) and CD163 (P=0.03) in mIDH oligodendrogliomas. In addition, IHC analysis from paired pre-treatment (archival) and post-treatment samples showed an increase of CD3+ T-cell infiltration (P=0.03) and CD8+ T-cell infiltration (P=0.01) in IVO- or VOR-treated samples with optimal 2-HG suppression (n=21). Single-cell RNAseq was conducted for a subset of samples, and the results will be presented. Overall, these data suggest that mIDH inhibition decreases DNA hypermethylation and tumor cell proliferation, and activates the immune microenvironment in mIDH LGG. In conclusion, these data elucidate the mechanisms underlying mIDH inhibition and support further development of mIDH inhibitors in mIDH LGG. Page 1 of 1 Citation Format: Min Lu, Ingo K. Mellinghoff, Aaron Diaz, Jennie W. Taylor, Sung Choe, Ania Tassinari, Dongwei Zhu, Katie Sellers, Kha Le, Feng Tai, Islam Hassan, Shuchi S. Pandya, Lori Steelman, Bin Wu. Inhibiting IDH mutations in low-grade glioma alters cellular function and the immune environment [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2046.

TPS2574 Background: Low-grade gliomas (LGGs; WHO grade II) are incurable and ultimately progress to high-grade gliomas. The current treatment options consist of surgery followed by observation (“watch and wait”) for pts with lower risk for disease progression or post-operative chemo-radiotherapy (high-risk population). There are no approved targeted therapies. IDH1 and IDH2 mutations (m IDH1/2) occur in approximately 70% and 4% of LGGs, respectively, and promote tumorigenesis via neomorphic production of D-2-hydroxyglutarate (2-HG). VOR, an oral, potent, reversible, brain-penetrant inhibitor of mIDH1/2, was evaluated in 76 pts with glioma in two phase 1 studies (dose escalation and perioperative) and was associated with a favorable safety profile at doses of < 100 mg daily. Preliminary clinical activity was observed in non-enhancing glioma pts in both studies, most recently with an objective response rate (ORR) of 30.8% at 50 mg QD in the perioperative study and > 90% 2-HG suppression at this dose level relative to untreated control samples (Mellinghoff et al., J Clin Oncol 2019). Methods: Approximately 366 pts will be randomized 1:1 to VOR (50 mg QD) or matched placebo and stratified by 1p19q status (intact vs co-deleted). Key eligibility criteria include: age ≥12 years; grade 2 oligodendroglioma or astrocytoma (per WHO 2016 criteria) not in need of immediate treatment and without high-risk features; centrally confirmed m IDH1/2 status; ≥1 prior surgery for glioma within the previous 5 years but no other anticancer therapy; Karnofsky performance status ≥80%; and centrally confirmed measurable, non-enhancing disease evaluable by magnetic resonance imaging. Crossover from placebo to the VOR arm is permitted upon centrally confirmed radiographic progression per RANO-LGG criteria. Primary endpoint is progression-free survival assessed by independent review. Secondary endpoints include safety and tolerability, tumor growth rate assessed by volume, time to next intervention, ORR, overall survival, quality of life assessed by the Functional Assessment of Cancer Therapy–Brain questionnaire, and plasma pharmacokinetics. Exploratory endpoints include seizure activity and neuro-cognitive function. Clinical data will be reviewed regularly throughout the study by an independent data monitoring committee. The study is currently enrolling pts in the US, with additional countries planned (NCT04164901). Clinical trial information: NCT04164901 .

2504 Background: Isocitrate dehydrogenase 1 and 2 mutations (m IDH1/2) occur in approximately 70% and 4% of low-grade gliomas (LGGs), respectively, promoting oncogenesis via increased production of D-2-hydroxyglutarate. In this ongoing phase 1 trial, VOR, a potent, oral, reversible, brain-penetrant, first-in-class dual inhibitor of mIDH1/2, is being evaluated in advanced m IDH1/2 solid tumors, including gliomas. Safety and preliminary results were presented previously (Mellinghoff et al., J Clin Oncol 2018). Here, we report updated data for the non-enhancing glioma pt population. Methods: Pts with recurrent/progressive m IDH1/2 glioma received VOR daily (continuous 28-day cycles). Key eligibility criteria included: ≥18 years; histologically or cytologically confirmed glioma with documented m IDH1/2; ECOG 0-2; and evaluable disease by RANO-LGG criteria. Dose escalation cohorts enrolled using a Bayesian logistic regression model (BLRM) escalation guided by the overdose control (EWOC). Tumor response was evaluated by MRI every 8 weeks using RANO-LGG criteria by local assessment. Results: As of 28 Nov 2019, 22 pts with non-enhancing glioma had received VOR and 8 (36%) remain on treatment. M/F, 8/14; grade 2/3, 17/5; median age, 47 years; m IDH1/2, 20/1; 1p19q intact, 9/22; median (range) number of prior systemic therapies, 2 (1–4). Common (≥5 pts) treatment-emergent adverse events (AEs) of any grade and regardless of causality included increased ALT/AST (63.6%/59.1%), headache (45.5%), nausea (40.9%), neutropenia (31.8%), fatigue and hyperglycemia (27.3% each), and seizures and decreased white blood cell count (22.7% each). Transaminase elevations were grade 1 in severity at dose levels < 100mg and were less frequent (5 [38.5%] of 13 pts). Three subjects had related grade ≥3 AEs; 2 discontinued due to AEs. Objective response rate was 13.6% (1 partial response, 2 minor responses), and 17 (77.3%) pts achieved stable disease. 60.5% of pts were progression free and alive at 24 months. Conclusions: In this previously treated population with non-enhancing glioma, VOR was associated with a favorable safety profile. The study results also show encouraging preliminary activity within that population, with PFS duration extending to 24 months or longer in 60% of participants. A global randomized phase 3 study of VOR in grade 2 non-enhancing glioma pts who have had surgery only is currently enrolling (NCT04164901). Clinical trial information: NCT02481154 .

Purpose: Radiomics is the extraction of multidimensional imaging features, which when correlated with genomics, is termed radiogenomics. However, radiogenomic biological validation is not sufficiently described in the literature. We seek to establish causality between differential gene expression status and MRI-extracted radiomic-features in glioblastoma. Experimental Design: Radiogenomic predictions and validation were done using the Cancer Genome Atlas and Repository of Molecular Brain Neoplasia Data glioblastoma patients (n = 93) and orthotopic xenografts (OX; n = 40). Tumor phenotypes were segmented, and radiomic-features extracted using the developed radiome-sequencing pipeline. Patients and animals were dichotomized on the basis of Periostin (POSTN) expression levels. RNA and protein levels confirmed RNAi-mediated POSTN knockdown in OX. Total RNA of tumor cells isolated from mouse brains (knockdown and control) was used for microarray-based expression profiling. Radiomic-features were utilized to predict POSTN expression status in patient, mouse, and interspecies. Results: Our robust pipeline consists of segmentation, radiomic-feature extraction, feature normalization/selection, and predictive modeling. The combination of skull stripping, brain-tissue focused normalization, and patient-specific normalization are unique to this study, providing comparable cross-platform, cross-institution radiomic features. POSTN expression status was not associated with qualitative or volumetric MRI parameters. Radiomic features significantly predicted POSTN expression status in patients (AUC: 76.56%; sensitivity/specificity: 73.91/78.26%) and OX (AUC: 92.26%; sensitivity/specificity: 92.86%/91.67%). Furthermore, radiomic features in OX were significantly associated with patients with similar POSTN expression levels (AUC: 93.36%; sensitivity/specificity: 82.61%/95.74%; P = 02.021E−15). Conclusions: We determined causality between radiomic texture features and POSTN expression levels in a preclinical model with clinical validation. Our biologically validated radiomic pipeline also showed the potential application for human–mouse matched coclinical trials.

PURPOSE: The mainstay imaging technique in brain tumor is Magnetic resonance imaging (MRI). However, early detection of tumor cell proliferation using MRI is limited due to inapparent disruption of normal brain architecture. Radiomics and machine learning techniques can quantitate thousands of imaging features that can depict neoplastic changes in apparently normal brain. Herein, we investigate the potential role radiomics can play in early detection of tumor cell proliferation in apparently normal MRI using a preclinically trained radiomic. METHODS: Two glioblastoma stem-like cell lines were transformed to stably express luciferase under a constitutive promoter. A stereotactic injection of tumor cells was performed to generate orthotopic mouse models (N=48). Tumor cell engraftment and in-vivo proliferation were assessed using bio-luminescence imaging (BLI) along with a weekly MRI (Bruker 7T). Images were analyzed, and ROIs were placed using 3D slicer software and radiomic features were extracted using Matlab. ROIs (0.75 mm) were placed on tumor injection sites and normal appearing contralateral brain. Radiomic features were compared for their significant alterations over time using comparative marker selection (CMS). Genomics and Histopathology of tumors were performed ex-vivo. Validation was performed in a cohort of brain cancer patients. RESULTS: Three stages of post-implantation tumor cell presence and proliferation were identified: 1. Immediate post implantation lag/engraftment phase. 2. Linear cellular proliferation phase (normal on conventional MRI). 3. Exponential cellular proliferation phase (apparent tumor on conventional MRI). Our data showed that 43% of extracted radiomic features were significantly changing (P Conclusion: Radiomic texture analysis and machine learning detects tumor cell presence and proliferation in normal-appearing brain prior to tumor development on conventional imaging. CLINICAL RELEVANCE: Radiomics and machine learning algorithms are predictive of tumor presence in seemingly normal MRIs. Early detection of tumors can allow earlier intervention, more extensive radiation planning and appropriately dose chemotherapeutic regimens.

Individual analysis of functional Magnetic Resonance Imaging (fMRI) scans requires user-adjustment of the statistical threshold in order to maximize true functional activity and eliminate false positives. In this study, we propose a novel technique that uses radiomic texture analysis (TA) features associated with heterogeneity to predict areas of true functional activity. Scans of 15 right-handed healthy volunteers were analyzed using SPM8. The resulting functional maps were thresholded to optimize visualization of language areas, resulting in 116 regions of interests (ROIs). A board-certified neuroradiologist classified different ROIs into Expected (E) and Non-Expected (NE) based on their anatomical locations. TA was performed using the mean Echo-Planner Imaging (EPI) volume, and 20 rotation-invariant texture features were obtained for each ROI. Using forward stepwise logistic regression, we built a predictive model that discriminated between E and NE areas of functional activity, with a cross-validation AUC and success rate of 79.84% and 80.19% respectively (specificity/sensitivity of 78.34%/82.61%). This study found that radiomic TA of fMRI scans may allow for determination of areas of true functional activity, and thus eliminate clinician bias.

A precise clinically relevant characterization of glioblastoma (GBM) heterogeneity and underlying genomic variability is urgently needed. To evaluate the true potential of radiogenomics, an emerging field for GBM research, we have tested its scope in a pre-clinical setting. First, glioblastoma stem cells (GSCs) are altered to express decreased levels of Periostin (POSTN), previously identified in a radiogenomic screen as a key pro-invasive gene. Second, orthotopic tumors arising from these GSCs, were scanned and analyzed to identify gene specific MRI texture feature (MRTF) signatures, which can simultaneously predict POSTN status in GBM patients. Doxycycline inducible short hairpin RNA mediated knockdown of POSTN in GSC lines were established. 5X10^6 cells were stereotactically implanted in nude mice frontal cortex and randomized into POSTN knockdown and control groups. Monitored tumor growth longitudinally by MRI (n = 3-4 per group). Region of interest (ROI) methods were applied to the rigid registration images based on axial T1-weighted imaging and corresponding fluid-attenuated inversion recovery sequences. After pre-processing, gray level co-occurrence matrices (GLCMs) were generated in 4 angular directions and 3 invariant measures (mean, range and angular variance) of each texture feature is calculated. A matrix of 3x20 invariant features is generated for each gray level. Mean values of normalized MRTFs from edema T1 post and T2, subgroup tumors arising from independent GSCs (p

BACKGROUND: FMRI maps commonly show multiple areas of false positive activity. We aimed to identify areas of true fMRI activation by using complex MRI texture analysis (TA) of raw EPI data, thus enhancing the identification of true activity. METHODS: 12 right handed healthy volunteers were recruited (IRB approved). All scans were performed on a 3.0T GE MR scanner. FMRI consisted of a high resolution 3D T1 weighted structural scan and a gradient echo EPI functional scan. FMRI data analysis was performed using SPM8 software for a sentence completion block design task. T map for each individual was displayed using xjview toolbox and thresholded individually to optimize visualization of language area. Each activity cluster was selected and saved. Board-certified neuroradiologists and neuroscientists classified different clusters into two separate groups Expected (E) and Non Expected (NE) based on their anatomical locations. TA was performed using the mean EPI volume for each individual, and 20 invariant texture features were obtained. Efficacy of TA in fMRI was assessed by decision tree and validated using a 4 fold cross validation. RESULTS: fMRI areas of activity in individual scans were identified based on their texture features with 95.3% accuracy, sensitivity 95.3% and specificity 95.3%. Sum of Variance, Cluster shade, sum of average and information measure of correlation were the most important texture features. These features had higher texture values in the NE ROIs indicating more homogeneous areas. Texture features were able to significantly differentiate areas of true versus false activity. CONCLUSIONS: Extracted features indicated that true activity has more heterogeneous texture compared to non-expected activity Quantitative TA of functional MRI using texture feature can enhance the accuracy and sensitivity of the test to true activity and help eliminate false activation

Dexamethasone is routinely administered to manage cerebral edema in glioblastoma (GBM). Its impact on molecular mechanisms driving GBM invasion is unknown. Utilizing radiogenomic strategies, we previously introduced Periostin as key mediator of GBM associated edema and cellular invasion. We observed that multiple molecular targets of Dexamethasone are significantly upregulated and overlap with Periostin correlated genes, including CEBPB. We hypothesized that Dexamethasone, by regulating Periostin correlated genes, promotes a mesenchymal program of tumor cells including Glioblastoma Stem Cells (GSCs). A panel of GSCs were profiled for Periostin correlated genes after Dexamethasone treatment, using microarray, qPCR and Western blotting. Tests for self-renewal (limiting dilution assay), differentiation (neural lineage marker analysis), invasion (Boyden chamber) and proliferation (BrdU) were performed after Dexamethasone exposure. Three independent GSC lines were used to generate orthotopic tumors and mice were then treated with Dexamethasone (intraperitoneal). Differentially expressed genes in GSC derived tumors (total RNA from cells of human origin were isolated using human specific Anti- HLA Class I ABC antibody by FACS) upon Dexamethasone exposure were evaluated with connectivity map (cmap) to screen for specific therapeutics. Cells treated with Dexamethasone showed an increased CEBPB expression, indicating a more aggressive mesenchymal gene signature. Histopathologic validation of orthotopic tumors supported this effect of Dexamethasone. Treatment with specific, FDA approved therapeutics in combination with Dexamethasone suppressed Periostin correlated gene levels and subsequently reduced this mesenchymal shift. In this preclinical study we showed that Dexamethasone promotes a molecular mesenchymal shift by elevating CEBPB expression levels in both, in vitro and in vivo. These results warrant an evaluation of Dexamethasone for managing edema in glioblastoma patients. Neutralizing side effects of Dexamethasone by adding our shortlisted drugs may improve GBM patient care.

INTRODUCTION Hypermutation is the excessive accumulation of DNA mutation in cancer cells. This specific hypermutated genotype has been reported in low and high grade gliomas, specifically post-temozolomide treatment and is associated with treatment-resistance. Herein, we sought to identify an imaging-based signature for hypermutated gliomas using a radiomics-based approach. MATERIALS AND METHODS In this IRB-approved retrospective study, we analyzed a total of 101 patients with primary gliomas from the University of Texas MD Anderson Cancer Center. Next generation sequencing (NGS) platforms (T200 and Foundation 1) were used to determine the Mutation burden status in post-biopsy (stereotactic/excisional). Patients were dichotomized based on their mutation burden; 77 hypomutated (=30 mutations or RESULTS We found 100 radiomic features that can discriminate between hypermutated versus hypomutated gliomas, AUC 96.3% (CI: 90.2%-98.9%), Sensitivity 100%, Specificity 95%, p-value=3.769e-6. CONCLUSION Hypermutated gliomas has a unique radiomic quantitative signature that can be used to predict mutation burden regardless of tumor grade or histopathology. Citation Format: Islam Hassan, Aikaterini Kotrotsou, Carlos Kamiya Matsuoka, Kristin D. Alfaro-Munoz, Nabil Elshafeey, Nancy El Shafei, Pascal O. Zinn, John F. de Groot, Rivka R. Colen. A radiomic-based MRI phenotype is uniquely associated with hypermutated genotype in gliomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2955.

BACKGROUND: Treatment-related imaging changes are often difficult to distinguish from true tumor progression. Treatment-related changes or pseudoprogression (PsP) subsequently subside or stabilize without any further treatment, whereas progressive tumor requires a more aggressive approach in patient management. Pseudoprogression can mimic true progression radiographically and may potentially alter the physician's judgment about the recurrent disease. Hence, it can predispose a patient to overtreatment or be categorized as a non-responder and exclude him from the clinical trials. This study aims at assessing the potential of radiomics to discriminate PsP from progressive disease (PD) in glioblastoma (GBM) patients. METHODS: We retrospectively evaluated 304 GBM patients with new or increased enhancement on conventional MRI after treatment, of which it was uncertain for PsP versus PD. 149 patients had the histopathological evidence of PD and 27 of PsP. Remaining 128 patients were categorized into PD and PsP based on RANO criteria performed by a board-certified radiologist. Volumetrics using 3D slicer 4.3.1 and radiomics texture analysis were performed of the enhancing lesion(s) in question. RESULTS: Using the MRMR feature selection method, we identified 100 significant features that were used to build a SVM model. Five texture features (E, CS, SA, MP, CP) were found to be most predictive of pseudoprogression. On Leave One Out Cross-Validation (LOOCV), sensitivity, specificity and accuracy were 97%, 72%, and 90%, respectively. Using 70% of the patient data for training and 30% for validation, an AUC of 94% was achieved, with the sensitivity of 97% and specificity of 75%. CONCLUSION: 3D radiomic texture features of conventional MRI successfully discriminated pseudoprogression from true progression in a large cohort of GBM patients. Citation Format: Srishti Abrol, Aikaterini Kotrotsou, Ahmed Hassan, Nabil Elshafeey, Tagwa Idris, Naveen Manohar, Anand Agarwal, Islam Hassan, Kamel Salek, Nikdokht Farid, Carrie McDonald, Shiao-Pei Weathers, Naeim Bahrami, Samuel Bergamaschi, Ahmed Elakkad, Kristin Alfaro-Munoz, Fanny Moron, Jason Huse, Jeffrey Weinberg, Sherise Ferguson, Evangelos Kogias, Amy Heimberger, Raymond Sawaya, Ashok Kumar, John de Groot, Meng Law, Pascal Zinn, Rivka R. Colen. Radiomics discriminates pseudo-progression from true progression in glioblastoma patients: A large-scale multi-institutional study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3040.

2022Background: Hypermutation is defined as the excessive accumulation of DNA mutation in cancer cells and is reported in several forms of cancer including low and high grade gliomas. Incidence of ...