Adult Tumor Patients Research Articles

A comparative study of pre-processing methods to improve glioma segmentation performance in brain MRI using deep learning

Background: Glioma is the most common brain tumor in adult patients and requires accurate treatment. The delineation of tumor boundaries must be accurate and precise, which is crucial for treatment planning. Currently, delineating boundaries for tumors is a tedious, time-consuming task and may be prone to human error among oncologists. Therefore, artificial intelligence plays a vital role in reducing these problems. Objective: This study aims to find a relationship between improving image enhancement and evaluating the performance of deep learning models for segmenting glioma image data on brain MRI images. Materials and methods: The BraTs2023 dataset was used in this study. The image dataset was converted from three dimensions to two dimensions and then subjected to pre-processing via four image enhancement techniques, including contrast-limited adaptive histogram equalization (CLAHE), gamma correction (GC), non-local mean filter (NLMF), and median and Wiener filter (MWF). Subsequently, it was evaluated for structural similarity index (SSIM) and mean squared error. The deep learning segmentation model was created using the U-Net architecture and assessed for dice similarity coefficient (DSC), accuracy, precision, recall, F1-score, and Jaccard index for tumor segmentation. Results: The performance of enhanced image results for CLAHE, GC, NLMF, and MWF techniques shows SSIM values of 0.912, 0.905, 0.999, and 0.911, respectively. The dice similarity coefficient (DSC) for segmentation without image enhancement was 0.817. The DSC of segmentation for CLAHE, GC, NLMF, and MWF techniques were 0.818, 0.812, 0.820, and 0.797, respectively. Conclusion: The enhanced image technique could affect the performance of tumor segmentation. by the enhanced image for use in a trained model may increase or decrease performance depending on the chosen image enhancement technique and the parameters determined by each method.

A Comprehensive Correlation of Clinicopathologic Prognostic Factors in Malignant Adult Renal Tumors: A Single Institutional Study.

To study the clinicopathologic prognostic parameters of malignant adult renal tumors as these have poor over-all survival (OS) and show frequent metastasis. This was a retrospective analysis of the clinical and pathologic features of malignant renal tumors in adult patients from January 2011 to December 2020. All the tumors were studied with respect to age, clinical presentation, tumor type/subtype, histologic grade (WHO/ISUP grading system), TNM stage and presence of necrosis. Correlation of histopathologic features and survival analysis was done using Kaplan-Meier survival curves and Cox-regression analysis. A total of 257 cases were included in the study period including 253 renal cell tumors of which clear cell renal cell carcinoma accounted for 69.3%. The age of the patients ranged from 20 to 87 years (median-52 years). The overall survival significantly reduced with increasing histologic grade, stage, and presence of necrosis. The comparison between the histological subtypes was not statistically significant. Univariate Cox-regression analysis found significant hazard ratio with increasing age, size, histologic grade (G4 vs G1), stage, and presence of necrosis. The correlation of OS with histological subtypes was not significant. Multivariate analysis also showed increased hazard ratio with increasing age, size, grade, and stage. However, the P-value was significant only for age. Clear cell renal cell carcinoma was the commonest type of adult renal tumor. Older age at presentation, larger tumor size, presence of necrosis, and higher histologic grade and stage were associated with poor prognosis in these patients.

Selecting the Appropriate Radiation Therapy Technique for Extensive Brain Metastases from Tens to Hundreds: Should the Latest Technique Always Be the Best Option?

Brain metastases (BMs) are one of the most common metastatic lesions in adult cancer patients and the most common intracranial neoplasms in adult patients. Especially for multiple BMs, historically, whole-brain radiotherapy (WBRT) has been performed as the mainstay of therapy, which improves neurological symptoms and median survival. However, WBRT could negatively impact the patient's quality of life due to late complications. Owing to these complications, attempts have been made to use the latest radiotherapy (LRT) such as stereotactic radiosurgery (SRS) and intensity-modulated radiotherapy (IMRT) to treat BMs. However, for the extensive BMs (ranging from tens to hundreds), there are currently no prospective studies comparing WBRT with LRT such as IMRT or SRS. For extensive brain metastases, LRT cannot be the best option. Instead, upfront WBRT should be considered given its advantages and disadvantages, rather than LRT. We hope that faster and more reliable LRT for extensive BMs will be applicable for clinical practice without any clinical concerns in the near future.

The use of artificial intelligence tools in cancer detection compared to the traditional diagnostic imaging methods: An overview of the systematic reviews.

In comparison to conventional medical imaging diagnostic modalities, the aim of this overview article is to analyze the accuracy of the application of Artificial Intelligence (AI) techniques in the identification and diagnosis of malignant tumors in adult patients. The acronym PIRDs was used and a comprehensive literature search was conducted on PubMed, Cochrane, Scopus, Web of Science, LILACS, Embase, Scielo, EBSCOhost, and grey literature through Proquest, Google Scholar, and JSTOR for systematic reviews of AI as a diagnostic model and/or detection tool for any cancer type in adult patients, compared to the traditional diagnostic radiographic imaging model. There were no limits on publishing status, publication time, or language. For study selection and risk of bias evaluation, pairs of reviewers worked separately. In total, 382 records were retrieved in the databases, 364 after removing duplicates, 32 satisfied the full-text reading criterion, and 09 papers were considered for qualitative synthesis. Although there was heterogeneity in terms of methodological aspects, patient differences, and techniques used, the studies found that several AI approaches are promising in terms of specificity, sensitivity, and diagnostic accuracy in the detection and diagnosis of malignant tumors. When compared to other machine learning algorithms, the Super Vector Machine method performed better in cancer detection and diagnosis. Computer-assisted detection (CAD) has shown promising in terms of aiding cancer detection, when compared to the traditional method of diagnosis. The detection and diagnosis of malignant tumors with the help of AI seems to be feasible and accurate with the use of different technologies, such as CAD systems, deep and machine learning algorithms and radiomic analysis when compared with the traditional model, although these technologies are not capable of to replace the professional radiologist in the analysis of medical images. Although there are limitations regarding the generalization for all types of cancer, these AI tools might aid professionals, serving as an auxiliary and teaching tool, especially for less trained professionals. Therefore, further longitudinal studies with a longer follow-up duration are required for a better understanding of the clinical application of these artificial intelligence systems. Systematic review registration. Prospero registration number: CRD42022307403.

P13.14.A PREDICTION OF OVERALL SURVIVAL IN HIGH-GRADE GLIOMA USING MULTIPARAMETRIC MRI-BASED RADIOMICS. APPLICATION TO A MULTICENTER COHORT

Abstract BACKGROUND High-grade gliomas are the most common type of primary brain tumor in adult patients. Despite a multimodal treatment, the prognosis remains poor. Accurate stratification of survival is crucial for choosing the best course of therapy. The objective of this study was to use radiomics analysis based on multiparametric MRI combined with clinical data of high-grade gliomas patients with incomplete resection to identify a predictive signature for the stratification of patients according to their overall survival. MATERIAL AND METHODS In this multicentric retrospective study, we included a sub-cohort of 237 patients treated for high-grade gliomas, from 2009 to 2021, at three French medical centers. This data collection was carried out as part of a national funding to promote the integration of AI tools into clinical routine in oncology (AI.DReAM project). Clinical and pathological data, together with the MR images before treatment and at the time of relapse were collected.Patients with gross tumor resection were excluded to homogenize the automatic contouring. Three tumor subregions were generated by a deep learning framework based in the BraTS challenge on the MR images at the time of radiotherapy: label 1, corresponding to the necrosis part of the tumor; label 2, the hypersignal in the T2/FLAIR sequence; and label 3, corresponding to the enhancing part after the injection of gadolinium. The cohort was split into a training data set of 189 patients with cross-validation to ensure robustness and evaluated using a test set of 48 patients. The survival stratification of the two classes was based on the median in month of overall survival (OS) in our cohort with short survival defined as OS inferior to 17 months. The open-source software Pyradiomics and the ensemble classifiers XGBoost, in conjunction with grid search were used for calculating radiomic parameters. RESULTS In total, 976 patients were collected. For this analysis, 237 patients with high-grade gliomas were included, 82 % being IDH-wildtype glioblastoma. One-hundred and nineteen patients underwent subtotal tumor resection. A total of 936 radiomics were extracted from the three tumor subregions and 14 clinical data features were added to the algorithm. The areas under the ROC curve (ROC-AUC) for survival prediction based on radiomic and clinical parameters alone were 0.61 and 0.60 respectively on the test set. The combination of radiomic features with clinical features showed superior performance with ROC-AUC of 0.67 in the 5-fold cross-validation and 0.64 in the test set. CONCLUSION In this preliminary study, we achieved a reproducible estimation of patient survival using radiological and clinical features. In future analyses, we will seek to better account for the biological heterogeneity of high-grade glioma by increasing the number of labels and having them corrected by experts in the field.

Use of Drugs in Clinical Practice and the Associated Cost of Cancer Treatment in Adult Patients with Solid Tumors: A 10-Year Retrospective Cohort Study.

Cancer is one of the leading causes of morbidity and mortality in the world. Its growing incidence and prevalence, as well as the advances in diagnostic and treatment tools, motivate an open debate about the economic burden it may place on health systems and have raised concerns about access to this technological innovation. There is a lack of information on the detailed costs of pharmacological treatment of cancer in our health setting. In this context, it is necessary to know the use of drugs in cancer treatment in conditions of real clinical practice. A real-word, evidence-based retrospective cohort study was conducted at Vall d'Hebron University Hospital (VHUH), the largest hospital complex in Catalonia, Spain, in order to determine the use of drugs and the associated cost in real clinical practice for the treatment of solid tumors in adult patients attended at this institution over 10 years (2010-2019). This was a single-center retrospective cohort study of adult cancer patients attended in clinical practice at the Medical Oncology Department of VHUH between 1 January 2010 and 31 December 2019. Data of prescription, preparation, and cost of antineoplastic treatments were analyzed by pharmacological class (cytotoxic drugs, immunotherapy, targeted therapy, radiopharmaceuticals, and others), by antineoplastic agent, and by type of tumor. The number of patients and the pharmaceutical expenditure corresponding to all these subgroups were recorded. The cost per patient in each tumor location was also calculated. The study population included 13,209 patients with an overall pharmaceutical antineoplastic expenditure of EUR 120,396,097, increasing from 7.67% in relation to the total HUVH pharmaceutical expenditure in 2010 to 12.82% in 2019. By pharmacological class, the specific weight of the cost of targeted therapy is relevant (75.22% of pharmaceutical antineoplastic expenditure, 21.3% of patients) compared to the group of conventional cytotoxics (17.25% of pharmaceutical antineoplastic expenditure, 76.37% of patients), while immunotherapy has represented the largest relative increase, from 5% in 2014 to 12% in 2019. Eight targeted therapy drugs represented 50% of the costs of the targeted therapy drug class (palbociclib, trastuzumab, pertuzumab, bevacizumab, nivolumab, cetuximab, pembrolizumab, and trastuzumab emtansine). Eleven tumor sites accounted for 90% of the expenditure in 71% of all patients. Breast cancer had the highest expenditure during the study period (EUR 34,332,210) and at each individual year. Melanoma showed the highest increase, with 9.7% of total pharmaceutical antineoplastic expenditure in 2019 (2% of patients), representing a paradigm of the rising costs of cancer treatment due to the incorporation of new high-cost therapies. The average annual cost per patient was highly variable depending on the pathology. There was a growing increase in costs per patient in most tumor locations, particularly in patients with melanoma (from EUR 1922 in 2010 to EUR 37,020 in 2019), prostate cancer (from EUR 2992 in 2010 to EUR 14,118 in 2019), and non-small cell lung cancer (from EUR 3545 in 2010 to EUR 8371 in 2019). The relevance of the difference in monthly cost per patient that has been identified for the different intrinsic subtypes in breast cancer patients during 2019 (HER2+ EUR 2661/month, Luminal EUR 881/month, Triple negative EUR 386/month) makes us consider suggesting differentiated reimbursement rates for certain clinical conditions. Finally, support treatment with antiemetic drugs, erythropoietin stimulating agents, granulocyte-colony stimulating factor (G-CSF), and bone resorption inhibitors has involved a cost of EUR 5,751,910, which represents 4.6% of the overall pharmacological cost of cancer treatment. This study provides detailed insights on the oncological pharmaceutical expenditure for the treatment for solid tumors in the VHUH, based on real cost information from our hospital practice and for all antineoplastic therapies and types of solid tumors. This type of information on all the different types of cancer can be useful to better understand the economic burden of the disease and can be decisive for allocating public resources and funds for research, especially in those areas where information is scarce and therefore where further studies are needed. The contribution to knowledge of the cost of oncology therapy is of great value due to its realism and scope.

Prevalence and clinical expression of germ line predisposition to myeloid neoplasms in adults with marrow hypocellularity

AbstractSystematic studies of germ line genetic predisposition to myeloid neoplasms in adult patients are still limited. In this work, we performed germ line and somatic targeted sequencing in a cohort of adult patients with hypoplastic bone marrow (BM) to study germ line predisposition variants and their clinical correlates. The study population included 402 consecutive adult patients investigated for unexplained cytopenia and reduced age-adjusted BM cellularity. Germ line mutation analysis was performed using a panel of 60 genes, and variants were interpreted per the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines; somatic mutation analysis was performed using a panel of 54 genes. Of the 402 patients, 27 (6.7%) carried germ line variants that caused a predisposition syndrome/disorder. The most frequent disorders were DDX41-associated predisposition, Fanconi anemia, GATA2-deficiency syndrome, severe congenital neutropenia, RASopathy, and Diamond-Blackfan anemia. Eighteen of 27 patients (67%) with causative germ line genotype were diagnosed with myeloid neoplasm, and the remaining with cytopenia of undetermined significance. Patients with a predisposition syndrome/disorder were younger than the remaining patients and had a higher risk of severe or multiple cytopenias and advanced myeloid malignancy. In patients with myeloid neoplasm, causative germ line mutations were associated with increased risk of progression into acute myeloid leukemia. Family or personal history of cancer did not show significant association with a predisposition syndrome/disorder. The findings of this study unveil the spectrum, clinical expressivity, and prevalence of germ line predisposition mutations in an unselected cohort of adult patients with cytopenia and hypoplastic BM.

Diagnosis and treatment of adult tumor patients with COVID-19

After the first outbreak of corona virus disease 2019 (COVID-19) at the end of 2019, it has caused multiple rounds of transmission in many countries around the world. Cancer patients are mainly elderly people, and the immunosuppression state caused by the tumor itself and anti-tumor treatment, more accompanying underlying diseases, and more hospital environmental exposure leading to a higher incidence of COVID-19 infection. The proportion of severe cases after infection is high, and the mortality is high. Therefore, based on the domestic and foreign research and clinical practice, the Expert Committee of Geriatric Cancer Prevention and Treatment of Chinese Society of Clinical Oncology launched a discussion based on the characteristics of cancer patients, including the epidemiology, clinical manifestations, differential diagnosis, definition and risk factors of severe cases, diagnosis and treatment recommendations, recovery of anti-tumor treatment and vaccination recommendations. To provide the corresponding suggestions for the clinical diagnosis and treatment of such patients.

Clinicopathological Patterns of Malignant Solid Tumors in Adult Patients: A Hospital-Based Study From Bangladesh.

Solid malignant tumors are abnormal masses of tissue that usually do not contain any cysts or liquid areas. The causation of these tumors is multifactorial, and the disease process differs at different sites. This study aims to determine the clinicopathological patterns of malignant solid tumors in adult patients admitted into the department of internal medicine of a tertiary care hospital in Bangladesh. This cross-sectional study was conducted between January 2018 and June 2018 at the Department of Medicine, Dhaka Medical College Hospital, Bangladesh. We recorded the complete socio-demographic characteristics, clinical patterns, and pathological characteristics of malignant solid tumors in adult patients. A total of 100 patients with confirmed malignant solid tumors were included in our study. The mean age of the patients was 47.5 years (SD: ±4.20); most of them (27%) were between 58 and 67 years of age. Male patients constitute 59% of the total study sample. Most of the patients were of the middle socio-economic class (59%) and most of them (61%) were nonsmokers. Among the patient diagnoses, 19% had lung cancer, 29.27% had breast cancer, and in 14%, lymphoma (tumorarising from the lymphatic system) was the common solid tumor. Lung cancer was found to be the most common form of cancer in males. Additionally, the majority of those diagnosed with lung cancer smoked. Breast cancer was found to be the most common type of cancer in females. This study reflects that solid malignant tumors can affect any socio-economic class of people. Based on findings in our study as well as others, prevention efforts should focus on the reduction in tobacco use and the incorporation of other lifestyle changes, such as diet modification and exercise. Additionally, the incorporation of economic factors and how they affect cancer presentation in different contexts is crucial.

Laminoplasty versus Laminectomy in the Treatment of Primary Spinal Cord Tumors in Adult Patients: A Systematic Review and Meta-analysis of Observational Studies.

The present systematic review and meta-analysis was conducted to compare the safety and efficacy of the two approaches for primary spinal cord tumors (PSCTs) in adult patients (laminoplasty [LP] vs. laminectomy [LE]). LE is one of the most common procedures for PSCTs. Despite advantages of LP, it is not yet widely used in the neurosurgical community worldwide. The efficacy of LP vs. LE remains controversial. Adult patients over 18 years of age with PSCT at the level of the cervical, thoracic, and lumbar spine were included in the study. A literature search was performed in MEDLINE via PubMed, EMBASE, The Cochrane Library, and Google Scholar up to December 2021. Operation time, hospital stay, complications, and incidence of postoperative spinal deformity (kyphosis or scoliosis were extracted. A total of seven retrospective observational studies with 540 patients were included. There were no significant differences between LP and LE group in operation time (p =0.25) and complications (p =0.48). The LE group showed larger postoperative spinal deformity rate than the LP group (odds ratio, 0.47; 95% confidence interval [CI], 0.27-0.84; p =0.01). The LP group had a shorter hospital stay (standardized mean differences, -0.68; 95% CI, -1.03 to -0.34; p =0.0001) than the LE group. Both LP and LE have comparable operative times and total complications in the treatment of PSCT. LP was superior to LE in hospital stay and postoperative spinal deformity rate. However, these findings are limited by the very low quality of the available evidence. Randomized controlled trials are needed for further comparison.

Metastatic Renal Cell Carcinoma to Duodenum and Pancreas 10 Years After Nephrectomy: A Case Report

Renal cell carcinoma (RCC) accounts for 2-3% of the malignant tumors in adult patients. The most common sites of metastasis are the lung, bone, liver and brain respectively. Unusual metastatic sites require attention during follow-up of renal cell carcinoma. The duodenum and pancreas are uncommon sites for metastasis from renal cell carcinoma. We describe here a 62-year-old man with metastastic renal cell carcinoma to the duodenum and pancreas. The patient presented with melena and bowel obstruction, 10 years after nephrectomy for renal cell carcinoma, then with initial diagnosis of ampula vater adenocarcinoma undergo an exploratory laparotomy and a mass was found in duodenum, vater ampulla and pancreas, then pancreaticoduodenectomy was performed. histopathological examination of mass showed a metastatic renal cell carcinoma with sarcomatoid component. In conclusion, patients after radical nephrectomy due to renal cell carcinoma require long-term systematic monitoring. Gastrointestinal metastasis from Renal cell carcinoma should be considered in nephrectomized patients with gastrointestinal symptoms.

NCMP-11. METASTATIC MENINGIOMA: AN UNUSUAL COURSE OF A COMMON DISEASE

Abstract BACKGROUND The most common central nervous system (CNS) tumor in adult patients is meningioma, accounting for 30% of all intracranial tumors. Despite this, extracranial meningioma metastases are exceedingly rare, accounting for 0.1% of cases, with common locations for metastases localized to the lungs, liver, lymph nodes, and bone. RESULTS We present a 55-year-old female with a past medical history of tobacco use, hypertension and depression, who initially presented due to a generalized tonic-clonic seizure. MRI brain revealed an intracranial lesion in the left occipital lobe with mass effect, requiring craniotomy and resection. Pathology was consistent with WHO grade I meningioma and post-operatively a small area of residual tumor remained. PET/CT found a left lung nodule, which was thought to be due to her smoking history and was followed with annual scans. Four years later, she had an increase in the size of the meningioma on surveillance MRI scans. The patient then required repeat craniotomy which redemonstrated pathology of WHO grade I meningioma, then treated with stereotactic radiation 14 Gy. The subsequent annual surveillance pulmonary scan showed a growth of left pulmonary nodule. She underwent a left lingual wedge resection and was found to have low grade spindle cell tumor, consistent with metastatic meningioma. CONCLUSION Although rare, metastatic meningioma should be included in the differential diagnosis of patients with concomitant extracranial lesions. Our case highlights the importance of annual, surveillance scans of extracranial lesions in meningioma patients.

CLRM-18 SCREEN FAILURES IN PHASE III GLIOBLASTOMA CLINICAL TRIALS

Glioblastoma (GBM) remains the most common and lethal malignant primary brain tumor in adult patients, with median overall survival ranging from 7 to 22 months. National Comprehensive Cancer Network guidelines encourage participation in clinical trials for both newly diagnosed and recurrent GBM patients. Multiple phase II trials in GBM have yielded promising, positive results, but the translation to phase III results is lacking and has failed to make strides in improving outcomes. These phase III trials universally require many participants, and the expenditure of phase III clinical trials is quite significant, with the median being 21.4 million dollars. With a paucity of ground-breaking phase III clinical trials and the cost expenditure to perform them, understanding screen failures in GBM clinical trials along with an evaluation of causes of screen failures is warranted. Using both ClinicalTrials.gov and PubMed, phase III clinical trials in GBM patients published from 1994 to 2021 were queried. This search, initially in ClinicalTrials.gov, involved using the terms: “glioblastoma” and “GBM” with filters “phase III,” “interventional,” “completed,” “suspended,” and “terminated.” This search was cross-referenced with PubMed for published full articles in English peer-reviewed journals. Fifty-one studies were identified, and 21 out of 51 were appropriate for evaluation of screen failures, with 15 being for newly diagnosed GBM and six being for recurrent GBM. Nine out of 21 (42.9%) did not publish information on screen failures, and in the remaining 12 studies, proportions of screen failures ranged from 0-84.0% for newly diagnosed studies and 9.2-23.2% for recurrent studies, with a combined median percentage of 28.9%. In this analysis, over one-fourth of patients screen failed for GBM clinical trials. Thus, it is prudent to explore the causes of these screen failures, their implications on clinical trial design, and their impact on patient outcomes clinically, financially, and holistically.

New insights in gastrointestinal "pediatric" neoplasms in adult patients: pancreatoblastoma, hepatoblastoma and embryonal sarcoma of the liver. A practical approach by GIPPI-GIPAD Groups.

SummaryPediatric solid neoplasms are rare and very different from those observed in adults. The majority of them are referred to as embryonal because they arise as a result of alterations in the processes of organogenesis or normal growth and are characterized by proliferation of primitive cells, reproducing the corresponding tissue at various stages of embryonic development. This review will focus on embryonal gastrointestinal pediatric neoplasms in adult patients, including pancreatoblastoma, hepatoblastoma, and embryonal sarcoma of the liver. Although they are classically considered pediatric neoplasms, they may (rarely) occur in adult patients. Hepatoblastoma represents the most frequent liver neoplasm in the pediatric population, followed by hepatocellular carcinoma and embryonal sarcoma of the liver; while pancreatoblastoma is the most common malignant pancreatic tumor in childhood. Both in children and adults, the mainstay of treatment is complete surgical resection, either up front or following neoadjuvant chemotherapy. Unresectable and/or metastatic neoplasms may be amenable to complete delayed surgery after neoadjuvant chemotherapy. However, these neoplasms display a more aggressive behavior and overall poorer prognosis in adults than in children, probably because they are diagnosed in later stages of diseases.

The Mechanism Study of Common Flavonoids on Antiglioma Based on Network Pharmacology and Molecular Docking.

Background Glioma is the most common primary intracranial tumor in adult patients. Among them, glioblastoma is a highly malignant one with a poor prognosis. Flavonoids are a class of phenolic compounds widely distributed in plants and have many biological functions, such as anti-inflammatory, antioxidant, antiaging, and anticancer. Nowadays, flavonoids have been applied to the therapy of glioma; however, the molecular mechanism underlying the therapeutic effects has not been fully elaborated. This study was carried out to explore the mechanism of selected active flavonoid compounds in treating glioma using network pharmacology and molecular docking approaches. Methods Active ingredients and associated targets of flavonoids were acquired by using the Traditional Chinese Medicine Database and Analysis Platform (TCMSP) and Swiss TargetPrediction platform. Genes related to glioma were obtained from the GeneCards and DisGeNET databases. The intersection targets between flavonoid targets and glioma-related genes were used to construct protein-protein interaction (PPI) network via the STRING database, and the results were analyzed by Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed and displayed by utilizing the Metascape portal and clusterProfiler R package. Molecular docking was carried out by iGEMDOCK and SwissDock, and the results were visually displayed by UCSF Chimera software. Results Eighty-four active flavonoid compounds and 258 targets overlapped between flavonoid targets and glioma-related genes were achieved. PPI network revealed potential therapeutic targets, such as AKT1, EGFR, VEGFA, MAPK3, and CASP3, based on their node degree. GO and KEGG analyses showed that core targets were mainly enriched in the PI3K-Akt signaling pathway. Molecular docking simulation indicated that potential glioma-related targets-MAPK1 and HSP90AA1 were bounded more firmly with epigallocatechin-3-gallate (EGCG) than with quercetin. Conclusions The findings of this study indicated that selected active flavonoid compounds might play therapeutic roles in glioma mainly through the PI3K-Akt signaling pathway. Moreover, EGCG had the potential antiglioma activity by targeting MAPK1 and HSP90AA1.

Papillary Glioneuronal Tumor of Third Ventricle Endoscopically Treated: Case Report and Review of Literature

Introduction: Papillary Glioneuronal Tumor (PGNT) is a grade I tumor based on the new World Health Organization CNS tumor classification. Its special feature concerns its biphasic histologic pattern of both glial and neuronal elements. Because of the rarity of this entity, literature is mostly based on case reports. Research Question: The objective of this paper is to display our experience treating endoscopically a papillary glioneuronal tumor located into the third ventricle in an adult patient and to highlight the main points of the literature. Material & Methods: A 75-year-old patient with known Parkinson disease presented with episodes of loss of consciousness and gait disorders in our institution. Brain MRI demonstrated enlargement of ventricular system due to an obstruction caused by an intraventricular tumor in the third ventricle. Results: Patient underwent an endoscopic subtotal removal of the tumor. Postoperative brain CT scan revealed minor residual of the tumor and patient was discharged 2 days after surgery in good clinical condition. Histopathological analysis of the tumor samples matched the diagnosis of PGNT. Postoperative follow-up in 1 month demonstrated great neurological improvement. Discussion & Conclusion: Literature reports that total surgical resection is the treatment of choice in almost all cases of PGNT giving the most favorable clinical outcome. Only 4 cases of PGNT located in 3rd ventricle have been recorded and data for endoscopic management found only for one of the cases concerning a pediatric patient. Therefore, we report for first time removal of third ventricle papillary glioneuronal tumor in adult patients via the endoscopic technique.

MET-11 Recent advances in targeted therapies and immunotherapy for metastatic brain tumors

This presentation outlines CQ2 of Chapter 2 from the forthcoming updated version of the Clinical Practice Guidelines for Brain Tumors, edited by the Society. These guidelines discuss chemotherapy and other drug therapies for metastatic brain tumors in adult patients. First, there is no noteworthy change in the principle of prioritizing local treatment of symptomatic metastatic brain tumors or those that require local treatment in the near future. However, with recent advances in molecular-targeted drugs and/or immune checkpoint inhibitors, many physicians now consider starting systemic treatment prior to local treatment of brain metastases, even in patients with solid tumors that were once considered insensitive to chemotherapy, given that their symptoms are well-controlled and do not require urgent treatment. In the treatment of non-small cell lung cancer (NSCLC), the molecular subtypes of metastatic brain tumors with EGFR mutations and ALK fusion genes have yielded favorable responses to molecular-targeted drugs. Because small molecule drugs are well delivered to the central nervous system, systemic drug therapy with such targeted drugs is commonly selected for patients with untreated metastatic brain tumors. A recent phase II trial has shown the effectiveness of anti-PD-1 antibody pembrolizumab monotherapy for metastatic brain tumors from NSCLC. Because untreated metastatic brain tumors from renal cell carcinoma are prone to bleeding, local treatment of brain metastases should be prioritized before systemic treatment, even if the patient is asymptomatic. Regardless of BRAF mutation status, immune checkpoint inhibitors alone or in combination (nivolumab and ipilimumab) are effective against malignant melanoma with brain metastases; moreover, a combined treatment with BRAF and MEK inhibitors is effective against BRAF mutation-positive malignant melanoma with brain metastases. A novel HER2 inhibitor, tucatinib (unapproved), is expected to be effective against metastatic brain tumors from HER2-positive breast cancer.

A Predictive Clinical-Radiomics Nomogram for Survival Prediction of Glioblastoma Using MRI.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adult patients with a median survival of around one year. Prediction of survival outcomes in GBM patients could represent a huge step in treatment personalization. The objective of this study was to develop machine learning (ML) algorithms for survival prediction of GBM patient. We identified a radiomic signature on a training-set composed of data from the 2019 BraTS challenge (210 patients) from MRI retrieved at diagnosis. Then, using this signature along with the age of the patients for training classification models, we obtained on test-sets AUCs of 0.85, 0.74 and 0.58 (0.92, 0.88 and 0.75 on the training-sets) for survival at 9-, 12- and 15-months, respectively. This signature was then validated on an independent cohort of 116 GBM patients with confirmed disease relapse for the prediction of patients surviving less or more than the median OS of 22 months. Our model insured an AUC of 0.71 (0.65 on train). The Kaplan–Meier method showed significant OS difference between groups (log-rank p = 0.05). These results suggest that radiomic signatures may improve survival outcome predictions in GBM thus creating a solid clinical tool for tailoring therapy in this population.

CYP3A Mediated Metabolism of Tyrosine Kinase Inhibitor Pexidartinib and Alleviated its Cytotoxicity to HepG2 Cells

Pexidartinib (PLX, TURALIOTM) is a novel small molecule tyrosine-kinase inhibitor with highly selective activity against colony-stimulating factor-1 receptor. PLX was developed for the treatment of symptomatic tenosynovial giant cell tumor in adult patients and approved by the US FDA in 2019. Despite its effectivity, frequently reported clinical cases with severe hepatotoxicity led to a black-box warning issued to PLX by the FDA. However, the mechanisms of PLX-induced hepatotoxicity remain largely unknown and the roles of PLX metabolism in its toxicity have not been investigated. Using liquid chromatography/mass spectrometry-based metabolomic approaches, this study revealed 36 PLX metabolites in human liver microsome (HLM) and mouse liver microsome (MLM), including characterized 11 glutathione (GSH) -PLX adducts and 3 methoxyamine-trapped aldehydes (hydrazones). Using recombinant cytochrome P450 enzymes, CYP3A4 and CYP3A5 were identified as the primary enzymes contributing to the formation of major metabolites, GSH-PLX adducts, and methoxyamine-trapped hydrazones. Their formation was significantly suppressed by the CYP3A inhibitor ketoconazole and in the liver S9 fraction of Cyp3a-null mice, further confirming the role of CYP3A in PLX Phase I metabolism. More interestingly, we found that PLX is less toxic to CYP3A4- or CYP3A5-overexpressed HepG2 cells compared to their counterpart HepG2 cells transduced with empty vector, indicating that CYP3A-mediated metabolism attenuates PLX cytotoxicity to HepG2. In summary, 36 PLX metabolites including 11 GSH adducts and 3 hydrazones were identified in HLM and MLM. CYP3A4 and CYP3A5 are responsible for the Phase I biotransformation of PLX and alleviate its cytotoxicity in HepG2. Further studies are warranted to elucidate the role of metabolism in PLX hepatotoxicity and the mechanism associated with PLX-induced liver injury.

MODL-28. IMMUNE PRIMING WITH INTERFERON-Γ COMBINED WITH EPIGENETIC MODULATION IN PEDIATRIC BRAIN TUMORS

Systemic interferon-γ (IFNγ) has been shown to induce major histocompatibility complex class I (MHC-I) and T cell infiltration in solid tumors in adult patients, demonstrating a potential strategy to abrogate tumor-intrinsic mechanisms of immune escape. Pediatric brain tumors (PBT) may be particularly sensitive to this approach but have a paucity of immunogenic tumor antigens for presentation on MHC-I. Decitabine and other DNA methyltransferase (DNMT) inhibitors promote expression of oncofetal antigens and endogenous immune responses through epigenetic alterations. We tested the convergence of these immune priming mechanisms using a novel combination of IFNγ and decitabine across a spectrum of PBT. Primary human cell lines (Med-411FH, PBT-05FH, GBM-511FH, CCHMC-GBM-1, CCHMC-GBM-4, ATRT-310FH) and murine transgenic models were treated with IFNγ alone or in combination with decitabine and evaluated expression of cell surface MHC-I and PD-L1, interferon response genes (ISGs), and oncofetal antigens. PBT showed exquisite sensitivity to IFNγ, increasing expression of MHC-1/PD-L1 along with ISGs (TAP1, MX1, IRF1). Decitabine enhanced IFNγ-induced gene expression of oncofetal antigens NY-ESO-1 and MAGE-A1. In a medulloblastoma flank tumor model, MHC-I was increased by 40-fold following intraperitoneal IFNγ treatment (p=0.01), with a 3-fold increase in PD-L1 (p=0.005) compared to untreated controls. Effect on CD8+ T cell killing and validation in humanized models is ongoing. Immune priming of PBT with IFNγ is feasible and results in more substantial MHC-I upregulation compared to hypomethylating agents alone. These results provide a strong rationale for priming prior to checkpoint inhibition as a compelling therapeutic strategy in immunologically-quiescent PBT.