المؤلفون: Friedman, Joshua, Jun, Tomi, Rashidipour, Omid, Huang, Kuan-Lin, Ellis, Ethan, Kadaba, Priyanka, Belani, Puneet, Nael, Kambiz, Tsankova, Nadejda, Sebra, Robert, Hormigo, Adília

المصدر: Cancer Immunology, Immunotherapy. 72(6)

مصطلحات موضوعية: EGFR amplification, Next-generation sequencing, Nivolumab, Pembrolizumab, Recurrent glioblastoma, Adult, Humans, Glioblastoma, Immune Checkpoint Inhibitors, Retrospective Studies, Antineoplastic Agents, Immunological, Prospective Studies, Neoplasm Recurrence, Local, ErbB Receptors

الوصف: PURPOSE: While immune checkpoint inhibitors (ICI) have had success with various malignancies, their efficacy in brain cancer is still unclear. Retrospective and prospective studies using PD-1 inhibitors for recurrent glioblastoma (GBM) have not established survival benefit. This study evaluated if ICI may be effective for select patients with recurrent GBM. METHODS: This was a single-center retrospective study of adult patients diagnosed with first recurrence GBM and received pembrolizumab or nivolumab with or without concurrent bevacizumab. Archival tissue was used for immunohistochemistry (IHC) and targeted DNA next-generation sequencing (NGS) analysis. RESULTS: Median overall survival (mOS) from initial diagnosis was 24.5 months (range 10-42). mOS from onset of ICI was 10 months (range 1-31) with 75% surviving > 6 months and 46% > 12 months. Additional IHC analysis on tumors from eight patients demonstrated a trend of longer survival after ICI for those with elevated PD-L1 expression. NGS of samples from 15 patients identified EGFR amplification at initial diagnosis and at any time point to be associated with worse survival after ICI (HR 12.2, 95% CI 1.37-108, p = 0.025 and HR 3.92, 95% CI 1.03-14.9, p = 0.045, respectively). This significance was corroborated with previously tested EGFR amplification via in situ hybridization. CONCLUSION: ICI did not extend overall survival for recurrent GBM. However, molecular sequencing identified EGFR amplification as associated with worse survival. Prospective studies can validate if EGFR amplification is a biomarker of ICI resistance and determine if its use can stratify responders from non-responders.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/6hk2v5zqTest
https://escholarship.org/content/qt6hk2v5zq/qt6hk2v5zq.pdfTest

المؤلفون: Mahmoudi, Keon, Kim, Daniel, Tavakkol, Elham, Kihira, Shingo, Bauer, Adam, Tsankova, Nadejda, Khan, Fahad, Hormigo, Adilia, Yedavalli, Vivek, Nael, Kambiz

المصدر: Cancers, vol 16, iss 3

مصطلحات موضوعية: MGMT, MRI, glioma, multiparametric, radiogenomics, texture analysis, tumor segmentation

الوصف: BACKGROUND: Clinical, histopathological, and imaging variables have been associated with prognosis in patients with glioblastoma (GBM). We aimed to develop a multiparametric radiogenomic model incorporating MRI texture features, demographic data, and histopathological tumor biomarkers to predict prognosis in patients with GBM. METHODS: In this retrospective study, patients were included if they had confirmed diagnosis of GBM with histopathological biomarkers and pre-operative MRI. Tumor segmentation was performed, and texture features were extracted to develop a predictive radiomic model of survival (<18 months vs. ≥18 months) using multivariate analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regularization to reduce the risk of overfitting. This radiomic model in combination with clinical and histopathological data was inserted into a backward stepwise logistic regression model to assess survival. The diagnostic performance of this model was reported for the training and external validation sets. RESULTS: A total of 116 patients were included for model development and 40 patients for external testing validation. The diagnostic performance (AUC/sensitivity/specificity) of the radiomic model generated from seven texture features in determination of ≥18 months survival was 0.71/69.0/70.3. Three variables remained as independent predictors of survival, including radiomics (p = 0.004), age (p = 0.039), and MGMT status (p = 0.025). This model yielded diagnostic performance (AUC/sensitivity/specificity) of 0.77/81.0/66.0 (training) and 0.89/100/78.6 (testing) in determination of survival ≥ 18 months. CONCLUSIONS: Results show that our radiogenomic model generated from radiomic features at baseline MRI, age, and MGMT status can predict survival ≥ 18 months in patients with GBM.

وصف الملف: application/pdf

العلاقة: qt1wz030k5; https://escholarship.org/uc/item/1wz030k5Test

الإتاحة: https://escholarship.org/uc/item/1wz030k5Test

المؤلفون: Kihira, Shingo, Derakhshani, Ahrya, Leung, Michael, Mahmoudi, Keon, Bauer, Adam, Zhang, Haoyue, Polson, Jennifer, Arnold, Corey, Tsankova, Nadejda M, Hormigo, Adilia, Salehi, Banafsheh, Pham, Nancy, Ellingson, Benjamin M, Cloughesy, Timothy F, Nael, Kambiz

المصدر: Cancers, vol 15, iss 4

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Biomedical Imaging, Brain Cancer, Brain Disorders, Cancer, Clinical Research, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Good Health and Well Being, deep learning, diffuse glioma, radiogenomic, T2-FLAIR mismatch, 1p, 19q co-deletion, 1p/19q co-deletion

الوقت: 1037

الوصف: PurposeThe T2-FLAIR mismatch sign has shown promise in determining IDH mutant 1p/19q non-co-deleted gliomas with a high specificity and modest sensitivity. To develop a multi-parametric radiomic model using MRI to predict 1p/19q co-deletion status in patients with newly diagnosed IDH1 mutant glioma and to perform a comparative analysis to T2-FLAIR mismatch sign+.MethodsIn this retrospective study, patients with diagnosis of IDH1 mutant gliomas with known 1p/19q status who had preoperative MRI were included. T2-FLAIR mismatch was evaluated independently by two board-certified neuroradiologists. Texture features were extracted from glioma segmentation of FLAIR images. eXtremeGradient Boosting (XGboost) classifiers were used for model development. Leave-one-out-cross-validation (LOOCV) and external validation performances were reported for both the training and external validation sets.ResultsA total of 103 patients were included for model development and 18 patients for external testing validation. The diagnostic performance (sensitivity/specificity/accuracy) in the determination of the 1p/19q co-deletion status was 59%/83%/67% (training) and 62.5%/70.0%/66.3% (testing) for the T2-FLAIR mismatch sign. This was significantly improved (p = 0.04) using the radiomics model to 77.9%/82.8%/80.3% (training) and 87.5%/89.9%/88.8% (testing), respectively. The addition of radiomics as a computer-assisted tool resulted in significant (p = 0.02) improvement in the performance of the neuroradiologist with 13 additional corrected cases in comparison to just using the T2-FLAIR mismatch sign.ConclusionThe proposed radiomic model provides much needed sensitivity to the highly specific T2-FLAIR mismatch sign in the determination of the 1p/19q non-co-deletion status and improves the overall diagnostic performance of neuroradiologists when used as an assistive tool.

وصف الملف: application/pdf

العلاقة: qt02725159; https://escholarship.org/uc/item/02725159Test

الإتاحة: https://escholarship.org/uc/item/02725159Test

المؤلفون: Chiu, Daniel, Qi, Jingjing, Thin, Tin Htwe, Garcia-Barros, Monica, Lee, Brian, Hahn, Mary, Mandeli, John, Belani, Puneet, Nael, Kambiz, Rashidipour, Omid, Ghatan, Saadi, Hadjipanayis, Constantinos G, Yong, Raymund L, Germano, Isabelle M, Brody, Rachel, Tsankova, Nadejda M, Gnjatic, Sacha, Kim-Schulze, Seunghee, Hormigo, Adilia

المصدر: Cancer Research Communications, vol 3, iss 1

مصطلحات موضوعية: Brain Cancer, Brain Disorders, Rare Diseases, Neurosciences, Cancer, Prevention, Clinical Research, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Good Health and Well Being, Humans, Middle Aged, Bevacizumab, Glioblastoma, Antibodies, Monoclonal, Vascular Endothelial Growth Factor A, B7-H1 Antigen

جغرافية الموضوع: 130 - 139

الوصف: PurposeThe treatment of glioblastoma (GBM) poses challenges. The use of immune checkpoint inhibition (ICI) has been disappointing as GBM is characterized by low mutational burden and low T-cell infiltration. The combination of ICI with other treatment modalities may improve efficacy.Patient and methodsPatients with recurrent GBM were treated with avelumab, a human IgG1 antibody directed against PD-L1 (part A), or avelumab within a week after laser interstitial thermal therapy (LITT) and continuation of avelumab (part B). Bevacizumab was allowed to be combined with ICI to spare steroid use. The primary objective was to characterize the tolerability and safety of the regimens. The secondary objectives included overall survival, progression-free survival (PFS), signatures of plasma analytes, and immune cells.ResultsA total of 12 patients (median age 64; range, 37-73) enrolled, five in part A and seven in part B. Two serious adverse events occurred in the same patient, LITT treated, not leading to death. The median survival from enrollment was 13 months [95% confidence interval (CI), 4-16 months] with no differences for part A or B. The median PFS was 3 months (95% CI, 1.5-4.5 months). The decrease in MICA/MICB, γδT cells, and CD4+ T cell EMRA correlated with prolonged survival.ConclusionsAvelumab was generally well tolerated. Adding bevacizumab to ICI may be beneficial by lowering cytokine and immune cell expression. The development of this combinatorial treatment warrants further investigation. Exploring the modulation of adaptive and innate immune cells and plasma analytes as biomarker signatures may instruct future studies in this dismal refractory disease.SignificanceOur phase I of PD-L1 inhibition combined with LITT and using bevacizumab to spare steroids had a good safety profile for recurrent GBM. Developing combinatory treatment may help outcomes. In addition, we found significant immune modulation of cytokines and immune cells by bevacizumab, which may enhance the effect of ICI.

وصف الملف: application/pdf

العلاقة: qt8162m7xn; https://escholarship.org/uc/item/8162m7xnTest

الإتاحة: https://escholarship.org/uc/item/8162m7xnTest

المؤلفون: Galanis, Evanthia, Anderson, S Keith, Twohy, Erin, Butowski, Nicholas A, Hormigo, Adilia, Schiff, David, Omuro, Antonio, Jaeckle, Kurt A, Kumar, Shaji, Kaufmann, Timothy J, Geyer, Susan, Kumthekar, Priya U, Campian, Jian, Giannini, Caterina, Buckner, Jan C, Wen, Patrick Y

المساهمون: Galanis, Evanthia, Anderson, S Keith, Twohy, Erin, Butowski, Nicholas A, Hormigo, Adilia, Schiff, David, Omuro, Antonio, Jaeckle, Kurt A, Kumar, Shaji, Kaufmann, Timothy J, Geyer, Susan, Kumthekar, Priya U, Campian, Jian, Giannini, Caterina, Buckner, Jan C, Wen, Patrick Y

مصطلحات موضوعية: CD105, TRC105, angiogenesi, bevacizumab, glioblastoma

الوصف: Background Patients with glioblastoma (GBM) have a poor prognosis and limited effective treatment options. Bevacizumab has been approved for treatment of recurrent GBM, but there is questionable survival benefit. Based on preclinical and early clinical data indicating that CD105 upregulation may represent a mechanism of resistance to bevacizumab, we hypothesized that combining bevacizumab with the anti-CD105 antibody TRC105 may improve efficacy in recurrent GBM.Methods Phase I dose-escalation/comparative randomized phase II trial in patients with GBM. During phase I, the maximum tolerated dose (MTD) of TRC105 in combination with bevacizumab was determined. In phase II, patients were randomized 1:1 to TRC105 and bevacizumab or bevacizumab monotherapy. Patients receivedTRC105 (10 mg/kg) weekly and bevacizumab (10 mg/kg) every 2 weeks. Efficacy, as assessed by progression-free survival (PFS), was the primary endpoint; safety, quality of life, and correlative outcomes were also evaluated.Results In total, 15 patients were enrolled in phase I and 101 in phase II; 52 patients were randomized to TRC105 with bevacizumab and 49 to bevacizumab monotherapy. The MTD was determined to be 10 mg/kg TRC105 weekly plus bevacizumab 10 mg/kg every 2 weeks. An increased occurrence of grade >= 3 adverse events was seen in the combination arm, including higher incidences of anemia. Median PFS was similar in both treatment arms: 2.9 months for combination versus 3.2 months for bevacizumab monotherapy (HR = 1.16, 95% CI = 0.75-1.78, P = .51). Quality of life scores were similar for both treatment arms.Conclusions TRC105 in combination with bevacizumab was well tolerated in patients with recurrent GBM, but no difference in efficacy was observed compared to bevacizumab monotherapy.

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35664553; info:eu-repo/semantics/altIdentifier/wos/WOS:000852789900052; volume:4; issue:1; firstpage:1; lastpage:11; numberofpages:11; journal:NEURO-ONCOLOGY ADVANCES; https://hdl.handle.net/11585/901909Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85134976099; https://academic.oup.com/noa/article/4/1/vdac041/6563099?login=trueTest

الإتاحة: https://doi.org/10.1093/noajnl/vdac041Test
https://hdl.handle.net/11585/901909Test
https://academic.oup.com/noa/article/4/1/vdac041/6563099?login=trueTest

المؤلفون: Kihira, Shingo, Mei, Xueyan, Mahmoudi, Keon, Liu, Zelong, Dogra, Siddhant, Belani, Puneet, Tsankova, Nadejda, Hormigo, Adilia, Fayad, Zahi A, Doshi, Amish, Nael, Kambiz

المصدر: Cancers, vol 14, iss 18

مصطلحات موضوعية: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Brain Disorders, Brain Cancer, Cancer, Rare Diseases, Neurosciences, deep learning, glioma, tumor segmentation, radiogenomic, isocitrate dehydrogenase 1, magnetic resonance imaging

الوقت: 4457

الوصف: (1) Background: Gliomas are the most common primary brain neoplasms accounting for roughly 40−50% of all malignant primary central nervous system tumors. We aim to develop a deep learning-based framework for automated segmentation and prediction of biomarkers and prognosis in patients with gliomas. (2) Methods: In this retrospective two center study, patients were included if they (1) had a diagnosis of glioma with known surgical histopathology and (2) had preoperative MRI with FLAIR sequence. The entire tumor volume including FLAIR hyperintense infiltrative component and necrotic and cystic components was segmented. Deep learning-based U-Net framework was developed based on symmetric architecture from the 512 × 512 segmented maps from FLAIR as the ground truth mask. (3) Results: The final cohort consisted of 208 patients with mean ± standard deviation of age (years) of 56 ± 15 with M/F of 130/78. DSC of the generated mask was 0.93. Prediction for IDH-1 and MGMT status had a performance of AUC 0.88 and 0.62, respectively. Survival prediction of <18 months demonstrated AUC of 0.75. (4) Conclusions: Our deep learning-based framework can detect and segment gliomas with excellent performance for the prediction of IDH-1 biomarker status and survival.

وصف الملف: application/pdf

العلاقة: qt6mh1p7wk; https://escholarship.org/uc/item/6mh1p7wkTest

الإتاحة: https://escholarship.org/uc/item/6mh1p7wkTest

المؤلفون: Brown, Christine E, Bucktrout, Samantha, Butterfield, Lisa H, Futer, Olga, Galanis, Evanthia, Hormigo, Adilia, Lim, Michael, Okada, Hideho, Prins, Robert, Marr, Sara Siebel, Tanner, Kirk

المصدر: Journal of Translational Medicine, vol 20, iss 1

مصطلحات موضوعية: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Orphan Drug, Pediatric, Clinical Research, Pediatric Cancer, Brain Cancer, Biotechnology, Immunization, Vaccine Related, Cancer, Brain Disorders, Neurosciences, Rare Diseases, Good Health and Well Being, Adult, Animals, Brain Neoplasms, Cell- and Tissue-Based Therapy, Child, Humans, Immunologic Factors, Immunotherapy, Tumor Microenvironment, Brain tumors, Cell therapy, Medical and Health Sciences, Health sciences

الوصف: Harnessing the effector mechanisms of the immune system to combat brain tumors with antigen specificity and memory has been in research and clinical testing for many years. Government grant mechanisms and non-profit organizations have supported many innovative projects and trials while biotech companies have invested in the development of needed tools, assays and novel clinical approaches. The National Brain Tumor Society and the Parker Institute for Cancer Immunotherapy partnered to host a workshop to share recent data, ideas and identify both hurdles and new opportunities for harnessing immunotherapy against pediatric and adult brain tumors. Adoptively transferred cell therapies have recently shown promising early clinical results. Local cell delivery to the brain, new antigen targets and innovative engineering approaches are poised for testing in a new generation of clinical trials. Although several such advances have been made, several obstacles remain for the successful application of immunotherapies for brain tumors, including the need for more representative animal models that can better foreshadow human trial outcomes. Tumor and tumor microenvironment biopsies with multiomic analysis are critical to understand mechanisms of response and patient stratification, yet brain tumors are especially challenging for such biopsy collection. These workshop proceedings and commentary shed light on the status of immunotherapy in pediatric and adult brain tumor patients, including current research as well as opportunities for improving future efforts to bring immunotherapy to the forefront in the management of brain tumors.

وصف الملف: application/pdf

العلاقة: qt1968r34g; https://escholarship.org/uc/item/1968r34gTest

الإتاحة: https://escholarship.org/uc/item/1968r34gTest

المؤلفون: Brown, Christine E., Bucktrout, Samantha, Butterfield, Lisa H., Futer, Olga, Galanis, Evanthia, Hormigo, Adilia, Lim, Michael, Okada, Hideho, Prins, Robert, Marr, Sara Siebel, Tanner, Kirk

المساهمون: Parker Institute for Cancer Immunotherapy, National Brain Tumor Society

المصدر: Journal of Translational Medicine ; volume 20, issue 1 ; ISSN 1479-5876

مصطلحات موضوعية: General Biochemistry, Genetics and Molecular Biology, General Medicine

الوصف: Harnessing the effector mechanisms of the immune system to combat brain tumors with antigen specificity and memory has been in research and clinical testing for many years. Government grant mechanisms and non-profit organizations have supported many innovative projects and trials while biotech companies have invested in the development of needed tools, assays and novel clinical approaches. The National Brain Tumor Society and the Parker Institute for Cancer Immunotherapy partnered to host a workshop to share recent data, ideas and identify both hurdles and new opportunities for harnessing immunotherapy against pediatric and adult brain tumors. Adoptively transferred cell therapies have recently shown promising early clinical results. Local cell delivery to the brain, new antigen targets and innovative engineering approaches are poised for testing in a new generation of clinical trials. Although several such advances have been made, several obstacles remain for the successful application of immunotherapies for brain tumors, including the need for more representative animal models that can better foreshadow human trial outcomes. Tumor and tumor microenvironment biopsies with multiomic analysis are critical to understand mechanisms of response and patient stratification, yet brain tumors are especially challenging for such biopsy collection. These workshop proceedings and commentary shed light on the status of immunotherapy in pediatric and adult brain tumor patients, including current research as well as opportunities for improving future efforts to bring immunotherapy to the forefront in the management of brain tumors.

الإتاحة: https://doi.org/10.1186/s12967-022-03438-zTest

المؤلفون: Kodysh, Julia, Bozkus, Cansu Cimen, Saxena, Mansi, Meseck, Marcia, Rubinsteyn, Alex, O’Donnell, Tim, Thin, Tin Htwe, Brody, Rachel, Mandeli, John, Bhardwaj, Nina, Hormigo, Adilia

المصدر: Regular and Young Investigator Award Abstracts

الإتاحة: https://doi.org/10.1136/jitc-2021-sitc2021.334Test

المؤلفون: Kihira, Shingo, Tsankova, Nadejda, Bauer, Adam, Sakai, Yu, Mahmoudi, Keon, Zubizarreta, Nicole, Houldsworth, Jane, Khan, Fahad, Salamon, Noriko, Hormigo, Adilia, Nael, Kambiz

المصدر: Neuro-Oncology Advances, vol 3, iss 1

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Clinical Research, Neurosciences, Brain Disorders, Rare Diseases, Brain Cancer, Biomedical Imaging, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, glioma, MR diffusion, multiparametric MRI, radiogenomics, texture analysis

الوصف: BackgroundEarly identification of glioma molecular phenotypes can lead to understanding of patient prognosis and treatment guidance. We aimed to develop a multiparametric MRI texture analysis model using a combination of conventional and diffusion MRI to predict a wide range of biomarkers in patients with glioma.MethodsIn this retrospective study, patients were included if they (1) had diagnosis of gliomas with known IDH1, EGFR, MGMT, ATRX, TP53, and PTEN status from surgical pathology and (2) had preoperative MRI including FLAIR, T1c+ and diffusion for radiomic texture analysis. Statistical analysis included logistic regression and receiver-operating characteristic (ROC) curve analysis to determine the optimal model for predicting glioma biomarkers. A comparative analysis between ROCs (conventional only vs conventional + diffusion) was performed.ResultsFrom a total of 111 patients included, 91 (82%) were categorized to training and 20 (18%) to test datasets. Constructed cross-validated model using a combination of texture features from conventional and diffusion MRI resulted in overall AUC/accuracy of 1/79% for IDH1, 0.99/80% for ATRX, 0.79/67% for MGMT, and 0.77/66% for EGFR. The addition of diffusion data to conventional MRI features significantly (P < .05) increased predictive performance for IDH1, MGMT, and ATRX. The overall accuracy of the final model in predicting biomarkers in the test group was 80% (IDH1), 70% (ATRX), 70% (MGMT), and 75% (EGFR).ConclusionAddition of MR diffusion to conventional MRI features provides added diagnostic value in preoperative determination of IDH1, MGMT, and ATRX in patients with glioma.

وصف الملف: application/pdf

العلاقة: qt80s7v9kh; https://escholarship.org/uc/item/80s7v9khTest

الإتاحة: https://escholarship.org/uc/item/80s7v9khTest