48 results on '"Wen, Patrick Y"'
Search Results
2. Updated Response Assessment in Neuro-Oncology (RANO) for Gliomas
- Author
-
Youssef, Gilbert and Wen, Patrick Y.
- Published
- 2024
- Full Text
- View/download PDF
3. Author Correction: Liquid biopsy epigenomic profiling for cancer subtyping
- Author
-
Baca, Sylvan C., Seo, Ji-Heui, Davidsohn, Matthew P., Fortunato, Brad, Semaan, Karl, Sotudian, Shahabbedin, Lakshminarayanan, Gitanjali, Diossy, Miklos, Qiu, Xintao, El Zarif, Talal, Savignano, Hunter, Canniff, John, Madueke, Ikenna, Saliby, Renee Maria, Zhang, Ziwei, Li, Rong, Jiang, Yijia, Taing, Len, Awad, Mark, Chau, Cindy H., DeCaprio, James A., Figg, William D., Greten, Tim F., Hata, Aaron N., Hodi, F. Stephen, Hughes, Melissa E., Ligon, Keith L., Lin, Nancy, Ng, Kimmie, Oser, Matthew G., Meador, Catherine, Parsons, Heather A., Pomerantz, Mark M., Rajan, Arun, Ritz, Jerome, Thakuria, Manisha, Tolaney, Sara M., Wen, Patrick Y., Long, Henry, Berchuck, Jacob E., Szallasi, Zoltan, Choueiri, Toni K., and Freedman, Matthew L.
- Published
- 2024
- Full Text
- View/download PDF
4. Cavitation monitoring, treatment strategy, and acoustic simulations of focused ultrasound blood-brain barrier disruption in patients with glioblastoma
- Author
-
McDannold, Nathan, Wen, Patrick Y., Reardon, David A., Fletcher, Stecia-Marie, and Golby, Alexandra J.
- Published
- 2024
- Full Text
- View/download PDF
5. PET-based response assessment criteria for diffuse gliomas (PET RANO 1.0): a report of the RANO group
- Author
-
Albert, Nathalie L, Galldiks, Norbert, Ellingson, Benjamin M, van den Bent, Martin J, Chang, Susan M, Cicone, Francesco, de Groot, John, Koh, Eng-Siew, Law, Ian, Le Rhun, Emilie, Mair, Maximilian J, Minniti, Giuseppe, Rudà, Roberta, Scott, Andrew M, Short, Susan C, Smits, Marion, Suchorska, Bogdana, Tolboom, Nelleke, Traub-Weidinger, Tatjana, Tonn, Joerg-Christian, Verger, Antoine, Weller, Michael, Wen, Patrick Y, and Preusser, Matthias
- Published
- 2024
- Full Text
- View/download PDF
6. Re-irradiation of recurrent IDH-wildtype glioblastoma in the bevacizumab and immunotherapy era: Target delineation, outcomes and patterns of recurrence
- Author
-
Christ, Sebastian M., Youssef, Gilbert, Tanguturi, Shyam K., Cagney, Daniel, Shi, Diana, McFaline-Figueroa, J. Ricardo, Chukwueke, Ugonma, Lee, Eudocia Q., Hertler, Caroline, Andratschke, Nicolaus, Weller, Michael, Reardon, David A., Haas-Kogan, Daphne, Guckenberger, Matthias, Wen, Patrick Y., and Rahman, Rifaquat
- Published
- 2024
- Full Text
- View/download PDF
7. Author Correction: Vorasidenib and ivosidenib in IDH1-mutant low-grade glioma: a randomized, perioperative phase 1 trial
- Author
-
Mellinghoff, Ingo K., Lu, Min, Wen, Patrick Y., Taylor, Jennie W., Maher, Elizabeth A., Arrillaga-Romany, Isabel, Peters, Katherine B., Ellingson, Benjamin M., Rosenblum, Marc K., Chun, Saewon, Le, Kha, Tassinari, Ania, Choe, Sung, Toubouti, Youssef, Schoenfeld, Steven, Pandya, Shuchi S., Hassan, Islam, Steelman, Lori, Clarke, Jennifer L., and Cloughesy, Timothy F.
- Published
- 2024
- Full Text
- View/download PDF
8. Evaluating the Base Excision Repair Inhibitor TRC102 and Temozolomide for patients with Recurrent Glioblastoma in the Phase 2 Adult Brain Tumor Consortium Trial BERT
- Author
-
Ahluwalia, Manmeet S., primary, Ozair, Ahmad, additional, Drappatz, Jan, additional, Ye, Xiaobu, additional, Peng, Sen, additional, Lee, Matthew, additional, Rath, Sanhita, additional, Dhruv, Harshil, additional, Hao, Yue, additional, Berens, Michael E., additional, Walbert, Tobias, additional, Holdhoff, Matthias, additional, Lesser, Glenn J., additional, Cloughesy, Timothy F., additional, Sloan, Andrew E., additional, Takebe, Naoko, additional, Couce, Marta, additional, Peereboom, David M., additional, Nabors, Burt, additional, Wen, Patrick Y., additional, Grossman, Stuart A., additional, and Rogers, Lisa R., additional
- Published
- 2024
- Full Text
- View/download PDF
9. A randomized, controlled, phase 2 trial of nivolumab plus standard-dose or low-dose bevacizumab for recurrent glioblastoma (NAVAL).
- Author
-
Ahluwalia, Manmeet Singh, primary, Peereboom, David M., additional, Ozair, Ahmad, additional, Khosla, Atulya Aman, additional, Rauf, Yasmeen, additional, Nayak, Lakshmi, additional, Ciolfi, Marci, additional, Alban, Tyler, additional, Grabowski, Matthew, additional, Rayman, Pat, additional, Diaz, Marcella, additional, Lathia, Justin, additional, Lee, Eudocia Quant, additional, Wen, Patrick Y., additional, and Reardon, David A., additional
- Published
- 2024
- Full Text
- View/download PDF
10. Phase 1 study of BDTX-1535, an oral 4th generation covalent EGFR inhibitor, in patients with recurrent glioblastoma: Preliminary dose escalation results.
- Author
-
Wen, Patrick Y., primary, Johnson, Melissa Lynne, additional, Henry, Jason Timothy, additional, Spira, Alex, additional, Battiste, James, additional, Alnahhas, Iyad, additional, Nam, Do-Hyun, additional, Patel, Jyoti D., additional, Edenfield, William Jeffery, additional, Hormigo, Adilia, additional, Yoon, Shinkyo, additional, Kim, Tae Min, additional, Eathiraj, Sudharshan, additional, Hajdenberg, Julio, additional, Yurasov, Sergey, additional, and Ahluwalia, Manmeet Singh, additional
- Published
- 2024
- Full Text
- View/download PDF
11. Phase 1b/2a study evaluating the combination of MN-166 (ibudilast) and temozolomide in patients with newly diagnosed and recurrent glioblastoma (GBM).
- Author
-
Youssef, Gilbert, primary, Lathia, Justin, additional, Lee, Eudocia Quant, additional, Chukwueke, Ugonma Nnenna, additional, Lauko, Adam, additional, Batchelor, Tracy, additional, Aquilanti, Elisa, additional, Nayak, Lakshmi, additional, Myers, Alexa, additional, Russ, Alyssa, additional, Westergaard, Catharina C, additional, Alban, Tyler, additional, Jarmula, Jakub, additional, Lee, Juyeun, additional, Vogelbaum, Michael A., additional, Matsuda, Kazuko, additional, Reardon, David A., additional, and Wen, Patrick Y., additional
- Published
- 2024
- Full Text
- View/download PDF
12. Phase 1 dose expansion and biomarker study assessing first-in-class tumor microenvironment modulator VT1021 in patients with advanced solid tumors
- Author
-
Chen, Jian Jenny, primary, Vincent, Melanie Y., additional, Shepard, Dale, additional, Peereboom, David, additional, Mahalingam, Devalingam, additional, Battiste, James, additional, Patel, Manish R., additional, Juric, Dejan, additional, Wen, Patrick Y., additional, Bullock, Andrea, additional, Selfridge, Jennifer Eva, additional, Pant, Shubham, additional, Liu, Joyce, additional, Li, Wendy, additional, Fyfe, Susanne, additional, Wang, Suming, additional, Zota, Victor, additional, Mahoney, James, additional, Watnick, Randolph S., additional, Cieslewicz, Michael, additional, and Watnick, Jing, additional
- Published
- 2024
- Full Text
- View/download PDF
13. Pilot trial of perampanel on peritumoral hyperexcitability and clinical outcomes in newly diagnosed high-grade glioma
- Author
-
Tobochnik, Steven, primary, Regan, Michael S., additional, Dorotan, Maria K. C., additional, Reich, Dustine, additional, Lapinskas, Emily, additional, Hossain, Md Amin, additional, Stopka, Sylwia, additional, Santagata, Sandro, additional, Murphy, Melissa M., additional, Arnaout, Omar, additional, Bi, Wenya Linda, additional, Chiocca, E. Antonio, additional, Golby, Alexandra J., additional, Mooney, Michael A., additional, Smith, Timothy R., additional, Ligon, Keith L., additional, Wen, Patrick Y., additional, Agar, Nathalie Y. R., additional, and Lee, Jong Woo, additional
- Published
- 2024
- Full Text
- View/download PDF
14. Liquid biopsy for improving diagnosis and monitoring of CNS lymphomas: a RANO review
- Author
-
Nayak, Lakshmi, primary, Bettegowda, Chetan, additional, Scherer, Florian, additional, Galldiks, Norbert, additional, Ahluwalia, Manmeet, additional, Baraniskin, Alexander, additional, von Baumgarten, Louisa, additional, Bromberg, Jacoline E C, additional, Ferreri, Andrés J M, additional, Grommes, Christian, additional, Hoang-Xuan, Khê, additional, Kühn, Julia, additional, Rubenstein, James L, additional, Rudà, Roberta, additional, Weller, Michael, additional, Chang, Susan M, additional, van den Bent, Martin J, additional, Wen, Patrick Y, additional, and Soffietti, Riccardo, additional
- Published
- 2024
- Full Text
- View/download PDF
15. Supplementary Table S3 from Clinical and Genomic Predictors of Adverse Events in Newly Diagnosed Glioblastoma
- Author
-
Lim-Fat, Mary Jane, primary, Iorgulescu, J. Bryan, primary, Rahman, Rifaquat, primary, Bhave, Varun, primary, Muzikansky, Alona, primary, Woodward, Eleanor, primary, Whorral, Sydney, primary, Allen, Marie, primary, Touat, Mehdi, primary, Li, Xiaomei, primary, Xy, Gongwen, primary, Patel, Jay, primary, Gerstner, Elizabeth R., primary, Kalpathy-Cramer, Jayashree, primary, Youssef, Gilbert, primary, Chukwueke, Ugonma, primary, McFaline-Figueroa, J. Ricardo, primary, Nayak, Lakshmi, primary, Lee, Eudocia Q., primary, Reardon, David A., primary, Beroukhim, Rameen, primary, Huang, Raymond Y., primary, Bi, Wenya Linda, primary, Ligon, Keith L., primary, and Wen, Patrick Y., primary
- Published
- 2024
- Full Text
- View/download PDF
16. Supplementary Figure S1 from Clinical and Genomic Predictors of Adverse Events in Newly Diagnosed Glioblastoma
- Author
-
Lim-Fat, Mary Jane, primary, Iorgulescu, J. Bryan, primary, Rahman, Rifaquat, primary, Bhave, Varun, primary, Muzikansky, Alona, primary, Woodward, Eleanor, primary, Whorral, Sydney, primary, Allen, Marie, primary, Touat, Mehdi, primary, Li, Xiaomei, primary, Xy, Gongwen, primary, Patel, Jay, primary, Gerstner, Elizabeth R., primary, Kalpathy-Cramer, Jayashree, primary, Youssef, Gilbert, primary, Chukwueke, Ugonma, primary, McFaline-Figueroa, J. Ricardo, primary, Nayak, Lakshmi, primary, Lee, Eudocia Q., primary, Reardon, David A., primary, Beroukhim, Rameen, primary, Huang, Raymond Y., primary, Bi, Wenya Linda, primary, Ligon, Keith L., primary, and Wen, Patrick Y., primary
- Published
- 2024
- Full Text
- View/download PDF
17. DNA damage response in brain tumors: A Society for Neuro-Oncology consensus review on mechanisms and translational efforts in neuro-oncology
- Author
-
Rahman, Rifaquat, primary, Shi, Diana D, additional, Reitman, Zachary J, additional, Hamerlik, Petra, additional, de Groot, John F, additional, Haas-Kogan, Daphne A, additional, D’Andrea, Alan D, additional, Sulman, Erik P, additional, Tanner, Kirk, additional, Agar, Nathalie Y R, additional, Sarkaria, Jann N, additional, Tinkle, Christopher L, additional, Bindra, Ranjit S, additional, Mehta, Minesh P, additional, and Wen, Patrick Y, additional
- Published
- 2024
- Full Text
- View/download PDF
18. ACTION: A randomized phase 3 study of ONC201 (dordaviprone) in patients with newly diagnosed H3 K27M-mutant diffuse glioma
- Author
-
Arrillaga-Romany, Isabel, primary, Lassman, Andrew, additional, McGovern, Susan L, additional, Mueller, Sabine, additional, Nabors, Burt, additional, van den Bent, Martin, additional, Vogelbaum, Michael, additional, Allen, Joshua E, additional, Melemed, Allen S, additional, Tarapore, Rohinton S, additional, Wen, Patrick Y, additional, and Cloughesy, Timothy, additional
- Published
- 2024
- Full Text
- View/download PDF
19. Challenges, limitations, and pitfalls of PET and advanced MRI in patients with brain tumors: A report of the PET/RANO group.
- Author
-
Galldiks, Norbert, Kaufmann, Timothy J, Vollmuth, Philipp, Lohmann, Philipp, Smits, Marion, Veronesi, Michael C, Langen, Karl-Josef, Rudà, Roberta, Albert, Nathalie L, Hattingen, Elke, Law, Ian, Hutterer, Markus, Soffietti, Riccardo, Vogelbaum, Michael A, Wen, Patrick Y, Weller, Michael, and Tonn, Joerg-Christian
- Published
- 2024
- Full Text
- View/download PDF
20. ONC201 (Dordaviprone) in Recurrent H3 K27M–Mutant Diffuse Midline Glioma
- Author
-
Arrillaga-Romany, Isabel, primary, Gardner, Sharon L., additional, Odia, Yazmin, additional, Aguilera, Dolly, additional, Allen, Joshua E., additional, Batchelor, Tracy, additional, Butowski, Nicholas, additional, Chen, Clark, additional, Cloughesy, Timothy, additional, Cluster, Andrew, additional, de Groot, John, additional, Dixit, Karan S., additional, Graber, Jerome J., additional, Haggiagi, Aya M., additional, Harrison, Rebecca A., additional, Kheradpour, Albert, additional, Kilburn, Lindsay B., additional, Kurz, Sylvia C., additional, Lu, Guangrong, additional, MacDonald, Tobey J., additional, Mehta, Minesh, additional, Melemed, Allen S., additional, Nghiemphu, Phioanh Leia, additional, Ramage, Samuel C., additional, Shonka, Nicole, additional, Sumrall, Ashley, additional, Tarapore, Rohinton S., additional, Taylor, Lynne, additional, Umemura, Yoshie, additional, and Wen, Patrick Y., additional
- Published
- 2024
- Full Text
- View/download PDF
21. Clinical and Genomic Predictors of Adverse Events in Newly Diagnosed Glioblastoma
- Author
-
Lim-Fat, Mary Jane, primary, Iorgulescu, J. Bryan, additional, Rahman, Rifaquat, additional, Bhave, Varun, additional, Muzikansky, Alona, additional, Woodward, Eleanor, additional, Whorral, Sydney, additional, Allen, Marie, additional, Touat, Mehdi, additional, Li, Xiaomei, additional, Xy, Gongwen, additional, Patel, Jay, additional, Gerstner, Elizabeth R., additional, Kalpathy-Cramer, Jayashree, additional, Youssef, Gilbert, additional, Chukwueke, Ugonma, additional, McFaline-Figueroa, J. Ricardo, additional, Nayak, Lakshmi, additional, Lee, Eudocia Q., additional, Reardon, David A., additional, Beroukhim, Rameen, additional, Huang, Raymond Y., additional, Bi, Wenya Linda, additional, Ligon, Keith L., additional, and Wen, Patrick Y., additional
- Published
- 2024
- Full Text
- View/download PDF
22. Adult Neuro-Oncology Trials in the United States over Five Decades: Analysis of Trials Completion Rate to Guide the Path Forward
- Author
-
Smith, Emily J, primary, Naik, Anant, additional, Goel, Mahima, additional, Wen, Patrick Y, additional, Lim, Michael, additional, Chang, Susan M, additional, and Germano, Isabelle M, additional
- Published
- 2024
- Full Text
- View/download PDF
23. Abnormal vascular structure and function within brain metastases is linked to pembrolizumab resistance.
- Author
-
Kim, Albert E, Lou, Kevin W, Giobbie-Hurder, Anita, Chang, Ken, Gidwani, Mishka, Hoebel, Katharina, Patel, Jay B, Cleveland, Mason C, Singh, Praveer, Bridge, Christopher P, Ahmed, Syed Rakin, Bearce, Benjamin A, Liu, William, Fuster-Garcia, Elies, Lee, Eudocia Q, Lin, Nancy U, Overmoyer, Beth, Wen, Patrick Y, Nayak, Lakshmi, and Cohen, Justine V
- Published
- 2024
- Full Text
- View/download PDF
24. Selective DRD2 antagonist and ClpP agonist ONC201 in a recurrent non-midline H3 K27M-mutant glioma cohort.
- Author
-
Odia, Yazmin, Hall, Matthew D, Cloughesy, Timothy Francis, Wen, Patrick Y, Arrillaga-Romany, Isabel, Daghistani, Doured, Mehta, Minesh P, Tarapore, Rohinton S, Ramage, Samuel C, and Allen, Joshua E
- Published
- 2024
- Full Text
- View/download PDF
25. Defining interventions and metrics to improve diversity in CNS clinical trial participation: A SNO and RANO effort.
- Author
-
Budhu, Joshua A, Chukwueke, Ugonma N, Jackson, Sadhana, Lee, Eudocia Q, McFaline-Figueroa, J Ricardo, Willmarth, Nicole, Dalmage, Mahalia, Kawachi, Ichiro, Arons, David, Chang, Susan M, Galanis, Evanthia, Hervey-Jumper, Shawn L, Wen, Patrick Y, and Porter, Alyx B
- Published
- 2024
- Full Text
- View/download PDF
26. Systematic characterization of antibody–drug conjugate targets in central nervous system tumors.
- Author
-
Coy, Shannon, Lee, Jong Suk, Chan, Sabrina J, Woo, Terri, Jones, Jacquelyn, Alexandrescu, Sanda, Wen, Patrick Y, Sorger, Peter K, Ligon, Keith L, and Santagata, Sandro
- Published
- 2024
- Full Text
- View/download PDF
27. A multicenter, phase 1, Adult Brain Tumor Consortium trial of oral terameprocol for patients with recurrent high-grade glioma (GATOR)
- Author
-
Ahluwalia, Manmeet S., Ozair, Ahmad, Rudek, Michelle, Ye, Xiaobu, Holdhoff, Matthias, Lieberman, Frank S., Piotrowski, Anna F., Nabors, Burt, Desai, Arati, Lesser, Glenn, Huang, Ru Chih, Glenn, Steve, Khosla, Atulya A., Peereboom, David M., Wen, Patrick Y., and Grossman, Stuart A.
- Published
- 2024
- Full Text
- View/download PDF
28. Brain tumor-related epilepsy management: A Society for Neuro-oncology (SNO) consensus review on current management.
- Author
-
Avila, Edward K, Tobochnik, Steven, Inati, Sara K, Koekkoek, Johan A F, McKhann, Guy M, Riviello, James J, Rudà, Roberta, Schiff, David, Tatum, William O, Templer, Jessica W, Weller, Michael, and Wen, Patrick Y
- Published
- 2024
- Full Text
- View/download PDF
29. Mutant IDH inhibitors induce lineage differentiation in IDH-mutant oligodendroglioma
- Author
-
Spitzer, Avishay, Gritsch, Simon, Nomura, Masashi, Jucht, Alexander, Fortin, Jerome, Raviram, Ramya, Weisman, Hannah R., Gonzalez Castro, L. Nicolas, Druck, Nicholas, Chanoch-Myers, Rony, Lee, John J.Y., Mylvaganam, Ravindra, Lee Servis, Rachel, Fung, Jeremy Man, Lee, Christine K., Nagashima, Hiroaki, Miller, Julie J., Arrillaga-Romany, Isabel, Louis, David N., Wakimoto, Hiroaki, Pisano, Will, Wen, Patrick Y., Mak, Tak W., Sanson, Marc, Touat, Mehdi, Landau, Dan A., Ligon, Keith L., Cahill, Daniel P., Suvà, Mario L., and Tirosh, Itay
- Published
- 2024
- Full Text
- View/download PDF
30. RANO 2.0: The revised Response Assessment in Neuro-Oncology (RANO) criteria for high- and low-grade glial tumors in adults designed for the future.
- Author
-
Wen, Patrick Y, van den Bent, Martin, Vogelbaum, Michael A, and Chang, Susan M
- Published
- 2024
- Full Text
- View/download PDF
31. Contemporary Prognostic Signatures and Refined Risk Stratification of Gliomas: An Analysis of 4,400 Tumors.
- Author
-
Ghosh HS, Patel RV, Woodward E, Greenwald NF, Bhave VM, Maury EA, Cello G, Hoffman SE, Li Y, Gupta H, Youssef G, Spurr LF, Vogelzang J, Touat M, Dubois F, Cherniack AD, Guo X, Tavakol S, Cioffi G, Lindeman NI, Ligon AH, Chiocca EA, Reardon DA, Wen PY, Meredith D, Santagata S, Barnholtz-Sloan JS, Ligon KL, Beroukhim R, and Bi WL
- Abstract
Background: With the significant shift in the classification, risk stratification, and standards of care for gliomas, we sought to understand how the overall survival of patients with these tumors is impacted by molecular features, clinical metrics, and treatment received., Methods: We assembled a cohort of patients with a histopathologically diagnosed glioma from The Cancer Genome Atlas, Project Genomics Evidence Neoplasia Information Exchange, and Dana-Farber Cancer Institute/Brigham and Women's Hospital. This incorporated retrospective clinical, histological, and molecular data alongside prospective assessment of patient survival., Results: 4,400 gliomas were identified: 2,195 glioblastoma, 1,198 IDH1/2-mutant astrocytoma, 531 oligodendroglioma, 271 other IDH1/2-wildtype glioma, and 205 pediatric-type glioma. Molecular classification updated 27.2% of gliomas from their original histopathologic diagnosis. Examining the distribution of molecular alterations across glioma subtypes revealed mutually exclusive alterations within tumorigenic pathways. Non-TCGA patients had significantly improved overall survival compared to TCGA patients, with 26.7%, 55.6%, and 127.8% longer survival for glioblastoma, IDH1/2-mutant astrocytoma, and oligodendroglioma respectively (all p<0.01). Several prognostic features were characterized, including NF1 alteration and 21q loss in glioblastoma, and EGFR amplification and 22q loss in IDH1/2-mutant astrocytoma. Leveraging the size of this cohort, nomograms were generated to assess the probability of overall survival based on patient age, the molecular features of a tumor, and the treatment received., Conclusions: By applying modern molecular criteria, we characterize the genomic diversity across glioma subtypes, identify clinically applicable prognostic features, and provide a contemporary update on patient survival to serve as a reference for ongoing investigations., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)
- Published
- 2024
- Full Text
- View/download PDF
32. Enhancing neuro-oncology care through equity-driven applications of artificial intelligence.
- Author
-
Mehari M, Sibih Y, Dada A, Chang SM, Wen PY, Molinaro AM, Chukwueke UN, Budhu JA, Jackson S, McFaline-Figueroa JR, Porter A, and Hervey-Jumper SL
- Abstract
The disease course and clinical outcome for brain tumor patients depend not only on the molecular and histological features of the tumor but also on the patient's demographics and social determinants of health. While current investigations in neuro-oncology have broadly utilized artificial intelligence (AI) to enrich tumor diagnosis and more accurately predict treatment response, postoperative complications, and survival, equity-driven applications of AI have been limited. However, AI applications to advance health equity in the broader medical field have the potential to serve as practical blueprints to address known disparities in neuro-oncologic care. In this consensus review, we will describe current applications of AI in neuro-oncology, postulate viable AI solutions for the most pressing inequities in neuro-oncology based on broader literature, propose a framework for the effective integration of equity into AI-based neuro-oncology research, and close with the limitations of AI., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
- Full Text
- View/download PDF
33. A real-world observation of patients with glioblastoma treated with a personalized peptide vaccine.
- Author
-
Latzer P, Zelba H, Battke F, Reinhardt A, Shao B, Bartsch O, Rabsteyn A, Harter J, Schulze M, Okech T, Golf A, Kyzirakos-Feger C, Kayser S, Pieper N, Feldhahn M, Wünsche J, Seitz C, Hadaschik D, Garbe C, Hauser TK, la Fougère C, Biskup D, Brooke D, Parker D, Martens UM, Illerhaus G, Blumenthal DT, Merrell R, Lorenzo LS, Hidvégi M, de Robles P, Kebir S, Li WW, Li VW, Williams M, Miller AM, Kesari S, Castro M, Desjardins A, Ashley DM, Friedman HS, Wen PY, Neil EC, Iwamoto FM, Sipos B, Geletneky K, Zender L, Glas M, Reardon DA, and Biskup S
- Subjects
- Humans, Female, Male, Middle Aged, Aged, Adult, Antigens, Neoplasm immunology, T-Lymphocytes immunology, Treatment Outcome, Protein Subunit Vaccines, Glioblastoma immunology, Glioblastoma therapy, Vaccines, Subunit immunology, Vaccines, Subunit therapeutic use, Cancer Vaccines immunology, Cancer Vaccines therapeutic use, Cancer Vaccines administration & dosage, Precision Medicine methods, Brain Neoplasms immunology, Brain Neoplasms therapy
- Abstract
Current treatment outcome of patients with glioblastoma (GBM) remains poor. Following standard therapy, recurrence is universal with limited survival. Tumors from 173 GBM patients are analysed for somatic mutations to generate a personalized peptide vaccine targeting tumor-specific neoantigens. All patients were treated within the scope of an individual healing attempt. Among all vaccinated patients, including 70 treated prior to progression (primary) and 103 treated after progression (recurrent), the median overall survival from first diagnosis is 31.9 months (95% CI: 25.0-36.5). Adverse events are infrequent and are predominantly grade 1 or 2. A vaccine-induced immune response to at least one of the vaccinated peptides is detected in blood samples of 87 of 97 (90%) monitored patients. Vaccine-specific T-cell responses are durable in most patients. Significantly prolonged survival is observed for patients with multiple vaccine-induced T-cell responses (53 months) compared to those with no/low induced responses (27 months; P = 0.03). Altogether, our results highlight that the application of personalized neoantigen-targeting peptide vaccine is feasible and represents a promising potential treatment option for GBM patients., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
34. Targeted radionuclide therapy for gliomas: emerging clinical trial landscape.
- Author
-
Weller M, Albert NL, Galldiks N, Bink A, Preusser M, Sulman EP, Treyer V, Wen PY, Tonn JC, and Le Rhun E
- Abstract
According to the new WHO classification of 2021, gliomas are a heterogeneous group of tumors with very different histology, molecular genetics and prognoses. In addition to glioblastomas, the most common gliomas, there are also numerous less common gliomas, some of which have a very favorable prognosis. Targeted radionuclide therapy is a therapeutic option that can be attractive if a tumor can be targeted based on its molecular characteristics. It is particularly useful when tumors cannot be completely resected or when conventional imaging does not fully capture the extent of the tumor. Numerous approaches to radionuclide therapy for gliomas are in early development. The most advanced approaches for patients with gliomas in the clinic employ L-type amino acid transporter 1 as an uptake mechanism for radiolabeled amino acids or target somatostatin receptor 2 or gastrin-releasing peptide receptor. Here, we discuss the various target structures of radionuclide therapy in gliomas and provide an outlook for which glioma entities radionuclide therapy could most likely provide a therapeutic alternative., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
- Full Text
- View/download PDF
35. A comparative analysis of IDH-mutant glioma in pediatric, young adult, and older adult patients.
- Author
-
Lim-Fat MJ, Cotter JA, Touat M, Vogelzang J, Sousa C, Pisano W, Geduldig J, Bhave V, Driver J, Kao PC, McGovern A, Ma C, Margol AS, Cole K, Smith A, Goldman S, Kaneva K, Truong AL, Nazemi KJ, Wood MD, Wright KD, London WB, Warren KE, Wen PY, Bi WL, Alexandrescu S, Reardon DA, Ligon KL, and Yeo KK
- Abstract
Background: The frequency and significance of IDH mutations in glioma across age groups is incompletely understood. We performed a multi-center retrospective age-stratified comparison of patients with IDH-mutant gliomas to identify age-specific differences in clinico-genomic features, treatments, and outcomes., Methods: Clinical, histologic, and sequencing data from patients with IDH-mutant, grade 2-4 gliomas, were collected from collaborating institutions between 2013-2019. Patients were categorized as pediatric (<19y), YA (19-39y) or older adult (≥40y). Clinical presentation, treatment, histologic, and molecular features were compared across age categories using Fisher's exact test or analysis-of-variance. Cox proportional-hazards regression was used to determine association of age and other covariates with overall (OS) and progression-free survival (PFS)., Results: We identified a cohort of 379 patients (204 YA) with IDH-mutant glioma with clinical data. There were 155 (41%) oligodendrogliomas and 224 (59%) astrocytomas. YA showed significantly shorter PFS and shorter median time-to-malignant transformation (MT) compared to pediatric and adult groups, but no significant OS difference. Adjusting for pathology type, extent of resection, and upfront therapy in multivariable analysis, the YA group was independently prognostic of shorter PFS than pediatric and adult groups. Among astrocytomas, CDK4/6 copy number amplifications were associated with both shorter PFS and shorter OS. Among oligodendrogliomas, PIK3CA and CDKN2A/2B alterations were associated with shorter OS., Conclusions: IDH-mutant glioma YA patients had significantly shorter PFS and time to MT but did not differ in OS compared to pediatric and adult groups. Treatment approach varied significantly by patient age and warrant further study as addressable age-associated outcome drivers., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
- Full Text
- View/download PDF
36. SNO-EANO-EURACAN consensus on management of pineal parenchymal tumors.
- Author
-
Liu APY, Li BK, Vasiljevic A, Dewan MC, Tamrazi B, Ertl-Wagner B, Hansford JR, Pfaff E, Mynarek M, Ng HK, Tsang DS, Gottardo NG, Gajjar A, Bouffet E, Dufour C, Pizer B, Schiff D, Jenkinson MD, Lombardi G, Wen PY, van den Bent MJ, and Huang A
- Abstract
Pineal parenchymal tumors are rare neoplasms for which evidence-based treatment recommendations are lacking. These tumors vary in biology, clinical characteristics, and prognosis, requiring treatment that ranges from surgical resection alone to intensive multimodal antineoplastic therapy. Recently, international collaborative studies have shed light on the genomic landscape of these tumors, leading to refinement in molecular-based disease classification in the 5th edition of the World Health Organization (WHO) classification of tumors of the central nervous system. In this review, we summarize the literature on diagnostic and therapeutic approaches, and suggest pragmatic recommendations for the clinical management of patients presenting with intrinsic pineal region masses including parenchymal tumors (pineocytoma, pineal parenchymal tumor of intermediate differentiation, and pineoblastoma), pineal cyst, and papillary tumors of the pineal region., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
- Full Text
- View/download PDF
37. RANO 2.0 criteria: concepts applicable to the neuroradiologist's clinical practice.
- Author
-
Sanvito F, Castellano A, Cloughesy TF, Wen PY, and Ellingson BM
- Abstract
Purpose of Review: The Response Assessment in Neuro-Oncology (RANO) 2.0 criteria aim at improving the standardization and reliability of treatment response assessment in clinical trials studying central nervous system (CNS) gliomas. This review presents the evidence supporting RANO 2.0 updates and discusses which concepts can be applicable to the clinical practice, particularly in the clinical radiographic reads., Recent Findings: Updates in RANO 2.0 were supported by recent retrospective analyses of multicenter data from recent clinical trials. As proposed in RANO 2.0, in tumors receiving radiation therapy, the post-RT MRI scan should be used as a reference baseline for the following scans, as opposed to the pre-RT scan, and radiographic findings suggesting progression within three months after radiation therapy completion should be verified with confirmatory scans. Volumetric assessments should be considered, when available, especially for low-grade gliomas, and the evaluation of nonenhancing disease should have a marginal role in glioblastoma. However, the radiographic reads in the clinical setting also benefit from aspects that lie outside RANO 2.0 criteria, such as qualitative evaluations, patient-specific clinical considerations, and advanced imaging., Summary: While RANO 2.0 criteria are meant for the standardization of the response assessment in clinical trials, some concepts have the potential to improve patients' management in the clinical practice., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
38. Velcrin molecular glues induce apoptosis in glioblastomas with high PDE3A and SLFN12 expression.
- Author
-
Aquilanti E, Goldoni S, Baker A, Kotynkova K, Andersen S, Bozinov V, Gao GF, Cherniack AD, Lange M, Lesche R, Kopitz C, Lienau P, Lewis TA, Garrido M, Gradl S, Seidel H, Tseng YY, Ligon KL, Wen PY, Meyerson M, and Greulich H
- Abstract
Background: Velcrins are molecular glues that kill cells by inducing the formation of a protein complex between the RNase SLFN12 and the phosphodiesterase PDE3A. Formation of the complex activates SLFN12, which cleaves tRNA
Leu (TAA) and induces apoptosis. Velcrins such as the clinical investigational compound, BAY 2666605, were found to have activity across multiple solid tumor cell lines from the cancer cell line encyclopedia, including glioblastoma cell lines. We therefore aim to characterize velcrins as novel therapeutic agents in glioblastoma., Materials and Methods: PDE3A and SLFN12 expression levels were measured in glioblastoma cell lines, the Cancer Genome Atlas (TCGA) tumor samples, and tumor neurospheres. Velcrin-treated cells were assayed for viability, induction of apoptosis, cell cycle phases, and global changes in translation. Transcriptional profiling of the cells was obtained. Xenograft-harboring mice treated with velcrins were also monitored for survival., Results: We identified several velcrin-sensitive glioblastoma cell lines and 4 velcrin-sensitive glioblastoma patient-derived models. We determined that BAY 2666605 crosses the blood-brain barrier and elicits full tumor regression in an orthotopic xenograft model of GB1 cells. We also determined that the velcrins BAY 2666605 and BRD3800 induce tumor regression in subcutaneous glioblastoma PDX models., Conclusions: Velcrins have antitumor activity in preclinical models of glioblastoma, warranting further investigation as potential therapeutic agents., Competing Interests: P.Y.W.: Research Support: Agios, Astra Zeneca/Medimmune, Beigene, Celgene, Eli Lily, Genentech/Roche, Kazia, MediciNova, Merck, Novartis, Nuvation Bio, Oncoceutics, Vascular Biogenics, VBI Vaccines. Advisory Board: Agios, Astra Zeneca, Bayer, Boston Pharmaceuticals, CNS Pharmaceuticals, Elevate Bio Immunomic Therapeutics, Imvax, Karyopharm, Merck, Novartis, Nuvation Bio, Vascular Biogenics, VBI Vaccines, Voyager, QED, Celularity, Sapience. J.G.D.: consults for Microsoft Research, Abata Therapeutics, Servier, Maze Therapeutics, BioNTech, Sangamo, and Pfizer; consults for and has equity in Tango Therapeutics; serves as a paid scientific advisor to the Laboratory for Genomics Research, funded in part by GSK; receives funding support from the Functional Genomics Consortium: Abbvie, Bristol Myers Squibb, Janssen, Merck, and Vir Biotechnology. M.M. is the scientific advisory board chair of Isabl; consults for Bayer, DelveBio, and Interline; is an inventor of patents licensed to LabCorp and Bayer; and receives research funding from Bayer and Janssen. M.M. and H.G. receive an inventor’s share of license revenue as part of their employment for certain patent filings, including US-2016-0016913 and US-2018-0235961, which relate to aspects of the work described in this manuscript. The co-owners of these patent filings are The Broad Institute, Inc., Dana-Farber Cancer Institute, Inc., and Bayer Pharma A.G., A.D.C, and H.G. also receive research funding from Bayer. A.D.C consults for KaryoVerse. K.L.L.: Research Support: BMS; Consulting: BMS, Travera, Integragen Equity: Travera., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)- Published
- 2024
- Full Text
- View/download PDF
39. A Neuroradiologist's Guide to Operationalizing the Response Assessment in Neuro-Oncology (RANO) Criteria Version 2.0 for Gliomas in Adults.
- Author
-
Ellingson BM, Sanvito F, Cloughesy TF, Huang RY, Villanueva-Meyer JE, Pope WB, Barboriak DP, Shankar LK, Smits M, Kaufmann TJ, Boxerman JL, Weller M, Galanis E, Groot J, Gilbert MR, Lassman AB, Shiroishi MS, Nabavizadeh A, Mehta M, Stupp R, Wick W, Reardon DA, Vogelbaum MA, van den Bent M, Chang SM, and Wen PY
- Abstract
Radiographic assessment plays a crucial role in the management of patients with central nervous system (CNS) tumors, aiding in treatment planning and evaluation of therapeutic efficacy by quantifying response. Recently, an updated version of the Response Assessment in Neuro-Oncology (RANO) criteria (RANO 2.0) was developed to improve upon prior criteria and provide an updated, standardized framework for assessing treatment response in clinical trials for gliomas in adults. This article provides an overview of significant updates to the criteria including (1) the use of a unified set of criteria for high and low grade gliomas in adults; (2) the use of the post-radiotherapy MRI scan as the baseline for evaluation in newly diagnosed high-grade gliomas; (3) the option for the trial to mandate a confirmation scan to more reliably distinguish pseudoprogression from tumor progression; (4) the option of using volumetric tumor measurements; and (5) the removal of subjective non-enhancing tumor evaluations in predominantly enhancing gliomas (except for specific therapeutic modalities). Step-by-step pragmatic guidance is hereby provided for the neuroradiologist and imaging core lab involved in operationalization and technical execution of RANO 2.0 in clinical trials, including the display of representative cases and in-depth discussion of challenging scenarios.ABBREVIATIONS: BTIP = Brain Tumor Imaging Protocol; CE = Contrast-Enhancing; CNS = Central Nervous System; CR = Complete Response; ECOG = Eastern Cooperative Oncology Group; HGG = High-Grade Glioma; IDH = Isocitrate Dehydrogenase; IRF = Independent Radiologic Facility; LGG = Low-Grade Glioma; KPS = Karnofsky Performance Status; MR = Minor Response; mRANO = Modified RANO; NANO = Neurological Assessment in Neuro-Oncology; ORR = Objective Response Rate; OS = Overall Survival; PD = Progressive Disease; PFS = Progression-Free Survival; PR = Partial Response; PsP = Pseudoprogression; RANO = Response Assessment in Neuro-Oncology; RECIST = Response Evaluation Criteria In Solid Tumors; RT = Radiation Therapy; SD = Stable Disease; Tx = Treatment., Competing Interests: The authors declare no conflicts of interest relative to the content of this article., (© 2024 by American Journal of Neuroradiology.)
- Published
- 2024
- Full Text
- View/download PDF
40. The biological significance of tumor grade, age, enhancement and extent of resection in IDH mutant gliomas: how should they inform treatment decision in the era of IDH inhibitors? Invited review.
- Author
-
van den Bent MJ, French PJ, Brat D, Tonn JC, Touat M, Ellingson BM, Young RJ, Pallud J, von Deimling A, Sahm F, Figarella Branger D, Huang RY, Weller M, Mellinghoff IK, Cloughsey TF, Huse JT, Aldape K, Reifenberger G, Youssef G, Karschnia P, Noushmehr H, Peters KB, Ducray F, Preusser M, and Wen PY
- Abstract
The 2016 and 2021 World Health Organization (WHO) 2021 Classification of Central Nervous System (CNS) tumors have resulted in a major improvement of the classification of IDH-mutant gliomas. With more effective treatments many patients experience prolonged survival . However, treatment guidelines are often still based on information from historical series comprising both patients with IDHwt and IDH mutant tumors. They provide recommendations for radiotherapy and chemotherapy for so-called high-risk patients, usually based on residual tumor after surgery and age over 40. More up-to-date studies give a better insight into clinical, radiological and molecular factors associated with outcome of patients with IDH-mutant glioma. These insights should be used today for risk stratification and for treatment decisions. In many patients with an IDH-mutant grade 2 and grade 3 glioma, if carefully monitored postponing radiotherapy and chemotherapy is safe, and will not jeopardize overall outcome of patients. With the INDIGO trial showing patient benefit from the IDH inhibitor vorasidenib, there is a sizable population in which it seems reasonable to try this class of agents before recommending radio-chemotherapy with its delayed adverse event profile affecting quality of survival. Ongoing trials should help to further identify the patients that are benefiting from this treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)
- Published
- 2024
- Full Text
- View/download PDF
41. Leptomeningeal metastases from solid tumors: A SNO and ASCO consensus review on clinical management and future directions.
- Author
-
Wilcox JA, Chukwueke UN, Ahn MJ, Aizer AA, Bale TA, Brandsma D, Brastianos PK, Chang S, Daras M, Forsyth P, Garzia L, Glantz M, Oliva ICG, Kumthekar P, Le Rhun E, Nagpal S, O'Brien B, Pentsova E, Lee EQ, Remsik J, Rudà R, Smalley I, Taylor MD, Weller M, Wefel J, Yang JT, Young RJ, Wen PY, and Boire AA
- Abstract
Leptomeningeal metastases are increasingly becoming recognized as a treatable, yet generally incurable, complication of advanced cancer. As modern cancer therapeutics have prolonged the lives of patients with metastatic cancer, specifically in patients with parenchymal brain metastases, treatment options and clinical research protocols for patients with leptomeningeal metastases from solid tumors have similarly evolved to improve survival within specific populations. Recent expansion in clinical investigation, early diagnosis, and drug development have given rise to new unanswered questions. These include leptomeningeal metastasis biology and preferred animal modeling, epidemiology in the modern cancer population, ensuring validation and accessibility of newer leptomeningeal metastasis diagnostics, best clinical practices with multi-modality treatment options, clinical trial design and standardization of response assessments, and avenues worthy of further research. An international group of multi-disciplinary experts in the research and management of leptomeningeal metastases, supported by the Society for Neuro-Oncology and American Society of Clinical Oncology, were assembled to reach a consensus opinion on these pressing topics and provide a roadmap for future directions. Our hope is that these recommendations will accelerate collaboration and progress in the field of leptomeningeal metastases and serve as a platform for further discussion and patient advocacy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)
- Published
- 2024
- Full Text
- View/download PDF
42. NRG-BN002: Phase I Study of Ipilimumab, Nivolumab, and the Combination in Patients with Newly Diagnosed GBM.
- Author
-
Sloan AE, Winter K, Gilbert MR, Aldape K, Choi S, Wen PY, Butowski N, Iwamoto FM, Raval RR, Voloschin AD, Kamiya-Matsuoka C, Won M, and Mehta MP
- Abstract
Background: Immune checkpoint inhibitors (ICIs) have efficacy in several solid tumors but limited efficacy in glioblastoma (GBM). This study evaluated the safety of anti-CTLA-4 and anti-PD-1 ICIs alone or in combination in newly diagnosed GBM after completion of standard radiochemotherapy with the subsequent intent to test combinatorial ICIs in this setting., Methods: The primary endpoint was dose limiting toxicity (DLT) for adults with unifocal, supratentorial newly diagnosed GBM after resection and chemoradiation. Ipilimumab and nivolumab were tested separately and in combination with a planned expansion cohort dependent upon DLT results., Results: Thirty-two patients were enrolled at 9 institutions; 6 to each DLT assessment cohort and 14 to the expansion cohort. Median age: 55 years, 67.7% male, 83.9% white. Treatment was well tolerated with a 16% Grade 4 events; the combination did not have unexpectedly increased toxicity, with no Grade 5 events. One DLT was seen in each single-agent treatment; none were observed in the combination, leading to expanded accrual of the combined treatment. Median follow-up was 19.6 mo. For all patients receiving combination treatment, median overall survival (OS) and progression-free survival (PFS) were 20.7 mo. and 16.1 mo., respectively., Conclusions: IPI and NIVO are safe and tolerable with toxicities similar to those noted with other cancers when given in combination with adjuvant TMZ for newly diagnosed GBM. Combination IPI+NIVO is not substantially more toxic than single agents. These results support a subsequent efficacy trial to test the combination of ICIs in a phase II/III for patients with newly diagnosed GBM., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
- Full Text
- View/download PDF
43. Non-invasive Blood-Brain Barrier Disruption using Acoustic Holography with a Clinical Focused Ultrasound System.
- Author
-
McDannold N, Zhang Y, Fletcher SM, Wen PY, Reardon DA, Golby AJ, and Livingstone M
- Abstract
Objective: Holographic methods can be used with phased array transducers to shape an ultrasound field. We tested a simple method to create holograms with a hemispherical 1024-element phased array transducer and explored how it could benefit ultrasound-mediated blood-brain barrier (BBB) disruption., Methods: With this method, individual acoustic simulations for each element of the transducer were simultaneously loaded into computer memory. Each element's phase was systematically modulated until the combined field matched a desired pattern. The method was evaluated with a 220 kHz transducer being tested clinically to enhance drug delivery via BBB disruption. The holograms were evaluated in a tissue-mimicking phantom and in vivo in experiments disrupting the BBB in rats and in a macaque. We also explored whether this approach could mitigate secondary reflections from the skull using simulations of transcranial focusing in clinical treatments of transcranial sonication for BBB disruption., Results: This approach can enlarge the focal volume in a patient-specific manner and could reduce the number of sonication targets needed to disrupt large volumes, improve the homogeneity of the disruption, and improve our ability to detect microbubble activity in tissues with low vascular density. Simulations suggest that the method could also mitigate secondary reflections during transcranial sonication.
- Published
- 2024
- Full Text
- View/download PDF
44. Glioma.
- Author
-
Weller M, Wen PY, Chang SM, Dirven L, Lim M, Monje M, and Reifenberger G
- Subjects
- Humans, Prognosis, Child, Isocitrate Dehydrogenase genetics, Mutation, Glioma genetics, Glioma physiopathology, Glioma therapy, Brain Neoplasms genetics, Brain Neoplasms therapy, Brain Neoplasms diagnosis, Brain Neoplasms physiopathology
- Abstract
Gliomas are primary brain tumours that are thought to develop from neural stem or progenitor cells that carry tumour-initiating genetic alterations. Based on microscopic appearance and molecular characteristics, they are classified according to the WHO classification of central nervous system (CNS) tumours and graded into CNS WHO grades 1-4 from a low to high grade of malignancy. Diffusely infiltrating gliomas in adults comprise three tumour types with distinct natural course of disease, response to treatment and outcome: isocitrate dehydrogenase (IDH)-mutant and 1p/19q-codeleted oligodendrogliomas with the best prognosis; IDH-mutant astrocytomas with intermediate outcome; and IDH-wild-type glioblastomas with poor prognosis. Pilocytic astrocytoma is the most common glioma in children and is characterized by circumscribed growth, frequent BRAF alterations and favourable prognosis. Diffuse gliomas in children are divided into clinically indolent low-grade tumours and high-grade tumours with aggressive behaviour, with histone 3 K27-altered diffuse midline glioma being the leading cause of glioma-related death in children. Ependymal tumours are subdivided into biologically and prognostically distinct types on the basis of histology, molecular biomarkers and location. Although surgery, radiotherapy and alkylating agent chemotherapy are the mainstay of glioma treatment, individually tailored strategies based on tumour-intrinsic dominant signalling pathways have improved outcome in subsets of patients., (© 2024. Springer Nature Limited.)
- Published
- 2024
- Full Text
- View/download PDF
45. Radioligand therapies in meningioma - evidence and future directions.
- Author
-
Mair MJ, Tabouret E, Johnson DR, Sulman EP, Wen PY, Preusser M, and Albert NL
- Abstract
Meningiomas are the most common intracranial neoplasms in adults. While most meningiomas are cured by resection, further treatment by radiotherapy may be needed, particularly in WHO grade 2 and 3 tumors which have an increased risk of recurrence, even after conventional therapies. Still, there is an urgent need for novel therapeutic strategies after exhaustion of local treatment approaches. Radionuclide therapies combine the specificity of tumor-specific antibodies or ligands with the cytotoxic activity of radioactive emitters. Alongside, integrated molecular imaging allows for a non-invasive assessment of predictive biomarkers as treatment targets. Whereas the concept of "theranostics" has initially evolved in extracranial tumors such as thyroid diseases, neuroendocrine tumors, and prostate cancer, data from retrospective case series and early phase trials underscore the potential of this strategy in meningioma. This review aims to explore the available evidence of radionuclide treatments and ongoing clinical trial initiatives in meningioma. Moreover, we discuss optimal clinical trial design and future perspectives in the field, including compound- and host-specific determinants of the efficacy of "theranostic" treatment approaches., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)
- Published
- 2024
- Full Text
- View/download PDF
46. Meningioma: International Consortium on Meningiomas (ICOM) consensus review on scientific advances & treatment paradigms for clinicians, researchers, and patients.
- Author
-
Wang JZ, Landry AP, Raleigh DR, Sahm F, Walsh KM, Goldbrunner R, Yefet LS, Tonn JC, Gui C, Ostrom QT, Barnholtz-Sloan J, Perry A, Ellenbogen Y, Hanemann CO, Jungwirth G, Jenkinson MD, Tabatabai G, Mathiesen TI, McDermott MW, Tatagiba M, la Fougère C, Maas SLN, Galldiks N, Albert NL, Brastianos PK, Ehret F, Minniti G, Lamszus K, Ricklefs FL, Schittenhelm J, Drummond KJ, Dunn IF, Pathmanaban ON, Cohen-Gadol A, Sulman EP, Tabouret E, Le Rhun E, Mawrin C, Moliterno J, Weller M, Bi WL, Gao A, Yip S, Niyazi M, Aldape K, Wen PY, Short S, Preusser M, Nassiri F, and Zadeh G
- Abstract
Meningiomas are the most common primary intracranial tumors in adults and are increasing in incidence due to the aging population and the rising availability of neuroimaging. While most exhibit non-malignant behaviour, a subset of meningiomas are biologically aggressive and lead to significant neurological morbidity and mortality. In recent years, meaningful advances in our understanding of the biology of these tumors have led to the incorporation of molecular biomarkers into their grading and prognostication. However, unlike other central nervous system tumors, a unified molecular taxonomy for meningiomas has not yet been established and remains an overarching goal of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official WHO (cIMPACT-NOW) working group. There also remains clinical equipoise on how specific meningioma cases and patient populations should be optimally managed. To address these existing gaps, members of the International Consortium on Meningiomas (ICOM) including field-leading experts, have prepared a comprehensive consensus narrative review directed towards clinicians, researchers, and patients. Included in this manuscript are detailed overviews of proposed molecular classifications, novel biomarkers, contemporary treatment strategies, trials on systemic therapies, health-related quality of life studies, and management strategies for unique meningioma patient populations. In each section we discuss the current state of knowledge as well as ongoing clinical and research challenges to road map future directions for further investigation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)
- Published
- 2024
- Full Text
- View/download PDF
47. Pilot trial of perampanel on peritumoral hyperexcitability and clinical outcomes in newly diagnosed high-grade glioma.
- Author
-
Tobochnik S, Regan MS, Dorotan MKC, Reich D, Lapinskas E, Hossain MA, Stopka S, Santagata S, Murphy MM, Arnaout O, Bi WL, Antonio Chiocca E, Golby AJ, Mooney MA, Smith TR, Ligon KL, Wen PY, Agar NYR, and Lee JW
- Abstract
Background: Glutamatergic neuron-glioma synaptogenesis and peritumoral hyperexcitability promote glioma growth in a positive feedback loop. The objective of this study was to evaluate the feasibility and estimated effect sizes of the AMPA-R antagonist, perampanel, on intraoperative electrophysiologic hyperexcitability and clinical outcomes., Methods: An open-label trial was performed comparing perampanel to standard of care (SOC) in patients undergoing resection of newly-diagnosed radiologic high-grade glioma. Perampanel was administered as a pre-operative loading dose followed by maintenance therapy until progressive disease or up to 12-months. SOC treatment involved levetiracetam for 7-days or as clinically indicated. The primary outcome of hyperexcitability was defined by intra-operative electrocorticography high frequency oscillation (HFO) rates. Seizure-freedom and overall survival (OS) were estimated by the Kaplan-Meier method. Tissue concentrations of perampanel, levetiracetam, and metabolites were measured by mass spectrometry., Results: HFO rates were similar between perampanel-treated and SOC cohorts. The trial was terminated early after interim analysis for futility, and outcomes assessed in 11 patients (7 perampanel-treated, 4 SOC). Over a median 281 days of post-enrollment follow-up, 27% of patients had seizures, including 14% treated with perampanel and 50% treated with SOC. OS in perampanel-treated patients was similar to a glioblastoma reference cohort (p=0.81). Glutamate concentrations in surface biopsies were positively correlated with HFO rates in adjacent electrode contacts and were not significantly associated with treatment assignment or drug concentrations., Conclusions: A peri-operative loading regimen of perampanel was safe and well-tolerated, with similar peritumoral hyperexcitability as in levetiracetam-treated patients. Maintenance anti-glutamatergic therapy was not observed to impact survival outcomes., Competing Interests: CONFLICT OF INTEREST S.T. received non-monetary research support for this study from Eisai, Inc (FYC-IIS-M001–1100) in the form of perampanel study drug, and has served in consulting roles for Blackrock Neurotech. K.L.L. is the founder and equity holder of Travera, a consultant for BMS, Integragen, Blaze Bioscience, and has received research support from BMS and Lilly. E.A.C. is an advisor to Bionaut Labs, Genenta Inc., Insightec Inc., Seneca Therapeutics, Theriva Biologics, has equity options in Bionaut Laboratories, Immunomic Therapeutics, Seneca Therapeutics, and Ternalys Therapeutics, is co-founder and on Board of Directors of Ternalys Therapeutics, has received research support from Advantagene, NewLink Genetics and Amgen, and has patents related to oncolytic viruses under the possession of Brigham and Women’s Hospital licensed to Candel Therapeutics, Inc. T.R.S. has equity options in Phebe Health. P.Y.W. has served in consulting or advisory roles to AstraZeneca, VBI Vaccines, Bayer, Prelude Therapeutics, Mundipharma, Black Diamond Therapeutics, Day One Biopharmaceuticals, Sapience Therapeutics, Celularity, Novartis, Merck, Chimerix, Servier, Insightec, Novocure, Sagimet Biosciences, Boehringer Ingelheim, Servier, Genenta Science, Prelude Therapeutics, GlaxoSmithKline, Anheart Therapeutics, Kintara Therapeutics, Mundipharma, Novocure, SymBio Pharmaceuticals, Tango Therapeutics, Telix Pharmaceuticals, and received research funding from AstraZeneca, Merck, Novartis, Lilly, MediciNova, Vascular Biogenics, VBI Vaccines, Bayer, Nuvation Bio, Chimerix, Karyopharm Therapeutics, Servier, Black Damond, Erasca, Inc, Quadriga Biosciences. N.Y.R.A. is a key opinion leader for Bruker Daltonics and receives research support from EMD Serono and Thermo Finnigan. J.W.L. is co-founder of Sotyera, a consultant for SK Biopharmaceuticals, and performs contract work for Bioserenity and Teladoc. The remaining authors declare no competing interests.
- Published
- 2024
- Full Text
- View/download PDF
48. Adult neuro-oncology trials in the United States over 5 decades: Analysis of trials completion rate to guide the path forward.
- Author
-
Smith EJ, Naik A, Goel M, Wen PY, Lim M, Chang SM, and Germano IM
- Abstract
Background: Clinical trials are important to close the gap between therapeutic unmet needs and scientific advances in neuro-oncology. This study analyzes the landscape of neuro-oncology trials to identify completion rates and guide strategies for the path forward., Methods: US-registered adult neuro-oncology clinical trials were extracted from www.clinicaltrials.gov (1966-2019), including funding source, trial type, scope, phase, and subjects' demographics. Completed trials defined as those that had completed participants' examinations or intervention administration for the purpose of the final collection of data for the primary outcome were dichotomized against those that failed to reach completion. Univariate and multivariate analyses were used to detect differences across factors comparing the last 2 decades (2000-2009, 2010-2019)., Results: Our search yielded 4522 trials, of which 1257 are eligible for this study. In 25 US states, neuro-oncology trial availability is <0.85/100,000 population. Comparing the past 2 decades, trial completion rate decreased from 88% to 64% ( P < .001) and National Institutes of Health funding decreased from 47% to 24% ( P < .001). Inclusion of subjects >65-year-old and women increased, while inclusion of Hispanic subjects decreased ( P < .001). The top 2 reasons for lack of completion included accrual and operational difficulties. A larger proportion of women, non-Hispanic subjects, and older adults were enrolled in completed trials than in those that failed completion., Conclusions: Our study is the first report on the neuro-oncology clinical trial landscape in the United States and supports the development of strategies to further improve access to these trials. Additionally, attention is needed to identify and modify other factors contributing to lack of completion., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)
- Published
- 2024
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.