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Articles by Patrick Y Wen
Neoadjuvant PD1 plus CTLA-4 immune checkpoint blockade in surgically resectable recurrent glioblastoma: a randomized surgical window-of-opportunity trial
Abstract We conducted a randomized surgical window-of-opportunity trial (NCT04606316) in recurrent, resectable glioblastoma. Between 2021 and 2024, 71 patients were screened, and 63 were randomized (intention-to-treat [ITT] population), and 58 received study treatment. Patients received pre-surgical immune checkpoint blockade (ICB) with dual anti-PD1 nivolumab + anti-CTLA4 ipilimumab (Arm 1), nivolumab alone (Arm 2), or placebo (Arm 3).
Exploring the landscape of targetable alterations in patients with glioblastoma
Abstract Glioblastomas remain the most lethal primary brain tumour in adults, with targeted therapies delivering only limited benefit despite deep molecular characterization. Several targeted drugs have received regulatory approval for low-grade gliomas, although progress in glioblastomas remains constrained by, among other aspects, extensive intratumoural heterogeneity, pathway redundancy, cellular plasticity and limited drug delivery to the central nervous system.
Anti-LAG-3 with or without anti-PD-1 in recurrent glioblastoma: a phase 1 trial
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Abstract Lymphocyte activation gene 3 (LAG-3) is an immune checkpoint implicated in T cell exhaustion and a potential therapeutic target in glioblastoma (GBM). We conducted a multicenter, open-label, phase 1 study with sequential allocation to evaluate the safety and preliminary activity of the anti-LAG-3 antibody relatlimab, administered alone or with the anti-programmed cell death protein 1 (PD-1) antibody nivolumab, in patients with recurrent GBM.
By Michael Lim, Arati Desai, Manmeet Ahluwalia, Tobias Walbert, Glenn J. Lesser, Benjamin M. Ellingson, David Peereboom, Joy Fisher, Christina Jackson, Ayush Pant, Aanchal Jain, Rohit Verma, Benjamin Oberlton, Hadeesha Piyadasa, Chetan Bettegowda, Logan Engle, Janis Taube, Sean C. Bendall, John Choi, Jan Drappatz, Frank Lieberman, Lawrence Kleinberg, Drew Pardoll, Louis B. Nabors, Patrick Y Wen, Stuart A Grossman, Xiaobu Ye, Anna F. Piotrowski, Serena Desideri
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Nature
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Publisher Correction: Tumor transcriptional state predicts survival in immune-checkpoint-blockade-treated glioblastoma
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Correction to: Nature Cancer https://doi.org/10.1038/s43018-026-01179-2, published online 3 June 2026. In the version of the article initially published, in the Abstract, “we profiled 181 ICB-treated GBM samples with bulk DNA sequencing” should have read “we profiled 181 ICB-treated GBM cases using bulk DNA sequencing”.
By Jack Ghannam, Julian Bryan, Jakob Weiss, Daniel Kovarsky, David Merrell, Conor Messer, Kristy Schlueter-Kuck, Geoffrey G Fell, Mary Jane Lim-Fat, Gilbert Youssef, Rifaquat Rahman, Lei Qin, J. Thomas Janes III, McKayla Van Orden, Kathleen L. Pfaff, Andrew Gans Verified, Emma Lin, Raymond Y. Huang, Brian P. Danysh, Laxmi Parida, Shuqiang Li, Patrick Y Wen, E. Antonio Chiocca, Donna S. Neuberg, Keith L. Ligon, Itay Tirosh, David A Reardon, Gad Getz, Catherine J. Wu
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Nature
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Tumor transcriptional state predicts survival in immune-checkpoint-blockade-treated glioblastoma
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Abstract The determinants of immune checkpoint blockade (ICB) response in glioblastoma (GBM) with wild-type isocitrate dehydrogenase remain poorly understood. Here we profiled 181 ICB-treated GBM samples with bulk DNA sequencing, bulk RNA sequencing and single-nucleus RNA sequencing to investigate the genomic features associated with ICB outcomes.
By Jack Ghannam, Julian Bryan, Jakob Weiss, Daniel Kovarsky, David Merrell, Conor Messer, Kristy Schlueter-Kuck, Geoffrey G Fell, Mary Jane Lim-Fat, Gilbert Youssef, Rifaquat Rahman, Lei Qin, Kathleen L. Pfaff, Andrew Gans Verified, Emma Lin, Raymond Y. Huang, Brian P. Danysh, Laxmi Parida, Shuqiang Li, Patrick Y Wen, E. Antonio Chiocca, Donna S. Neuberg, Keith L. Ligon, Itay Tirosh, David A Reardon, Gad Getz, Catherine J. Wu, J. Thomas Janes III, McKayla Van Orden
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Nature
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Evaluation of Regorafenib in Newly Diagnosed and Recurrent Glioblastoma: GBM AGILE Phase II/III Bayesian Randomized Platform Trial
1 Standard therapy is maximal safe surgical resection followed by radiotherapy with temozolomide chemotherapy.
Author Correction: Stereotactic radiosurgery for patients with brain metastases: current principles, expanding indications and opportunities for multidisciplinary care | Nature Reviews Clinical Oncology
Correction to: Nature Reviews Clinical Oncology https://doi.org/10.1038/s41571-025-01013-1, published online 19 March 2025. In the version of the article initially published, in the second paragraph of the “Mitigating iatrogenic seeding of brain parenchyma and leptomeninges” section, two percentages were switched in the sentence “...the LMD development rate at 2 years was 16.6% among 114 patients who underwent neoadjuvant SRS (n = 114) versus 3.2% in 66 patients who received adjuvant SRS”.
Author Correction: RANO criteria for response assessment of brain metastases based on amino acid PET imaging - Nature Medicine
Correction to: Nature Medicine https://doi.org/10.1038/s41591-025-03633-7, published online 8 May 2025. In the version of the article initially published, the first name of Evanthia Galanis appeared incorrectly (as Eva) and has now been amended in the HTML and PDF versions of the article. About this article Albert, N.L., Galldiks, N., Ellingson, B.M. et al. Author Correction: RANO criteria for response assessment of brain metastases based on amino acid PET imaging. Nat Med (2025).
RANO criteria for response assessment of brain metastases based on amino acid PET imaging - Nature Medicine
Abstract Novel diagnostic and therapeutic opportunities are needed to improve medical care and outcome of patients with brain metastases, a frequent and severe complication of several cancer types. Currently, magnetic resonance imaging (MRI) is the primary method used for detection, treatment planning and disease monitoring in patients with brain metastases, but this method has limitations.
Stereotactic radiosurgery for patients with brain metastases: current principles, expanding indications and opportunities for multidisciplinary care - Nature Reviews Clinical Oncology
Abstract The management of brain metastases is challenging and should ideally be coordinated through a multidisciplinary approach.
Leptomeningeal metastatic disease: new frontiers and future directions - Nature Reviews Clinical Oncology
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Abstract Leptomeningeal metastatic disease (LMD), encompassing entities of ‘meningeal carcinomatosis’, neoplastic meningitis’ and ‘leukaemic/lymphomatous meningitis’, arises secondary to the metastatic dissemination of cancer cells from extracranial and certain intracranial malignancies into the leptomeninges and cerebrospinal fluid.
By Ahmad Ozair, Nicholas Mikolajewicz, Stuart A Grossman, Arjun Sahgal, Emilie Le Rhun, Michael Weller, Tobias Weiss, Patrick Y Wen, Daphne A Haas-Kogan, Mustafa Khasraw, Roberta Rudà, Riccardo Soffietti, Philipp Vollmuth, Vivek Subbiah, Chetan Bettegowda, Lily Pham, Graeme Woodworth, Manmeet Ahluwalia
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Nature
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Dr Wen on the Evaluation of Vorasidenib in IDH1- and IDH2-Mutated Low-Grade Glioma
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RANO 2.0: Update to the Response Assessment in Neuro-Oncology Criteria for High- and Low-Grade Gliomas in Adults
CONTEXT Key Objective Response Assessment in Neuro-Oncology (RANO) 2.0 is an update of the response criteria for gliomas in adults on the basis of data from evaluation of the original RANO criteria and variations such as the modified RANO criteria (mRANO) and the immunotherapy RANO criteria (iRANO). Knowledge Generated RANO 2.0 recommends a standard set of criteria for both high- and low-grade gliomas, to be used for all trials regardless of the treatment modalities being evaluated.
Understanding the patient experience and treatment benefits in patients with non-small‐cell lung cancer with brain metastasis
Study design This qualitative research project was conducted in a stepwise approach consistent with regulatory recommendations.23 The first step was to conduct a targeted literature review to identify the symptoms and impacts reported by patients who had been diagnosed with BM and to determine whether any previously developed patient-reported instrument adequately assessed these concepts.
World Health Organization 2021 Classification of Central Nervous System Tumors and Implications for Therapy for Adult-Type Gliomas: A Review
[Skip to Navigation] Figure 1. The 2021 World Health Organization Classification of Tumors of the Central Nervous System Updated Diagnosis of Adult Gliomas Figure 2. Immunohistochemistry Staining of Astrocytoma, Isocitrate Dehydrogenase (IDH) Mutant A, Immunohistochemistry of a grade 2 IDH-mutant astrocytoma composed of mildly atypical tumor cells, without mitotic figures (hematoxylin-eosin, original magnification ×400).
ROAR trial: which treatment is effective after progression? - Authors' reply
We thank Osman Sütcüoğlu and colleagues for their response to our Article on treatment with dabrafenib–trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma. 1 Wen PY Stein A van den Bent M et al. Dabrafenib plus trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trial. Lancet Oncol.
Therapeutic avenues for cancer neuroscience: translational frontiers and clinical opportunities
1. Young HH On the presence of nerves in tumours and of other structures in them as revealed by a modification of Ehrlich's method of “ vital staining “ with methylene blue. J Exp Med. 1897; 2: 1-12 2. Scherer HJ Structural development in gliomas. Am J Cancer. 1938; 34: 333-351 3. Batsakis JG Nerves and neurotropic carcinomas. Ann Otol Rhinol Laryngol. 1985; 94: 426-427 4. Liebig C Ayala G Wilks JA Berger DH Albo D Perineural invasion in cancer: a review of the literature. Cancer. 2009; 115: 3379-3391 5.
Dabrafenib plus trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trial
Summary Background Effective treatments are needed to improve outcomes for high-grade glioma and low-grade glioma. The activity and safety of dabrafenib plus trametinib were evaluated in adult patients with recurrent or progressive BRAFV600E mutation-positive high-grade glioma and low-grade glioma.
A Phase 2 Study of the Efficacy and Safety of Oral Selinexor in Recurrent Glioblastoma
Research Article Andrew B. Lassman, Patrick Y. Wen, Martin J van den Bent, Scott R Plotkin, Annemiek M. E. Walenkamp, Adam L. Green, Kai Li, Christopher J. Walker, Hua Chang, Sharon Tamir, Leah Henegar, Yao Shen, Mariano J. Alvarez, Andrea Califano, Yosef Landesman, Michael G. Kauffman, Sharon Sacham and Morten Mau-Sørensen DOI: 10.1158/1078-0432.CCR-21-2225 Abstract Purpose: Selinexor is an oral selective inhibitor of exportin-1 (XPO1) with efficacy in various solid and hematological tumors.
Exploring Predictors of Response to Dacomitinib in EGFR-Amplified Recurrent Glioblastoma
Article Tools ORIGINAL REPORTS Andrew S. Chi, MD, PhD1; Daniel P. Cahill, MD, PhD1; David A. Reardon, MD2; Patrick Y. Wen, MD2; Tom Mikkelsen, MD3,4; David M. Peereboom, MD5; Eric T. Wong, MD6; Elizabeth R. Gerstner, MD1; Jorg Dietrich, MD, PhD, MMSc, MBA1; Scott R. Plotkin, MD, PhD1; Andrew D. Norden, MD2; Eudocia Q. Lee, MD, MPH2; Lakshmi Nayak, MD2; Shota Tanaka, MD, PhD1; Hiroaki Wakimoto, MD, PhD1; Nina Lelic, BS1; Mara V. Koerner, MD1; Lindsay K. Klofas, BA1; Mia S. Bertalan, BA1; Isabel C.
NRG/RTOG 1122: A phase 2, double‐blinded, placebo‐controlled study of bevacizumab with and without trebananib in patients with recurrent glioblastoma or gliosarcoma
Original Article Eudocia Q. Lee MD Corresponding Author E-mail address: eqlee@partners.org https://orcid.org/0000-0003-3355-5179 Dana‐Farber/Brigham and Women's Cancer Center, Boston, Massachusetts Corresponding Author: Eudocia Q.
First-in-human Phase I study to evaluate the brain-penetrant PI3K/mTOR inhibitor GDC-0084 in patients with progressive or recurrent high-grade glioma
Research Article Patrick Y. Wen, Timothy F. Cloughesy, Alan G Olivero, Kari M Morrissey, Timothy R Wilson, Xuyang Lu, Lars U. Mueller, Alexandre F Coimbra, Benjamin M Ellingson, Elizabeth Gerstner, Eudocia Q Lee and Jordi Rodon DOI: 10.1158/1078-0432.CCR-19-2808 Abstract Purpose: GDC-0084 is an oral, brain-penetrant small molecule inhibitor of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR).
Glioma progression through synaptic activity
Two new studies show that gliomas can manipulate normal elements of neuronal development and plasticity to create neuron–glia synapses, activation of which leads to glioma proliferation. Interventions that target the AMPA receptor could slow down tumour growth by altering this synaptic transmission. References 1. Venkatesh, H. S. et al. Electrical and synaptic integration of glioma into neural circuits. Nature 573, 539–545 (2019). 2. Venkataramani, V. et al.
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