Publications by authors named "Patrick Wen"

This joint practice guideline/procedure standard was collaboratively developed by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neuro-Oncology (EANO), and the PET task force of the Response Assessment in Neurooncology Working Group (PET/RANO). Brain metastases are the most common malignant central nervous system (CNS) tumors. PET imaging with radiolabeled amino acids and to lesser extent [F]FDG has gained considerable importance in the assessment of brain metastases, especially for the differential diagnosis between recurrent metastases and treatment-related changes which remains a limitation using conventional MRI.

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  • CheckMate 204 study found that the combination of nivolumab and ipilimumab resulted in high intracranial objective response rates (icORRs) for patients with melanoma brain metastases (MBMs), prompting a need for standardized response criteria.
  • Different assessment criteria (like mRECIST and volumetric measurements) showed higher icORRs and stronger correlations with progression-free survival (icPFS) and overall survival (OS) compared to RANO-BM and RECIST.
  • The analysis suggests that mRECIST and volumetric criteria are reliable scales for future MBM trials, and response can be effectively measured even in patients with small lesions (<10 mm).
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  • Glioblastoma is described as immunologically "cold," making it resistant to solo immune-checkpoint inhibitors (ICI) like pembrolizumab, although neoadjuvant use may improve survival based on prior studies.
  • A study involving 25 additional patients analyzed tumor tissue for gene signatures and found that neoadjuvant pembrolizumab led to decreased cancer proliferation genes and increased T-cell activity, indicating a specific response to this treatment.
  • Despite observing these molecular changes, the study did not confirm an overall survival benefit from neoadjuvant pembrolizumab, suggesting that some patients may inherently resist ICI and may need additional therapies for effective treatment.
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Importance: Molecular techniques, including next-generation sequencing, genomic copy number profiling, fusion transcript detection, and genomic DNA methylation arrays, are now indispensable tools for the workup of central nervous system (CNS) tumors. Yet there remains a great deal of heterogeneity in using such biomarker testing across institutions and hospital systems. This is in large part because there is a persistent reluctance among third-party payers to cover molecular testing.

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  • IDH-mutant gliomas are the most common malignant brain tumors in young adults, causing significant challenges for patients, including cognitive deficits and high mortality due to tumor progression.
  • Current treatments like surgery, radiation, and chemotherapy enhance survival but can have negative impacts on cognitive function and quality of life.
  • The recent FDA approval of vorasidenib, a drug targeting mutant IDH1/2 proteins, represents a promising new approach, with ongoing trials exploring its use alongside other therapies for better patient outcomes.
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Background: This study is a phase II clinical trial to evaluate the efficacy, safety, and tolerability of the blood-brain barrier (BBB) permeable peptide-paclitaxel conjugate ANG1005 in patients with recurrent high-grade glioma (HGG) (NCT01967810).

Methods: Seventy-three patients were enrolled in 3 separate arms-recurrent glioblastoma (GBM) (Arm 1), bevacizumab refractory GBM (Arm 2), and grade 3 anaplastic gliomas (AGs) (Arm 3). The study was started in October 2013, and the data were locked on September 29, 2017.

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Subgroup analyses are essential to generate new hypotheses or to estimate treatment effects in clinically meaningful subgroups of patients. They play an important role in taking the next step towards personalized surgical treatment for brain tumor patients. However, subgroup analyses must be used with consideration and care because they have significant potential risks.

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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. The clinical burden of LMD has been increasing secondary to more sensitive diagnostics, aggressive local therapies for discrete brain metastases, and improved management of extracranial disease with targeted and immunotherapeutic agents, resulting in improved survival. However, owing to drug delivery challenges and the unique microenvironment of LMD, novel therapies against systemic disease have not yet translated into improved outcomes for these patients.

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  • Molecular features, particularly CDKN2A/B loss, impact survival outcomes in IDH1/2-mutant astrocytomas, with grade 2/3 tumors showing varied survival based on molecular characteristics.
  • In a study of 998 patients, those with intact CDKN2A/B and no focal amplifications had the longest survival, while variations in CDKN2A/B status correlated with poorer outcomes, particularly in grade 4 tumors.
  • The research highlights the potential for improved prognostic predictions in IDHmut-astrocytomas by integrating molecular data with histological grading, revealing distinct profiles linked to survival outcomes.
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Meningiomas are the most common primary intracranial tumors of adults. For meningiomas that progress or recur despite surgical resection and radiotherapy, additional treatment options are limited due to lack of proven efficacy. Meningiomas show recurring molecular aberrations, which may serve as predictive markers for systemic pharmacotherapies with targeted drugs or immunotherapy, radiotherapy or radioligand therapy.

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Purpose: Radiation therapy may enhance anti-tumor immune responses by several mechanisms including induction of immunogenic cell death. We performed a phase 2 study of pembrolizumab with re-irradiation in patients with recurrent glioblastoma.

Methods: Sixty recurrent glioblastoma patients received pembrolizumab with re-irradiation alone (cohort A, bevacizumab-naïve; n=30) or with bevacizumab continuation (cohort B, n=30).

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  • The study explored the effect of perampanel, an AMPA receptor antagonist, on reducing hyperexcitability around gliomas, which could promote tumor growth.
  • An open-label trial compared perampanel with standard care in patients with high-grade glioma undergoing surgery, measuring outcomes like high-frequency oscillation rates and seizure occurrence.
  • Results showed no significant difference in hyperexcitability outcomes between perampanel and standard care, and early termination of the trial indicated similar seizure rates and overall survival for both treatments.
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Background: Following surgery, patients with newly diagnosed glioblastoma frequently enter clinical trials. Nuanced risk assessment is warranted to reduce imbalances between study arms. Here, we aimed (I) to analyze the interactive effects of residual tumor with clinical and molecular factors on outcome and (II) to define a postoperative risk assessment tool.

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Adolescents and young adults (AYAs; ages 15-39 years) are a vulnerable population facing challenges in oncological care, including access to specialized care, transition of care, unique tumor biology, and poor representation in clinical trials. Brain tumors are the second most common tumor type in AYA, with malignant brain tumors being the most common cause of cancer-related death. The 2021 WHO Classification for central nervous system (CNS) Tumors highlights the importance of integrated molecular characterization with histologic diagnosis in several tumors relevant to the AYA population.

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Purpose: Mutations in the Isocitrate Dehydrogenase (IDH) genes, IDH1 or IDH2, define a group of adult diffuse gliomas associated with a younger age at diagnosis and better prognosis than IDH wild-type glioblastoma. Within IDH mutant gliomas, a small fraction of astrocytic tumors present with grade 4 histologic features and poor prognosis. In molecular studies, homozygous deletion of CDKN2A/B is independently predictive of poor prognosis and short survival.

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The standard of care for adult patients with gliomas, glioneuronal and neuronal tumors consists of combinations of surgery, radiotherapy, and chemotherapy. For many systemic cancers, targeted treatments are a major part of the standard treatment, however, the predictive significance of most of the targets for treatment in systemic cancer are less well established in central nervous system (CNS) tumors . In 2023 the EANO Guideline Committee presented evidence based recommendations for rational testing of molecular targets for targeted treatments.

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  • Biomarker-based clinical trials for targeted treatments in brain tumors are increasing due to improved testing and understanding of tumor biology.
  • The design of these trials is essential for assessing safety and effectiveness, especially when considering unique challenges faced by brain tumor patients.
  • Trial methodologies like surgical window studies, basket and umbrella trials, and platform trials are helping to evaluate various biomarker-driven approaches while addressing issues of patient diversity and health disparities.
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Theranostics is a new treatment modality integrating molecular imaging with targeted radionuclide therapy. Theranostic agents have received regulatory approval for some systemic cancers and have therapeutic potential in neuro-oncology. As clinical trials are developed to evaluate the efficacy of theranostic agents in brain tumors, specific considerations will have to be considered, taking into account lessons learned from previous studies examining other treatment modalities in neuro-oncology.

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  • Neurosurgical resection can provide significant benefits for breast cancer patients with brain metastases, particularly for those with HER2-positive disease, despite potential delays in systemic therapy.
  • A study analyzed 633 patients with brain metastases from breast cancer to identify outcomes based on breast cancer subtypes, revealing that HER2-positive patients require more subsequent treatments when surgery is omitted.
  • The findings suggest that upfront neurosurgical resection may reduce local recurrence and improve overall treatment outcomes for HER2-positive patients compared to other subtypes, highlighting the need for careful patient selection.
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  • The article reviews the impact of isocitrate dehydrogenase (IDH) mutations on glioma classification and targeted therapies, highlighting the recent advancements in treatment options.
  • The phase 3 INDIGO trial demonstrated that the mIDH1/2 inhibitor vorasidenib significantly increased progression-free survival for patients with non-enhancing grade 2 IDH-mutant gliomas and received FDA approval in August 2024.
  • The findings suggest vorasidenib is a well-tolerated treatment with potential benefits for certain patients, and ongoing research may expand its effectiveness through new agents and combination therapies.
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Purpose Of Review: This article discusses commonly encountered medical and neurological complications in patients with brain tumors and highlights recommendations for their management based on updated evidence.

Recent Findings: Use of dexamethasone is correlated with worse prognosis in patients with glioblastoma, and in brain metastases, high doses may lead to increased side effects without additional clinical benefit. There are multiple antiseizure medications (ASM) to choose from and possible interactions and toxicity must be considered when choosing an agent.

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