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The Current Status of Immune Checkpoint Inhibitors in Neuro-Oncology: A Systematic Review.

ABSTRACT: The introduction of immune checkpoint inhibitors (ICI), as a novel treatment modality, has transformed the field of oncology with unprecedented successes. However, the efficacy of ICI for patients with glioblastoma or brain metastases (BMs) from any tumor type is under debate. Therefore, we systematically reviewed current literature on the use of ICI in patients with glioblastoma and BMs. Prospective and retrospective studies evaluating the efficacy and survival outcomes of ICI in patients with glioblastoma or BMs, and published between 2006 and November 2019, were considered. A total of 88 studies were identified (n = 8 in glioblastoma and n = 80 in BMs). In glioblastoma, median progression-free (PFS) and overall survival (OS) of all studies were 2.1 and 7.3 months, respectively. In patients with BMs, intracranial responses have been reported in studies with melanoma and non-small-cell lung cancer (NSCLC). The median intracranial and total PFS in these studies were 2.7 and 3.0 months, respectively. The median OS in all studies for patients with brain BMs was 8.0 months. To date, ICI demonstrate limited efficacy in patients with glioblastoma or BMs. Future research should focus on increasing the local and systemic immunological responses in these patients.

SUBMITTER: Brahm CG

PROVIDER: S-EPMC7139638 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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The Current Status of Immune Checkpoint Inhibitors in Neuro-Oncology: A Systematic Review.

Brahm Cyrillo G CG van Linde Myra E ME Enting Roelien H RH Schuur Maaike M Otten René H J RHJ Heymans Martijn W MW Verheul Henk M W HMW Walenkamp Annemiek M E AME

Cancers 20200304 3

The introduction of immune checkpoint inhibitors (ICI), as a novel treatment modality, has transformed the field of oncology with unprecedented successes. However, the efficacy of ICI for patients with glioblastoma or brain metastases (BMs) from any tumor type is under debate. Therefore, we systematically reviewed current literature on the use of ICI in patients with glioblastoma and BMs. Prospective and retrospective studies evaluating the efficacy and survival outcomes of ICI in patients with ...[more]

PMID: 32143288

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Project description:Biomarker discovery and development are popular for detecting the subtle diseases. However, biomarkers are needed to be validated and approved, and even fewer are ever used clinically. Imaging biomarkers have a crucial role in the treatment of cancer patients because they provide objective information on tumor biology, the tumor's habitat, and the tumor's signature in the environment. Tumor changes in response to an intervention complement molecular and genomic translational diagnosis as well as quantitative information. Neuro-oncology has become more prominent in diagnostics and targeted therapies. The classification of tumors has been actively updated, and drug discovery, and delivery in nanoimmunotherapies are advancing in the field of target therapy research. It is important that biomarkers and diagnostic implements be developed and used to assess the prognosis or late effects of long-term survivors. An improved realization of cancer biology has transformed its management with an increasing emphasis on a personalized approach in precision medicine. In the first part, we discuss the biomarker categories in relation to the courses of a disease and specific clinical contexts, including that patients and specimens should both directly reflect the target population and intended use. In the second part, we present the CT perfusion approach that provides quantitative and qualitative data that has been successfully applied to the clinical diagnosis, treatment and application. Furthermore, the novel and promising multiparametric MR imageing approach will provide deeper insights regarding the tumor microenvironment in the immune response. Additionally, we briefly remark new tactics based on MRI and PET for converging on imaging biomarkers combined with applications of bioinformatics in artificial intelligence. In the third part, we briefly address new approaches based on theranostics in precision medicine. These sophisticated techniques merge achievable standardizations into an applicatory apparatus for primarily a diagnostic implementation and tracking radioactive drugs to identify and to deliver therapies in an individualized medicine paradigm. In this article, we describe the critical principles for imaging biomarker characterization and discuss the current status of CT, MRI and PET in finiding imaging biomarkers of early disease.

Project description:IntroductionAcral melanoma (AM) has different biological characteristics from cutaneous melanoma. Although systemic therapeutic strategies for advanced AM resemble those for advanced cutaneous melanoma, the evidence of the clinical use of immune checkpoint inhibitors (ICIs) for AM is still inadequate. We aimed to systematically analyze the therapeutic effects and safety profile of ICI treatments in advanced AM.MethodsThis systematic review was conducted in line with a previously registered protocol. Three electronic databases, conference abstracts, clinical trial registers, and reference lists of included articles were searched for eligible studies. The primary outcomes were therapeutic effects, and the secondary outcomes were the safety profiles.ResultsThis systematic review included six studies investigating anti-CTLA-4 immunotherapy, 12 studies investigating anti-PD-1 immunotherapy, one study investigating the combination therapy of anti-CTLA-4 and anti-PD-1, and one study investigating anti-PD-1 immunotherapy in combination with radiotherapy. In most studies investigating ipilimumab, the anti-CTLA-4 antibody, the objective response rate ranged from 11.4 to 25%, the median progression-free survival ranged from 2.1 to 6.7 months, and the median overall survival was more than 7.16 months. For studies discussing anti-PD-1 immunotherapy with nivolumab, pembrolizumab, or JS001, the objective response rate ranged from 14 to 42.9%, the median progression-free survival ranged from 3.2 to 9.2 months, and the median overall survival was more than 14 months. The combination therapy of anti-CTLA-4 and anti-PD-1 immunotherapy showed better efficacy with an objective response rate of 42.9% than single-agent therapy. The retrospective study investigating the combination therapy of anti-PD-1 immunotherapy and radiation showed no overall response. Few outcomes regarding safety were reported in the included studies.ConclusionsICIs, especially anti-CTLA-4 monoclonal antibodies combined with anti-PD-1 antibodies, are effective systematic treatments in advanced AM. However, there remains a lack of high-level evidence to verify their efficacy and safety and support their clinical application.

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The Current Status of Immune Checkpoint Inhibitors in Neuro-Oncology: A Systematic Review.

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The Current Status of Immune Checkpoint Inhibitors in Neuro-Oncology: A Systematic Review.

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