Translation of the 27-gene immuno-oncology test (IO score) to predict outcomes in immune checkpoint inhibitor treated metastatic urothelial cancer patients.
| Title: | Translation of the 27-gene immuno-oncology test (IO score) to predict outcomes in immune checkpoint inhibitor treated metastatic urothelial cancer patients. |
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| Authors: | Seitz, Robert S., Hurwitz, Michael E., Nielsen, Tyler J., Bailey, Daniel B., Varga, Matthew G., Ring, Brian Z., Metts, Carrie F., Schweitzer, Brock L., McGregor, Kimberly, Ross, Douglas T. |
| Source: | Journal of Translational Medicine; 8/16/2022, Vol. 20 Issue 1, p1-11, 11p |
| Abstract: | |
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| Database: | Complementary Index |
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| Items | – Name: Title Label: Title Group: Ti Data: Translation of the 27-gene immuno-oncology test (IO score) to predict outcomes in immune checkpoint inhibitor treated metastatic urothelial cancer patients. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Seitz%2C+Robert+S%2E%22">Seitz, Robert S.</searchLink><br /><searchLink fieldCode="AR" term="%22Hurwitz%2C+Michael+E%2E%22">Hurwitz, Michael E.</searchLink><br /><searchLink fieldCode="AR" term="%22Nielsen%2C+Tyler+J%2E%22">Nielsen, Tyler J.</searchLink><br /><searchLink fieldCode="AR" term="%22Bailey%2C+Daniel+B%2E%22">Bailey, Daniel B.</searchLink><br /><searchLink fieldCode="AR" term="%22Varga%2C+Matthew+G%2E%22">Varga, Matthew G.</searchLink><br /><searchLink fieldCode="AR" term="%22Ring%2C+Brian+Z%2E%22">Ring, Brian Z.</searchLink><br /><searchLink fieldCode="AR" term="%22Metts%2C+Carrie+F%2E%22">Metts, Carrie F.</searchLink><br /><searchLink fieldCode="AR" term="%22Schweitzer%2C+Brock+L%2E%22">Schweitzer, Brock L.</searchLink><br /><searchLink fieldCode="AR" term="%22McGregor%2C+Kimberly%22">McGregor, Kimberly</searchLink><br /><searchLink fieldCode="AR" term="%22Ross%2C+Douglas+T%2E%22">Ross, Douglas T.</searchLink> – Name: TitleSource Label: Source Group: Src Data: Journal of Translational Medicine; 8/16/2022, Vol. 20 Issue 1, p1-11, 11p – Name: Abstract Label: Abstract Group: Ab Data: <bold>Background: </bold>The IO Score is a 27-gene immuno-oncology (IO) classifier that has previously predicted benefit to immune checkpoint inhibitor (ICI) therapy in triple negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC). It generates both a continuous score and a binary result using a defined threshold that is conserved between breast and lung. Herein, we aimed to evaluate the IO Score's binary threshold in ICI-naïve TCGA bladder cancer patients (TCGA-BLCA) and assess its clinical utility in metastatic urothelial cancer (mUC) using the IMvigor210 clinical trial treated with the ICI, atezolizumab.<bold>Methods: </bold>We identified a list of tumor immune microenvironment (TIME) related genes expressed across the TCGA breast, lung squamous and lung adenocarcinoma cohorts (TCGA-BRCA, TCGA-LUSQ, and TCGA-LUAD, 939 genes total) and then examined the expression of these 939 genes in TCGA-BLCA, to identify patients as having high inflammatory gene expression. Using this as a test of classification, we assessed the previously established threshold of IO Score. We then evaluated the IO Score with this threshold in the IMvigor210 cohort for its association with overall survival (OS).<bold>Results: </bold>In TCGA-BLCA, IO Score positive patients had a strong concordance with high inflammatory gene expression (p < 0.0001). Given this concordance, we applied the IO Score to the ICI treated IMvigor210 patients. IO Score positive patients (40%) had a significant Cox proportional hazard ratio (HR) of 0.59 (95% CI 0.45-0.78 p < 0.001) for OS and improved median OS (15.6 versus 7.5 months) compared to IO Score negative patients. The IO Score remained significant in bivariate models combined with all other clinical factors and biomarkers, including PD-L1 protein expression and tumor mutational burden.<bold>Conclusion: </bold>The IMvigor210 results demonstrate the potential for the IO Score as a clinically useful biomarker in mUC. As this is the third tumor type assessed using the same algorithm and threshold, the IO Score may be a promising candidate as a tissue agnostic marker of ICI clinical benefit. The concordance between IO Score and inflammatory gene expression suggests that the classifier is capturing common features of the TIME across cancer types. [ABSTRACT FROM AUTHOR] – Name: Abstract Label: Group: Ab Data: <i>Copyright of Journal of Translational Medicine is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1186/s12967-022-03563-9 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 11 StartPage: 1 Titles: – TitleFull: Translation of the 27-gene immuno-oncology test (IO score) to predict outcomes in immune checkpoint inhibitor treated metastatic urothelial cancer patients. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Seitz, Robert S. – PersonEntity: Name: NameFull: Hurwitz, Michael E. – PersonEntity: Name: NameFull: Nielsen, Tyler J. – PersonEntity: Name: NameFull: Bailey, Daniel B. – PersonEntity: Name: NameFull: Varga, Matthew G. – PersonEntity: Name: NameFull: Ring, Brian Z. – PersonEntity: Name: NameFull: Metts, Carrie F. – PersonEntity: Name: NameFull: Schweitzer, Brock L. – PersonEntity: Name: NameFull: McGregor, Kimberly – PersonEntity: Name: NameFull: Ross, Douglas T. IsPartOfRelationships: – BibEntity: Dates: – D: 16 M: 08 Text: 8/16/2022 Type: published Y: 2022 Identifiers: – Type: issn-print Value: 14795876 Numbering: – Type: volume Value: 20 – Type: issue Value: 1 Titles: – TitleFull: Journal of Translational Medicine Type: main |
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