Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses.

Autor:	Chen WC; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA. william.chen@ucsf.edu.; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA. william.chen@ucsf.edu.; Department of Pathology, University of California San Francisco, San Francisco, CA, USA. william.chen@ucsf.edu., Choudhury A; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.; Department of Pathology, University of California San Francisco, San Francisco, CA, USA.; Medical Scientist Training Program, University of California San Francisco, San Francisco, CA, USA., Youngblood MW; Department of Neurological Surgery, Northwestern University, Chicago, IL, USA., Polley MC; NRG Statistics and Data Management Center, NRG Oncology, Philadelphia, PA, USA., Lucas CG; Department of Pathology, Johns Hopkins University, Baltimore, MD, USA., Mirchia K; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.; Department of Pathology, University of California San Francisco, San Francisco, CA, USA., Maas SLN; Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.; Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands., Suwala AK; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.; Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research, German Cancer Research Center, Heidelberg, Germany., Won M; NRG Statistics and Data Management Center, NRG Oncology, Philadelphia, PA, USA., Bayley JC; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA., Harmanci AS; Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA., Harmanci AO; Center for Secure Artificial Intelligence for Healthcare, Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center, Houston, TX, USA., Klisch TJ; Department of Molecular and Human Genetics, Baylor College of Medicine, and Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA., Nguyen MP; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.; Department of Pathology, University of California San Francisco, San Francisco, CA, USA., Vasudevan HN; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA., McCortney K; Department of Neurological Surgery, Northwestern University, Chicago, IL, USA., Yu TJ; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA., Bhave V; Department of Neurosurgery, Brigham and Women's Hospital, and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Lam TC; Department of Clinical Oncology, The University of Hong Kong, Pokfulam, China., Pu JK; Division of Neurosurgery, Department of Surgery, The University of Hong Kong, Pokfulam, China., Li LF; Division of Neurosurgery, Department of Surgery, The University of Hong Kong, Pokfulam, China., Leung GK; Division of Neurosurgery, Department of Surgery, The University of Hong Kong, Pokfulam, China., Chan JW; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA., Perlow HK; Department of Radiation Oncology, Ohio State University, Columbus, OH, USA., Palmer JD; Department of Radiation Oncology, Ohio State University, Columbus, OH, USA., Haberler C; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria., Berghoff AS; Division of Oncology, Department of Medicine, Medical University of Vienna, Vienna, Austria., Preusser M; Division of Oncology, Department of Medicine, Medical University of Vienna, Vienna, Austria., Nicolaides TP; Caris Life Sciences, Phoenix, AZ, USA., Mawrin C; Department of Neuropathology, University of Magdeburg, Magdeburg, Germany., Agnihotri S; Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, USA., Resnick A; Department of Neurological Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Rood BR; Brain Tumor Institute, Children's National Hospital, Washington, DC, USA., Chew J; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA., Young JS; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.; Department of Pathology, University of California San Francisco, San Francisco, CA, USA., Boreta L; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA., Braunstein SE; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA., Schulte J; Neurosciences Department, University of California San Diego, La Jolla, CA, USA., Butowski N; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.; Department of Neurology, University of California San Francisco, San Francisco, CA, USA., Santagata S; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Spetzler D; Caris Life Sciences, Phoenix, AZ, USA., Bush NAO; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA., Villanueva-Meyer JE; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA., Chandler JP; Department of Neurological Surgery, Northwestern University, Chicago, IL, USA., Solomon DA; Department of Pathology, University of California San Francisco, San Francisco, CA, USA., Rogers CL; NRG Statistics and Data Management Center, NRG Oncology, Philadelphia, PA, USA., Pugh SL; NRG Statistics and Data Management Center, NRG Oncology, Philadelphia, PA, USA., Mehta MP; NRG Statistics and Data Management Center, NRG Oncology, Philadelphia, PA, USA.; Miami Neuroscience Institute, Baptist Health, Miami, FL, USA., Sneed PK; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA., Berger MS; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA., Horbinski CM; Department of Neurological Surgery, Northwestern University, Chicago, IL, USA.; Department of Pathology, Northwestern University, Chicago, IL, USA., McDermott MW; Miami Neuroscience Institute, Baptist Health, Miami, FL, USA., Perry A; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.; Department of Pathology, University of California San Francisco, San Francisco, CA, USA., Bi WL; Department of Neurosurgery, Brigham and Women's Hospital, and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA., Patel AJ; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA., Sahm F; Department of Neuropathology, University Hospital Heidelberg and CCU Neuropathology, German Consortium for Translational Cancer Research, German Cancer Research Center, Heidelberg, Germany., Magill ST; Department of Neurological Surgery, Northwestern University, Chicago, IL, USA. stephen.magill@northwestern.edu., Raleigh DR; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA. david.raleigh@ucsf.edu.; Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA. david.raleigh@ucsf.edu.; Department of Pathology, University of California San Francisco, San Francisco, CA, USA. david.raleigh@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Nature medicine [Nat Med] 2023 Dec; Vol. 29 (12), pp. 3067-3076. Date of Electronic Publication: 2023 Nov 09.
DOI:	10.1038/s41591-023-02586-z
Abstrakt:	Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (N = 1,856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker improved discrimination of outcomes compared with all other systems tested (N = 9) in the clinical validation cohort for local recurrence (5-year area under the curve (AUC) 0.81) and overall survival (5-year AUC 0.80). The increase in AUC compared with the standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval 0.07 to 0.17, P < 0.001). The gene expression biomarker identified meningiomas benefiting from postoperative radiotherapy (hazard ratio 0.54, 95% confidence interval 0.37 to 0.78, P = 0.0001) and suggested postoperative management could be refined for 29.8% of patients. In sum, our results identify a targeted gene expression biomarker that improves discrimination of meningioma outcomes, including prediction of postoperative radiotherapy responses. (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze:	MEDLINE
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