Multiparametric MRI along with machine learning predicts prognosis and treatment response in pediatric low-grade glioma.

Journal: Nature communications
PMID:

Abstract

Pediatric low-grade gliomas (pLGGs) exhibit heterogeneous prognoses and variable responses to treatment, leading to tumor progression and adverse outcomes in cases where complete resection is unachievable. Early prediction of treatment responsiveness and suitability for immunotherapy has the potential to improve clinical management and outcomes. Here, we present a radiogenomic analysis of pLGGs, integrating MRI and RNA sequencing data. We identify three immunologically distinct clusters, with one group characterized by increased immune activity and poorer prognosis, indicating potential benefit from immunotherapies. We develop a radiomic signature that predicts these immune profiles with over 80% accuracy. Furthermore, our clinicoradiomic model predicts progression-free survival and correlates with treatment response. We also identify genetic variants and transcriptomic pathways associated with progression risk, highlighting links to tumor growth and immune response. This radiogenomic study in pLGGs provides a framework for the identification of high-risk patients who may benefit from targeted therapies.

Authors

  • Anahita Fathi Kazerooni
    Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Adam Kraya
    Center for Data-Driven Discovery in Biomedicine (D3b), The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Komal S Rathi
    Center for Data-Driven Discovery in Biomedicine (D3b), The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Meen Chul Kim
    Center for Data-Driven Discovery in Biomedicine (D3b), The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Arastoo Vossough
    Division of Radiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
  • Nastaran Khalili
    Center for Data-Driven Discovery in Biomedicine (D3b), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
  • Ariana M Familiar
    Center for Data-Driven Discovery in Biomedicine (D3b), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
  • Deep Gandhi
    From the Center for Data Driven Discovery in Biomedicine (A.V., N.K., A.M.F., D.G., K.V., D.H., S.B., H.A., P.B.S., A.R., A.N., A.F.K.), Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
  • Neda Khalili
    Center for Data-Driven Discovery in Biomedicine (D3b), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
  • Varun Kesherwani
    Center for Data-Driven Discovery in Biomedicine (D3b), The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Debanjan Haldar
    From the Center for Data Driven Discovery in Biomedicine (A.V., N.K., A.M.F., D.G., K.V., D.H., S.B., H.A., P.B.S., A.R., A.N., A.F.K.), Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
  • Hannah Anderson
    Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Run Jin
    Center for Data-Driven Discovery in Biomedicine (D3b), The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Aria Mahtabfar
    Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA, USA.
  • Sina Bagheri
    From the Center for Data Driven Discovery in Biomedicine (A.V., N.K., A.M.F., D.G., K.V., D.H., S.B., H.A., P.B.S., A.R., A.N., A.F.K.), Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
  • Yiran Guo
    The Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA. guoy@email.chop.edu.
  • Qi Li
    The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei, China.
  • Xiaoyan Huang
    Department of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310015, P.R. China.
  • Yuankun Zhu
    Center for Data-Driven Discovery in Biomedicine (D3b), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
  • Alex Sickler
    Center for Data-Driven Discovery in Biomedicine (D3b), The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Matthew R Lueder
    Center for Data-Driven Discovery in Biomedicine (D3b), The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Saksham Phul
    Center for Structural Biology, Vanderbilt University, Nashville, Tennessee, United States of America.
  • Mateusz Koptyra
    Center for Data-Driven Discovery in Biomedicine (D3b), The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Phillip B Storm
    Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Jeffrey B Ware
    Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Yuanquan Song
    Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Christos Davatzikos
    Artificial Intelligence in Biomedical Imaging Laboratory (AIBIL), Center for and Data Science for Integrated Diagnostics (AID), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Jessica B Foster
    Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Sabine Mueller
    From the Artificial Intelligence in Medicine (AIM) Program, Mass General Brigham, Harvard Medical School, Boston, Mass (A.B., Z.Y., Y.Z., A.Z., H.H., R.C., H.J.W.L.A., B.H.K.); Department of Radiation Oncology (A.B., Z.Y., M.C.T., Y.Z., A.Z., H.H., R.C., K.X.L., D.A.H.K., H.J.W.L.A., B.H.K.) and Department of Radiology (H.J.W.L.A.), Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, 75 Francis St, Boston, MA 02115; Department of Radiology, Boston Children's Hospital, Harvard Medical School, Boston, Mass (S.P.P., S.V., T.Y.P.); Department of Biostatistics and Computational Biology, Harvard T.H. Chan School of Public Health, Boston, Mass (P.J.C.); Center for Data-Driven Discovery in Biomedicine (D3b) (A.N., A.C.R.) and Department of Neurosurgery (A.C.R.), Children's Hospital of Philadelphia, Philadelphia, Pa; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa (A.N.); Departments of Neurology, Pediatrics, and Neurologic Surgery, University of California, San Francisco, San Francisco, Calif (S.M.); and Department of Radiology and Nuclear Medicine, CARIM & GROW, Maastricht University, Maastricht, the Netherlands (H.J.W.L.A.).
  • Michael J Fisher
    Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Adam C Resnick
    Center for Data-Driven Discovery in Biomedicine (D3b), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
  • Ali Nabavizadeh
    Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.