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Enhancing NSCLC recurrence prediction with PET/CT habitat imaging, ctDNA, and integrative radiogenomics-blood insights

  • Sheeba J. Sujit,
  • Muhammad Aminu,
  • Tatiana V. Karpinets,
  • Pingjun Chen,
  • Maliazurina B. Saad,
  • Morteza Salehjahromi,
  • John D. Boom,
  • Mohamed Qayati,
  • James M. George,
  • Haley Allen,
  • Mara B. Antonoff,
  • Lingzhi Hong,
  • Xin Hu,
  • Simon Heeke,
  • Hai T. Tran,
  • Xiuning Le,
  • Yasir Y. Elamin,
  • Mehmet Altan,
  • Natalie I. Vokes,
  • Ajay Sheshadri,
  • Julie Lin,
  • Jianhua Zhang,
  • Yang Lu,
  • Carmen Behrens,
  • Myrna C. B. Godoy,
  • Carol C. Wu,
  • Joe Y. Chang,
  • Caroline Chung,
  • David A. Jaffray,
  • Ignacio I. Wistuba,
  • J. Jack Lee,
  • Ara A. Vaporciyan,
  • Don L. Gibbons,
  • John Heymach,
  • Jianjun Zhang,
  • Tina Cascone,
  • Jia Wu

摘要

While we recognize the prognostic importance of clinicopathological measures and circulating tumor DNA (ctDNA), the independent contribution of quantitative image markers to prognosis in non-small cell lung cancer (NSCLC) remains underexplored. In our multi-institutional study of 394 NSCLC patients, we utilize pre-treatment computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to establish a habitat imaging framework for assessing regional heterogeneity within individual tumors. This framework identifies three PET/CT subtypes, which maintain prognostic value after adjusting for clinicopathologic risk factors including tumor volume. Additionally, these subtypes complement ctDNA in predicting disease recurrence. Radiogenomics analysis unveil the molecular underpinnings of these imaging subtypes, highlighting downregulation in interferon alpha and gamma pathways in the high-risk subtype. In summary, our study demonstrates that these habitat imaging subtypes effectively stratify NSCLC patients based on their risk levels for disease recurrence after initial curative surgery or radiotherapy, providing valuable insights for personalized treatment approaches.