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

Nat Commun. 2024 Apr 11;15(1):3152. doi: 10.1038/s41467-024-47512-0.


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.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Fluorodeoxyglucose F18
  • Humans
  • Lung Neoplasms* / diagnostic imaging
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Neoplasm Recurrence, Local / diagnostic imaging
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Positron Emission Tomography Computed Tomography / methods
  • Positron-Emission Tomography
  • Radiopharmaceuticals
  • Retrospective Studies
  • Tomography, X-Ray Computed


  • Fluorodeoxyglucose F18
  • Radiopharmaceuticals