AUTHOR=Aminu Muhammad , Daver Naval , Godoy Myrna C. B. , Shroff Girish , Wu Carol , Torre-Sada Luis F. , Goizueta Alberto , Shannon Vickie R. , Faiz Saadia A. , Altan Mehmet , Garcia-Manero Guillermo , Kantarjian Hagop , Ravandi-Kashani Farhad , Kadia Tapan , Konopleva Marina , DiNardo Courtney , Pierce Sherry , Naing Aung , Kim Sang T. , Kontoyiannis Dimitrios P. , Khawaja Fareed , Chung Caroline , Wu Jia , Sheshadri Ajay TITLE=Heterogenous lung inflammation CT patterns distinguish pneumonia and immune checkpoint inhibitor pneumonitis and complement blood biomarkers in acute myeloid leukemia: proof of concept JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1249511 DOI=10.3389/fimmu.2023.1249511 ISSN=1664-3224 ABSTRACT=Background

Immune checkpoint inhibitors (ICI) may cause pneumonitis, resulting in potentially fatal lung inflammation. However, distinguishing pneumonitis from pneumonia is time-consuming and challenging. To fill this gap, we build an image-based tool, and further evaluate it clinically alongside relevant blood biomarkers.

Materials and methods

We studied CT images from 97 patients with pneumonia and 29 patients with pneumonitis from acute myeloid leukemia treated with ICIs. We developed a CT-derived signature using a habitat imaging algorithm, whereby infected lungs are segregated into clusters (“habitats”). We validated the model and compared it with a clinical-blood model to determine whether imaging can add diagnostic value.

Results

Habitat imaging revealed intrinsic lung inflammation patterns by identifying 5 distinct subregions, correlating to lung parenchyma, consolidation, heterogenous ground-glass opacity (GGO), and GGO-consolidation transition. Consequently, our proposed habitat model (accuracy of 79%, sensitivity of 48%, and specificity of 88%) outperformed the clinical-blood model (accuracy of 68%, sensitivity of 14%, and specificity of 85%) for classifying pneumonia versus pneumonitis. Integrating imaging and blood achieved the optimal performance (accuracy of 81%, sensitivity of 52% and specificity of 90%). Using this imaging-blood composite model, the post-test probability for detecting pneumonitis increased from 23% to 61%, significantly (p = 1.5E − 9) higher than the clinical and blood model (post-test probability of 22%).

Conclusion

Habitat imaging represents a step forward in the image-based detection of pneumonia and pneumonitis, which can complement known blood biomarkers. Further work is needed to validate and fine tune this imaging-blood composite model and further improve its sensitivity to detect pneumonitis.