Heterogenous Lung Inflammation CT Patterns Distinguish Pneumonia and Immune Checkpoint Inhibitor Pneumonitis and Complement Blood Biomarkers in Acute Myeloid Leukemia: Proof of Concept

Authors

Muhammad Aminu
Naval Daver
Myrna C B Godoy
Girish Shroff
Carol Wu
Luis F Torre-Sada
Alberto Goizueta
Vickie R Shannon
Saadia A Faiz
Mehmet Altan
Guillermo Garcia-Manero
Hagop Kantarjian
Farhad Ravandi-Kashani
Tapan Kadia
Marina Konopleva
Courtney DiNardo
Sherry Pierce
Aung Naing
Sang T Kim
Dimitrios P Kontoyiannis
Fareed Khawaja
Caroline Chung
Jia Wu
Ajay Sheshadri

Publication Date

9-29-2023

Journal

Frontiers in Immunology

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 (

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.

Keywords

Humans, Immune Checkpoint Inhibitors, Pneumonia, Tomography, X-Ray Computed, Inflammation, Biomarkers, Leukemia, Myeloid, Acute

DOI

10.3389/fimmu.2023.1249511

PMID

37841255

PMCID

PMC10570510

PubMedCentral® Posted Date

September 2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes