LeMaheiu, A.

Abstract Rationale Immune checkpoint inhibitors (ICI) have become standard care for many cancers. Their mechanism of action mediates immune related adverse events including ICI pneumonitis. Diagnosis of this is difficult to differentiate from infectious and radiation pneumonitis as it is a diagnosis of exclusion often requiring bronchoscopy and imaging interpreted by expert radiologists. This study investigates the use of CALIPER, a computer-aided lung informatics program, in identifying differences between Computed Tomography (CT) patterns in ICI, radiation, and infectious pneumonitis that may aid in diagnosis noninvasively. Methods CT images of ten patients with ICI pneumonitis, ten patients with infectious pneumonitis, and nine patients with radiation pneumonitis, all diagnosed by clinical expertise and evaluation with bronchoalveolar lavage, were analyzed with CALIPER. CALIPER classified each CT voxel into either vessel-related structures (VRS), normal, mild low-attenuation area (LAA), moderate LAA, severe LAA, reticular (R), honeycomb (HC) or ground-glass (GG) features. Each lung was divided into upper, middle, and lower lobes. Exploratory analyses explored the relationship between CALIPER components and diagnosis, comparing ICI and radiation pneumonitis with infectious pneumonitis. Diagnosis was analyzed using multinomial logistic regression adjusted for presence of pleural effusion. Additionally, diagnosis was assessed as infectious versus a pooled group of radiation and ICI pneumonitis and analyzed using logistic regression adjusted for pleural effusion. Due to the exploratory nature of analysis, no correction was applied for multiplicity of testing. Results Twenty-nine patients were analyzed. ICI pneumonitis patients had less moderate low attenuation in the left upper (p = 0.016) and middle peripheral lung (p = 0.038), and radiation pneumonitis patients had less moderate low attenuation in the left upper peripheral lung (p = 0.031). When comparing the pooled group of ICI and radiation pneumonitis images with infectious pneumonitis, there was more moderate LAA in left upper (0.012) and middle (0.034) peripheral lung in the pooled group compared to infectious pneumonitis. There was no association with VRS, GG, HC, R, mild, or severe LAA patterns. Conclusions Although areas of moderate low attenuation were more prevalent for infectious pneumonitis, these results taken in the context of low sample size, exploratory analysis, and lack of clinical reasoning to support these findings make them likely insignificant. Based on this limited exploratory analysis, it is unlikely that we can solely use CALIPER as noninvasive evaluation to differentiate radiation and ICI pneumonitis from infectious pneumonitis. This highlights the need for a more robust program to aid in noninvasive diagnosis.