Everolimus-induced pneumonitis in neuroendocrine neoplasms: correlation of CT findings and clinical signs

Abstract

Background Everolimus, a mammalian target of rapamycin (mTOR)-inhibitor, is approved for the treatment of advanced neuroendocrine neoplasms (NEN). A rare major adverse event is the occurrence of drug-induced pneumonitis. Purpose To evaluate the correlation between clinical signs and computed tomography (CT) findings in everolimus-induced pneumonitis in patients with NEN. Material and Methods Ninety patients with NEN treated with everolimus were retrospectively enrolled (approved by our Institutional Review Board). All patients received chest CTs before the initiation of everolimus and during the treatment along with physical examinations. Clinical signs of pneumonitis were scored (symptomatic score) according to CTCAE v5.0. Pulmonary function tests (PFT) were evaluated if available. CT images were analyzed based on the severity of interstitial lung disease (ILD), the overall pneumonitis extent (PnE), and regarding presence of typical lung opacification patterns. Follow-up examinations of patients with pneumonitis were analyzed. Results Pneumonitis was diagnosed in 18 (20%) patients. There was no significant correlation between symptomatic score or PFT and ILD score or PnE. In case of a cryptogenic organizing pneumonia pattern (n = 14), symptomatic scores were significantly lower ( P = 0.035) than in case of other opacification patterns (n = 4). In the follow-up analysis, we could identify four different clinical courses. Conclusion CT detects everolimus-induced pneumonitis at a subclinical stage. In this setting, CT findings, clinical severity, and PFT do not clearly correlate. Opacification pattern analysis seems to be of importance when assessing the severity of CT findings. Asymptomatic patients with positive CT findings should be closely monitored to timely initiate specific treatment.