Incidence and prognostic factors in severe drug-induced interstitial lung disease caused by antineoplastic drug therapy in the real world

Sawako Kaku,Narikazu Boku,Akira Kawai,Hidehito Horinouchi,Masahiko Kusumoto,Takuji Okusaka,Kan Yonemori,Yuichiro Ohe,Hirokazu Watanabe,Naoya Yamazaki

doi:10.1007/s00432-022-03932-3

Abstract

PurposeInvestigate the frequency and prognostic factors of severe drug-induced interstitial lung disease (DILD) caused by antineoplastic drugs regardless of cancer types or type of drugs.MethodsFrom 2014 to 2018, we reviewed patients with a history of antineoplastic agents administration in the real-world database of our hospital's electronic medical record and extracted patients who experienced "severe" DILD, requiring hospitalization with treatment or developed during hospitalization and required treatment. We collected patients' backgrounds, clinical and radiological features, laboratory data, treatment, and survival outcomes.Results19,132 cancer patients received antineoplastic drug therapy during the study period, and 120 (0.62%) experienced severe DILD. The incidence of severe DILD in patients with thoracic cancer was highest among the patients included in this analysis (2.52% vs. 0.34% other cancers). Diffuse alveolar damage (DAD) pattern on CT was associated with higher mortality in patients with severe DILD compared with non-DAD pattern (hazard ratio [HR], 11.24; 95% CI, 4.82–26.2). Multivariate analysis revealed that the DAD pattern at diagnosis as severe DILD (HR, 3.59; 95% CI, 1.17–11.03), concurrent/previous interstitial lung disease (HR, 3.20; 95% CI, 1.27–8.10), and ECOG performance status of 2–4 (HR, 3.81; 95% CI, 1.10–13.17) were independent risk factors for mortality in patients with severe DILD.ConclusionsThe frequency of severe DILD was highest in patients with thoracic cancer. The DAD pattern was associated with a poor outcome. From the perspective of DILD, special attention should be paid when administering antineoplastic agents to patients with thoracic cancer.

Highlights

Drug-induced interstitial lung disease (DILD), known as drug-induced pneumonitis or drug-induced pulmonary toxicity, is a significant treatment-related complication in cancer treatment (Sakurada et al 2015; Leger et al 2017)
The incidence of severe DILD among all patients who received antineoplastic drugs was highest for patients with thoracic cancer (2.52%), taking the frequency of each type of cancer into consideration
We examined 19,132 consecutive patients who received antineoplastic drug therapy and underwent regular thoracic computed tomography (CT) examinations

Summary

Introduction

Drug-induced interstitial lung disease (DILD), known as drug-induced pneumonitis or drug-induced pulmonary toxicity, is a significant treatment-related complication in cancer treatment (Sakurada et al 2015; Leger et al 2017). DILD is known to have substantial adverse clinical consequences in severe cases, including treatment-related death (Ando et al 2006). A population-based study reported an incidence of respiratory failure attributable to druginduced interstitial lung disease of 6.6 per 100,000 patientyears, with more than half of the cases associated with chemotherapeutic agents (Dhokarh et al 2012). Among cancer-specific reports, chemotherapy-related pneumonitis reportedly occurs in approximately 30% of lung cancer patients and is believed to be the most common cause of treatment-related death (Minami-Shimmyo et al 2012)

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