**1. Introduction**

Anti-cancer drug-induced pneumonia is a potentially fatal disease in lung cancer patients. Pre-existing chronic interstitial lung disease (ILD) is considered a risk factor for anti-cancer drug-induced pneumonia, as is being male, being elderly, having a poor Eastern Cooperative Oncology Group performance status (ECOG-PS), a history of smoking, and low forced vital capacity [1–4]. The American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic

Association guidelines for the classification of idiopathic interstitial pneumonia (IIP) are often employed for evaluating ILD [5–7]. Several clinical trials of anti-cancer drugs have included lung cancer patients with ILD, which was evaluated according to the IIP guidelines [8–12].

However, the IIP guidelines do not include and evaluate mild pre-existing ILD without honeycombing or traction bronchiectasis. The 2018 idiopathic pulmonary fibrosis (IPF) guidelines define mild ILD as "indeterminate for usual interstitial pneumonia (UIP) HRCT pattern" [13]. Nevertheless, few studies regarding anti-cancer drug-induced pneumonia have referred to mild pre-existing ILD [1,2]. Thus, a quantitative method for evaluating pre-existing ILD, including mild ILD, has not yet been established.

The quantitative high-resolution computed tomography (HRCT) scores of acute interstitial pneumonia and acute respiratory distress syndrome (ARDS) have been reported to correlate with pathology and prognosis [14–17]. The HRCT fibrosis score (HFS) was modified from this score in order to evaluate lung fibrosis easily, with an increased HFS over the course of 6 months indicating poor prognosis [18]. We hypothesized that the HFS could reflect the degree of the lung fibrosing process, resulting in the exact evaluation of the risk of anti-cancer drug-induced pneumonia in lung cancer patients with pre-existing ILD. This retrospective cohort study was designed to determine whether the quantitative HFS correlates with the risk of anti-cancer drug-induced pneumonia in lung cancer patients, including those with mild pre-existing ILD.
