*2.2. Chest HRCT Scoring System*

HRCT (Aquilion ONETM, Canon Medical Systems, Ohtawara, Japan) scans were obtained with 0.5 mm collimation and a 1 mm slice thickness at 1 mm intervals from the lung apices to the bases in the supine position at full inspiration. Two experienced pulmonologists (H.G. and H.I. with 11 and 19 years of experience, respectively), who were blinded to the clinical data, individually assessed the degree of pre-existing ILD using the HFS.

In detail, the HFS was calculated in three areas of each lung before the first administration of anti-cancer drugs: the level of the carina, the level of the right inferior pulmonary vein, and the middle of the two levels. First, the HRCT findings were scored as follows: normal attenuation (score 1), reticular abnormality (score 2), both reticular abnormality and traction bronchiectasis (score 3), and honeycombing (score 4). We did not evaluate extensive pure ground glass opacity, and we organized the lesions after pneumonia, operation, and radiotherapy. Second, the extent of the interstitial abnormalities was estimated as the percentage of the 5% intervals. We multiplied the score and the extent percentage and summed the points for each of the six areas. Finally, we averaged the summed points of the six areas. ILD was categorized as no ILD (HFS = 100), mild ILD (HFS = 101–200), moderate ILD (HFS = 201–300), and severe ILD (HFS = 301–400).

Furthermore, the two independent pulmonologists also evaluated the degree of emphysema using the Goddard score (GS) for the six areas analyzed above [19]. The extent of LAA (low-attenuation areas) was scored as follows: < 5% LAA (score of 0), 6%–25% LAA (score of 1), 26%–50% LAA (score of 2), 51%–75% (score of 3), and > 75% LAA (score of 4). The six scores were summed, and emphysema was graded as no emphysema (GS = 0), mild emphysema (GS = 1–7), moderate emphysema (GS = 8–15), and severe emphysema (GS = 16–24).
