Radiological Patterns of Drug-induced Interstitial Lung Disease (DILD) in Early-phase Oncology Clinical Trials

Abstract

Purpose: Drug induced interstitial lung disease (DILD) is a rare, but potentially fatal toxicity. Clinical and radiological features of DILD in the early experimental setting are poorly described. Experimental Design: 2499 consecutive advanced cancer patients on phase I clinical trials were included. DILD was identified by a dedicated radiologist and investigators, categorized per internationally recognized radiological patterns and graded per CTCAE and the Royal Marsden Hospital DILD score. Clinical and radiological features of DILD were analysed. Results: 60 patients overall (2.4%) developed DILD. Median time to onset of DILD was 63 days (range 14-336 days). 45% of patients who developed DILD were clinically asymptomatic. Incidence was highest in patients receiving drug conjugates (7.4%), followed by inhibitors of the PI3K/AKT/mTOR pathway (3.9%). Commonest pattern seen was hypersensitivity pneumonitis (33.3%), followed by non-specific interstitial pneumonia (30%) and cryptogenic organising pneumonia (26.7%). A higher DILD score (OR 1.47, 95% CI: 1.19-1.81, p <0.001) and the pattern of DILD (OR 5.83 for acute interstitial pneumonia, 95% CI: 0.38-90.26, p=0.002) were significantly associated with a higher CTCAE grading. The only predictive factor for an improvement in DILD was an interruption of treatment (OR 0.05, 95% CI: 0.01-0.35, p=0.01). Conclusions: DILD in early phase clinical trials is a toxicity of variable onset, with diverse clinical and radiological findings. Radiological findings precede clinical symptoms. The extent of the affected lung parenchyma, scored by the RMH DILD score, correlates with clinical presentation. Most events are low grade, and improve with treatment interruption which should be considered early.