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).
Conclusion: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.Research.
Stereotaxic biopsy was performed in 17 pts (71%); 9 (53%) had grade II diffuse astrocytoma, and 3 (18%) pilocytic astrocytoma; glioblastoma (GBM) was found in 1 patient at diagnosis and in another at a late recurrence of a glial proliferation. Pons and bulb were the main sites of the tumor (N¼10/10). Among the 21 treated pts, all underwent radiotherapy (RT); 7 received sequential radiotherapy and chemotherapy (RT+CT). Median OS was 45.2 months and 5-y OS was 48.7% (95% CI 24.5-69.2%). No statistically significant association was found between OS and age, tmt modality, or MRI contrast enhancement. ECOG-PS 3-4 was identified as negative PF; although no statistically significant, there was a numerical difference of outcomes regarding histological grade (Table ).
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