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

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Date
2020-09
ICR Author
Lopez, Juanita
Banerji, Udai
Tunariu, Nina
De Bono, Johann
Author
Terbuch, A
Tiu, C
Candilejo, IM
Scaranti, M
Curcean, A
Bar, D
Estevez Timon, M
Ameratunga, M
Ang, JE
Ratoff, J
Minchom, AR
Banerji, U
de Bono, JS
Tunariu, N
Lopez, JS
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Type
Journal Article
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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.Patients and methods A total of 2,499 consecutive patients with advanced cancer 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 Common Terminology Criteria for Adverse Events (CTCAE) and the Royal Marsden Hospital (RMH) DILD score. Clinical and radiological features of DILD were analyzed.Results Sixty patients overall (2.4%) developed DILD. Median time to onset of DILD was 63 days (range, 14-336 days). A total of 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%). The most common pattern seen was hypersensitivity pneumonitis (33.3%), followed by nonspecific interstitial pneumonia (30%), and cryptogenic organizing pneumonia (26.7%). A higher DILD score [OR, 1.47, 95% confidence interval (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.
URI
https://repository.icr.ac.uk/handle/internal/3599
DOI
https://doi.org/10.1158/1078-0432.ccr-20-0454
Collections
  • Cancer Therapeutics
  • Clinical Studies
Research team
Medicine (de Bono Prostate)
Clinical Pharmacology – Adaptive Therapy
Prostate Cancer Targeted Therapy Group
Language
eng
Date accepted
2020-04-21
License start date
2020-09
Citation
Clinical cancer research : an official journal of the American Association for Cancer Research, 2020, 26 (18), pp. 4805 - 4813

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