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Radiological Patterns of Drug-induced Interstitial Lung Disease (DILD) in Early-phase Oncology Clinical Trials.
Clin Cancer Res. 2020 Apr 24 [Online ahead of print]CC

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.

Authors+Show Affiliations

Phase I Drug Development Unit, The Royal Marsden Hospital and The Institute of Cancer Research, Sutton, United Kingdom. Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.Phase I Drug Development Unit, The Royal Marsden Hospital and The Institute of Cancer Research, Sutton, United Kingdom.Phase I Drug Development Unit, The Royal Marsden Hospital and The Institute of Cancer Research, Sutton, United Kingdom. Division of Medical Oncology, START Madrid-HM Sanchinarro CIOCC Early Phase Program, Medical University Hospital of Sanchinarro, Madrid, Spain.Phase I Drug Development Unit, The Royal Marsden Hospital and The Institute of Cancer Research, Sutton, United Kingdom.Phase I Drug Development Unit, The Royal Marsden Hospital and The Institute of Cancer Research, Sutton, United Kingdom.Phase I Drug Development Unit, The Royal Marsden Hospital and The Institute of Cancer Research, Sutton, United Kingdom.Phase I Drug Development Unit, The Royal Marsden Hospital and The Institute of Cancer Research, Sutton, United Kingdom.Phase I Drug Development Unit, The Royal Marsden Hospital and The Institute of Cancer Research, Sutton, United Kingdom. Monash University, Melbourne, Australia.Phase I Drug Development Unit, The Royal Marsden Hospital and The Institute of Cancer Research, Sutton, United Kingdom. Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.Phase I Drug Development Unit, The Royal Marsden Hospital and The Institute of Cancer Research, Sutton, United Kingdom. Epsom and St. Helier University Hospitals NHS Trust, Epsom, United Kingdom.Phase I Drug Development Unit, The Royal Marsden Hospital and The Institute of Cancer Research, Sutton, United Kingdom.Phase I Drug Development Unit, The Royal Marsden Hospital and The Institute of Cancer Research, Sutton, United Kingdom.Phase I Drug Development Unit, The Royal Marsden Hospital and The Institute of Cancer Research, Sutton, United Kingdom.Phase I Drug Development Unit, The Royal Marsden Hospital and The Institute of Cancer Research, Sutton, United Kingdom.Phase I Drug Development Unit, The Royal Marsden Hospital and The Institute of Cancer Research, Sutton, United Kingdom. juanita.lopez@icr.ac.uk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32332017

Citation

Terbuch, Angelika, et al. "Radiological Patterns of Drug-induced Interstitial Lung Disease (DILD) in Early-phase Oncology Clinical Trials." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 2020.
Terbuch A, Tiu C, Candilejo IM, et al. Radiological Patterns of Drug-induced Interstitial Lung Disease (DILD) in Early-phase Oncology Clinical Trials. Clin Cancer Res. 2020.
Terbuch, A., Tiu, C., Candilejo, I. M., Scaranti, M., Curcean, A., Bar, D., Estevez Timon, M., Ameratunga, M., Ang, J. E., Ratoff, J., Minchom, A. R., Banerji, U., de Bono, J. S., Tunariu, N., & Lopez, J. S. (2020). Radiological Patterns of Drug-induced Interstitial Lung Disease (DILD) in Early-phase Oncology Clinical Trials. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. https://doi.org/10.1158/1078-0432.CCR-20-0454
Terbuch A, et al. Radiological Patterns of Drug-induced Interstitial Lung Disease (DILD) in Early-phase Oncology Clinical Trials. Clin Cancer Res. 2020 Apr 24; PubMed PMID: 32332017.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Radiological Patterns of Drug-induced Interstitial Lung Disease (DILD) in Early-phase Oncology Clinical Trials. AU - Terbuch,Angelika, AU - Tiu,Crescens, AU - Candilejo,Irene Moreno, AU - Scaranti,Mariana, AU - Curcean,Andra, AU - Bar,Dan, AU - Estevez Timon,Miriam, AU - Ameratunga,Malaka, AU - Ang,Joo Ern, AU - Ratoff,Jonathan, AU - Minchom,Anna R, AU - Banerji,Udai, AU - de Bono,Johann S, AU - Tunariu,Nina, AU - Lopez,Juanita S, Y1 - 2020/04/24/ PY - 2020/02/10/received PY - 2020/04/08/revised PY - 2020/04/21/accepted PY - 2020/4/26/pubmed PY - 2020/4/26/medline PY - 2020/4/26/entrez JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. N2 - 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. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/32332017/Radiological_patterns_of_drug_induced_interstitial_lung_disease_(DILD)_in_early_phase_oncology_clinical_trials L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=32332017 DB - PRIME DP - Unbound Medicine ER -
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