Show simple item record

dc.contributor.authorTerbuch, A
dc.contributor.authorTiu, C
dc.contributor.authorCandilejo, IM
dc.contributor.authorScaranti, M
dc.contributor.authorCurcean, A
dc.contributor.authorBar, D
dc.contributor.authorEstevez Timon, M
dc.contributor.authorAmeratunga, M
dc.contributor.authorAng, JE
dc.contributor.authorRatoff, J
dc.contributor.authorMinchom, AR
dc.contributor.authorBanerji, U
dc.contributor.authorde Bono, JS
dc.contributor.authorTunariu, N
dc.contributor.authorLopez, JS
dc.date.accessioned2020-04-28T10:35:24Z
dc.date.issued2020-09
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research, 2020, 26 (18), pp. 4805 - 4813
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3599
dc.identifier.eissn1557-3265
dc.identifier.doi10.1158/1078-0432.ccr-20-0454
dc.description.abstractPurpose 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.
dc.formatPrint-Electronic
dc.format.extent4805 - 4813
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.titleRadiological Patterns of Drug-induced Interstitial Lung Disease (DILD) in Early-phase Oncology Clinical Trials.
dc.typeJournal Article
dcterms.dateAccepted2020-04-21
rioxxterms.versionofrecord10.1158/1078-0432.ccr-20-0454
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2020-09
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfClinical cancer research : an official journal of the American Association for Cancer Research
pubs.issue18
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicine (de Bono Prostate)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Pharmacology – Adaptive Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicine (de Bono Prostate)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Pharmacology – Adaptive Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group
pubs.publication-statusPublished
pubs.volume26
pubs.embargo.termsNot known
icr.researchteamMedicine (de Bono Prostate)en_US
icr.researchteamClinical Pharmacology – Adaptive Therapyen_US
icr.researchteamProstate Cancer Targeted Therapy Groupen_US
dc.contributor.icrauthorLopez, Juanitaen
dc.contributor.icrauthorBanerji, Udaien
dc.contributor.icrauthorTunariu, Ninaen
dc.contributor.icrauthorDe Bono, Johannen


Files in this item

Thumbnail

This item appears in the following collection(s)

Show simple item record