Radiological Patterns of Drug-induced Interstitial Lung Disease (DILD) in Early-phase Oncology Clinical Trials
| Autor: | Miriam Estevez Timon, Juanita Lopez, Mariana Scaranti, Joo Ern Ang, Dan Bar, Anna Minchom, Johann S. de Bono, Udai Banerji, Malaka Ameratunga, Andra Curcean, Crescens Tiu, Nina Tunariu, Jonathan Ratoff, Irene Moreno Candilejo, Angelika Terbuch |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Time Factors Antineoplastic Agents Asymptomatic 03 medical and health sciences 0302 clinical medicine Neoplasms Internal medicine medicine Humans 030212 general & internal medicine Lung Aged Neoplasm Staging Clinical Trials Phase I as Topic business.industry Incidence Incidence (epidemiology) Interstitial lung disease Common Terminology Criteria for Adverse Events Middle Aged medicine.disease Clinical trial Oncology 030220 oncology & carcinogenesis Radiological weapon Female medicine.symptom Lung Diseases Interstitial business Hypersensitivity pneumonitis Cryptogenic Organizing Pneumonia |
| Zdroj: | Clinical Cancer Research. 26:4805-4813 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-20-0454 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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