Incidence of interstitial lung disease in patients with mesothelioma in the west part of Japan

Our plain-English summary of Incidence of interstitial lung disease in patients with mesothelioma in the west part of Japan, by S. Nojiri, K. Gemba, K. Aoe, et al (Pharmacoepidemiology and Drug Safety, 2011).

The study

• Authors: S. Nojiri, K. Gemba, K. Aoe, K. Kato, T. Yamaguchi, T. Sato, K. Kubota, T. Kishimoto
• Journal: Pharmacoepidemiology and Drug Safety
• Published: 2011;20(6):643-52
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: In order to evaluate the incidence of an adverse event encountered when using a new therapeutic intervention, it is essential to know the background rate of this adverse event in the same patient population. Interstitial lung disease (ILD) often develops in Japanese patients receiving treatment with anti-neoplastic agents or other drugs. In our study, we estimated the background rate of ILD in patients with malignant mesothelioma (MM).

Methods: We conducted a retrospective cohort study of 328 Japanese patients diagnosed with MM during the period between 1996 and 2006.

Results: After the diagnosis of MM had been made, 21 (15 new and 6 exacerbation) of the 328 patients developed ILD. The crude baseline rate of ILD was estimated to be 0.023 (95%CI, 0.009-0.054) per patient-year, and the baseline rate using the Poisson regression model was estimated to be 0.032 (95%CI, 0.017-0.059) per patient-year where major therapeutic interventions were incorporated in the model. The risk of ILD was increased by surgical excision (rate ratio, 8.87; 95%CI, 2.39-33.0), pleurodesis with picibanil (rate ratio, 5.14; 95%CI, 1.63-16.3), and systemic chemotherapy using vinorelbine (rate ratio, 5.95; 95%CI, 1.22-29.0).

Conclusions: Our results have implications for evaluating the safety outcomes of future studies in patients receiving treatment for MM. The development of ILD in such studies at an incidence rate higher than 0.02-0.03 per patient-year might indicate an excess occurrence as a result of a therapeutic intervention.

Copyright © 2011 John Wiley & Sons, Ltd.

In plain English

This retrospective cohort study measured how often interstitial lung disease (ILD), a group of scarring lung disorders, developed in 328 patients diagnosed with malignant mesothelioma from 1996 to 2006 at 26 western Japanese hospitals. Most had pleural mesothelioma (314), and 12 had peritoneal mesothelioma. After diagnosis, 21 of the 328 patients developed ILD: 15 new cases and 6 worsenings of existing disease. Counting only time outside treatment and the 60 days after it, the estimated baseline ILD rate was 0.023 per patient-year (95% CI 0.009 to 0.054) by simple calculation, and 0.032 (0.017 to 0.059) from a model accounting for four major treatments. After adjustment, ILD risk was higher with surgical removal (rate ratio 8.87; 95% CI 2.39 to 33.0), pleurodesis with picibanil (5.14; 1.63 to 16.3) and vinorelbine chemotherapy (5.95; 1.22 to 29.0). The authors found no notable association between ILD and past asbestos exposure. They noted wide confidence intervals and possible information bias. The authors concluded that ILD rates above 0.02 to 0.03 per patient-year in future treatment studies might indicate an excess caused by treatment.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective cohort study using historical hospital data collected by questionnaire, with central review of mesothelioma diagnoses and ILD cases
• Who was studied: 328 confirmed malignant mesothelioma patients diagnosed March 1996 to March 2006 at 26 hospitals in seven prefectures in western Japan. 314 had pleural, 12 peritoneal, and 2 pericardial or tunica vaginalis testis mesothelioma. 87% were men, and the median age was 66.5 years.
• Exposure: Treatments for mesothelioma (surgical excision, pleurodesis including with picibanil, systemic chemotherapy such as gemcitabine and vinorelbine, radiation therapy) and baseline characteristics. Past asbestos exposure was recorded only as exposure, no exposure or unknown, with no fiber types or quantities.
• Main results:
  • 21 of the 328 patients developed ILD after mesothelioma diagnosis: 15 new cases and 6 exacerbations of existing lung disease
  • Estimated baseline ILD rate, with treatment periods and a 60-day carry-over period after treatment assigned to treatment-related risk: crude 0.023 per patient-year (95% CI 0.009 to 0.054); 0.032 per patient-year (95% CI 0.017 to 0.059) from a Poisson model including four major interventions
  • Adjusted rate ratios for ILD: surgical excision 8.87 (95% CI 2.39 to 33.0), pleurodesis with picibanil 5.14 (95% CI 1.63 to 16.3), vinorelbine chemotherapy 5.95 (95% CI 1.22 to 29.0)
  • Gemcitabine: crude rate ratio 3.16, falling to 1.12 after adjustment
  • No notable association between ILD and smoking status or past asbestos exposure. Table 4: 12 ILD cases among 202 exposed patients versus 8 among 76 unexposed; rate ratio 0.73 (95% CI 0.30 to 1.78).
  • Patients with a prior ILD history had about five times the ILD rate of those without (rate ratio 4.68; 95% CI 1.36 to 16.1)
  • None of the 21 ILD cases were women, although 43 of the 328 patients were female
  • 3 of 66 patients (4.5%) given pleurodesis with picibanil developed ILD within 60 days
• The authors' conclusion: The authors concluded that, in future studies of mesothelioma treatments, ILD occurring at a rate above 0.02 to 0.03 per patient-year might indicate an excess caused by a treatment
• Limitations the authors state:
  • Patients came only from western Japan, which may limit generalizability
  • Because of the limited number of patients, confidence intervals for rate ratios were generally wide
  • Possible information bias. Quantitative information on asbestos exposure and smoking was lacking, and smoking history may be inaccurate because the study was retrospective.
  • The rate of ILD associated with pneumonia could not be estimated because of insufficient information
  • The authors could not exclude that gemcitabine, rather than vinorelbine, contributed to ILD
  • For some patients, the mesothelioma diagnosis could be neither excluded nor confirmed

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Interstitial Lung Disease, Mesothelioma, Background Rate, Cohort Study, rate ratio, Pleurodesis, Chemotherapy, Vinorelbine.

Related studies

• Survival and prognostic factors in malignant pleural mesothelioma: a retrospective study of 314 patients in the west part of Japan — S. Nojiri, K. Gemba, et al. (2011)
• Pemetrexed and interstitial lung disease — B. Adhikari, R.M. Dongol, et al. (2016)
• Possible value of antifibrotic drugs in patients with progressive fibrosing non-IPF interstitial lung diseases — S.E. Torrisi, N. Kahn, et al. (2019)
• Interstitial Lung Diseases in Developing Countries — P. Rivera-Ortega, M. Molina-Molina (2019)
• Treatment and survival analyses of malignant mesothelioma in Japan — K. Gemba, N. Fujimoto, et al. (2013)
• Year in review 2011: acute lung injury, interstitial lung diseases, physiology, sleep and lung cancer — K. Takahashi, N.D. Eves, et al. (2012)

Browse return to medical research.