Idiopathic pulmonary fibrosis in small cell lung cancer as a predictive factor for poor clinical outcome and risk of its exacerbation

PLoS One. 2019 Aug 23;14(8):e0221718. doi: 10.1371/journal.pone.0221718. eCollection 2019.


Objective: Lung cancer frequently co-exists with idiopathic interstitial pneumonia (IIP), which can be subdivided into idiopathic pulmonary fibrosis (IPF) and IIP other than IPF (other IIP). Although chemotherapy in small cell lung cancer (SCLC) patients with IIP may result in the exacerbation of IIP, these patients commonly receive chemotherapy. This study aimed to assess the risks and benefits of chemotherapy in SCLC patients with IIP.

Methods: We retrospectively analyzed the medical records of 122 patients with SCLC who received chemotherapy. Patients with secondary interstitial lung disease (ILD) of known etiology were excluded. Eligible patients were divided into two groups: SCLC with and without IIP. The former group was subdivided into those with IPF and other IIP.

Results: Of the 47 (39.2%) SCLC patients with IIP, 20 had IPF and 27 had other IIP. The frequency of chemotherapy-induced ILD development or IIP exacerbation was higher in patients with IPF (40.0%) than in those with other IIP (3.7%) and non-IIP (1.4%). Logistic regression analysis demonstrated that ILD development or IIP exacerbation was independently associated with IPF (P = 0.007). Time to treatment failure (P < 0.001) and overall survival (P = 0.001) were different among the groups., Cox proportional hazard model revealed that IPF was independently associated with time to treatment failure (P = 0,017) and overall survival (P = 0.006). Other IIP had no impact on time to treatment failure or overall survival. Development of ILD or exacerbation of IIP independently reduced time to treatment failure and overall survival.

Conclusions: Comorbid IPF can be an independent, negative prognostic indicator and at high risk of ILD development or IIP exacerbation in SCLC patients. Early diagnosis and intervention for chemotherapy-induced IIP exacerbation will be beneficial for SCLC patients with IPF, who need close monitoring for its onset.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Disease Progression*
  • Female
  • Humans
  • Idiopathic Interstitial Pneumonias / etiology
  • Idiopathic Pulmonary Fibrosis / etiology*
  • Idiopathic Pulmonary Fibrosis / pathology*
  • Kaplan-Meier Estimate
  • Logistic Models
  • Lung Diseases, Interstitial / drug therapy
  • Lung Diseases, Interstitial / etiology
  • Lung Neoplasms / complications*
  • Lung Neoplasms / drug therapy
  • Male
  • Multivariate Analysis
  • Risk Factors
  • Small Cell Lung Carcinoma / complications*
  • Treatment Outcome

Grant support

This work received a research grant from JSPS KAKENHI Grant Number JP17K09671 to NK. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.