Characteristics and Prognostic Impact of Pneumonitis during Systemic Anti-Cancer Therapy in Patients with Advanced Non-Small-Cell Lung Cancer

Abstract

Background: Data on characteristics, outcomes, and prognosis of advanced non-small-cell lung cancer (NSCLC) patients who develop pneumonitis during systemic anti-cancer therapy (pneumonitis) are currently lacking.

Methods: We conducted a retrospective cohort study of 910 consecutive patients diagnosed with advanced NSCLC between January 2004 and January 2014. Of these, 140 patients were excluded because they did not receive systemic anti-cancer therapy at this hospital.

Results: A total of 770 patients were included in the study, of whom 44 (6%) were diagnosed with pneumonitis. The mortality rate of pneumonitis was 36%. The incidence of pneumonitis was independently associated with pre-existing ILD (adjusted odds ratio, 2.99, P = 0.008), and survivors were significantly associated with younger age (P = 0.003) and radiographic non-acute interstitial pneumonia pattern (P = 0.004). In all patients, pneumonitis was identified as an independent predictor of overall survival (OS) (adjusted hazard ratio 1.53, 95% CI, 1.09-2.09, P = 0.015). Performance status was poor in 82% of survivors of pneumonitis; in 62% of survivors, the PS worsened after the pneumonitis improved. Additionally, 54% of survivors received no further systemic anti-cancer therapy after pneumonitis. The median survival time of survivors after pneumonitis was 3.5 months (95% CI, 2.3-7.2 months).

Conclusions: Our study indicated that 6% of patients with advanced NSCLC developed pneumonitis during systemic anti-cancer therapy. The early mortality rate of pneumonitis is high, and the survival and PS after pneumonitis is extremely poor. Additionally, pneumonitis has an adverse impact on the survival of patients with advanced NSCLC. These data should be considered for the management of pneumonitis, and we recommend that future work focuses on pneumonitis particularly to improve the survival of patients with advanced NSCLC.

Fig 1. Patient selection and exclusion criteria.

NSCLC: non-small cell lung cancer;

Fig 2

Kaplan–Meier overall survival curves after the diagnosis of NSCLC in all patients with or without pneumonitis during systemic anti-cancer therapy (pneumonitis) (Fig 2A) and those who did not have pre-existing ILD with or without pneumonitis (Fig 2B), and survival time after the onset of pneumonitis in survivors of pneumonitis (Fig 2C).

Fig 3

Pre-existing interstitial lung disease (ILD) showing subpleural distribution, honeycomb cysts, and bronchiectasis (usual interstitial pneumonia [UIP] pattern) (Fig 3A). Pre-existing ILD showing patchy ground-glass opacity with reticulation, traction bronchiectasis and bronchovascular bundle thickening (non-UIP pattern) (Fig 3B). Drug-related pneumonitis showing new diffuse ground-glass opacities, consolidation and traction bronchiectasis as well as pleural effusion, indicative of AIP pattern (Fig 3C). Drug-related pneumonitis showing new ground-glass opacities and bronchovascular bundle thickening, indicative of on-specific interstitial pneumonia (NSIP) pattern (Fig 3D). Drug-related pneumonitis showing new ground-glass opacities and consolidations with multifocal distribution, indicative of OP pattern (Fig 3E). Drug-related pneumonitis showing new diffuse faint ground glass opacities, indicative of HP pattern (Fig 3F). Drug-related pneumonitis showing diffuse new ground-glass opacities. Since the CT showed multiple consolidation (lung cancer) in both lungs, we could not classify the type of drug-related pneumonitis (unclassifiable pneumonitis) (Fig 3G).