Stereotactic body radiotherapy for early stage non-small cell lung cancer in patients with subclinical interstitial lung disease

Abstract

Background: For lung cancer patients with subclinical (untreated and asymptomatic) interstitial lung disease (ILD), there is a lack of relatively safe and effective treatment. Stereotactic body radiation therapy (SBRT) can achieve a high level of tumor control with low toxicity in early-stage non-small cell lung cancer (NSCLC). This study aimed to evaluate the efficacy and toxicity of early stage NSCLC patients with subclinical ILD receiving SBRT.

Methods: A total of 109 early stage NSCLC patients receiving SBRT treatment between December 2011 and August 2016 were reviewed in our institutions; patients with clinical ILD were excluded. The median dose of SBRT was 50 Gy in 5 fractions. The median biologically effective dose (BED; α/β=10) was 100 Gy (range, 72-119 Gy). An experienced radiation oncologist and an experienced radiologist reviewed the presence of subclinical ILD in the CT findings before SBRT. The relationships among the efficacy, radiation-induced lung injury (RILI) and subclinical ILD were explored.

Results: In all, 38 (34.9%) of 109 patients were recognized with subclinical ILD before SBRT, 48 (44.0%) of 109 patients were recognized with grade 2-5 RILI after SBRT, and 18 (47.4%) of 38 patients with subclinical ILD were observed with grade 2-5 RILI. Subclinical ILD was not a significant factor of grade 2-5 RILI (P=0.608); however, 3 patients had extensive RILI, and they all suffered from subclinical ILD. Dosimetric factor of the lungs, such as mean lung dose (MLD) was significantly related with Grade 2-5 RILI in patients with subclinical ILD (P=0.042). The progression-free survival (PFS) rates at 3 years in the subclinical ILD patients and those without ILD were 61.6% and 66.8%, respectively (P=0.266).

Conclusions: Subclinical ILD was not a significant factor for RILI or PFS in early stage NSCLC patients receiving SBRT; however, patients with subclinical ILD receiving SBRT may experience uncommon extensive RILI.

Keywords: Non-small cell lung cancer (NSCLC); outcome; stereotactic body radiotherapy (SBRT); subclinical interstitial lung disease; toxicity.

Figure 1

The CT appearance of extensive pneumonitis. (A) Dose distribution on computed tomography (CT). Red and yellow lines are 40 and 2 Gy, respectively. (B) CT image before stereotactic body radiotherapy. CT at the level of bilateral lower lobes shows focal subpleural ground-glass abnormalities. In this case, the abnormality was less than 5% of the lung (interstitial lung disease score 1); (C,D) 3 months after stereotactic body radiotherapy. CT at the level of the upper lobes (C) and lower lobes (D) showing extensive ground-glass abnormalities and pulmonary fibrosis.

Figure 2

Estimated cumulative incidence curves illustrating (A) progression-free survival (PFS) in the patients with subclinical interstitial lung disease (ILD) patients and those without ILD and (B) PFS in the patients with Grade 0–1 radiation-induced lung injury (RILI) and those with Grade 2–5 RILI by Kaplan-Meier analysis.