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.

Hypofractionated Proton Beam Therapy for cT1-2N0M0 Non-small Cell Lung Cancer Patients With Interstitial Lung Disease

“…As shown in Table IV, the incidences of grade ≥2, ≥3, and 5 pneumonitis after SBRT in patients with ILD were 18.7-55.0%, 10.0-38.8%, and 0- 21%, respectively (5)(6)(7)(8)(18)(19)(20). Because there is an apparent dose-volume effect of SBRT in the lung on radiationinduced pneumonitis in patients with lung tumors (7,8,20), particle therapy including PBT, which can provide a better dose distribution compared with SBRT, is theoretically safer than photon-based SBRT for providing curative radiation doses in patients with ILD. In our study, the incidence of grade ≥2 pneumonitis in patients with ILD was 17.6% and was comparable with the rates reported in previous particle therapy studies (14,21,22).…”

“…Yoshitake et al reviewed 260 patients who received SBRT for lung cancer, including 18 with interstitial changes on pretreatment CT, and reported a significantly higher 6-month cumulative rate of grade ≥2 pneumonitis in the patients with than in those without interstitial changes (44.4% vs. 4.1%, p<0.0001), whereas there was no significant difference in the lung V5, V10, or V20 or the MLD (7). Liu et al evaluated 109 early-stage NSCLC patients receiving SBRT, including 38 with subclinical ILD, and reported that the MLD was significantly higher in patients with grade ≥2 pneumonitis than in those with grade ≤1 pneumonitis among patients with subclinical ILD (5.5 Gy vs. 3.4 Gy, p=0.042) (20). Their findings suggest that stricter dose constraints of the lung are required when treating patients with ILD.…”

“…SBRT for early-stage lung cancer in patients with ILD can cause severe or fatal pneumonitis. There are several studies so far that have evaluated the outcomes of SBRT for lung tumors in patients with ILD, many of which have been conducted in Japan (5)(6)(7)(8)(18)(19)(20). As shown in Table IV, the incidences of grade ≥2, ≥3, and 5 pneumonitis after SBRT in patients with ILD were 18.7-55.0%, 10.0-38.8%, and 0- 21%, respectively (5)(6)(7)(8)(18)(19)(20).…”

“…There are several studies so far that have evaluated the outcomes of SBRT for lung tumors in patients with ILD, many of which have been conducted in Japan (5)(6)(7)(8)(18)(19)(20). As shown in Table IV, the incidences of grade ≥2, ≥3, and 5 pneumonitis after SBRT in patients with ILD were 18.7-55.0%, 10.0-38.8%, and 0- 21%, respectively (5)(6)(7)(8)(18)(19)(20). Because there is an apparent dose-volume effect of SBRT in the lung on radiationinduced pneumonitis in patients with lung tumors (7,8,20), particle therapy including PBT, which can provide a better dose distribution compared with SBRT, is theoretically safer than photon-based SBRT for providing curative radiation doses in patients with ILD.…”

Risk factors for radiation-induced lung injury in patients with advanced non-small cell lung cancer: implication for treatment strategies

“…Studies [ 30 , 38 ] have pointed out that factors such as smoking, COPD, and ventilatory dysfunction can increase the risk of RILI. It is recommended that lung diffusion function be tested before radiotherapy to evaluate lung function status [ 39 ]. Therefore, in radiotherapy, attention should be paid to the exposure volume and exposure dose [ 40 ].…”