Assessment of precision irradiation in early non-small cell lung cancer and interstitial lung disease (ASPIRE-ILD): study protocol for a phase II trial

Abstract

Background: Stereotactic ablative radiotherapy (SABR) has become an established treatment option for medically-inoperable early-stage (Stage I-IIA) non-small cell lung cancer (ES-NSCLC). SABR is able to obtain high rates of local control with low rates of symptomatic toxicity in this patient population. However, in a subset of patients with fibrotic interstitial lung disease (ILD), elevated rates of SABR-related toxicity and mortality have been described. The Assessment of Precision Irradiation in Early Non-Small Cell Lung Cancer and Interstitial Lung Disease (ASPIRE-ILD) study will conduct a thorough prospective evaluation of the clinical outcomes, toxicity, changes in diagnostic test parameters and patient-related outcomes following SABR for ES-NSCLC for patients with fibrotic ILD.

Methods: ASPIRE-ILD is a single-arm Phase II prospective study. The accrual target is 39 adult patients with T1-2N0M0 non-small cell lung cancer with co-existing ILD who are not candidates for surgical excision. Pathological confirmation of diagnosis is strongly recommended but not strictly required. Enrolled patients will be stratified by ILD-related mortality risk. The starting SABR dose will be 50 Gy in 5 fractions every other day (biologically effective dose: 100 Gy₁₀ or 217 Gy₃), but the radiation dose can be de-escalated up to two times to 50 Gy in 10 fractions daily (75 Gy₁₀ or 133 Gy₃) and 45 Gy in 15 fractions daily (58 Gy₁₀ or 90 Gy₃). Dose de-escalation will occur if 2 or more of the first 7 patients in a cohort experiences grade 5 toxicity within 6 months of treatment. Similarly, dose de-escalation can also occur if 2 or more of the first 7 patients with a specific subtype of ILD experiences grade 5 toxicity within 6 months of treatment. The primary endpoint is overall survival. Secondary endpoints include toxicity (CTC-AE 4.0), progression-free survival, local control, patient-reported outcomes (cough severity and quality of life), rates of ILD exacerbation and changes in pulmonary function tests/high-resolution computed tomography findings post-SABR.

Discussion: ASPIRE-ILD will be the first prospective study specifically designed to comprehensively evaluate the effectiveness and safety of SABR for ES-NSCLC in patients with co-existing ILD.

Trial registration: Clinicaltrials.gov identifier: NCT03485378. Date of registration: April 2, 2018.

Keywords: Cancer; Interstitial lung disease; Lung; Stereotactic radiotherapy; Survival; Toxicity.

Fig. 1

Study Schema. Patients with T1–2N0M0 non-small cell lung cancer and co-existing fibrotic interstitial lung disease will be enrolled in this single-arm study. Analysis will be stratified by interstitial lung disease severity. NSCLC: non-small cell lung cancer, ILD: interstitial lung disease, ILD-GAP: interstitial lung disease – gender/age/physiology model