Assessment of Precision Irradiation in Early Non-Small Cell Lung Cancer and Interstitial Lung Disease (ASPIRE-ILD): Primary Analysis of a Phase II Trial

Abstract

The use of stereotactic ablative radiotherapy (SABR) in patients with fibrotic interstitial lung disease (ILD) has been associated with an increased risk of toxicity, but patients with ILD and lung cancer may have no other options for curative-intent treatment. The goal of the ASPIRE-ILD trial was to assess the benefits and toxicities of SABR in patients with fibrotic ILD. We enrolled patients with fibrotic ILD and a diagnosis of T1-2N0 NSCLC who were not candidates for surgery. All patients were centrally reviewed prior to enrollment to confirm the presence and subtype of ILD. After stratification by the ILD-GAP score (a measure of ILD severity and prognosis), patients were treated with SABR to a dose of 50 Gy in 5 fractions EOD (BED = 100 Gy10), with a built-in de-escalation protocol in case of unacceptable toxicity. The primary endpoint was overall survival (OS), powered to distinguish 1-year OS >70% vs. an unacceptable rate of ≤50%. Secondary endpoints included toxicity (CTC-AE version 4.0), progression-free survival (PFS), local control (LC), patient-reported outcomes (FACT-L quality of life and cough severity), and changes in pulmonary function tests (PFTs). The study pre-specified that SABR would be considered worthwhile if median OS was >1 year, with a grade 3-4 toxicity risk <35% and a grade 5 toxicity risk <15%. Target accrual was 39 treated patients. Thirty-nine patients were enrolled and treated with SABR between March 2019 and January 2022, all to a dose of 50 Gy in 5 fractions, at 5 institutions in Canada and 1 in Scotland. Median age was 78 years (interquartile range: 67-83), 59% were male, and 92% had a history of smoking (median 43 pack-years). At baseline, 70% reported dyspnea, median FEV1 was 80% predicted and median DLCO was 49% predicted. ILD-GAP scores were as follows: ≤2 (i.e., best ILD status): n = 14; 3-5: n = 23; ≥6 (i.e., worst ILD status): n = 2. Median follow-up was 19 months. OS at 1-year was 78.9% (p<0.001 by binomial test vs. the unacceptable rate). Median OS was 25 months, median PFS was 19 months, and 2-year LC was 92%. AE rates (possibly, probably or definitely related) were as follows (highest grade per patient): grade 1-2: n = 12 (31%); grade 3: n = 4 (10%); grade 4; n = 0; grade 5 n = 3 (7.7%, all due to respiratory deterioration). AE rates did not differ by ILD-GAP category or ILD subtype. FACT-L scores trended downward over time (p = 0.07), and cough severity scale scores worsened over time (p = 0.02). Comparing last-available PFTs with baseline, DLCO declined (median: -4%; p = 0.046), FVC trended downward (median: -2.5%; p = 0.11), and FEV1 remained stable (median change: 0%). The use of SABR in patients with ILD met the pre-specified acceptability thresholds for both toxicity and efficacy, supporting the use of SABR for curative-intent treatment after a careful discussion of risks and benefits. Further studies exploring pharmacologic options to reduce toxicity may be beneficial in this population. ().