3491 - Secondary Analysis of a Phase II Trial of Primary Lung Tumor SBRT Followed by Concurrent Mediastinal Chemoradiation and Consolidation Immunotherapy for Locally-Advanced Non-Small Cell Lung Cancer: Analysis of Lung Texture Changes after Chemoradiation

Purpose/Objective(s): To report on lung texture volume changes after primary tumor SBRT followed by conventional chemoradiation to lymph nodes and consolidation immunotherapy in patients (pts) with unresectable LA-NSCLC and correlation with pulmonary toxicity and PFT changes after chemoradiation.

Materials/Methods: Eligible pts included stage II-III LA NSCLC with peripheral primary tumors = 7cm or centrally located tumors with at least 2 cm separation from involved nodal disease. Pts received SBRT to primary tumor (50-54 Gy in 3-5 fractions) followed by standard radiation to 60 Gy in 30 fractions to involved lymph nodes with concurrent platinum doublet chemotherapy, with eligible patients receiving consolidation immunotherapy. The primary endpoint was previously reported. Lung texture analysis (LTA) was analyzed at baseline, 3-6 months (mo), and 9-12 mo post treatment on follow-up high resolution CT scans using previously described quantitative software (4d Medical LTA, Los Angeles, CA) to measure lung texture % volumes including ground glass, reticular, honeycomb, hyperlucent, total fibrosis (reticulation + honeycombing), and total ILD (ground glass + reticulation + honeycombing). Pulmonary function tests (PFTs) were acquired at baseline and 6 mo post chemoradiation. Least-square means and standard errors were estimated from mixed models for repeated LTA measures, with fixed effects for time point and group, and a random effect for pt. P-values from contrast statements compared lung texture volumes at timepoints between groups.

Results: 45 of 61 patients had quantification of lung textures at all 3 timepoints for this secondary analysis, 36 of whom had PFTs at baseline and 6 mo post chemoradiation. Pts with grade 2 or higher (G2+) pneumonitis had significantly higher volume of ground glass % (p=0.02) and total ILD % at 6 mo (p=0.02). Pts who developed G2+ non-pneumonitis respiratory toxicity also had significantly higher ground glass % (p<0.01), total fibrosis % (p=0.02) and total ILD % (p<0.01) at 6 mo. These pts also had significant differences in ground glass % (p=0.01) and total ILD % (p=0.01) at baseline. Pts with DLCO decline of =10% from baseline to 6 mo had significantly higher ground glass % (p=0.02) and total ILD% (p=0.02) at 6 mo than pts without significant DLCO decline. Patients receiving =6 cycles of immunotherapy after chemoradiation did not have significant differences in LTA volumes at baseline, 6 mo, or 12 mo compared to those who received <6 cycles.

Conclusion: Lung texture quantified volumes predict for G2+ pneumonitis and respiratory toxicity in patients undergoing SBRT to the primary tumor followed by conventional chemoradiation to the involved lymph nodes. Patients with higher baseline or 6 mo ground glass %, total fibrosis %, and total ILD% may benefit from earlier intervention to prevent G2+ respiratory toxicities or significant PFT changes when receiving chemoradiation. These findings have direct implications for the currently accruing NRG Oncology LU008 phase III trial.