Impact of antibiotic use before definitive concurrent chemoradiation in patients with locally advanced non-small cell lung cancer

Abstract

Purpose: This study evaluated whether antibiotic treatment before chemoradiotherapy influenced outcomes in patients with locally advanced non-small cell lung cancer (LA-NSCLC).

Methods: The records of LA-NSCLC patients treated with chemoradiotherapy between 2010 and 2017 at West China Hospital of Sichuan University were retrospectively examined together with their antibiotic use (antibiotic type, duration of treatment, and time between discontinuation and chemoradiotherapy). The influence of antibiotics on progression-free survival (PFS) and overall survival (OS) was evaluated with Kaplan-Meier curves and univariate and multivariate Cox regression.

Results: Of 522 patients, 176 had received intravenous broad-spectrum antibiotics in the month before chemoradiotherapy. Antibiotic use was linked to both reduced PFS (7.9 vs. 13.4 months, p < 0.001) and OS (20.4 vs. 25.3 months, p = 0.049). Multivariate regression demonstrated that antibiotic treatment was an unfavorable independent prognostic factor for LA-NSCLC patients who received chemoradiotherapy (HR 1.234; 95% CI 1.019-1.494; p = 0.031). Prognosis was also influenced by antibiotic type, length of treatment, and interval between discontinuation and chemoradiotherapy initiation. β‑lactamase inhibitors were found to be the most harmful (median OS for β‑lactamase inhibitors/fluoroquinolones/cephalosporins: 16.5/19.9/25.9 months, p = 0.045). Cutoff values for interval and duration calculated by the X‑tile procedure showed that intervals of 7-16 days or durations ≤ 6 days did not significantly affect OS relative to untreated patients (intervals: p = 0.9; duration: p = 0.93).

Conclusion: Antibiotic treatment for longer than 6 days, especially with β‑lactamase inhibitors, was associated with poor prognosis. Furthermore, delaying chemoradiotherapy for 7-16 days after antibiotic discontinuation may reduce these negative effects.

Keywords: Antibiotic treatment; Chemotherapy; Non-small cell lung cancer; Prognosis; Radiotherapy.