Propensity score analysis of high-dose rate brachytherapy, immune checkpoint inhibitors, and docetaxel in second-line advanced NSCLC treatment

Abstract

This study evaluated the efficacy and safety of combining high-dose-rate brachytherapy, immune checkpoint inhibitors, and docetaxel as second-line treatment for advanced NSCLC, given the poor prognosis after first-line therapy. We conducted a single-center, retrospective, propensity score-matched study comparing HDR brachytherapy plus ICIs and docetaxel (study group) versus ICIs plus docetaxel (control group) in patients with advanced NSCLC who progressed after prior treatment without known driver gene mutations or uninvestigated mutation status. After propensity score matching, 21 patients were included in each group. The study group had a higher ORR (42.9% vs. 28.6%). Median OS was 18.6 months for the study group and 12.8 months for the control group (HR 0.45, 95% CI 0.20-0.85, P = 0.042). Median PFS was 8.6 vs. 5.6 months (HR 0.29, 95% CI 0.15-0.55, P < 0.001). The DCR was higher in the study group (71.4% vs. 61.9%). Treatment-related AEs were manageable, with no significant increase in grade 3/4 toxicities in the study group. Results suggest that combining high-dose rate brachytherapy, immune checkpoint inhibitors, and docetaxel may improve survival and response rates in advanced NSCLC after first-line therapy. Prospective randomized trials are necessary to confirm these findings and validate the strategy's effectiveness.

Keywords: High-dose-rate brachytherapy; Immune checkpoint inhibitors; Non-small cell lung cancer; Propensity score matching; Treatment-related adverse events.

Fig. 1

Flow diagram showing enrollment and exclusion of patients with advanced NSCLC treated with brachytherapy + ICIs + Docetaxel or ICIs + Docetaxel.

Fig. 2

Panel A shows the Kaplan-Meier estimates of overall survival for the two treatment groups. The median overall survival was 18.6 months in the Brachytherapy + ICIs + Docetaxel group and 12.8 months in the ICIs + Docetaxel group. The hazard ratio for death was 0.45 (95% CI,0.20–0.85; P = 0.042).Panel B shows the Kaplan-Meier estimates of Progression-free Survival for the two treatment groups. The median progression-free survival was 8.6 months in the Brachytherapy + ICIs + Docetaxel group and 5.6 months in the ICIs + Docetaxel group. The hazard ratio for death was 0.29 (95% CI, 0.15–0.55; P < 0.001).

Fig. 3

. Hazard ratios for overall survival according to the baseline characteristic.

Fig. 4

.The best mRECIST of the matched Brachytherapy + ICIs + Docetaxel and ICIs + Docetaxel patients. PR, partial responses; SD, stable disease; PD, progressive disease.

Fig. 5

. Waterfall plots of best overall response of the target lesion(s) as per mRECIST v1.1. (A) Brachytherapy + ICIs + Docetaxel arm. (B) ICIs + Docetaxel arm. PR, partial responses; SD, stable disease; PD, progressive disease.