Survival outcomes and safety of adding high-dose-rate intraluminal brachytherapy (HDR-ILBT) utilizing the novel balloon applicator (BRAXX) following concurrent chemoradiotherapy (CCRT) for non-surgical esophageal cancer: a prospective pilot and real-world comparative study.

To investigate the local control and safety of adding high-dose-rate intraluminal brachytherapy (HDR-ILBT) with novel balloon applicator (BRAXX) after concurrent chemoradiation (CCRT) for non-surgery patients with esophageal cancer. The study enrolled 178 patients with esophageal cancer. A total of 13 patients were prospectively recruited to receive HDR-ILBT after CCRT and compared with two standard-of-care cohorts treated between 2022 and 2024. Brachytherapy was delivered via the BRAXX balloon applicator (Taiwan Food and Drug Administration approval No. 006603) using an Iridium-192 Nucletron remote afterloading system (Elekta, Stockholm, Sweden). The primary endpoint was freedom from local tumor recurrence (FFLTR). Secondary endpoints included overall survival (OS), disease progression-free survival (DPFS), and toxicities. Sankey diagrams and swimmer plot were utilized to visualize the longitudinal tumor response dynamics and individual survival trajectories. The median follow-up was 25.2 months. The 1-year and 2-year FFLTR rates were 93.3% and 81.2% (nCCRT + surgery), 84.6% and 67.7% (CCRT + ILBT), and 62.5% and 52.9% (dCCRT alone), respectively (P < 0.001). Consistent survival improvements were observed in both OS and DPFS in CCRT + ILBT cohort. Sankey diagrams demonstrated a favorable dynamic evolution in treatment response within the CCRT + ILBT cohort, achieving a clinical complete response (cCR) rate of 61.5% and overall response rate (ORR) of 69.2% at the end of per-protocol 1-year follow-up. Swimmer plot illustrated that response conversion and consolidation translated into long-term survival. The addition of HDR-ILBT did not exacerbate treatment-related esophageal strictures or fistula formations necessitating intervention. The addition of HDR-ILBT utilizing BRAXX applicator following CCRT is a feasible and promising strategy to enhance local control and prolong survival for non-surgical patients with esophageal cancer. By leveraging its distinct dosimetric advantages and streamlined workflow, ILBT holds the potential to consolidate disease-free status and eradicate residual disease. Further validation through large-scale, prospective clinical trials is still warranted to confirm its clinical benefit and long-term safety. If further validated, this strategy could offer a meaningful addition to the current treatment paradigm.