S1123
Clinical – Upper GI
ESTRO 2026
13 Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands. 14 Department of Research, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, Netherlands. 15 Department of Medical Oncology, Zuyderland Medisch Centrum, Sittard-Geleen, Netherlands Purpose/Objective: Radiation-induced lymphopenia (RIL) is an established prognostic factor associated with poorer pathologic response, disease-free survival (DFS), and overall survival (OS) in locally advanced esophageal cancer patients undergoing concurrent chemoradiotherapy (CRT). In resectable patients, standard treatment can consist of neoadjuvant CRT followed by surgery, with adjuvant nivolumab indicated (since 2022) for incomplete pathologic response. As immunotherapy efficacy relies on lymphocyte function, we hypothesize that RIL may attenuate nivolumab benefit. This study evaluates whether RIL during neoadjuvant CRT predicts nivolumab efficacy in esophageal cancer. Material/Methods: In this multicenter retrospective cohort study (2020– 2024), patients from six hospitals with esophageal cancer showing incomplete pathologic response after neoadjuvant CRT and esophagectomy and available absolute lymphocyte counts (ALCs) at baseline and during CRT, were analyzed. To avoid immortal time bias, only patients surviving ≥ 90 days post-surgery were included. Severe RIL was predefined as grade ≥ 3 lymphopenia (ALC <0.5K/µL) in week 3 of CRT; the threshold best distinguishing survival in the largest series to date.(1) Baseline characteristics were compared between groups with versus without severe RIL, and subsequent survival analyses for patients with nivolumab versus without nivolumab were analyzed within each group. DFS and OS were calculated from esophagectomy using Kaplan-Meier analyses, and compared between nivolumab and no nivolumab using Cox regression analyses. Baseline differences between nivolumab and no nivolumab groups were primarily driven by diagnosis year (i.e. reimbursement), but residual imbalances were adjusted via inverse-probability-of-treatment- weighting (IPTW). Results: Among 264 patients, those with severe RIL (n=117 [44%]) had significantly higher cN- and overall clinical stage, and lower baseline ALC. In the 147 patients without severe RIL, significantly better outcomes were observed with nivolumab (n=63; DFS: hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.20-0.90; OS: HR 0.20, 95%CI 0.08-0.53; Figure 1), even after IPTW- adjustment (DFS: HR 0.44, 95%CI 0.19-1.01; OS: HR 0.19, 95%CI 0.07-0.54). In the 117 patients with severe RIL, no significant outcome advantages were observed
with nivolumab (n=55; DFS: HR 0.92, 95%CI 0.47-1.82; OS: HR 0.67, 95%CI 0.34-1.32; Figure 2), also not after IPTW-adjustment (DFS: HR 0.64, 95%CI 0.41-1.74; OS: HR 0.56, 95%CI 0.27-1.15).Figure 1:
Figure 2:
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