Effects of lymphatic ablation approaches on immunotherapy efficacy in esophageal squamous cell carcinoma.

Abstract

e16046 Background: In the era of chemotherapy, extended radical lymphadenectomy was demonstrated to be associated with improved survival of esophageal squamous cell carcinoma (ESCC). Currently, combination of chemotherapy and immunotherapy has become the standard first-line treatment for recurrent or advanced ESCC. Tumor-draining lymph nodes (TDLNs) play a pivotal role in antigen presentation and immune activation and are regarded as key immune organs. In the era of immunotherapy, the potential role of the extent of lymphatic ablation on immunotherapy efficacy deserves further exploration. Methods: Patients diagnosed with recurrent ESCC after surgery or radiotherapy (relapse) and advanced (treatment-naive) ESCC who were treated by PD-1 inhibitors at Shandong Cancer Hospital between 2018 and 2023 were included retrospectively. Patients with relapse were divided into surgery and radiotherapy group based on the lymph node status. The survival analyses were performed between postoperative relapse, post-radiotherapy and treatment-naive patients. In the subgroup of postoperative relapse patients, the number of lymph nodes resected during surgery was calculated (median, IQR: 17, 13–24). Patients were divided into three groups based on the number of DLNs: DLN≤17, 17 < DLN≤24, and DLN > 24. The baseline characteristics between the different group were compared using the chi-squared test. Kaplan-Meier curve analyses were performed to compare the progression-free survival (PFS) between different groups and analyzed by the log-rank test. Results: A total of 296 patients were included in this study, with 173 in the relapse group and 123 in the treatment-naive group. No significant difference in PFS was observed between the postoperative and post-radiotherapy relapse group and the treatment-naive group. In the postoperative relapse group, a statistically significant difference in PFS was observed between the groups DLN≦17 and 17 < DLN≤24 (7.27 vs 11.37months, P = 0.0385), as well as between the groups 17 < DLN≤24 and DLN > 24 (11.37 vs 6.87months, P = 0.0211). Multivariate Cox regression analysis identified DLN grouping as an independent prognostic factor for the PFS after immunotherapy. In the post-radiotherapy relapse population, an increasing interval between the first radiotherapy and immunotherapy (cut-off: 8.2 months) was associated with improved PFS from immunotherapy (4.93 vs 10.67 months, P = 0.142). Conclusions: In the era of immunotherapy, the optimal range for DLN dissection is between 18 and 24 lymph nodes which is associated with improved immunotherapy efficacy. To strike a balance between lymphatic ablation approach and preserving immune responses is critical for optimizing treatment outcomes.