Data from Radiation Dose–Volume Effects on Negative Tumor-Draining Lymph Nodes Affected T-cell Activation and Prognosis in Esophageal Cancer with Chemoradiotherapy

<div>AbstractPurpose:<p>A preclinical model found that elective nodal irradiation attenuated the efficacy of radiotherapy (RT) and radio-immunotherapy. However, limited clinical studies have explored the correlation between radiation dose–volume parameters of negative tumor-draining lymph nodes (TDLN) and T-cell activation/prognosis for patients with cancer treated with definitive radiochemotherapy.</p>Experimental Design:<p>Patients with locally advanced esophageal cancer undergoing definitive chemoradiotherapy (CRT) were selected from two prospective trials. Dose–volume parameters of TDLN as well as other lymphocyte-related organs at risk and lymphocyte subsets such as CD3⁻CD19⁺ B cells, CD8⁺CD28⁺ T cells, and activated T cells (CD3⁺CD8⁺HLA-DR⁺) before and at the end of RT were collected. Logistic analysis was utilized to correlate dose–volume parameters with reductions in lymphocyte subsets. Prognosis of TDLN irradiation was investigated through Kaplan–Meier analysis and Cox hazards models.</p>Results:<p>Among 512 patients, the median mean dose of TDLN and negative non-TDLN was 25.6 and 15.1 Gy, respectively. Multivariable analyses indicated that TDLN V15 >50% was an independent predictor of poorer local recurrence–free survival (HR, 1.31; <i>P</i> = 0.029) and distant metastasis–free survival (HR, 1.39; <i>P</i> < 0.001), as well as greater reductions in CD3⁻CD19⁺ B cells (OR, 1.98; <i>P</i> = 0.002), CD8⁺CD28⁺ T cells (OR, 3.42; <i>P</i> < 0.001), and CD3⁺CD8⁺HLA-DR⁺ T cells (OR, 4.67; <i>P</i> = 0.002) after RT.</p>Conclusions:<p>A higher radiation dose–volume parameter of TDLNs in patients with esophageal cancer undergoing CRT was significantly associated with suppression of T-cell activation and a worse prognosis. Limiting the percentage of TDLN V15 may be beneficial for improving the prognosis of CRT with or without PD-1 inhibitors.</p></div>