Prognostic value of absolute lymphocyte count in patients with advanced esophageal cancer treated with immunotherapy: a retrospective analysis

Background: Immunotherapy has become the standard of treatment for recurrent metastatic esophageal cancer (EC), and the value of efficacy predictive markers represented by programmed death-ligand 1 (PD-L1) is limited. The purpose of this study is to analyze the prognostic value of peripheral blood absolute lymphocyte count (ALC) at baseline in patients with recurrent metastatic EC treated with immunotherapy, and to further investigate the relationship between the minimal ALC value (Min ALC) and radiotherapy (RT) parameters. Methods: The main inclusion criteria were: histologically or imaging confirmed recurrent or metastatic EC; complete routine blood test data. A total of 105 patients were included in a single-center institution, 65 of whom had previously received RT. The optimal cut-off value for baseline lymphopenia was determined by the receiver operating characteristic (ROC) curve. The prognostic value of baseline phase lymphopenia for immunotherapy were determined by cox regression analysis and the associated factors affecting lymphopenia were explored by logistic regression analysis. Results: The cut-off value for baseline ALC predicting 1-year overall survival (OS) was 625 cells/mu L. The OS was significantly lower in the lymphopenia group (ALC <= 625 cells/mu L) than in the non-lymphopenia group (ALC >625 cells/mu L) (median OS: 6 vs. 12 months, P=0.002). Multivariate analysis showed that pre-immunotherapy lymphopenia was an important factor influencing patient prognosis [hazard ratio (HR): 1.771, 95% confidence interval (CI): 1.051-2.985; P=0.032)] (adjusted for clinical factors including sex, age, tumor location, histology, degree of differentiation, distant metastasis, use of RT). Patients with a previous grade 4 (G4) Min ALC during RT were more likely to develop pre-immunotherapy lymphopenia following diagnosis of recurrent metastasis [odds ratio (OR): 10.809, 95% CI: 2.185-53.471; P=0.004]. Planning target volume (PTV) volume greater than 521.2 cm3 (OR: 19.981, 95% CI: 1.372-290.985; P=0.028) was an independent risk factor affecting the G4 Min ALC during RT. Conclusions: Lymphopenia is associated with a poorer immunotherapy prognosis in patients with recurrent metastatic EC and those with previous G4 Min ALC after RT. RT-related parameters, especially irradiation volume, can significantly affect lymphocyte counts.