Time-specific lymphocyte kinetics predict prognosis for patients with locally advanced cervical adenocarcinoma undergoing definitive radiotherapy: insights from a retrospective cohort study

Abstract Background Lymphocytes are the foundation of anti-cancer immune response and effective immunotherapy, yet they are unavoidably compromised during radiotherapy (RT). This results in unsatisfactory treatment efficacy for cervical adenocarcinoma, which is a radio-resistant subtype of cervical cancer. In this study, we systematically evaluated the prognostic value of peripheral lymphocyte counts measured before, during and after RT for cervical adenocarcinoma (ADC) patients. Methods A single center, retrospective study was conducted. Longitudinal lymphocytes counts were collected for 193 patients with locally advanced ADC, beginning 1 week before the initiation of definitive RT and continuing up to 6 months post-RT. Survival analyses were performed to evaluate and compare the prognostic significance of lymphocyte counts across different time points. RNA-sequencing data of tumor tissues was analyzed to explore the underlying mechanism. Results Patients with high lymphocyte counts exhibited better overall survival (OS) and progression free survival (PFS) at most time points assessed. The maximal survival advantage was observed during the 1st week of RT. Among patients who didn’t undergo surgery following RT, during the 1st week of RT the low lymphocyte group had a hazard ratio (HR) of 2.45 (95% CI: 1.09–5.5) for OS and 2.21 (95% CI: 1.21–4.04) for PFS, as determined by the multivariate COX regression. Analyses with limited samples suggested that lymphocyte counts 3–6 months post-RT might also be prognostic. No correlation was observed between patients’ peripheral lymphocyte counts and levels of tumor infiltrating immune cells. Conclusions Low lymphocyte counts during and post-RT, particularly in the 1st week of RT, are associated with poor prognosis for ADC patients, illustrating the clinical value of mitigating the impact of RT on lymphocytes in the early stage of RT.