Prognostic implications of lymphopenia and sociodemographic factors on anal cancer patients undergoing definitive therapy: 10-year experience at a multi-site institution

Summary: The neutrophil-to-lymphocyte ratio (NLR) and treatment-related lymphopenia (TRL) have been shown to have a prognostic role in various solid tumors in patients undergoing definitive radiotherapy or chemoradiotherapy (CRT); however, the literature remains limited in anal cancer. Furthermore, the association between sociodemographic factors, lymphopenia, and anal cancer outcomes have not been well studied. We aim to evaluate the relationship of NLR, TRL, and sociodemographic factors with overall survival (OS) in anal cancer patients. We conducted a retrospective analysis of anal cancer patients treated with definitive CRT or RT alone between 2014 – 2024. Baseline/pretreatment neutrophil and lymphocyte count, as well as lymphocyte nadir, were collected. A high NLR was classified as >4. Sociodemographic data (i.e. gender, race, marital status, and income) were obtained from patient and census data. OS was estimated using Kaplan-Meier analysis and compared across groups using the log-rank test. Multivariate logistic regression analysis was used to identify predictors of grade 3 lymphopenia and univariate Cox regression analysis was used to identify predictors of OS. 180 patients (72.8% female and 63.9% non-Hispanic white) were included in the study with a median OS of 30 months (range 1 – 119 months). The median dose received was 54Gy (range 41.4 - 59.4Gy). 86/168 (51.2%) patients experienced grade 3 lymphopenia and 50/168 (29.8%) experienced grade 4 lymphopenia. Grade 3+ lymphopenia was associated with female gender (OR: 3.48, 95% CI: 1.34 - 9.00, p = 0.01), but not with race or household income (p = 0.7, 0.2, respectively). Patients with a NLR >4 vs. NLR ≤4 had a 5-year OS of 71.2% vs 88.2%, respectively (p = 0.031). 85/180 (47.2%) of patients had a >90% decrease in lymphocyte count. Those with >90% vs. ≤90% decrease from lymphocyte baseline to nadir had a worse 5-year OS of 72.0% vs 90.4%, respectively (p = 0.019). RT dose, pretreatment white blood cell (WBC) count, and absolute neutrophil count (ANC) were associated with OS (HR: 1.55, 1.304, 1.2 and p = 0.04, < 0.0001, 0.001, respectively). Grade 3+ lymphopenia, race, gender, and income were not significantly associated with OS (HR: 0.86, 1.66, 0.92, 0.65 and p = 0.80, 0.26, 0.87, 0.44, respectively). Lymphocyte count and lymphocyte nadir (>90% from baseline) may serve as a prognosticator for overall survival. Additionally, patients with a high NLR >4 may predict poorer outcomes. There was no association between sociodemographic factors and treatment outcomes. Yen-Ruh Wuu (he/him/his), MD (Presenting Author) - Northwell Health; Bin Gui, MD (Co-Author) - Northwell; Dylan Cooper, MD (Co-Author) - SUNY Downstate; Joseph Herman, MD (Co-Author) - Northwell; Leila Tchelebi, MD (Co-Author) - Northwell Health