The Association of Chemoradiation Induced Lymphopenia with Racial Disparity and Its Prognostic Impact on Survival for Anal Cancer

Abstract

While the association between chemoradiation induced lymphopenia (CIL) and poor overall survival (OS) is established in multiple solid malignancies, it has not been studied in anal cancer. Racial and socioeconomic disparities as potential predictors of lymphopenia have not been reported. We hypothesize that race and socioeconomic status is associated with increased incidence of severe CIL, which can predict worse overall survival for patients with anal cancer. A cohort of 75 patients treated with definitive chemoradiation (CRT) for squamous cell anal cancer from January 2014 to December 2020 was reviewed. Total lymphocyte counts (TLC) at baseline and TLC nadir at 1 month post-CRT were analyzed. Logistic regression was used to identify associations between race, gender, ethnicity, median household income by zip code, marital status, baseline hematopoietic cell counts, and post-CRT Grade 3+ lymphopenia (TLC <0.5k/μL). Kaplan-Meier method and Cox regression model were used to perform survival analysis. Of the 75 patients identified, mean age was 66.9 years and median follow-up time was 37.1 months. There were 63 females, 53 non-Hispanic whites, 22 minorities (12 Blacks, 9 Hispanics, 1 Asians) Radiation dose ranged from 41.4 Gray to 56 Gray. At 1 month post CRT, 85.3% developed lymphopenia (G1 9.3%, G2 26.7%, G3 37.3%, G4 12.0%). On multivariate logistic regression, non-white race demonstrated a trend to have more Grade 3+ lymphopenia (OR = 3.5, p = 0.07). On univariate Cox regression, poorer overall survival was associated with race (HR 3.7, p = 0.04), baseline white blood count (HR 1.3, p = 0.04), baseline hemoglobin (HR 0.6, p = 0.04), and post-CRT Grade 3+ lymphopenia (HR 5.8, p = 0.03). On multivariate Cox regression, only post-CRT Grade 3+ lymphopenia was associated with worse OS (HR 7.5, p = 0.049). 5-year OS significantly differed between patients with and without post-CRT Grade 3+ lymphopenia (62.3% vs 94.7%, P = 0.01). Lymphopenia is commonly observed after chemoradiation for anal cancer. Racial disparity is associated with severe lymphopenia induced by chemoradiation, which is a robust predictor of poor survival in anal cancer. More attention to lymphopenia induced by chemoradiation for anal cancer is needed, particularly in racial minorities.