Impact of Lymphopenia on Definitive Treatment of Locally Advanced Cervical Cancer

Abstract

Pre-treatment lymphopenia prior to initiating treatment has been correlated with reduced survival in a number of different cancers. The purpose of this study is to evaluate the association between lymphopenia and survival in women with locally advanced cervical cancer (LACC) treated with primary chemoradiation (CRT). We retrospectively reviewed patients with LACC treated at a single institution from 2005 - 2021 with available lymphocyte information. Patient and treatment characteristics were recorded including age, tumor size and stage, EBRT dose/fractionation, and brachytherapy dosimetry data. Absolute lymphocyte counts (ALC) were collected prior to initiating CRT and at 3-month intervals following CRT and graded based on severity of lymphopenia using CTCAE v 5.0. Overall survival (OS), progression free survival (PFS), and local control (LC) were calculated from the start of treatment to date of last follow-up. Kaplan-Meier survival analysis was performed to evaluate whether lymphocyte changes were associated with OS, PFS, or LC. A total of 124 patients met study inclusion criteria with stage IB - IV disease (41 stage I, 41 stage II, 36 stage III, 6 stage IV) and a median follow up of 3.6 years (range 0.2-16.5 years). The median age was 49 years (range 26-77). The median EBRT dose was 45 Gy (range: 26-57.5 Gy) and 44.2% of patients received para-aortic (PA) nodal EBRT (28.8% elective and 15.4% with positive PA nodes). 5-year OS, PFS, and LC were 60.3% (95% CI 51.5-70.7), 47.5% (95% CI 39-58), and 75.5% (95% CI 67.3-82.9), respectively. Pre-treatment lymphopenia (ALC <1000 cells/mm3) was present in 11 (9%) patients. When the total cohort was divided into patients with and without pre-treatment lymphopenia, OS was statistically improved in the patients without baseline lymphopenia, with a 5-year OS of 63.2% (95% CI 53.9-73.9) versus 35.3% (95% CI 14.5-86.3) in the lymphopenia group (p = 0.034). LC also trended to being improved in the patients without lymphopenia, though this did not reach statistical significance in our small sample size of lymphopenic patients, with 5-year LC of 76.8% (95% CI 68.4-84.3) versus 67.5% (05% CI 36.6-93.8), p = 0.45. In this single institution experience of LACC treated with definitive CRT, we found that baseline lymphopenia is associated with inferior OS. Patients with higher pre-CRT ALC may represent a population with more robust immune systems, producing more favorable tumor responses to treatment. Additional studies are warranted to investigate the evolving role of combined EBRT and systemic therapy in LACC.