Early Onset Of Severe Lymphopenia During Definitive Concurrent Chemoradiotherapy Predicts Poor Survival In Patients With Cervical Cancer

To examine the reduction speed of lymphocytes during definitive concurrent chemoradiotherapy and explore its impact on survival in patients with cervical cancer. This is a retrospective analysis of cervical carcinoma patients who received definitive concurrent chemoradiotherapy (CCRT) from January 2015 through January 2019. The FIGO stage distributions were 4, 37, 27, and 4 for stage I, II, III and IV, respectively. All patients received 3D conformal or Rapidarc pelvic external beam radiotherapy plus concurrent weekly cisplatin, followed by image guided brachytherapy. All patients had baseline total lymphocyte count (TLC), then weekly during the course of treatment. The extent of lymphopenia was graded by CTCAE V4.03. Relationships between lymphopenia (onset time and grade) and patient or tumor characteristics were analyzed using Chi-square test, Fisher exact test or t test. The significance of lymphopenia on progression-free survival (PFS) and overall survival (OS) were evaluated by Kaplan-Meier curves and the Cox proportional hazard model. A total of 72 consecutive patients were eligible. The median follow-up was 22.7 months (range 7.1-50.3months). Compared to corresponding pre-treatment values, TLC decreased significantly during CCRT (P< 0.001). The degree of lymphopenia during CCRT were 1 (1.4%), 2 (2.8%), 39 (54.2%), and 30 (41.7%) for grade 1, 2, 3, and 4 lymphopenia, respectively. The median time to the nadir lymphopenia from the start of treatment were 34 days (range 14-51 days). FIGO stage (P = 0.007), pre-treatment lymphocyte (P = 0.001), pre-treatment hemoglobin (P = 0.010) were significantly associated with the lymphopenia during CCRT. Patients with the onset of grade 3-4 lymphopenia during the first 2 weeks had significantly poorer PFS (2-yr 59.7% vs. 87.5%, P = 0.008) and OS (2-yr 73.1% vs. 94.0%, P = 0.037) than those with onset of grade 3-4 lymphopenia beyond 2 weeks. Multivariate analysis showed that onset of grade 3-4 lymphopenia during the first 2 weeks and concurrent cisplatin less than 5 cycles during CCRT were poor prognostic factors for PFS (HR [95%CI] 11.04 [2.54-47.94], P = 0.001 and 13.54 [3.31-55.41], P<0.001; respectively) and OS (HR [95%CI] 4.83 [1.04-22.43], P = 0.044 and 8.14 [1.63-40.65], P = 0.01; respectively). Earlier onset of grade 3-4 lymphopenia during definitive concurrent chemoradiotherapy predicts poor survival in patients with cervical cancer. Prospective evaluations with larger sample sizes are needed to validate this finding.