Lymphopenia and its association with survival in patients with locally advanced cervical cancer

Abstract

Objective To evaluate the association between lymphopenia and survival in women with cervical cancer treated with primary chemoradiation. Methods A single institution, retrospective analysis of patients with stage IB2-IVA cervical cancer who received upfront chemoradiation from 1998 to 2013 was performed. Complete blood counts from pre-treatment to 36 months post-treatment were analyzed. Lymphopenia and known prognostic factors were evaluated for an association with progression-free (PFS) and overall survival (OS). Results Seventy-one patients met study criteria for whom 47 (66%) had a documented total lymphocyte count (TLC) two months after initiating chemoradiation. FIGO stage distribution was 6% Stage I, 46% Stage II, 45% Stage III and 3% Stage IV. Pre-treatment TLC was abnormal (<1000 cells/mm3) in 15% of patients. The mean reduction in TLC was 70% two months after initiating chemoradiation. Severe post-treatment lymphopenia (TLC <500 cells/mm3) was observed in 53% of patients; they experienced inferior median OS (21.2 vs 45.0 months, P = 0.03) and similar 25th percentile PFS (6.3 vs 7.7 months, P = 0.06) compared to patients without severe lymphopenia. Multivariate analysis demonstrated pre-treatment TLC ≥1000 cells/mm3 and post-treatment TLC >500 cells/mm3 had a 77% (HR: 0.23; 95% CI 0.05–1.03; P = 0.053) and 58% decrease in hazards of death (HR: 0.42; 95% CI 0.12–1.46; P = 0.17) respectively. Conclusion More than half of cervical cancer patients treated with chemoradiation experienced severe and prolonged lymphopenia. Although statistical significance was not reached, the findings suggest that pre- and post-treatment lymphopenia may be associated with decreased survival. Further research is warranted, given that lymphopenia could be a reversible prognostic factor.

The Utility of Pretreatment and Posttreatment Lymphopenia in Cervical Squamous Cell Carcinoma Patients Treated With Definitive Chemoradiotherapy

“…In addition, the authors reported a significant decline in TLC, with values lower than 500/KL in 29 (73%) of 40 patients. Similarly, Wu et al 15 reported severe lymphopenia (TLC G500 cells/KL) in 53% of patients. In the current study, posttreatment lymphopenia was observed in 61% of patients.…”

“…Although we found that OS and DFS were inferior for patients with pretreatment lymphopenia compared with those without, on multivariate analysis, posttreatment lymphopenia had no significant impact on OS and DFS, similar to previous findings. 15 The present study had clear limitations, primarily because of its retrospective nature. In addition, newer marrow-sparing irradiation techniques will be better to assess the effect of tumor-related posttreatment lymphopenia, not radiation-induced lymphopenia.…”

“…Although the impact of radiation therapy on lymphopenia is well documented, there are few studies correlating posttreatment lymphopenia with survival, particularly in gynecological cancers. 15,25,35 Lissoni et al 35 demonstrated that the decline in total lymphocyte number was significantly greater in patients who had no tumor regression in response to RT among 40 cervical cancer patients treated with pelvic RT. In addition, the authors reported a significant decline in TLC, with values lower than 500/KL in 29 (73%) of 40 patients.…”

“…Pretreatment lymphopenia was defined as TLC of less than 1000 cm/KL based on commonly accepted reference values. 15,17,18 For assessing posttreatment lymphopenia, TLC 2 months after starting ChRTwas used. If a TLC was not available at 2 months, the closest value within 2 weeks was used.…”

Effects of propofol and sevoflurane on perioperative immune response in patients undergoing laparoscopic radical hysterectomy for cervical cancer

“…[16–19] Furthermore, Wu et al suggested that pre- and post-treatment lymphopenia might be associated with deceased survival in patients with cervical cancer. [20] …”