Decrease in Neutrophil-to-Lymphocyte Ratio during Neoadjuvant Chemotherapy as a Predictive and Prognostic Marker in Advanced Ovarian Cancer

Abstract

Since chronic inflammation is associated with ovarian cancer growth and progression, some clinical studies have assessed the association between the pre-treatment neutrophil-to-lymphocyte ratio (NLR) and the prognosis of ovarian cancer. The purpose of this study was to assess the dynamic behavior of the NLR during the course of neoadjuvant chemotherapy (NACT) in patients with high grade serous (HGS) advanced epithelial ovarian cancer and assess its correlation with clinical response, progression free survival (PFS) and changes in other inflammatory indexes. We performed a prospective observational study on 161 patients who underwent NACT at the Department of Gynecologic Oncology, ARNAS G. Brotzu, Cagliari, between 2009 and 2019. NLR was evaluated before starting and after three cycles of NACT. Based on response after three cycles of NACT, patients were divided into two groups: responsive and non-responsive. The primary endpoint was to assess the predictive role of NLR by comparing the responsive and non-responsive patients at baseline and after three cycles of NACT. Secondary endpoints were (a) to correlate NLR with other inflammation markers (CRP, fibrinogen, ferritin, IL-6), albumin, and modified Glasgow Prognostic Score (mGPS) with NLR at baseline and after NACT; (b) to assess the association between NLR and PFS. We found that the NLR value at baseline was not associated with response to NACT, while a decrease in NLR after three cycles was correlated with a better response to NACT. Also, values of CRP, IL-6, ferritin, and mGPS after three cycles of NACT (but not at baseline) were significantly associated with clinical response. Moreover, we found that patients with a low NLR value after 3 cycles of NACT, but not at baseline, had a significantly higher PFS than patients with high NLR after 3 cycles of NACT. In conclusion, NLR change during treatment could serve as a predictive marker of response to NACT in patients with HGS advanced ovarian cancer. This allows for the early identification of non-responsive patients who will need treatment remodeling.

Elevated Interleukin-6 Levels in the Circulation and Peritoneal Fluid of Patients with Ovarian Cancer as a Potential Diagnostic Biomarker: A Systematic Review and Meta-Analysis

“…All selected articles passed the STROBE checklist criteria (Supplementary Table S2). These include the articles of Sanna et al [35], Micheli et al [36], de Lima et al [37], Rodrigues et al [38], Kampan et al [25], Wertel et al [39], Zhang et al [40], Crispim et al [41], Shi et al [42], Li et al [43], Dalal et al [44], Han et al [45], Kumar et al [46], Martins-Filho et al [47], Cantón-Romeo et al [48], Sanguinette et al [49], Hao et al [50], Mikuła-Pietrasik et al [51], Chudecka-Głaz et al [ S1 and S2).…”

Pathogenic and Prognostic Roles of Paraneoplastic Leukocytosis in Cervical Cancer: Can Genomic-Based Targeted Therapies Have a Role? A Literature Review and an Emblematic Case Report

“…Hence, leukocytosis with high NLR alone related to the progression of the neoplastic disease may not be a determining prognostic factor, as we have recently clearly demonstrated in ovarian cancer. Indeed, in advanced ovarian cancer patients, we found that pretreatment NLR value does not represent a prognostic, while the increase in the number of lymphocytes, and consequently the reduction of NLR, during the chemotherapy regimen constitutes one of the most valid predictors of response to treatment and patient prognosis [ 56 ].…”

“…Some clinical studies have reported the correlation between pre-treatment NLR and the prognosis of cervical cancer [ 49 , 55 ]. Meanwhile, more recently, we have demonstrated in a population of patients with ovarian cancer that the pretreatment NLR value does not constitute a prognostic and predictive factor, but only the evidence of the extent of the systemic inflammation in progress; conversely, the increase in the number of lymphocytes during chemotherapy treatment, and therefore the reduction of NLR, constitutes one of the most valid predictors of response to treatment [ 56 ].…”

Correlation between the neutrophil-to-lymphocyte ratio and clinicopathological parameters in epithelial ovarian cancer patients and its effect on prognosis—a retrospective cohort study

“…In recent years, the relationship between the neutrophil-to-lymphocyte ratio (NLR) and malignant tumors has gradually attracted increasing attention from scholars, and studies have confirmed that NLR can predict patient prognosis in breast, liver, lung, and bladder cancers, these studies showed that a higher level of NLR was associated with a poor prognosis ( 5 - 8 ). Studies have also shown that NLR is associated with the efficacy of neoadjuvant chemotherapy in patients with ovarian cancer, a higher level of NLR is associated with a poor efficacy of neoadjuvant chemotherapy ( 9 , 10 ), but whether this change in efficacy translates into a long-term mortality benefit is unclear. Therefore, we designed this study to explore the correlation between the NLR and clinicopathological parameters in patients with epithelial ovarian cancer and its effect on prognosis, so as to promote the application of NLR in patients with ovarian cancer.…”