A Study of Inflammation-Based Predictors of Tumor Response to Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

Abstract

Background: The ability of pretreatment laboratory markers of acute-phase inflammatory reactions like serum albumin level (SAL), hemoglobin (Hb), and absolute blood cell counts to predict complete pathological response (CPR) to neoadjuvant chemoradiotherapy (NACRT) in patients with locally advanced rectal cancer (LARC) has not yet been fully studied. Methods: We retrospectively examined the relation between SAL, Hb and absolute blood cell counts, and CPR rates in 140 LARC patients treated with NACRT. Results: Univariate analysis showed a significantly higher probability of CPR to NACRT in patients with clinical stage (CS) III LARC who had SAL >3.5 mg/dl (OR = 2.39; p = 0.04) and a neutrophil-to-lymphocyte ratio (NLR) value <5 (OR = 2.86; p = 0.03). The relation of CPR with SAL (OR = 2.11; p = 0.048) and NLR (OR = 2.54; p = 0.04) was confirmed by multivariate analysis in the same subset of patients. None of the parameters studied predicted CPR in patients with CS II disease. Patients who achieved CPR to NACRT had a higher probability of 5-year overall survival (HR 0.48; p = 0.01) and 5-year disease-free survival (HR 0.33; p = 0.003). Conclusions: Our data indicate that SAL >3.5 mg/dl and NLR <5 may be positively related to CPR after NACRT in patients with CS III LARC. Hypoalbuminemia and a high NLR may be considered an indication for a more aggressive approach to NACRT and postoperative adjuvant chemotherapy in this subset of patients. This hypothesis requires confirmation in a randomized study.

Prognostic Impact of Neutrophil-to-Lymphocyte Ratio in Patients with Advanced Low Rectal Cancer Treated with Preoperative Chemoradiotherapy

“…Krauthamer et al [22] showed that high NLR (>5.0) was independently associated with pCR in multivariate analysis. Kitayama et al [23] reported that the percentage of lymphocytes in WBC were independent predictors of pCR.…”

“…They chose 5.0 as the NLR cut-off value, but they did not document the proportion of high and low NLR patients. However, there is no consensus about an NLR cut-off value, and the cutoff values that were used in previous reports targeting rectal cancer patients with NACRT were 2.8, 3.0, and 5.0 [18][19][20][21][22] . Shen et al [18] used both cut-off values of 2.8 and 5.0, and an NLR of ≥ 5.0 was also independently associated with worse OS.…”

“…However, there were only 7.5% of patients with an NLR of ≥ 5.0 in the analysis by Shen et al [18] , and there were only 8 (4.0%) patients with an NLR of ≥ 5.0 in our present study. The optimal cut-off value for OS with highest sensitivity and specificity was 3.2 in this study, but we chose 3.0 as the closest cut-off value to 3.2 among the previously reported NLR cut-off value [9,[18][19][20][21][22]29] . Further investigations are needed to identify an adequate cut-off value that accurately predicts prognosis and takes into account optimal sensitivity and specificity.…”

“…The area under the curve was 0.591 for OS, and NLR of 3.2 had the highest sensitivity (42.1%) and specificity (84.6%). However, because previous studies, which analyzed the utility of NLR as a prognostic indicator in patients with CRC, used 2.5, 2.8, 3.0 or 5.0 as the cut-off value [9,[18][19][20][21][22]29] , the cut-off value of 3.0 was chosen as the closest value to 3.2. Categorical variables were compared using the chi-square test or Fisher's exact test where appropriate.…”

Neutrophil-lymphocyte ratio predicts pathologic tumor response and survival after preoperative chemoradiation for rectal cancer

“…However, in our study, the lymphocyte counts and ratios were not significantly different when the good and poor response groups were compared. Krauthamer et al [19] studied predictors of tumor response to preoperative CRT in rectal cancer and determined that serum albumin (>3.5 mg/dl) and NLR (<5) were predictors for complete pathologic response in clinical stage III (n = 71) patients but not in clinical stage II patients. They explained that no association between NLR and clinical stage II disease may be due to small study samples.…”