Baseline and Longitudinal Neutrophil-to-Lymphocyte Ratio as Prognostic Factor for Metastatic Colorectal Cancer: A Secondary Analysis of the ITACa Randomized Trial.

PURPOSE: We aimed to investigate the prognostic role of baseline and longitudinal levels of neutrophil-to-lymphocyte ratio (NLR) in patients with metastatic colorectal cancer (mCRC) treated with chemotherapy + bevacizumab (CT + B) or chemotherapy only. Additionally, we investigated whether treatment outcomes were mediated by the longitudinal biomarker. METHODS: Data from an Italian randomized phase III trial were used. The main end point was progression-free survival (PFS). To address research questions, a series of joint models of longitudinal and survival data were specified, and the direct and indirect treatment effects were quantified. RESULTS: Data for 239 patients, 113 (47.3%) treated with CT + B and 126 (52.7%) with CT only, were included in the analyses. The effect of NLR seemed to be mediated by the longitudinal trajectory of the biomarker. Only in the patient subgroup treated with CT + B, the baseline NLR retained a direct effect on PFS. Regarding the effect of treatment on PFS, two scenarios were observed. In the subgroup of patients with low baseline, NLR bevacizumab showed a direct protective effect only (hazard ratio [HR], 0.66 [95% CI, 0.45 to 0.98]), whereas in the subgroup with high baseline NLR, there was evidence for an adverse direct effect (HR, 1.63 [95% CI, 1.03 to 2.57]) and a protective indirect-which is mediated by the longitudinal biomarker-effect (HR, 0.71 [95% CI, 0.55 to 0.90]). CONCLUSION: In our study, inflammatory indexes collected longitudinally showed a significant adverse prognostic role, thus suggesting the collection and use of such data for better clinical decision making. In the specific setting, we considered this is particularly important as the treatment effect seemed to be modified by both the baseline and longitudinal inflammation statuses. However, further research is needed to understand the possible factors underlying these results.

Inflammatory indices as prognostic markers in metastatic colorectal cancer patients treated with chemotherapy plus Bevacizumab.

Background: Validated predictors of sensitivity or resistance to Bevacizumab (Bev) are not available, and Inflammatory Indexes (IIs) has been reported to be useful prognostic factors in various malignant solid tumours, including metastatic colorectal cancer (mCRC). Objectives: To explore the prognostic value of IIs in mCRC patients treated with first-line chemotherapy plus Bev. Design: One hundred and eighty-two patients diagnosed with mCRC and treated with first line chemotherapy plus Bev were considered for this prospective non-pharmacological study. Neutrophil, lymphocyte, platelet, aspartate transaminase (AST) and lactate dehydrogenase (LDH) tests were carried out at baseline and before each treatment cycle, according to clinical practice. Methods: Pre-treatment Systemic Immune-inflammation Index (SII), Colon Inflammatory Index (CII) and Aspartate aminotransferase-Lymphocyte Ratio Index (ALRI) were evaluated to assess a correlation with progression-free survival (PFS) and overall survival (OS). Results: In the overall population, PFS and OS were lower in patients with high SII (HR 1.64, p = 0.006 and HR 1.75, p = 0.004, respectively) and high ALRI (HR 2.13, p = 0.001 and HR 1.76, p = 0.02, respectively), but no difference was detected according to CII value. The multivariate analysis confirmed both SII and ALRI as independent prognostic factors for PFS (HR 1.64 and 2.82, respectively) and OS (HR 1.65 and 2.12, respectively). Conclusion: Our results demonstrate and confirm that IIs, and in particular SII and ALRI, are easy to measure prognostic markers for patient candidates to first line chemotherapy plus Bev for mCRC.

Inflammatory Indexes can predict the efficacy of bevacizumab in metastatic colorectal cancer Bevacizumab (Bev) is a humanized monoclonal antibody with antiangiogenic activity, used in combination with chemotherapy as a standard first line treatment for many metastatic colorectal cancer patients. Validated predictors of sensitivity or resistance to Bevacizumab are not available, although several studies have investigated this issue in recent years. In this study, we investigated whether some selected baseline inflammatory indexes levels, namely Systemic Immune-inflammation Index (SII) and Aspartate aminotransferase-Lymphocyte Ratio Index (ALRI) could predict the survival in patients with metastatic colorectal cancer treated with Bevacizumab plus chemotherapy. We enrolled 182 patients diagnosed with mCRC and treated with first line chemotherapy plus Bev. For each patient we tested blood neutrophils, lymphocytes, platelets, aspartate transaminase (AST) and lactate dehydrogenase (LDH) before each treatment cycle, according to clinical practice. We calculated the SII value as platelet count × neutrophil count/lymphocyte count, and ALRI as AST/lymphocyte count. We found that patients with high SII and high ALRI values had lower survival as compared to those with low values. These parameters represent reproducible, inexpensive and easy to measure biomarkers to be used in both clinical practice and clinical trials, for patient selection.