Improvement in the neutrophil-lymphocyte ratio after combined FOLFOX chemotherapy for stage III colon cancer is associated with improved minimal resdiual disease and outcome

Introduction: Minimal residual disease (MRD) is the net result of the biological properties of disseminated tumour cells and the effect of the immune system and treatment to eliminate them. The aim of this study was to analyse the effect of combined chemotherapy on the immune function as determined by the neutrophil-lymphocyte ratio (NLR) and if it was associated with changes in the subtype of minimal residual disease and outcome in stage III colon cancer. Methods and Patients: A prospective, single centre observational study; the NLR was determined immediately prior to and one, two and three months after completing chemotherapy. Circulating tumour cells (CTCs) and bone marrow micro-metastasis (mM) using immunocytochemistry with anti-CEA were determined prior to and one month after chemotherapy. The association of changes in the NLR with MRD subtypes classified as Group I (negative for CTCs and mM), Group II (positive for mM) and Group III (positive for CTCs) as a result of chemotherapy and five-year disease free progression (DFS) analysed. Results: One hundred and eighty eight patients participated of whom 83 (44.9%) relapsed. In non-relapsing patients the NLR significantly increased and was higher after chemotherapy compared with relapsing patients. Significant increases in the NLR were associated with changes to a better MRD prognostic subtype and decreases with a worse MRD subtype. Neither baseline NLR nor MRD subtype predicted response to chemotherapy. DFS for MRD subgroups were 88%, 56% and 6% for Groups I to III respectively. Conclusions: Immune function as measured by the NLR is associated with MRD prognostic subtypes, improvements in the NLR are associated with improvements in MRD post chemotherapy but neither baseline NLR or MRD predicted outcome.

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Funded by the Western Metropolitan Health Authority. The research grant paid for direct costs of the study, the funding source did not participate in the design, collection, analysis or interpretation of the data, in the writing of the report, its conclusions or decision to submit the paper for consideration to be published. The corresponding author participated actively in the study, had full access to all the study data and had final responsibility for the decision to submit the article for publication Ethical Considerations The study was approved by the health authorites ethics and science committee and fully complied with the Declaration of Helsinki and Chilean law on patient’s rights. All patients provided written informed consent prior to their participation. Due to Chilean law on patients rights and confidentiality the data are not available for general study purposes. Conflicts of Interest The authors report no conflicts of interest

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