Abstract
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.
Highlights
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
Immune function as measured by the neutrophil-lymphocyte ratio (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
Using NLR cut off values of 3.0, 4.0 and 5.0; the frequency of patients with a lower NLR was significantly higher post-chemotherapy for each cut off value
Summary
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 presence of MRD depends on two principal factors; firstly the biological properties of the tumour cells within the primary tumour to disseminate, implant in distant tissues, survive and cause immunosuppression versus the effect of the immune response and treatment to eliminate them. Both innate and acquired host immune mechanisms may act during the differing stages of metastasis; eliminating tumour cells within the primary tumour, during their dissemination and in the metastatic niches. Clonal instability of cancer cells, selection of resistant cancer cells or the reduction of tumour load as a result of treatment may all modulate the immune response and as such the presence or absence of MRD
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