Abstract
Objective:Within 5 years after curative surgery for stage II colon cancer 25% of patients will relapse due to minimal residual disease (MRD). MRD is the net result of the biological properties of subpopulations of primary tumour cells which enable them to disseminate, implant in distant tissues and survive and the immune system’s ability to eliminate them. We hypothesize that markers of immune dysfunction such as the systemic inflammation index (SII) are associated with the sub-type of MRD defined by bone marrow micro-metastasis (mM) and circulating tumour cells (CTCs). A higher immune dysfunction being associated with a more aggressive MRD and worse prognosis. Methods and Patients:Blood and bone marrow samples were taken to detect CTCs and mM using immunocytochemistry with anti-CEA one month after surgery. The SII, absolute neutrophil, platelet and lymphocyte counts (ANC, APC, ALC) were determined immediately pre-surgery and one month post-surgery. These were compared with the sub-types of MRD; Group I MRD (-); Group II mM positive and Group III CTC positive; cut-off values of SII of >700 and >900 were used. Follow-up was for up to 5 years or relapse and survival curves using Kaplan-Meier (KM) were calculated. Results:One hundred and eighty one patients (99 women) participated, mean age 68 years, median follow up 4.04 years; I: = 105 patients, II: N= 36 patients, III: N=40 patients. The SII significantly decreased post-surgery only in Group I patients. The frequency of SII >700 and >900 was significantly higher in Group III, between Groups I and II there was no significant difference. The SII was significantly associated with the number of CTCs detected. The 5-year KM was 98% Group I, 68% Group II and 7% Group III. Conclusions:The results of the study suggest that the severity of immune dysfunction as determined by the SII is associated with differing sub-types of MRD and a worse prognosis; increasing immune dysfunction is associated with a more aggressive CTC positive MRD sub-type; a more severe immune dysfunction is associated with a higher number of CTCs detected.
Highlights
Colon cancer is the fourth most common cancer worldwide, representing 6.1% of all cancers and is the third commonest cause of cancer mortality in males and females (Bray et al, 2018)
We hypothesize that markers of immune dysfunction such as the systemic inflammation index (SII) are associated with the sub-type of minimal residual disease (MRD) defined by bone marrow micro-metastasis and circulating tumour cells (CTCs)
The results of the study suggest that the severity of immune dysfunction as determined by the SII is associated with differing sub-types of MRD and a worse prognosis; increasing immune dysfunction is associated with a more aggressive CTC positive MRD sub-type; a more severe immune dysfunction is associated with a higher number of CTCs detected
Summary
Colon cancer is the fourth most common cancer worldwide, representing 6.1% of all cancers and is the third commonest cause of cancer mortality in males and females (Bray et al, 2018). In stage II patients who relapse after curative surgery the development of metastasis is the result of occult tumour dissemination prior to treatment. These disseminated tumour cells that remain after curative surgery is termed minimal residual disease (MRD). Three groups of MRD can be identified, those patients positive for bone marrow micro-metastasis have an increased risk for delayed relapse, those with circulating tumour cells (CTCs) detected in blood are at high risk of early treatment failure and those patients negative for both have a very high 5-year disease free survival (Murray et al, 2020). A positive test was defined as the detection of at least one cell/8ml venous blood (Figures 1 and 2)
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