Based On Immunoscore And Cost-effectiveness Analysis To Explore The Value Of Adjuvant Chemotherapy In Stage Ⅱ Colon Cancer

Background and Objective:Colon cancer was one of the highest morbidity and mortality cancers worldwide.For stage II colon cancer,radical resection was the primary treatment,but whether adjuvant chemotherapy was necessary was under heating debate.Currently,most guidelines only recommend chemotherapy for stage II colon cancer patients with high risk factors.The immunoscore system facilitated further accurate stratification to assess the benefit of stage II colon cancer.In addition,once receiving adjuvant chemotherapy,it was necessary to pay a certain price,including economic loss and reduced quality of life.Therefore,in our study,Meta-analysis was performed to determine the benefit of adjuvant chemotherapy and survival of patients with high-risk stage II colon cancer.On this basis,the benefit of chemotherapy in high-risk stage II colon cancer patients was analyzed and evaluated through cost-effectiveness analysis.Finally,a cohort of stage II colon cancer was established to explore the role of immunoscore in guiding clinical decision making.Methods:(1)A comprehensive literature search of the Pub Med,Cochrane Library,EMBASE,CNKI and Wanfang databases(up to December,2021)was conducted to identify studies on chemotherapy for high-risk stage II colon cancer.Independently screened literatures,extracted data,and assessed the risk of bias for the included literatures.Meta-analysis of stage II colon cancer was performed using R4.2.0 software.(2)The Disease Free Survival(DFS)curves of patients receiving chemotherapy or observation in the IDEA study,MOSAIC study and IMPACTB2 study were extracted by Getdata software.The individual patient data(IPD)of the time-to-event outcome was reconstructed by R4.2.0 software.The Kaplan-Meier curve(KM)was constructed according to the IPD to compare the survival difference between the chemotherapy group and the observation group.By using KM curve and weibull curve simulation method,the probability of disease-free survival(DFS)being converted into disease recurrence was obtained for cost-effectiveness analysis.(3)Two Markov models were established using Treeage Pro 2011 software to represent the period of chemotherapy and follow-up,and the results of chemotherapy period were passed to the Markov model of follow-up period as the initial cost and utility value of the first 6 months.The cost came from medical insurance,hospital data,and local prices and income levels.The results were measured by quality-ajusted life years(QALYs)and sensitivity analysis was performed according to the results.(4)According to the establishment of colon cancer cohort in our hospital,paraffin specimens of 50 patients with colon cancer were selected.A wax block containing center of tumor and invasive margin was used for CD3 and CD8 staining,respectively.After immunohistochemical staining,CD3~+and CD8~+T lymphocytes were quantified and immunoscore was performed to screen out the population that could benefit from adjuvant chemotherapy.Results:(1)A total of 16 articles were included in the Meta-analysis,with a total of 188 909 patients,including 40 229 patients in the adjuvant chemotherapy group and 148 680 patients in the observation group.The results showed that postoperative adjuvant chemotherapy improved overall survival(HR=0.67,95%CI:0.55-0.81)and disease-free survival(HR=0.57,95%CI:0.33-0.99).(2)The method of IPD was used to reconstruct a new simulation cohort based on the IDEA study,MOSAIC study,and IMPACTB2 study.In the constructed simulated cohort,there were3 560 patients in the chemotherapy group and 509 patients in the observation group.Results showed that postoperative adjuvant chemotherapy improved DFS in high-risk stage II patients(P<0.0001).Further analysis of the different chemotherapy regimens showed that FOLFOX(6months)had an advantage in prolonged DFS(P<0.0001).(3)Among the chemotherapy regimens for stage II colon cancer,the incremental cost effectiveness Ratio(ICER)of the LV/5FU was negative,which was absolute inferior regimens.The ICER values of FOLFOX(3 months),FOLFOX(6 months),CAPEOX(3 months)and CAPEOX(6 months)compared with the observation group were 40 149.83 yuan/QALY,18913.88 yuan/QALY,10 144.95 yuan/QALY and 16 922.55 yuan/QALY,respectively.When willingness-to-pay=216 600yuan,Monte Carlo simulation analysis indicated that the ICER of FOLFOX(6 months)had a probability of 100%.The results of the above analysis were further verified by the data from our hospital.(4)In our own cohort,a total of 50 patients were enrolled,including 30 patients(60%)in the low immunoscore group and 20 patients(40%)in the high immunoscore group.The results showed that patients with high immunoscore had longer OS than those with low immunoscore(P=0.042).Among the patients with low immunoscore,17 patients(56.7%)received adjuvant chemotherapy.The results showed that chemotherapy had a tendency to prolong the OS of patients with low immunoscore,but the difference was not statistically significant(P=0.91).Conclusion:Chemotherapy could improve the prognosis of patients with high-risk stage II colon cancer.From the perspective of pharmacoeconomics,when WTP=216 600 yuan,FOLFOX(6 months)regimen was more cost-effective and recommended for medical decision makers and clinicians.The guiding significance of low immunoscore for adjuvant chemotherapy decision-making needed to be further explored.