Analysis Of The Relationships Between Neo-adjuvant Chemotherapy-induced Neutropenia And Pathological Responses And Outcomes In Colorectal Liver Metastases

Objective:To investigate the predictive value of neo-adjuvant chemotherapy(NAC)-induced neutropenia for the pathological response and prognosis in colorectal liver metastases(CRLM)patients.Material and methods:A retrospective review was performed in 141 CRLM patients receiving NAC followed by liver resection.A neutrophil count<3000/μL was defined as indicating neutropenia.Those in the ranges of 1500-2999/μ L,1000-1499/μ L,500-999/μ L,and<500/μ L were classified as grades 1,2,3,and 4 neutropenia,respectively.Neutropenia grade 3-4 was defined as severe neutropenia.The pathological responses to NAC were evaluated according to tumour regression grade(TRG)1-5.Pathological TRG 1-3 was defined as a favourable response to NAC.Each post-operative complication was allocated a severity grade using the Clavien-Dindo classification system,and major complications were classified as Clavien-Dindo Ⅲ-Ⅴ.A logistic regression was applied to analyse potential predictors of pathological response and major complications.The survival analysis was determined with a Kaplan-Meier analysis.Multivariate analyses of survival were performed using Cox regression models.Results:Neutropenia due to NAC was observed in 42.6%(60/141)of all patients,and grade 3/4 neutropenia was noted in 31.7%(19/60).A pathological response(tumour regression grade[TRG]1-3)was reported in 46.1%(65/141)of patients.Multivariate analysis showed that neutropenia significantly predicted the favourable pathological response(OR=3.718,95%CI:1.716-8.329,P=0.001),as well as targeted therapy,good differentiation and preoperative CEA<10 ng/ml as independent predictors of favourable histological response.Of the patients,54.6%(77/141)had post-operative complications,including 28 major complications(28/77,36.4%).Severe neutropenia significantly predicted post-operative major complications in multivariate analysis(OR=4.077,95%CI:1.184-14.038,P=0.026).Compared to patients without neutropenia,patients with neutropenia had significantly better progression-free survival(PFS)(P=0.007,mPFS:10.2 months versus 6.7 months).Patients with histological response had significantly better PFS than patients with no histological response(P=0.001,mPFS:10.0 months versus 5.5 months).According to multivariate analyses,neutropenia was a significant predictor for better PFS(HR=0.613,95%CI:0.406-0.925,P=0.020)but not OS.Conclusion:For CRLM patients receiving NAC followed by liver resection,NAC-induced neutropenia was a significant predictor of favourable pathological response,post-operative major complications and better prognosis,which makes it useful for CRLM patients in guiding treatment approaches and prognosis assessments.