The Predictive Role Of Peripheral Blood NLR,PLR And SII On The Efficacy Of First-Line Cetuximab-Based Regimen In Patients With Ras Wild-Type Metastatic Colorectal Cancer

Background and objective: Colorectal cancer is the second leading cause of cancer death worldwide,with approximately 1.9 million cases and 900,000 deaths per year.It was found that 20% of patients have metastasis at presentation,and 25% of patients with early-stage cancer will have metastasis later.The survival rate of patients with metastatic colorectal cancer(m CRC)is low,and chemotherapy,targeted therapy and immunotherapy prolong the survival of patients.Cetuximab combined with chemotherapy is the first-line standard treatment for patients with RAS wild-type m CRC,but it has not achieved a satisfactory response rate.The majority of wild-type RAS patients who initially responded to cetuximab therapy also experienced tumor progression,suggesting that unknown alternative mechanisms that could influence therapeutic efficacy still exist.There is an urgent need to find more convenient indicators to predict treatment efficacy.There is growing evidence of the important role of local and systemic inflammatory responses in the prognosis of cancer patients.This study investigated the predictive role of neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR)and systemic immune-inflammation index(SII)on the efficacy of first-line cetuximab-based regimen in patients with m CRC and established an effective prognostic nomogram combining NLR,PLR and SII to predict progression-free survival(PFS)of m CRC patients.Methods: Baseline blood parameters and clinical case data of 1360 m CRC patients receiving cetuximab-based regimen as first-line treatment were retrospectively analyzed,and a total of 143 patients had complete follow-up data and met the inclusion criteria.The patients were divided into a training cohort and a validation cohort.In the training cohort,Kaplan-Meier method was used for survival analysis,univariate analysis was used to determine the factors related to PFS,and multivariate analysis was used to screen out independent prognostic factors.A prognostic nomogram was constructed jointly for all independent prognostic factors,and the predictive efficacy,stability and net benefit of the model were evaluated.The stability and net benefit of the model were validated in the validation cohort.Results: The cut-off value were 3.9 for NLR,152.2 for PLR,and 464.3 for SII.Chi-square tests showed significant differences in PFS between the NLR<3.9 and NLR≥3.9 groups,PLR<152.2 and PLR≥152.2 groups,and SII<464.3 and SII≥464.3groups(P≤0.001).Kaplan-Meier analysis showed longer PFS in the NLR<3.9 group compared to the NLR≥3.9 group(11.0 vs.5.1 months,P<0.001),longer PFS in the PLR<152.2 group compared to the PLR≥152.2 group(11.5 vs.6.9 months,P<0.001),and longer PFS in the SII<464.3 group compared to the SII≥464.3 group(12.6 vs.6.9months,P<0.001).Univariate analysis showed that the resected primary tumor,liver metastasis,NLR,PLR,and SII were significantly associated with PFS(P<0.05).Multivariate analysis showed that the resected primary tumor(HR: 0.551,95%CI:0.329～0.924,P=0.024),liver metastasis(HR: 2.033,95%CI: 1.212～3.407,P=0.007),NLR(HR: 2.596,95%CI: 1.378～4.888,P=0.003),PLR(HR: 2.002,95%CI:1.235～3.246,P=0.005),and SII(HR: 2.202,95%CI: 1.292～3.751,P=0.004)were independent prognostic factors affecting PFS.A prognostic nomogram model was developed combining all independent prognostic factors,and the model showed good predictive efficacy(AUC=0.870).The nomogram showed good stability and predictive value in both the training(C-index=0.827)and validation cohorts(C-index=0.870).Decision curve analysis(DCA)demonstrated the clinical value of the prognostic nomogram.Conclusion: The resected primary tumor,liver metastasis,NLR,PLR and SII were independent prognostic factors for PFS in m CRC patients receiving cetuximab-based regimen as first-line treatment,and high levels of baseline peripheral blood NLR,PLR,and SII may indicate poorer treatment efficacy.The resected primary tumor,liver metastasis,NLR,PLR and SII were combined to create a valid prognostic nomogram for predicting shorter PFS in patients with m CRC.