Comparison Of Different Chemotherapy Regimens In Neoadjuvant Chemoradiotherapy For Patients With Locally Advanced Esophageal Carcinoma

Background: The current standard of treatment for locally advanced esophageal cancer(LA-ESCC)is neoadjuvant chemoradiotherapy(NCRT)followed by radical surgery.Carboplatin plus paclitaxel(TC)and cisplatin plus paclitaxel(TP)are mainly chemotherapy for patients with esophageal cancer.However,those two rigmen lack of head-to-head randomized controlled trials.Meanwhile,many patients experience dose reduction or early termination of chemotherapy with treatment related toxicity,which may increase the risk of patient survival.However,this strategy may result in underdosing LA-ESCC patients.Thus,the purpose of this study is compare the safety and efficacy of TC versus TP in NCRT for LA-ESCC.And further investigated the association between relative dose intensity(RDI)and survival outcomes.Methods: Herein,we retrospectively reviewed patients’ clinical and treatment data with LA-ESCC who had received NCRT followed by surgery at Sichuan Cancer Hospital and Institute between May 2017 and June 2021.The chemotherapy regimen for the patient was TC and TP regimen.The therapeutic effect was evaluated by pathological complete response(p CR),tumor regression grade(TRG),overall survival(OS)and progression-free survival(PFS).Safety evaluations included the Common Terminology Criteria for Adverse Events(CTCAE)version 4.0 graded chemoradiotherapy related adverse reactions,Radiation Therapy Oncology Group(RTOG)criteria graded esophageal injuries and Clavien-Dindo methodology classified postoperative complications.RDI was defined as the ratio between the delivered dose intensity and the planned dose intensity per unit of time.The best RDI cut-off value 0.7was obtained by the receiver operating characteristic(ROC)curve.Statistical analysis was performed using R language(R version 4.0.3).Kaplan-Meier survival curves were compared using the log-rank test.For descriptive statistics,continuous variables with normal distribution are presented as the mean ± standard deviation,whereas continuous variables with non-normal distribution are presented as median values(range).Categorical variables are described as counts and percentages.Statistical comparisons were made using paired t-test or unpaired,two-tailed t-test(as appropriate),with p < 0.05 deemed statistically significant.The survival benefit was measured using hazard ratios(HR)and its 95% confidence intervals(CI).Results: According to the inclusion and exclusion criteria,201 eligible LA-ESCC patients who received surgery after NCRT were enrolled.Patients were separated into TC group(n=151)and TP group(n=50)according to chemotherapy treatment.The baseline demographic and clinical characteristics were well balanced among the two groups.The TP group exhibited significantly higher hematologic and non-hematologic AEs than the TC group,and the noticeable difference was the incidence of febrile neutropenia of grade 3 or higher(P = 0.011).No significant intergroup differences were noted considering postoperative complications,resection margins,or pathological complete remission rate(all P > 0.05).OS and progression-free survival(PFS)did not significantly differ between groups.The estimated 3-year OS and PFS rates were 65.1%versus 69.4% and 58.4% versus 53.5% for TP and TC groups,respectively.Thus,we recommend TC regimen as an optimal chemotherapy regimen for NCRT,given its superiorsafety profile and comparable efficacy.We further analyzed the relationship between RDI and prognosis in patient who completed TC regimen.According to the best cut-off value,we divided the patients into two groups(RDI≥0.7 group and RDI<0.7group).Patient characteristics,such as gender,age,tumor location and tumor stage did not differ between the twe groups.Kaplan–Meier survival analysis revealed a better prognosis in the RDI≥0.7 group.The RDI≥0.7 have better 1-,3 year OS than RDI<0.7group.There was no statistically significant difference in the R0 resection rate,p CR rate and TRG grade.There was no evidence that,in those patients RDI≥0.7,LA-ESCC patients experienced more toxicity or that RDI<0.7 patients resulted in less toxicity.Correlational analysis showed dose delay was the only factor significantly associated with RDI,and the analysis revealed an inverse correlation.Conclusion: In patients with LA-ESCC,we recommend TC as an optimal chemotherapy regimen for NCRT,given its superiorsafety profile and comparable efficacy.And these results do not support the policy of chemotherapy doses RDI<0.7for LA-ESCC patients who received NCRT.