A Real World Study Of Second-line Chemotherapy For Advanced Small Intestinal Adenocarcinoma

Background:Primary small intestinal carcinomas(PSBA)is known as a kind of very low incidence of gastrointestinal malignant tumor,while has been shown rising trends in recent years by epidemiological studies.The difficulties in diagnosis by gastrointestinal endoscopy and lack of specific symptom causing diagnosis stage late,which lead to few radical surgical treatment,thus the treatment effect is significantly worse the treatment effect colorectal cancer.Because of the low incidence of small intestinal adenocarcinoma,there is a lack of data from large clinical studies,so currently there is no standard regimen for systemic treatment of the metastatic small intestine adenocarcinoma.However,the testimony of evidence-based medical for second-line treatment of small intestinal adenocarcinoma is particularly insufficient,only a few small-data retrospective studies have explored the value of second-line chemotherapy of small intestine adenocarcinoma.Prospective studies are too difficult due to the extremely low incidence of small intestinal adenocarcinoma.Therefore,we collected the clinical data of patients with small intestinal adenocarcinoma from four large-scale third-class hospitals in Jiangxi province to explore the second-line treatment of small intestinal adenocarcinoma in the real world.Objective:The diagnosis and treatment of 46 patients with small intestinal adenocarcinoma who received second-line treatment in four large third-class hospitals with complete traceable medical records were analyzed in the real world,to describe the efficacy and adverse reactions of second-line chemotherapy,and to analysis the efficacy of different second-line treatment plans 、adverse reactions of chemotherapy 、Survival outcome and prognostic factors.Methods:Medical records of patients with primary small bowel adenocarcinoma diagnosed and treated in the First Affiliated Hospital of Nanchang University,the Second Affiliated Hospital of Nanchang University,Jiangxi Provincial People’s Hospital and Jiangxi Provincial Cancer Hospital with complete pathological and follow-up data from January 1,2005 to June 1,2021 were collected.All patients were second-line chemotherapy patients who progressed after receiving first-line therapy or who received second-line therapy after failing to tolerate first-line therapy.PS score,gender,age distribution,tumor site,degree of tumor differentiation,operation or not(surgical method),site of metastasis,chemotherapy regimen,number of second-line chemotherapy cycles(≥4),number of metastatic organs(≥2),recurrence or concurrent metastasis,serum CEA level,adverse reactions of second-line treatment.The main measures were disease control rate(DCR),objective response rate(ORR),overall survival(OS),second-line progression-free survival(PFS),and adverse reactions.Kaplan-meier method was used to plot survival curves.Univariate analysis was performed on the parameters that might affect the prognosis by Cox regression model.Statistically significant variables in univariate analysis were included in Cox regression model to obtain independent prognosis factors affecting survival of small bowel adenocarcinoma,P < 0.05 was considered statistically significant.Results:1.Among 46 patients,median survival was 14.0 months(95CI:8.5-19.5),3-year overall survival rate was 10.9%,5-year overall survival rate was 0%;By follow-up time,no patients had CR,10 patients(21.7%)had PR,15 patients(32.6%)had SD,and13 patients(28.3%)had PD.ORR and DCR were 21.7%(95%CI: 9.8-33.6)and 54.4%(95CI:51.4-57.4),respectively.2、The efficacy and adverse of second-line chemotherapy: FOLFIRI and FOLFOX regimens had higher OS and PFS than other chemotherapy regimens.Median PFS in FOLFIRI and FOLFOX groups were 4.0 months(95%CI%:2.7-5.2)and 3.0 months(95%CI:1.71-4.28),respectively.Median OS was18.0 months(95%CI:9.8-26.2)and 21.0 months(95CI:8.17-33.8)P < 0.05,ORR and DCR were 35.3%/28.6% and 58.8%/42.8%,respectively.There were no statistically significant differences in OS,first-line mPFS and second-line mPFS in FOLFOX and FOLFIRI alternant regimens.3、Prognosis analysis :Univariate analysis showed that patients’ PS score,number of metastatic organs,simultaneous metastasis,second-line treatment plan,number of cycles of second-line chemotherapy plan(≥4)and peritoneal metastasis were significantly correlated with the survival time of patients of small intestine adenocarcinoma.Among them,number of metastatic organs,number of cycles of second-line chemotherapy plan(≥4)and peritoneal metastasis are independent adverse prognostic factors of small intestinal adenocarcinoma.Patients’ PS score,second-line treatment plan,achieved objective remission,and number of cycles of second-line chemotherapy regimens(≥4)were correlated with mPFS2,and the number of cycles of second-line chemotherapy was an independent prognostic factor with mPFS2.Conclusion:The results of our real-world study showed that second-line treatment for advanced small bowel adenocarcinoma was effective,with ORR and DCR of 21.7%(95%CI: 9.8-33.6)and 54.4%(95%CI:51.4-57.4),median OS 14.0 months(95%CI:8.5-19.5),median PFS 3.5 months(95%CI: 2.6-4.4),acceptable adverse reactions;The number of metastatic organs,the number of cycles of second-line chemotherapy,and peritoneal metastasis were independent adverse prognostic factors for OS,while the number of cycles of second-line chemotherapy was an independent prognostic factor for PFS.