| Study 1:Clinical efficacy evaluation of Jianpi Huatan dispensing granule for preventing postoperative recurrence of high-risk stage Ⅱ and Ⅲ colorectal cancerObjectiveTo evaluate the clinical efficacy and safety of Jianpi Huatan dispensing granule for high-risk stage Ⅱ and Ⅲ colorectal cancer patients after radical surgeryMethodsThis study was conducted simultaneously in 8 hospitals and included high-risk stage Ⅱ and Ⅲ postoperative colorectal cancer patients from December 2018 to November 2021 as the main subjects.In this study,a large-sample,multi-center,randomized,controlled,double-blind clinical trial design was adopted.The experimental group was treated with Jianpi Huatan dispensing granule,while the control group was given oral placebo.Main outcome measures are Disease-free survival time(DFS)and recurrence and Metastasis rate in 1 year.Results1.General informationThe data analysis deadline was January 31,2022.A total of 307 patients were included in the analysis,including 156 patients in the experimental group and 151 patients in the control group.The median follow-up time was 11.9 months in experimental group and 11.7 months in control group.The two groups were comparable in demographic information and basic information of tumors.2.Recurrence and metastasisRecurrence and metastasis occurred in 46 of 307 patients.The median time of recurrence and metastasis was 7.03 months in the experimental group and 7.33 months in the control group.The 1-year recurrence and metastasis rate of the experimental group was 20.4%,and that of the control group was 20.2%,and there was no significant difference between the two groups(P>0.05).3.Survival AnalysisThe 3-year DFS of the experimental group was 73.2%,which was higher than that of the control group(69.3%),and there was no statistical significance between the two groups(HR=1.05,95%CI 0.59-1.89,P=0.862).The 2-year DFS of the experimental group was 80.5%,and that of the control group was 80.9%,with no significant difference between the two groups(HR=1.05,95%CI 0.58-1.92,P=0.863).4.Survival analysis of subgroupsThere were no significant differences in gender,age≥65 years or<65 years,BMI,primary site,TNM stage,ECOG score and TCM syndrome type between the two groups(P>0.05).5.Quality of life evaluation(1)Traditional Chinese medicine symptom rating scaleThere was no significant difference in the scores of TCM symptom rating scale between 2 groups(P>0.05).After 3 months of treatment,there was no statistical significance in the total scores of TCM symptom grading scale between the two groups(P>0.05),but there were significant differences in TCM symptoms of abdominal distension,loose stools and shortness of breath between the experimental group and the control group(P<0.05).The effective rate of TCM symptom improvement in the experimental group was 45.51%,higher than that in the control group 41.72%,but the difference between the two groups was not statistically significant(P>0.05).(2)ESAS scaleThere was no significant difference in the total score and the score of each item between the two groups at the time of enrollment(P>0.05).After 3 months of treatment,the total score of ESAS scale in the experimental group was lower than that before treatment,but there was no significant difference between the total score of ESAS scale in the control group after treatment(P>0.05).After 3 months of treatment,the score of sleep symptoms in experimental group was significantly lower than that before treatment,and the difference was statistically significant compared with that in control group.(3)ECOG scaleThere was no significant difference in ECOG score of physical condition between 2 groups before and after treatment(P>0.05).(4)Spleen deficiency scale of Traditional Chinese medicineAfter 3 months of medication,the score of spleen deficiency scale in experimental group was significantly lower than that before medication,and the difference was statistically significant compared with experimental group(P<0.01).6.SaftyNo serious adverse events occurred in both groups.The incidence of adverse events in the experimental group was 2.99%,and the main adverse events were diarrhea,abdominal incisional hernia,and upper respiratory tract infection;the incidence of adverse events in the control group was 2.42%,and the main adverse events were urticaria,upper respiratory tract infection,and urinary tract infection.There was no statistical difference in the incidence of adverse events between the two groups(P>0.05).It was determined that the adverse events were not related to the test drug.Conclusions1.There was no significant difference in 1-year recurrence and metastasis rate of high-risk stage Ⅱ and Ⅲ patients with CRC with treatment of Jianpi Huatan dispensing granule.2.Jianpi Huatan dispensing granule can improve the symptoms of abdominal distention,loose stools and shortness of breath in high-risk stage Ⅱ and Ⅲ colorectal cancer patients,and improve sleep quality,thus improving the quality of life of patients with colorectal cancer.3.Jianpi Huatan dispensing granule can improve the main symptoms of spleen deficiency in high-risk stage Ⅱ and Ⅲ patients with CRC,and improve the syndrome of spleen deficiency in patients with CRC.4.After taking Jianpi Huatan dispensing granule for 3 months,there was no increase in adverse events in high-risk stage Ⅱ and Ⅲ colorectal cancer patients compared with placebo,indicating that Jianpi Huatan prescription is safe.Study 2:Correlation between clinical features and circulating tumor cells in colorectal cancerObjectiveTo observe the correlation between clinical characteristics and peripheral blood circulating tumor cell detection in patients with colorectal cancer.MethodsA cross-sectional observational study design was used.Patients with colorectal cancer from Xiyuan Hospital of China Academy of Chinese Medical Sciences were selected as the main research objects.The number of CTCs in peripheral blood of patients with colorectal cancer was detected by polypeptide magnetic cell capture and immunofluorescence method,and the correlation between CTCs and clinical characteristics of colorectal cancer was observed.ResultsA total of 123 patients with colorectal cancer were enrolled from June 2021 to January 2022.There were 97 patients with positive CTCs test results,and 26 patients with negative CTCs test results.In this study,the positive rate of CTCs in 123 colorectal cancer patients was 78.86%.The number of CTCs detected in colorectal cancer patients was not significantly correlated with age,sex,height,weight,history of drinking,smoking history,course of diseases,the primary site,pathological tissue credit transfer type,degree of differentiation,tumor stage,part number,mismatch repair proteins expression,microsatellite instability,KRAS mutations,BRAF mutations,NARS mutations,diabetes mellitus or hypertension,TCM syndrome elements and TCM syndrome types(P>0.05).There was a positive correlation between the number of CTCs and ECOG score(r=0.263,P=0.004).There was a positive correlation between the number of CTCs and TCM syndrome scale score(r=0.219,P=0.016).When patients in the group with the number of CTCs≥ 3 and in the group with the number of CTCs<3,there was a significant difference in the score of TCM syndrome grading scale in 2 groups(P=0.0029).When patients in the group with the number of CTCs≥4 and in the group with the number of CTCs<4,there was a significant difference in the TCM syndrome grading scale score in 2 groups(P=0.0003).There were no significant differences in primary tumor site,tumor pathological classification,invasion depth,tumor stage,lymph node metastasis,whether chemotherapy was received or not in patients with CRC and the positive status of CTCs in peripheral blood(P>0.05).Pearson correlation analysis showed that there was no significant correlation between CTCs positive and primary tumor site,degree of differentiation,tumor stage,lymph node metastasis and liver and lung metastasis in patients with CRC(P>0.05).Positive CTCs was correlated with histological grade type and age(P<0.05),positive CTCs was positively correlated with histological grade type(R=0.211,P=0.020).When the number of CTC test results≥3,there was a positive correlation with tumor stage of colorectal cancer patients(R=0.202,P=0.025).Conclusions1.CTCs count was correlated with ECOG score and TCM syndrome scale score of colorectal cancer patients.2.When the CTCs test result is≥3,it is correlated with the pathological stage of colorectal cancer patients,so the peripheral blood CTCs test result can provide reference for the clinical stage diagnosis of colorectal cancer.Study 3:Clinical significance and prognostic analysis of peripheral blood circulating tumor cells detection after radical surgery for high-risk stage Ⅱ andⅢ colorectal cancerObjectiveTo evaluate the prognostic value of peripheral blood circulating tumor cells detection after radical surgery for high-risk stage Ⅱ and Ⅲ colorectal cancer.MethodsThis study used a prospective clinical study design.Circulating tumor cells(CTCs)in peripheral blood of patients who met the inclusion criteria in Xiyuan Hospital of Chinese Academy of Chinese Medical Sciences,Cancer Hospital of Chinese Academy of Medical Sciences,Peking University First Hospital and Nanjing Hospital of Chinese Medicine from December 2018 to November 2021,were detected by using polypeptide magnetic cell capture and immunofluorescence method.The number of CTCs per 2mL of peripheral blood was detected,and tumor recurrence and metastasis were observed.Results1.Genera informationA total of 61 high-risk stage Ⅱ and Ⅲ colorectal cancer patients were included in this study for peripheral blood CTCs detection.The data analysis deadline was January 31,2022,and the median follow-up time was 9.97 months.Among the 61 subjects,9 cases had recurrence and metastasis.There was a significant difference in the number of CTCs between patients with recurrent metastasis and patients without recurrent metastasis(P=0.0172).2.recurrence and metastasisThere were 49 patients with positive CTCs test,and 1 patient had recurrence and metastasis.There were 12 patients with negative CTCs test and 8 patients had recurrence and metastasis.There was no significant difference in recurrence and metastasis between CTCs positive group and negative group(P>0.05).There were 48 patients with CTCs ≤2,including 5 patients had recurrence and metastasis,and 13 patients with CTCs>2,including 4 patients had recurrence and metastasis.There was no significant difference in recurrence and metastasis between the two groups(P>0.05).There were 53 patients with CTCs≤3,including 5 patients had recurrent metastasis,and 8 patients with CTCs>3,including 4 patients had recurrent metastasis.There was a significant difference between the two groups(P=0.013).3.Survival analysisPatients with the number of CTCs>3 had worse disease-free survival than those with CTCs≤3,and the difference was statistically significant(P=0.0045).Compared with the disease-free survival rate of patients with CTCs≤4 group,the disease-free survival rate of patients with CTCs>4 group was worse,and the difference was statistically significant(P=0.0245).4.Correlation between clinical features and recurrence and metastasisThe depth of tumor invasion at T4 was significantly different from that at T2 or T3(P=0.047).There was no significant difference in recurrence and metastasis between poorly differentiated tumors group and non-poorly differentiated tumors group(P>0.05).There was no significant difference in the incidence of recurrence and metastasis in patients in ECOG score and TCM symptom scale(P>0.05).Conclusions1.When CTCs cutoff is 3,it is significantly correlated with recurrence and metastasis of patients with high-risk stage Ⅱ and Ⅲ colorectal cancer,and peripheral blood circulating tumor cell detection has potential application value in predicting recurrence and metastasis of colorectal cancer patients.2.Patients with high-risk stage Ⅱ and Ⅲ colorectal cancer showed worse disease-free survival when the number of CTCs detected in peripheral blood was greater than 3,and CTCs detection can predict the prognosis of patients with colorectal cancer.Study 4:Effect of Jianpi Huatan dispensing granule on circulating tumor cells of high-risk stage Ⅱ and Ⅲ colorectal cancer after operationObjectiveTo observe the changes of peripheral blood circulating tumor cells in patients with high-risk stage Ⅱ and Ⅲ colorectal cancer after treatment with Jianpi Huatan dispensing granule.MethodsA prospective,controlled clinical study design was used in this study.Patients in Xiyuan Hospital of Chinese Academy of Chinese Medical Sciences,Cancer Hospital of Chinese Academy of Medical Sciences,Peking University First Hospital and Nanjing Hospital of Chinese Medicine were selected.Subjects meeting the admission criteria were enrolled into the experimental group or the control group from December 2018 to November 2021.The experimental group was treated with Jianpi Huatan dispensing granule,while the control group was given placebo orally.Peripheral blood samples were taken from all subjects at enrollment and 3 months after medication,respectively,to observe the changes of CTCs in the two groups before and after treatment.ResultsA total of 33 high-risk patients with stage Ⅱ and Ⅲ colorectal cancer were included in this study,including 16 patients in experimental group and 17 patients in control group.The study was followed up to January 31,2022,with a median followup of 24.87 months.Recurrence and metastasis occurred in 5 patients,2 in the experimental group and 3 in the control group.Before treatment,the positive rate of CTCs was 81.25%(13/16)in the experimental group and 70.58%(12/17)in the control group.After 3 months of treatment,the positive rate of CTCs in the experimental group was 62.5%,significantly decreased by 18.75%compared with before treatment,and the positive rate of CTCs in the control group was 64.70%,only decreased by 5.88%.There was no statistical significance in the decrease of positive rate between the two groups(P>0.05).Before treatment,there was no significant difference in the number of CTCs detected between the two groups(P>0.05),and the two groups were comparable.After 3 months of treatment,there was no significant difference in the number of CTCs between the two groups(P>0.05).In the experimental group,there were 3 patients with increased CTCs after treatment,1 patient with recurrence and metastasis(33.3%),13 patients with decreased or unchanged CTCs after treatment,and 1 patient with recurrence and metastasis(7.7%).There was no significant difference in the recurrence and metastasis of subjects with increased CTCs in the experimental group and those with reduced or unchanged CTCs(P>0.05),but the recurrence and metastasis rate of 7.7%patients with reduced or unchanged CTCs before and after treatment was significantly lower than that of 33.3%patients with increased CTCs before and after treatment.Conclusions1.After 3 months of treatment with Jianpi Huatan dispensing granule,the positive rate of CTCs in the experimental group was significantly lower than that before treatment,but the difference was not statistically significant compared with the control group. |
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