Construction Of TCM Syndrome Distribution And Prediction Model For Platinum-resistant Recurrent Ovarian Cance

Objective and significance:The mortality rate of ovarian cancer ranks the first among the three major gynecological malignancies.70%of the patients have been in the middle and late stage when diagnosed,the disease is serious,the prognosis is poor,and the five-year survival rate is about 40%.Platinum is currently the key drug in ovarian cancer chemotherapy.The effective rate of first-line platinum-based combination chemotherapy is about 70%-80%,and most patients can obtain a high clinical remission rate,but about 70%of patients will relapse within 3 years.Clinically,recurrent ovarian cancer can be divided into two categories according to the time interval from the end of the last platinum-containing chemotherapy to the occurrence of tumor progression:① Platinum-resistant recurrence:the tumor progresses in the course of platinum-based firstline chemotherapy(platinum-refractory type),or the time interval from the last platinumcontaining chemotherapy to tumor progression is less than 6 months;② Platinum-sensitive recurrence:the interval from the last platinum-containing chemotherapy to tumor progression was≥ 6 months.Even patients with platinum-sensitive relapses of ovarian cancer after initial chemotherapy will eventually develop platinum resistance as progression-free survival is gradually shortened.Currently,there is no significant effective treatment plan for platinumresistant recurrent ovarian cancer and no objective index to effectively predict platinumresistant recurrent ovarian cancer.How to prevent and reduce platinum-resistant recurrent ovarian cancer patients is a difficult clinical problem to be solved urgently.The purpose of this study was to clarify the distribution characteristics of TCM syndrome types of platinumresistant ovarian cancer recurrence,and to construct a prediction model with TCM syndrome type characteristics.The risk of platinum resistance recurrence was predicted by the model,and the high risk population was treated with TCM syndrome differentiation.Research methods:1 Study on distribution characteristics of TCM syndrome types of platinum-resistant ovarian cancer recurrenceA total of 324 patients with platinum-resistant and platinum-sensitive ovarian cancer were included in the retrospective study.The basic information,four diagnostic information and medical records of the two groups of patients were collected,and TCM syndrome differentiation was conducted according to the national guidelines to summarize the TCM syndrome type distribution and influencing factors of platinum-resistant recurrent ovarian cancer.2 Construction and validation of a prediction model for platinum resistance recurrence of ovarian cancerPatients with recurrent epithelial ovarian cancer containing platinum chemotherapy were retrospectively collected and divided into platinum-resistant group and platinum-sensitive group.Medical records of patients were collected in the form of questionnaire.Independent influencing factors of platinum resistance recurrence of ovarian cancer were selected as model predictors by univariate and multivariate logistic regression analysis.Clinical prediction model of platinum resistance recurrence of ovarian cancer based on TCM syndrome type was constructed,and the model was presented by using RStudio to make a line graph.The clinical data of 60 patients with epithelial ovarian cancer were prospectively collected as a validation set for external validation of the predictive model.Finally,the Receiver Operating Characteristic Curve(ROC)and calibration curve were drawn to evaluate the efficiency of the model.The prediction model of platinum-resistant recurrence in patients with high-grade serous cancer was constructed by using the data of patients with high-grade serous cancer whose pathological type was in the modeling set and validation set,and external validation and model evaluation were conducted.Research results:1 Study results of distribution characteristics of TCM syndrome typesIn the distribution of TCM syndrome types of platinum resistance recurrence of ovarian cancer,qi stagnation and blood stasis syndrome accounted for 22.6%,cold congealing and blood stasis syndrome was 20.1%,followed by deficiency of both qi and yin syndrome 17.7%,positive deficiency and blood stasis syndrome 11.0%,phlegm-dampness and spleen obstruction syndrome 10.4%,Yang deficiency and water stasis syndrome 9.8%,damp-heat accumulation syndrome 8.5%.In the distribution of TCM syndrome types of platinum-sensitive recurrence of ovarian cancer,qi stagnation and blood stasis and deficiency of both qi and yin accounted for the highest proportion,both of which were 21.9%,followed by positive deficiency and blood-stasis syndrome 20.0%,phlegm-dampness and spleen obstruction syndrome 14.4%,cold congealing and blood stasis syndrome 10.0%,Yang deficiency and water stasis syndrome 6.9%,damp-heat accumulation syndrome 5.0%.Pathological types had statistical difference in the distribution of TCM syndrome types of platinum resistance recurrence(P<0.05).Age,family history,duration(time interval from diagnosis to recurrence of ovarian cancer),FIGO stage,number of recurrence,CA125 of the last chemotherapy,lipid metabolism,surgical satisfaction and metastasis were not statistically different in the distribution of syndrome types(P>0.05).2 Prediction model construction and verification resultsUnivariate analysis showed that the duration of disease,pathological type,satisfactory tumor reduction surgery,FIGO stage,CA125 of the last chemotherapy,lipid metabolism,lymph node metastasis,and TCM syndrome type were all P<0.1.Multivariate binary Logistic regression analysis showed that P values of pathological type,FIGO stage,TCM syndrome type,course of disease,and last chemotherapy of CA125 were all<0.05,which was an independent factor affecting the occurrence of platinum resistance recurrence in ovarian cancer patients.The prediction model equation of binary logistic regression is:LogitP=-20.171+1.293*Pathological type(D1)+22.649*Pathological type(D2)-2.162*Pathological type(D3)+20.455*Pathological type(D4)-1.364*Pathological type(D5)-1.486*Satisfied with tumor reduction(D1)+17.795*Satisfied with tumor reduction Tumor reduction(D2)+19.978*staging(D1)+21.129*staging(D2)+21.333*staging(D3)+0.335*lymph node metastasis-0.401*syndrome type(Dl)-0.918*syndrome type(D2)+0.436*syndrome type(D3)+0.376*syndrome type(D4)-0.168*syndrome Type Ⅰ(D5)+0.172*Syndrome type(D6)-1.164*course of disease(Dl)-0.816*course of disease(D2)-0.965*course of disease(D3)+1.532*CA125-0.662*lipid metabolism.According to Yoden index,the diagnostic threshold of platinum resistance recurrence was 0.415,corresponding sensitivity was 86.0%,and specificity was 61.9%.The χ2 value of Hosmer-Lemeshow(HL)test was 4.779,P=0.781>0.05.The calibration line and standard line fit well in the calibration curves of modeling set and verification set,which indicates that the prediction model is accurate.The Area Under Curve(AUC)of the modeling set was 0.794,and the AUC of the verification set was 0.769,indicating that the model had good prediction efficiency.Univariate analysis of patients with high-grade serous carcinoma showed that P<0.1 for disease duration,satisfaction with tumor reduction surgery,FIGO staging,CA125 after the last chemotherapy,lipid metabolism,lymph node metastasis and TCM syndrome type.Multivariate binary Logistic regression equation analysis showed that lipid metabolism,FIGO stage,TCM syndrome type,course of disease,and CA125 level in the last chemotherapy were independent factors influencing the occurrence of platinum resistance recurrence in ovarian cancer patients.LogitP=-19.941-1.741*Satisfactory tumor reduction+20.457*staging(D1)+21.768*staging(D2)+21.743*staging(D3)-0.041*lymph node metastasis-0.584*syndrome type(D1)1.391*syndrome type(D2)+0.214*syndrome type(D3)-0.182*Syndrome type(D4)-0.407*Syndrome type(D5)-0.462*Syndrome type(D6)-1.172*disease course(D1)-0.727*disease course(D2)-0.915*Disease course(D3)+1.591*CA125-0.965*lipid metabolism.The diagnostic threshold for platinum-resistant recurrence of high-grade serous ovarian cancer was 0.465,and the corresponding sensitivity(i.e.,sensitivity)was 84.6%and specificity was 65.7%.The χ2 value of HL test was 12.479,P=0.131>0.05.The calibration curves of modeling set and verification set show that the prediction model is accurate.The modeling set AUC was 0.777,and the validation set AUC was 0.758,indicating that the model had good prediction efficiency.Conclusion:1 The TCM syndrome types of platinum-resistant recurrent ovarian cancer are mainly qi stagnation and blood stasis,cold congealing and blood stasis syndrome and deficiency of both qi and yin,while the TCM syndrome types of patients with platinum-sensitive recurrent ovarian cancer are mainly qi stagnation and blood stasis,deficiency of both qi and yin and positive deficiency and blood stasis.The syndrome of cold congealing and blood stasis and the syndrome of positive deficiency and blood stasis are the characteristic syndroms of platinumresistant relapse,which is different from that of platinum-sensitive relapse,providing a certain basis for the individualized treatment of TCM syndrome differentiation.2 There is a certain correlation between TCM syndrome type and platinum-resistant recurrence of ovarian cancer,which can be combined with pathological type,stage,course of disease,CA125 level of the last chemotherapy and other predictive indicators to predict the risk of platinum-resistant recurrence,screen high risk groups,and carry out TCM syndrome differentiation individualized treatment for them as soon as possible.3 After external validation and model performance evaluation,the prediction model constructed in this study was effective in predicting platinum-resistant recurrence of ovarian cancer and high-grade serous ovarian cancer.