Analysis Of Factors Related To Drug Resistance Of Osteosarcoma

Objectives:1.A retrospective study was conducted on the patients with osteosarcoma admitted to Tumor Hospital of Yunnan Province between January 2014 and December 2019 to explore their treatment characteristics and prognostic factors.2.Explored the factors.related to chemotherapy efficacy and drug resistance.of osteosarcoma.Methods:According to the inclusion criteria and exclusion criteria,a retrospective study was conducted on osteosarcoma eligible for inclusion admitted to Tumor Hospital of Yunnan Province from January 2014 to December 2019,the collecting covariates included general situations,Clinical manifestations,laboratory indicators,pathological indicators,treatment patterns,therapeutic efficacy,and survival indicators.The statistical analysis was completed by SPSS 25.0,and the statistical graph was drawn by GraphPad Prism 8.0.Results:1.A total of 119 patients with osteosarcoma were included in this study.The ratio of male to female was about 2.4:1;The average age was 20.47 years;79 cases(66.4%)were KPS<90,40 cases(33.6%)were KPS≥90;The pathological type of 92 cases(77.3%)was osteogenic;The average initial diagnosis time was 67.34 days;21 cases(17.6%)were BMI>24;The primary site of 62 cases(52.1%)was the lower femur segment;42 cases(35.3%)ocurred transferred;The clinical manifestations of 71 cases(59.7%)were local pain.2.OS and PFS were significantly higher in osteosarcoma patients underwent preoperative neoadjuvant chemotherapy compared to those who did’t(P<0.05).3.Efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumours(RECIST 1.1),78 patients were evaluated as stable disease(SD),41 patients were evaluated as stable disease(SD).There were significant difference in neoplasm staging,initial diagnosis time,chemotherapy cycle,types of chemotherapy drugs,initial primary size,lymphocyte/leukocyte ratio pre-chemotherapy,neutrophil/lymphocyte ratio pre-chemotherapy,albumin pre-chemotherapy,glutamate transaminase pre-chemotherapy,uric acid pre-chemotherapy,urea nitrogen post-chemotherapy,uric acid post-chemotherapy,low density lipoprotein pre-chemotherapy between SD group and PD group(P<0.05).4.TGF-β expression was detected in 94 patients with available pathological specimens,indicated there was no significant difference in positive cell rate score and staining intensity score between SD group and PD group(P>0.05).The product of the positive cell rate and staining intensity score was defined as the total score,and 8 was the median value of all total scores,also set as the cutoff value.A score that was>8 indicated high expression,whereas that was<8 indicated low expression.There were 28 patients(43.8%)with high expression and 36 patients(56.2%)with low expression in SD group,as well as 17 patients(57.7%)with high expression and 13 patients(43.3%)with low expression in PD group,there were significant difference(P<0.05).Compared to the low TGF-β expression group,the OS of the high TGF-β expression group was significantly decreased(P<0.05),PFS was not statistically significantly different between the two groups(P>0.05).5.The tumor necrosis rate was detected in 92 cases in pre-chemotherapy and post-chemotherapy.The results show that 25 cases(66.1%)were TCNR>90%and 37 cases(33.9%)were TCNR<90%in SD group,as well as 5 cases(40%)were TCNR>90%,and 25 cases(60%)were TCNR≤90%in PD group.there were significant difference(P<0.05).OS and PFS were statistically significantly different between TCNR≤90%group and TCNR>90%group(P<0.05).6.ROC curve analysis indicated that chemotherapy cycle,types of chemotherapy drugs,lymphocytes/leukocytes pre-chemotherapy,neutrophils/lymphocytes pre-chemotherapy,albumin pre-chemotherapy,urea nitrogen post-chemotherapy,uric acid post-chemotherapy and TGF-βotal score had poor predictive power for chemotherapy resistance of osteosarcoma(AUC=0.5～0.7).Neoplasm staging could predict chemotherapy resistance of osteosarcoma to a certain extent(AUC=0.7～0.9).Stage≥Ⅲ,chemotherapy cycle ≤2,types of chemotherapy drugs<3,lymphocytes/leukocytes<0.32 before chemotherapy,neutrophils/lymphocytes≤1.98 before chemotherapy,albumin>48g/L before chemotherapy,urea nitrogen>4.22mmol/L after chemotherapy,uric acid>305umol/L after chemotherapy,and TGF-β total score≥8.5 were risk factors for chemotherapy resistance in OS patients.The results of multi-indicator combined statistical analysis suggested that the combined predictive value of chemotherapy drug type+pre-chemotherapy albumin(P=0.020)was better than that of tumor stage+chemotherapy drug(P=0.040)and tumor stage+chemotherapy drug type+pre-chemotherapy albumin(P=0.020),indicated that multi-index combination could improve the predictive efficacy of chemotherapy resistance of osteosarcoma.7.The median survival time of OS in PD group was 44.9 months,The median survival time of OS in SD group was 67.7 months,there was statistically significantly different between two groups(P=0.005);The median survival time of PFS in PD group was 32.2 months,The median survival time of OS in SD group was 66.1 months,there was statistically significantly different between two groups(P<0.001);The results of univariate analysis found that KPS score,initial diagnosis time,metastasis,initial primary size,alkaline phosphatase before chemotherapy,and tumor necrosis rate were the influencing factors of OS with chemotherapy resistance patients,the multivariate COX analysis indicated that neoplasm staging,KPS score,initial diagnosis time,metastasis,ALP before chemotherapy and TGF-βscore were independent risk factors for OS with chemotherapy resistance patients.P<0.05.The results of univariate analysis found that age,pathological type,initial diagnosis time,metastases,initial primary size,TGF-β score were the influencing factors of PFS in patients with chemotherapy resistance,the multivariate COX analysis indicated that pathological type,metastases,tumor necrosis rate were independent risk factors of PFS in patients with chemotherapy resistance(P<0.05).Conclusions:1.Comparing the neoadjuvant chemotherapy group with the non-neoadjuvant chemotherapy group,preoperative neoadjuvant chemotherapy could significantly improve OS and PFS in patients with osteosarcoma.2.Neoplasm staging,chemotherapy cycle,types of chemotherapy drugs,pre-chemotherapy lymphocytes/leukocytes,pre-chemotherapy neutrophils/lymphocytes,pre-chemotherapy albumin,post-chemotherapy urea nitrogen,post-chemotherapy uric acid and TGF-βtotal score were independent risk factors for chemotherapy resistance The combination of the two indexes could improve the predictive efficacy of chemotherapy resistance in osteosarcoma.3.OS and PFS of chemotherapy resistance group were significantly lower than that of control group;Neoplasm staging,KPS score,initial diagnosis time,metastasis,ALP before chemotherapy and TGF-β score were independent risk factors for OS in patients with chemotherapy resistance;Pathological type,metastasis,tumor necrosis rate were independent risk factors for PFS in patients with chemotherapy resistance.