Application Of DCE-MRI And IVIM-DWI In Evaluating The Efficacy Of Neoadjuvant Chemotherapy In Breast Cancer

PARTIApplication of dynamic contrast-enhanced magnetic resonance imaging in evaluating the efficacy of neoadjuvant chemotherapy in breast cancer Objective:To explore the application value of background parenchymal enhancement(BPE)in predicting the early efficacy of neoadjuvant chemotherapy(NAC),by analyzing the BPE changings before and after two cycles of NAC of unilateral invasive ductal breast cancer on breast dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI).Methods:A total of 87 female patients confirmed unilateral invasive ductal breast cancer by preoperative biopsy,with complete MRI examination,postoperative histopathology and clinical data before and after NAC,were enrolled in this study from July 2015 to September 2018.The plain MRI and DCE-MRI images of breast cancer patients were observed by two professional breast radiologists,and BPE of the contralateral normal breast was qualitatively evaluated(1=minimal,2=mild,3 moderate,4=severe).After NAC,all patients underwent surgery.Histopathological evaluation was performed on the pathological responses of surgical specimens and the biopsy sections before chemotherapy,and the pathological response was evaluated according to the Miller-Payne grading system.The patients were divided into two groups:the major histological response(MHR)group and non-MHR(NMHR)group.Hormone receptor(HR)status(estrogen receptor and progesterone receptor),human growth factor receptor 2(HER2),and cell value-added nuclear antigen Ki-67 were also recorded before biopsy.The maximum diameter of the lesion was measured in accordance with the response evaluation criteria in solid tumors standard.The baseline characteristics of the MHR and NMHR groups,such as age,tumor maximum diameter,menopause status,axillary lymph node status,tumor enhancement mode,and histological grade,were recorded and compared with χ2-test and independent sample t-tests.Wilcoxon test was applied to evaluate the changes in BPE levels before and after two cycles of NAC.Mann-Whitney U test was conducted to analyze the difference in BPE levels between premenopausal and postmenopausal groups,MHR and NMHR groups.Spearman rank correlation test was performed to describe the correlation between the changes in BPE before NAC,BPE after two cycles of NAC,BPE and tumor reduction rate.Kappa test was carried out to assess the consistency of the qualitative evaluation of BPE by two radiologists.Factors influencing the efficacy of NAC were analyzed by multinomial Logistic regression modelResults:According to Miller-Payne classification,35 patients were in the MHR group and 52 in the NMHR group.No significant difference was observed in the baseline characteristics of age,tumor maximum diameter,menopause status,axillary lymph node status,tumor enhancement mode,and histological grade between MHR and NMHR groups(P>0.05).HR status,HER2 status,and Ki-67 expression were significantly different between MHR and NMHR groups(P<0.05).The BPE level in premenopausal women before NAC(n=48)was higher than that in postmenopausal women(n=39)(P<0.001).The BPE level in premenopausal women after two cycles of NAC was also higher than that in postmenopausal women.However,the level of BPE decreased in both groups,and the decrease of BPE in premenopausal women(37/48)was higher than that in postmenopausal women(21/39)(P=0.014)There was significant difference in BPE between premenopausal and postmenopausal groups before and after two cycles of NAC(P=0.023).Before NAC,no significant difference was observed in BPE between MHR and NMHR groups(P=0.669).After two cycles of NAC,no increase in BPE level was observed,the BPE level in MHR group decreased to a greater extent than that in NMHR group(P=0.004).In MHR group,BPE decreased in 28(80.00%)of 35 patients,and significant differences were observed between before NAC and after two cycles of NAC(P<0.001).In NMHR group,BPE decreased in 30(57.69%)of 52 patients,and significant differences were detected between before NAC and after two cycles of NAC(P<0.001).The changes in BPE between MHR and NMHR groups were significantly differed before and after two cycles of NAC(P=0.041).No significant correlation was found between BPE and tumor reduction rate before NAC(r=0.133,P=0.221),nor between BPE and tumor reduction rate after two cycles of NAC(r=-0.082,P=0.451),but there was a positive correlation between BPE decrease and tumor regression rate(r=0.266,P=0.013).The qualitative evaluation of the distribution of BPE before and after two cycles of NAC was consistent between the two radiologists(Kappa=0.713,0.706)Multinomial Logistic regression model analysis showed that changes in BPE,HR status and tumor reduction rate after two cycles of NAC were independent factors affecting the efficacy.Conclusion:1.The change of BPE in contralateral breast of breast cancer was affected by menopause state and NAC,the decrease in BPE after NAC could predict the effect of chemotherapy.2.Decreased BPE levels after NAC were directly associated with tumor reduction rate,decreased BPE of patients with breast cancer may serve as an indicator of NAC effectiveness.3.Patients with HR-negative tumors,the greater the decrease of BPE and the greater the tumor reduction rate after NAC.the easier it was to achieve better pathological reactionPART ⅡPredictive value of intravoxel incoherent motion diffusion weighted imaging in the efficacy evaluation of neoadjuvant chemotherapy in breast cancerObjective:To explore the predictive value of intravoxel incoherent motion diffusion-weighted imaging(IVIM-DWI)model parameters in evaluating the efficacy of neoadjuvant chemotherapy(NAC)in breast cancer treatmentMethods:From January 2016 to October 2018,41 female patients confirmed by preoperative biopsy pathology as unilateral invasive ductal carcinoma of breast and treated with NAC in our hospital were enrolled in this study.All patients underwent bilateral breast MRI plain scan,dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)and IVIM-DWI examination before and after two cycles of NAC.All patients underwent surgical treatment after NAC,and the histopathological evaluation was performed on the surgical specimens and the biopsy sections before chemotherapy by the Miller-Payne grading system.The patients were divided into the major histological response(MHR)group and the non-major histological response(NMHR)group according to the pathological response of tumor cell.The post-processing software MITK Diffusion was used to analyze the IVIM-DWI images of the breast,and the region of interest in the most obvious part of the lesion was selected referencing to DCE-MRI images.The three parameters,f value,D value,and D*value,were automatically calculated and generated according to the double-exponential model formula.The f value difference(△f),D value difference(△D),and D*value difference(△D*)before and after two cycles of NAC were calculated,applicated with the formula Af=fpost-fpre,△D=Dpost-Dpre and △D*＝D*post-D*pre-The maximum diameter(MD)of the lesion was measured in accordance with the response evaluation criteria in solid tumors guidelines standard.The baseline characteristics of the MHR and NMHR groups were compared by χ2-test and independent sample t-test,including age,MD of the tumor,menopausal status,clinical stage,molecular typing,axillary lymph nodes,tumor enhancement and histological grading.The measurement indexes of the normal distribution of the two groups were compared by the independent sample t-test.The measurement parameters before and after two cycles of NAC were compared through the paired sample t-test.The measurement indices of non-normal distribution were compared between groups by using the Mann-Whitney U test and those before and after two cycles of NAC were compared through the Wilcoxon test.Medcalc software was employed to draw the receiver operating characteristic(ROC),and area under the curve(AUC)was utilized to evaluate the predictive efficacy of each parameter before and after NAC The diagnostic threshold of each parameter was determined in accordance with the Jordan index.The corresponding diagnostic sensitivity and specificity of each parameter were calculated.The Spearman correlation test was used to analyze the relationship between the parameters of the IVIM-DWI model and tumor reduction rate(%)before and after two cycles of NAC.The correlation between IVIM-DWI model parameters and the curative effect of NAC on tumor was analyzed.Results:According to Miller-Payne classification,there were 15 cases in the MHR group and 26 cases in the NMHR group.There was no significant difference in baseline characteristics between the two groups,including ages,MD of tumor,menopause statuses,clinical stages,molecular classification results,axillary lymph node metastases,tumor enhancement modes,and histological grades(P>0.05)Comparison of the IVIM-DWI model parameters before and after two cycles of NAC showed that the D value increased after NAC,and there was a significant difference between before and after NAC(P<0.001).The D*value increased after two cycles of NAC too,but the difference between before and after NAC was not significantly(P=0.059).The f value decreased after two cycles of NAC,with significantly different from that of before NAC(P<0.001).Before NAC,the D and D*values of the MHR group were higher than those of NMHR group,but no significantly differences were found between them(P>0.05).While the f value of the MHR group was significantly higher than that of the NMHR group,and the difference was significant(P<0.001).After two cycles of NAC,the D and D*values of MHR group and NMHR group were both increased,and the D value difference between the two groups was statistically significant(P<0.001),but no significance difference was showed on the D*value(P=0.208).The f value of the MHR group decreased and was significant difference from that of the NMHR group(P=0.004).Before and after two cycles of NAC,the increase degree of D value and the decrease degree of f value in the MHR group were significantly higher than those in the NMHR group,and the differences between the two groups were statistically significant(P<0.05);and the increase of D*value in the NMHR group was greater than that in the MHR group,but the difference of D*value between the two groups was not statistically significant(P=0.612).Before NAC,MD value in the MHR group was lower than that in the NMHR group,and the difference between the two groups was not statistically significant(P=0.085).After two cycles of NAC,MD values in both groups decreased,and the difference between the two groups was statistically significant(P<0.001).The tumor reduction rate in the MHR group was greater than that in the NMHR group(P<0.001).Correlation analysis between the three parameters of the IVIM-DWI model and tumor reduction rate showed that the tumor reduction rate before NAC was positively correlated with the D*and f values(r=0.376,P=0.015;r=0.428,P=0.005),but was not significantly correlated with the D value(P>0.05)The D value after two cycles of NAC was positively correlated with tumor reduction rate(r=0.315,P=0.045),while D*value and f value were not significantly correlated with the tumor reduction rate(P>0,05).Analyzing the correlation between the change in IVIM-DWI parameters and tumor reduction rate before and after two cycles of NAC showed that AD was positively correlated with tumor reduction rate(r0.446,P=0.003),and Af was negatively correlated with tumor reduction rate(r=-0.389,P=0.012),but no significant correlation for △D*(P>0.05).The ROC curve analysis for IVIM-DWI parameters on the prediction of NAC efficiency before and after two cycles of NAC showed that the AUC of the f value before NAC was the highest(AUC=0.879),and the diagnostic efficiency was better than D and D*values(AUC=0.572,AUC=0.622,respectively).After two cycles of NAC,the diagnostic efficiency of the D and f values(AUC=0.862,AUC=0.774,respectively)was better than that of D*value(AUC=0.615).Analysis of the difference values of IVIM-DWI parameters before and after two cycles of NAC showed that the diagnostic efficiencies of AD,Af,and AMD values were good(AUC=0.872,AUC=0.751,AUC=0.833,respectively),and that of △D value was the best,significantly higher than the △D*(AUC=0.615).The AUC of the f value before NAC was the largest,followed by the AD value,but the difference between them was not statistically significant(P>0.05).When the cutoff value was 22.31%,the sensitivity and specificity of the f value before NAC were 73.33%and 92.31%,respectively.When the △D cutoff value was 0.15×10-3 mm2/s,the sensitivity and specificity of △D for differentiating MHR and NMHR after two cycles of NAC were 86.67%and 80.77%,respectivelyConclusion:1.Increments in the D value and decrements in the f value in IVIM-DWI model could be used as indices to evaluate the curative effect of NAC in breast cancer 2.The higher the f value of patients before NAC,the better the pathological response of patients after NAC.3.Dramatic increments in the D value and drastic reductions in the f value were indicative of a better pathological reaction after two cycles of NAC.4 Among the IVIM-DWI model parameters before and after two cycles of NAC,the pre-NAC f value and the △D value had the same diagnostic efficiency and the highest efficacy in predicting the curative effect of NAC.The diagnostic efficiencies of the D value,post-NAC f value,and Af value were good,but that of the D*value was poor.