| Background and objective:Lung cancer is a malignant tumor with the highest incidence and mortality in the world[1].Non small cell lung cancer(NSCLC)is the main pathological type in lung cancer.Chemotherapy is a common yet important treatment of advanced lung cancer,and the timely and effective evaluation of treatment efficacy and prognosis is extremely called-for.At present,chest CT,chest x-ray,PET/CT and other imaging studies are used to assess the efficacy of chemotherapy by changes in tumor diameter.However,the changes in tumor size are not obvious in the short term after treatment,and the internal and pathophysiological changes of early tumors cannot be evaluated.Therefore its application to early efficacy monitoring is limited[2].In addition,chest CT and chest X-ray examinations are radioactive,which is not suitable for long-term multiple inspection,and PET/CT is too expensive to be universal.The prognosis of patients with lung can cer is usually combined with clinical features,treatment method and treatment efficacy.In recent years,the molecular biology index of lung cancer has been paid more and more attention as one of the prognostic methods to evaluate the prognosis of patients with lun g cancer because of its simple operation,easy follow-up observation,high sensitivity and high specificity [3-6].Diffusion weighted imaging(DWI)is the only functional imaging technique for the microscopic movement of water molecules in biological tissues.It is widely used in examination for various organs such as brain,liver,pancreas and prostate [7-9.].The apparent diffusion coefficient(ADC)is the sum of the dispersal motion of water molecule s in DWI,which can reflect the diffusing characteristics of water molecules in the whole tissue structure and therefore can evaluate the internal and pathophysiological changes of early tumors.Studies have found that after effective anti-tumor treatment,the dispersal motion of water molecules inside the tumor has significant changes at the early stage,and that ADC is expected to assess the early efficacy of tumor chemotherapy as DWI specific quantitative indicators[10].So far,the correlation between ADC and prognostic related molecular biology indicators is lacking [11],and all of them are small sample studies.At present,whether ADC can be considered as an early efficacy monitoring and prognostic indicators for advanced NSCLC patients are still controversial [12].Therefore,this study intends to use magnetic resonance diffusion weighted imaging to dynamically observe the changes of water molecules in DWI before and after chemotherapy in patients with advanced NSCLC.Quantitative analysis is conduct ed in terms of ADC and the change rate of the maximal diameter and the minimum diameter before and after chemotherapy.Combined with ADC before treatment,we can analyze its correlation with cancer embryo antigen(CEA)in serum,Ki67 in organs,thyroid transcription factor 1(TTF-1),epidermal growth factor receptor(EGFR)and other prognostic related molecules biology.The feasibility of ADC as an indicator of early efficacy monitoring and prognosis evaluation in patients with advanced NSCLC has been discussed,with a view to providing new ideas for early clinical efficacy monitoring and prognosis analysis of clinical lung cancer.Methods:Part one:Study objects are included in accordance with the criteria,and DWI examination has been carried out to measure ADC,the maximum diameter and the minimum diameter of the target lesion before the chemotherapy as well as after the first and second chemotherapy.According to RECIST1.1 standard [2],and taking the tumor diameter change between the second cycle of chemotherapy and before the treatment as the standard,complete response(CR)and partial response(PR)are defined as the effective group,while stable disease(SD)and progressive disease(PD)are defined as the ineffective group.ADC,the maximal diameter and the minimum diameter of the effective group and of the ineffective group before and after the treatment are analyzed,and the receiver operating characteristic curve(ROC)has been plotted.Part two:The NSCLC patients who meet the inclusion criteria from April 2015 to September 2016 in Southwest Hospital are collected,DWI has been examined within 1 week after diagnosis.The retrospective analysis has been done on the clinical characteristics(such as sex,age,smoking history,pathological type,stages),serum CEA levels,immunohistochemistry of pathological sections and gene sequencing results.CEA in serum,Ki67,TTF-1 and EGFR in tissue are compared with ADC in terms of expression level in order to analyze the correlation between ADC and the above biological prognosis indicators.Results:Part one:1.The basic situation of the patientsThere are 21 cases of NSCLC patients,including 7 cases of squamous cell carcinoma and 14 cases of adenocarcinoma.According to RECIST1.1 standard,effective group has 6 people and all of them are PR,while ineffective group has 15 people,including 11 of SD and 4 of PD.There are no statistical differences in sex,age,smoking history,pathological type,stages and other general data(P > 0.05).2.Changes in ADC before and after the chemotherapy in NSCLC patients2.1 ADC of the effective group is 1.03 ± 0.13 × 10-3 mm2 / s before the chemotherapy,and ADC of the ineffective group is 1.07 ± 0.18 × 10-3 mm2 / s.There is no significant difference between the two groups(t = 0.530,p = 0.602).2.2 There are statistically significant differences in ADC values between the effective and ineffective groups after the first and second chemotherapy(t =-2.442,p = 0.025;t =-3.757,p = 0.001),and the effective group's ADC is significantly higher than that of the ineffective group.2.3 ADC has significantly increased after the second week of chemotherapy in the effective group compared with ADC after the first week of chemotherapy and there is statistical difference(F=4.812,P<0.05).In the ineffective group there is no statistical difference between ADC before and after the chemotherapy(F = 0.299,p> 0.05).3.Comparison of changes in ADC change rate,maximum diameter and minimum diameter of patients with NSCLC after the chemotherapy3.1 After the first week of chemotherapy,there is no significant difference between the Part two: maximum diameter and the minimum diameter of the effective and ineffective groups(T =-0.712,p = 0.099;t =-0.812,p = 0.427).The change rate of ADC in the effective group however is significantly higher than that in the ineffective group(t =-1.820,p = 0.040).3.2 The change rate of maximum diameter,the minimum diameter as well as ADC in the two groups are significantly different after the second chemotherapy.The change rate of the effective group is higher than that of the ineffective group(t =-4.368,p = 0.000;t =-3.003,p = 0.007;t =-2.922,p = 0.009).4.Receiver operating characteristic(ROC)analysis of ADC change rate in patients with NSCLC after the chemotherapy4.1 In the ROC of ADC change rate after the first week of the chemotherapy,if we take whether ADC is not less than 11.80% as the criterion for judging the efficiency of chemotherapy,the sensitivity is 83% and the specificity is 67%.4.2 In the ROC of ADC change rate after the second week of the chemotherapy,if we take whether ADC is not less than 24.78% as the criterion for judging the efficiency of chemotherapy,the sensitivity is 67% and the specificity is 93%.4.3 Considering ADC change rate,the efficiency of the second week of chemotherapy is better than that of the first week.(AUC = 0.822 vs AUC = 0.722).Part two:1.The basic situation of the patientsA total of 39 NSCLC patients are enrolled by the standard.There are 31 males and 8 females,with 17 cases of squamous cell carcinoma and 22 cases of adenocarcinoma.There are 2 cases of stage?,4 cases of stage?,19 cases of stage III and 14 cases of stage IV.There is no significant difference in ADC among NSCLC patients of different sex,age,smoking history,pathological type and stage(P?0.050).2.Discrepant comparison in the expression level of ADC and molecular biology prognosis indicators in NSCLC patientsThere are ADC difference in patients with different blood CEA,Ki67 in tissue,TTF-1 and EGFR expression levels and it has a statistical significance: patients with lower blood CEA levels has higher ADC,yet patients with higher blood CEA levels has lower ADC(P <0.01).Patients whose Ki67 <10% has higher ADC,while patients whose Ki67 >10% has lower ADC(P <0.01);TTF-1-negative patients has higher ADC,while TTF-1-positive patients has lower ADC;ADC of EGFR mutant patients is lower than that of the wild typ e(P = 0.01).3.Correlation between ADC and prognostic molecules biology indexThere is a negative correlation between ADC and serum CEA,tissue Ki67,TTF-1 as well as EGFR(The relevant coefficients respectively are: r =-0.77,P = 0.01;r =-0.58,P = 0.01;r =-0.47,P = 0.003;R =-0.40,P = 0.012).Conclusions:1.ADC has something to do with the chemotherapy efficacy in NSCLC patients before and after the chemotherapy,and the increase in ADC often suggests that the chemotherapy is effective.2.ADC change rate can be used as the monitoring treatment indicators after the first cycle of chemotherapy,while the change rate of ADC,the maximum diameter and the minimum diameter can be used as the monitoring treatment indicators of the second cycle of chemotherapy,suggesting that DWI may be a new assessment method for the early efficacy of chemotherapy in NSCLC patients.3.There is a negative correlation between ADC and prognostic molecules biology index blood CEA,Ki67 in tissue,TTF-1 as well as EGFR in NSCLC patients,suggesting that ADC is expected to be one of the indicators of NSCLC prognosis assessment.DWI may have important value in NSCLC patients' prognosis assessment. |
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