A Series Of Studies On The Population Of Low- And Medium-risk Differentiated Thyroid Cancer Using The Treatment Response Evaluation System

Part Ⅰ:131Ⅰ therapy could improve the prognosis of patients with intermediate-risk papillary thyroid cancer:A short term study based on therapy response reassessmentObjective:Whether the patients with intermediate-risk papillary thyroid cancer(PTC)could benefit from 131Ⅰ therapy,and whether131 Ⅰ therapy should be routinely recommended for them remains controversial.In this self pre-and post-control study,the therapy response system which recommended by American Thyroid Association(ATA)guideline(Version 2015)was used for response assessment.Initial therapy response and final therapy response pre-and post-131Ⅰ therapy have been assessed in order to identify whether intermediate-risk PTC patients could benefit from 131Ⅰ therapy.Methods:Totally,274 intermediate-risk PTC patients underwent total thyroidectomy and 131Ⅰ therapy were retrospectively enrolled after excluding patients with positive thyroglobulin antibody(TgAb),whose medical records such as TNM status,serum thyroid stimulating hormone(TSH),stimulated thyroglobulin(sTg),TgAb,neck ultrasonography,chest CT and 131ⅠI whole body scan(131Ⅰ-WBS)were obtained for the evaluation of initial and final therapy response.Both of initial and final therapy response were assessed with TSH stimulated through thyroid hormone withdrawal before and after 131Ⅰ therapy.Response to 131Ⅰ therapy was evaluated as excellent,indeterminate,biochemical incomplete,or structural incomplete response(ER,IDR,BIR,or SIR)according the ATA guideline(Version 2015).The change of therapy response was analyzed.The univariate and multivariate analyses were further conducted to identify the independent factors for predicting the benefit from the 131Ⅰ therapy in this short term study.Results:Before 131Ⅰ therapy,74.1%(203/274)of patient initially assessed as IDR and 25.9%(71/274)of patient initially assessed as BIR.Reassessment of therapy response 7.1(6.5-8.2)months after 131Ⅰ therapy was significantly different from initial therapy response(P<0.05),44.5%(122/274)of patient finally achieved ER,46.7%(128/274),8.4%(23/274),0.4%(1/274)of patient reassessed as IDR,BIR and SIR,respectively.After 131Ⅰtherapy,response classification downgraded in 57.3%(157/274)of patients,final therapy response reassessment was same as initial in 41.6%(114/274)of patients and response classification upgraded inl.1%(3/274)of patients.Significantly decreased Tg level was observed in therapy response reassessed as both downgraded and maintained patients(5.30(3.30-10.65)vs.0.4(0.20-0.92),6.2(4.08-8.81)vs.2.93(1.96-6.69),all P<0.05).Logistics analyses identified female and early N status(N0+1a)could predict the benefit from the 131Ⅰ therapy(OR=1.649,2.473,all P<0.05).Conclusions:The short-term therapy response of the intermediate-risk PTC patients might be improved by 131Ⅰ therapy,which indicating intermediate-risk PTC patients could benefit from 131Ⅰ therapy.Female and patients with early N status may be more likely to benefit from 131Ⅰ therapy presented as therapy response downgraded.Part Ⅱ:Delayed initial 131Ⅰ therapy related to incomplete response in low-to intermediate-risk differentiated thyroid cancerObjective:Whether the initiating time of 131Ⅰ therapy will affect the clinical outcome in differentiated thyroid cancer(DTC)remains controversial.The objective of this study was to evaluate the impact of 131Ⅰ therapy initiating time on response to initial therapy in low-to intermediate-risk DTC.Methods:A total of 235 consecutive patients with low-to intermediate-risk DTC were retrospectively reviewed.According to the time interval between thyroidectomy and 131Ⅰtherapy,patients were divided into Group 1(interval<3 months,n=187)and Group 2(interval≥3 months,n=48).Response to 131Ⅰ therapy was evaluated as excellent,indeterminate,biochemical incomplete,or structural incomplete response(ER,IDR,BIR,or SIR)according the American Thyroid Association guideline(Version 2015),with a median follow-up of 780 days.The univariate and multivariate analyses were further conducted to identify independent factors associated with incomplete response(IR,including BIR and SIR).Results:Response to initial therapy was significantly different between 2 groups(P<0.05),after excluding the impact of other risk factors(age,gender,histological type,status of T and N,RAI dose,thyrotropin,stimulated thyroglobulin and follow-up time).A significant higher IR rate(18.8%vs 4.3%,P=0.001)and a lower ER proportion(62.5%vs 78.1%,P=0.027)were observed in Group2.By univariate analysis,both T and N status,stimulated thyroglobulin and time interval were significant risk factors for IR(P<0.05).Multivariate analysis demonstrated time interval was an independent risk factors for IR(P=0.008).Conclusions:Delayed initial RAI therapy(≥3 months after thyroidectomy)related to incomplete response in low-to intermediate-risk DTC.Part Ⅲ:Risk factors analysis for positive Tg and negative 131Ⅰ whole body scan(biochemical incomplete response)in intermediate-risk PTC patients after 131ⅠtherapyObjective:The management of patients with positive Tg and negative 131Ⅰ whole body scan(131Ⅰ-WBS)(Tg+I-)is one of the clinical difficulties.The purpose of this study was to analyze the risk factors related to Tg+I-(a kind of status of biochemical incomplete response)in intermediate-risk PTC patients after 131Ⅰ therapy.Methods:Totally,273 intermediate-risk PTC patients underwent thyroidectomy and 131Ⅰtherapy were retrospectively reviewed after excluding patients with positive TgAb.After 131Ⅰ therapy,patients with negative 131Ⅰ-WBS and sTg>10ng/mL was definited as Tg+I-.According to Tg+I-or not,patients were divided into Tg+I-Group(n=23)and non-Tg+I-Group(n=250).The Logistics univariate and multivariate analyses were conducted to identify the independent risk factors for Tg+I-status.Results:Cut-off value of sTg at 11.26ng/mL(area under curve(AUC)was 0.910,sensitivity was 0.870,specificity was 0.852)and sTg/TSH at 0.088 ng/μIU(AUC was 0.891,sensitivity was 0.957,specificity was 0.776)were obtained by receiver operating characteristic curve for differentiating Tg+I-from non-Tg+I-.Multivariate analysis demonstrated N status(N1b/N0+1a),sTg(≥11.26/<11.26 ng/mL)and sTg/TSH(≥0.088/<0.088 ng/μIU)were independent risk factors related to Tg+I-in intermediate-risk PTC patients after 131Ⅰ therapy(OR was 2.883,6.145 and 21.073,respectively,P<0.05).Conclusions:Nlb status,high sTg level and high sTg/TSH pre-131Ⅰ therapy were independent risk factors related to Tg+I-status(a kind of status of biochemical incomplete response)in intermediate-risk PTC patients after 131Ⅰ therapy.