Series Research On The Influencing Of Minimal Extra-thyroid Invasion And Thyroglobulin In Radioactive Active Iodine Therapy For Patients With Differentiated Thyroid Carcinoma

With an increasing incidence,thyroid cancer has become the largest endocrine tumor.In the 2015 ATA(American Thyroid Association)recurrence-risk stratification,minor violations of the thyroid capsule and extracapsules are independent intermediate risk factors in recurrence.The eighth editon of TNM canceled the risk of it to tumor related death.So,it is introversial about the influence of it to recurrence.Thyroglobulin is the tumor marker in the follow-up of differentiated thyroid cancer(DTC).It is divided into stimulated thyroglobulin and suppressed thyroglobulin.With the improvement of Tg detection method,stimulated thyroglobulin attracted more attraction.Whether it performed better than suppressed thyroglobulin still need more study.Recent study indicated that post-operation stimulated thyroglobulin has potential significance in radioiodine treatment.This study investigated the effects of microscopic violations of thyroid capsule to recurrence-risk,the role of ps-Tg to radioiodine treatment,and compared the superiority of stimulated thyroglobulin and suppressed thyroglobulin in the follow-up of DTC.This three-part study is now reported as follows:Part 1:Correlation between minimal extra-thyroid invasion and recurrence indifferentiated thyroid cancerPurpose:It cancelled the effect of minimal extra-thyroid invasion(MEI)on mortality in differentiated thyroid cancer(DTC)patients in the 8th TNM staging system.This study aims to analyze the correlation between MEI and recurrence risk in DTC patients.Methods:Retrospectively analyzed 942 non-distant metastasic DTC patients treated in Peking Union Medical College Hospital with a median follow-up of 24 months,patients were divided into two groups as SIR group(Structural Incomplete Response,disease recurrence/persistence,S1,n=55)and NSIR group(Non SIR,n=887)according to their response to therapy.Chi-square test and rank-sum text were used to evaluate the statistic differences of basic clinicopathologic features in two groups and multivariate analysis was used to quantify the influence factors to SIR.Correlation analysis was conducted between MEI and recurrence,and we compared the clinical pathologic features and responses between low-risk group(G1,n=39)and minimal extra-thyroid invasion group(G2,no other risk factors,n=65).Result:There were statistic differences in tumor size(P=0.018),lymph node stage(P=0.008)and macro extra-thyroid invasion(P=0.008)between SIR group and NSIR group,and no significant difference in MEI(P=0.244).Tumor size and macro extra-thyroid invasion(P=0.007)were two independent influence factors to SIR in multivariate analysis.It showed no correlation between MEI and SIR(r=-0.026,P=0.425).G2 showed a high rate of female(P=0.018)and age at diagnosis(P=0.033)than G1;there was no significant difference in tumor size(P=0.517),tumor multifocality(P= 1.000)and dose of RAI(P= 1.000),as well as the recurrence between G1 and G2(1.5%vs 2.6%,P=0.244).Conclusions:MEI should not be an independent factor to recurrence risk in DTC patients.Part 2:Suppressed thyroglobulin performs better than stimulated thyroglobulin in defining an excellent response in patients with differentiated thyroid cancerPurpose:According to the American Thyroid Association(ATA)guidelines in 2015,both an unstimulated thyroglobulin(u-Tg)below 0.2 ng/mL and a stimulated Tg(s-Tg)below 1.0 ng/mL were required along with negative imaging findings to define an excellent response(ER).This study aimed to investigate whether a u-Tg below 0.2 ng/mL coincides with a s-Tg below 1 ng/mL.Methods:A total of 290 patients with non-metastatic DTC were retrospectively evaluated with a median follow-up of 36 months.The levels of s-Tg were observed in patients whose u-Tg levels were below 0.2 ng/mL after radioiodine therapy,and risk factors associated with the increase of s-Tg to above 1 ng/mL from below 0.2 ng/mL were analyzed.Results:In total,52.8%(153/290)of the patients achieved a u-Tg below 0.2 ng/mL 3 months after remnant ablation,most of whom(83.7%,128/153)also achieved a s-Tg below 1 ng/mL.A total of 25 patients(16.3%)had an increased s-Tg above 1 ng/mL.A comparative analysis showed no significant difference between patients who showed an increase in Tg from below 0.2 ng/mL to above 1 ng/mL and those who did not.In a subgroup analysis assessing the influence of thyrotropin(TSH)on s-Tg,we enrolled 43 patients with at least two s-Tg measurements.We found that a higher level of TSH(118.23±30.72 μIU/mL vs.59.99±26.12 μIU/mL)increased the s-Tg in 88.4%patients(P=0.00),which led to more patients(from 18.6%to 30.2%)with an increased s-Tg(to above 1 ng/mL)after thyroxin withdrawal.Conclusion:Assessing the level of u-Tg might be a better parameter to use for defining ER since u-Tg is more stable,convenient,economical,and is not associated with hypothyroidism as a side effect.Part 3:ps-Tg dependent RAI dose selection in low to intermediate-risk DTCpatientsPurpose:Dose selection in radio active iodine(RAI)remnant ablation treatment for differentiated thyroid cancer(DTC)patients with low to intermediate-risk is controversial.The level of post-operation stimulated thyroglobulin(ps-Tg)has become a sensitive serum biomarker in disease status assessment after thyroidectomy.The objective of this study was to evaluate whether ps-Tg could be a reliable indicator in the dose choice of RAI.Methods:Low to intermediate-risk DTC patients with negative Tg antibody(n=582)were enrolled in this retrospective study,with a median follow-up of 2 years.Patients received low or high-doses of RAI(30 mCi vs 100 mCi)randomly,and responses were individually evaluated to identify the relationship between ps-Tg and dose of RAI.Results:ps-Tg was associated with the increasing rate of Incomplete Response/Failing Remnant Ablation(IR/FRA)independent of the RAI dose.The rate of IR increased from about 10%to above 50%with the rise of ps-Tg from 1 ng/mL to 15 ng/mL.IR rate in patients with ps-Tg level<8 ng/mL was similar,while in those with ps-Tg level>8 ng/mL,high-dose RAI patients had a lower rate of IR than low-dose patients.Further analysis suggested that patients with higher ps-Tg(>8 ng/mL),were more likely to have extensive lymph node metastases,which might cause increased IR rate in the low-dose RAI group.Conclusion:A ps-Tg cutoff of 8 ng/mL could be a reliable in dose choice of RAI,Low-dose for patients with ps-Tg below the cutoff while higher dose for patients above it could achieve better response.