Serum Tg Was Used To Evaluate The Efficacy Of ¹³¹I Therapy In Differentiated Thyroid Cancer Patients With Distant Metastasis In A Series Of Studies

Part I:Serological Thyroglobulin in Evaluating the Response to 131I Treatment in Patients with Distant-metastatic Differentiated Thyroid CancerObjective:To explore the significance of serological thyroglobulin(Tg)in the decisionmaking of response to 131I therapy and subsequent treatment for distant-metastatic differentiated thyroid cancer(DM-DTC).Methods:Retrospectively analyzed 62 papillary thyroid cancer(PTC)patients(20 males and 42 females,average age 38.06 ± 15.90 years)with pulmonary metastasis.Patients were divided into two groups:Non-radioactive iodine(RAI)-avid group(n=25)and RAI-avid group(n=37),according to post-treatment whole-body scan(Rx-WBS).Compared the serum response namely thyroglobulin response to 131I therapy,including Tg change and Tg change speed,between two groups,and explored the relationship between serum Tg level and structural progression.To further explore the benefits of 131I therapy for nonRAI-avid group,we compared the Tg response to different treatment schemes(131I treatment group vs follow-up group).Clinicopathological characteristics and Tg response were compared by t test,X2 test?Fisher's exact test and Mann-Whitney u test,and receiver operating characteristic(ROC)curve was used to find the best threshold of Tg change speed to predict the imaging progress.Results:After 131I treatment,Increased Tg level was found in 60.0%(15/25)patients of non-RAI-avid group,while only 21.6%(8/37)patients of RAI-avid group(?2=9.417,P=0.002);Non-RAI-avid group showed an overall increased Tg trend,with a median speed of 0.05?g/L/month,while RAI-avid group showed a general decreased Tg trend,with a median speed of 0.18?g/L/month(u=265,P=0.005).A significant correlation between Tg change and structural response(P<0.001)was found.When speed of Tg rising was more than 0.135?g/L/month,structural progression could be well predicted.In comparison to non-RAI-avid patients with merely follow-up,further 131I treatment for such patients did not yield significant benefit in terms of the change and speed of Tg(X2=0.071,u=394;P=0.791,0.114,respectively).Conclusions:The serum Tg monitoring could be more sensitive in evaluating the therapeutic response to 131I for DM-DTC in whom Response Evaluation Criteria in Solid Tumors(RECIST)evaluation might not be sensitive enough to reflect the minor change.For patients with non-RAI-avidity,Tg evaluation would offer more sensitive evidence to tailor the necessity of further 131I treatment.Part II:Exploration for the Value of Empiric 131I Therapy for Papillary Thyroid Cancer Patients with Non-RAI-avid PulmonaryMetastasisObjective:It is still controversial whether the papillary thyroid cancer(PTC)patients with pulmonary metastasis but negative 131I whole-body scan(131I-WBS)can benefit from empiric radioactive iodine(RAI)therapy.This study aimed to explore the necessity of empiric 131I therapy for PTC patients with non-RAI-avid pulmonary metastasis.Methods:We included 45 PTC patients with only pulmonary metastasis.The changes of serum thyroglobulin(Tg)levels before and after empiric 131I treatment in which the posttreated whole-body scan(Rx-WBS)showed that the metastatic lesions were non-RAI-avid,as well as Tg change rate and imaging changes of the same patients under the two schemes of empiric 131I treatment and just thyroid stimulating hormone(TSH)suppressive therapy was compared.The progression-free survival(PFS)according to the imaging change was observed during just TSH suppressive therapy.Results:Serum Tg levels of 45 PTC patients after 131I treatment was higher than that before 131I treatment(P=0.001).There was no significant difference of Tg change rate(P=0.123),as well as imaging change(P=1.000)between two schemes of empiric 131I treatment and just TSH suppressive therapy.The median PFS was 54.4(46.5,66.2)months during just TSH suppressive therapy.Conclusion:Empiric 131I therapy has little benefit on PTC patients with non-RAI-avid pulmonary metastasis,and it may contribute to disease progression.Terminating empiric 131I therapy in time should be recommended in such patients.Part ?:Effect of BRAFV600E and TERT Promoter Mutations on Thyroglobulin Response in Distant-metastatic Differentiated Thyroid CancerObjective:To assess the impact of BRAFV600E and telomerase reverse transcriptase(TERT)promoter mutations in distant-metastatic differentiated thyroid cancer(DM-DTC)patients based on thyroglobulin(Tg)response to radioactive iodine(RAI)therapy.Methods:BRAFV600E and TERT mutations in primary tumors or metastatic lymph nodes of 114 DM-DTC patients were retrospectively examined.According to the status of the two genes,the patients were divided into four groups:neither mutation,BRAFV600E mutation,TERT mutation and both mutations.RAI avidity was evaluated based on posttreated whole-body scan(Rx-WBS),and it was defined as RAI-resistant initially(I-RAIR),RAI-resistant gradually(G-RAIR)and RAI-avid continually(C-RAIA).Tgresponse was dynamically assessed with a median follow-up of 56.50 months(interquartile range,28.4397.98 months).Results:BRAFV600E was detected in 38.6%of cases and TERT mutation in 21.1%of cases,and both BRAFV600E and TERT mutations were observed in 14.9%of cases.Patients with both mutations tended to be older at diagnosis(P<0.001),less multifocal(P=0.011)and have more aggressive histologic subtypes(P=0.011)and a higher Ki-67 index(P=0.003).Patients with neither mutation tended to be more RAI-avid than those with the BRAFV600E mutant alone or both mutations(P=0.001,<0.001,respectively).Patients with both mutations presented more unfavorable Tg response than those without both mutations or with the BRAFV600E mutant alone(P=0.001,0.013,respectively).Tg progression-free survival(Tg-PFS)was shorter in patients with TERT mutation alone than in those with neither mutation(P=0.021),and it tended to be shorter when BRAFV600E coexisted(P<0.001);however,no significant difference was observed between BRAFV600E alone and neither mutation(P=0.890).Conclusion:Coexistence of BRAFV600E and TERT promoter mutations synergistically induce loss of RAI avidity and an undesirable Tg response in DM-DTC.In comparison to BRAFV600E mutation,TERT promoter mutation appears to affect more on the clinical process of Tg response.