| Background:Thyroid cancer is the most common malignancy of the endocrine system.It was the most rapidly growing entity tumor accounting for about 1%of all human tumors in recent years.The World Cancer Report(2014)showed that the incidence of thyroid cancer had increased exponentially over the past few decades.The incidence of thyroid cancer in our country had risen rapidly in the past 30 years,especially in the past 10 years,with average annual growth rate over 14%.Thyroid cancer had become a hot topic in medicine and society.In spite of the incidence of thyroid cancer was growing rapidly,the mortality was not increasing rapidly.The reason was that the rapidly growing incidence of thyroid cancer was mainly caused by differentiated thyroid carcinoma(DTC).DTC originated from thyroid follicular cells,which were composed of papillary thyroid carcinoma(PTC)and follicular thyroid carcinoma(FTC).DTC accounting for 90%of thyroid cancer had become the most active area in thyroid cancer research.At present many scholars believe that "thyroidectomy +131I therapy +TSH inhibition therapy" is the best comprehensive treatment for DTC patients.DTC cells express the sodium iodine symporter(NIS)with the functions of absorbing iodine.It is the biological basis for postoperative 131I ablation therapy.The beta ray of 131I can completely destroy thyroid remnant and DTC metastatic lesions.It reaches these targets reducing the recurrence and metastatic rate and improving the survival of DTC patients,increasing the successful ablation rate of the metastases,improving the sensitivity of thyroid globulin to predict DTC metastases and recurrence.Therefore,the treatment of 131I ablation after thyroidectomy was significant for DTC patients.However,there were some controversies over the 131I treatment after thyroidectomy,such as the appropriate dose of 131I ablation.The advantages of low dose were lower incidence of side effects,shorter duration of hospital stays and lower incidence of secondary tumors caused by 132I.The advantage of high dose was that the benefit getting from high dose could completely offset the mild side effects caused by high dose.The American Thyroid Association(ATA)guideline of "2015 American Association management for adult patients with thyroid nodules and differentiated thyroid cancer" tended to limit the number and the dose of 131I therapy.It supported low doses for low and intermediate risk DTC patients.However,there were different viewpoints on this issue.Leonard Wartofsky professor,the ATA co-founder,had been firmly opposed to low dose.He considered that low dose did not kill cancer cells,but destroy cancer cells.It caused iodine resistance.The experts of the European Nuclear Medical Association(EANM)also believed that the ATA guideline of 131I ablation lacked a solid foundation from the long-term follow-up.The Chinese Society of Nuclear Medicine issued "The clinical guideline of 131I therapy for differentiated thyroid cancer" in 2014.It recommended that the DTC patients could be treated with 30?100mCi 131I in accordance with the individual situation.The guideline suggests that ablation of thyroid tissue use minimum dose.There were many factors influencing 131I ablation,such as the residual thyroid tissue?the dose of 131I,the 131I absorption rate,the postoperative TSH level,the interval from surgery to 131I treatment,gender and age.Considering the high costs of 131I therapy,the high medical cost burdens and the side effects of radiation,the optimal treatment plan according to the individual situation should be taken into account to improve the success rate of the primary 131I ablation.In order to improve the success rate of the primary 131I ablation and reduce the electron radiation damage,this research analyzed the differences of successful rate and incidence of side effects between low-dose and high-dose 131I ablation for low and intermediate risk differentiated thyroid cancer and studied the factors which can affect the primary success rate of 131I ablation after thyroidectomy for the purpose of giving support for the dose selection and making individualized treatment plan for DTC patients.Part 1 Study on influencing factors of the first 131I therapy in patients with differentiated thyroid cancer after thyroidectomyObjectives:The purpose of this study was to investigate the effect and the influencing factors of 131I therapy in the first ablation of residual thyroid tissues in patients with differentiated thyroid cancer after total or near-total thyroidectomy.Methods:Samples:The DTC patients treated in nuclear medicine department of our hospital from January 2015 to October 2016.275 DTC patients(79 males and 196 females)were treated with 131I for the first ablation after surgery.All patients signed the informed consent form of 131I treatment for the DTC patients after thyroidectomy.Entry criteria:All patients underwent total or near-total thyroidectomy.The pathology was confirmed as DTC.All patients were suitable for 131I treatment and were treated and regularly followed up in our hospital.The data was complete and true.Exclusion criteria:The data was incomplete.The TgAb was positive.Data collection procedures:By the CIS,PACS and Ruimei laboratory system,We collected the following patient data:sex,age,surgical method,pathological type,the number of thyroid leaf affected by DTC,the number of DTC lesions,the diameter of lesion,lymph node metastasis,distant metastasis,TSH level before 131I ablation,the 131I absorption rate(%)of the residual thyroid tissue,sTg level before 131I ablation,the time interval between operation and 131I ablation,taking L-T4 or not,99mTcO4-thyroid imaging,the rank of recurrence risk,and 131I dose,the neck color ultrasound,chest CT,131I whole body imaging and so on.Evaluation criteria:The efficacy of 1311 treatment evaluated by the criteria recommended in the guideline of 131I treatment for DTC patients(2014).Observation parameters:The success rate of the first 131I ablation of the residual thyroid tissue.The independent influencing factors for the first 131I ablation of the residual thyroid tissue.The predictive value of independent influencing factors for efficacy of the first 131I ablation.Statistical methods:IBM SPSS 24.0 and PEMS 3.1 statistical software were used for analysis.The measurement data of the non-normal distribution was expressed in the median and quartile(P25,P75)and the inter-group comparison was performed using the Wilcoxon rank sum test.Qualitative data describe the number and the percentage of cases and the inter-group comparison was performed using the chi-square test.The multiple comparisons of rates was performed using Scheffe method.The multifactor analysis was performed using Logistic regression analysis.The predictive value of influential factors was analyzed using the ROC.Differences were considered significant at P<0.05.Results:(1)The success rate of the first 131I ablation of the residual thyroid tissue was 62.9%.(2)The single factor analysis showed that the surgical method,the diameter of lesion,lymph node metastasis,distant metastasis,TSH level before 131l ablation,the 131I absorption rate(%)of the residual thyroid tissue,sTg level before 131I ablation,99mTcO4-thyroid imaging,the rank of recurrence risk,and 131I dose were significant differences between the successful and unsuccessful groups of the first 131I ablation of residual thyroid tissue,(all P<0.05).(3)The single factor analysis showed that sex,age,pathological type,the number of thyroid leaf affected by DTC,the number of DTC lesions,the time interval between operation and 131I ablation,taking L-T4 or not were not significant differences between the successful and unsuccessful groups of the first 131I ablation of residual thyroid tissue,(all P>0.05).(4)The Logistic regression analysis showed that the diameter of lesion,the rate of 131I absorption(%),the level of sTg and lymph node metastasis were independent influential factors for the success rate of the first 131I ablation,(all P<0.05).(5)By ROC analyzing,the diameter of lesion,the 131I absorption rate(%)of the residual thyroid tissue and the sTg level before 131I ablation were predictive factors.The areas under curve(AUC)Were 0.674,0.668 and 0.913 respectively.The thresholds were 1.5 cm,4.5%and 4.70 ug,/L respectively.The sensitivities were 63.7%,63.7%and 86.3%.The specificities were 61.8%,63.0%and 81.1%respectively.The positive predictive values were 49.6%,50.4%and 72.7%,respectively.The negative predictive values were 74.3%,74.7%and 95.9%respectively.Conclusions:(1)The first 131I ablation of the residual thyroid tissue for the DTC patients is effective,and the success rate is 62.9%.(2)The diameter of the lesion,the rate of 131I absorption(%),the sTg level and(?)lymph node metastasis are independent influential factors for the first 131I ablation of the remnant.(3)The diameter of the lesion,the rate of 131I absorption(%)and the sTg level are predictive factors for efficacy of the first 131I ablation of the remnant and the sTg level had higher predictive value for the efficacy of first 131I ablation.Part 2:Low-dose versus high-dose 131I therapy for low and intermediate risk differentiated thyroid cancer:a randomized controlled clinical studyObjectives:The purpose of this study was to explore the differences of the success rates,therapeutic responses and side effects between low dose and high dose 131I treatment for the low and intermediate risk DTC patients.Methods:Samples:The low and intermediate risk DTC patients were treated in nuclear medicine department of our hospital from January 2016 to January 2017.198 low and intermediate risk DTC patients(51 males and 147 females)were treated with 131I ablation after surgery.The study was reviewed and approved by ethical committee of the hospital.All patients signed the informed consent form of 131I treatment for the DTC patients after thyroidectomy.Entry criteria:Age ? 18 years old.The pathology was confirmed as low and intermediate risk DTC.All patients underwent total or near total thyroidectomy and lymph-node dissection.No serious heart,liver or kidney diseases.WBC>3.0 X 109/L.Without hematological system diseases.Exclusion criteria:Pregnant women.Lactating women.Women in preparation for pregnancy.No major coexisting conditions(including other cancers)within 5 years.131I therapy procedures:All Patients avoided using food and drug containing iodine before 1 month.All patients were assigned to low-dose or high-dose group randomly and were given 30 mCi or 100 mCi131I respectively.131I whole body scan was done after 5 days of 131I treatment.The effects of treatment were evaluated after 6 months.The failure patients were given the same dose for ablation.Side effects of the patient in 1 week,1 month and 3 months after treatment were followed up.Blood routine examination before the treatment and in 5,30 and 60 days after treatment were detected.Evaluation criteria:The guideline of the 131I treatment for DTC patients.Common Terminology Criteria for Adverse Events 4.0.Observation parameters:The different success rates,therapeutic effects,common side effects and the blood WBC,Neu and LY levels between the low dose and high dose group.Statistical methods:Continuous variables were presented as mean ± SD and were compared between groups by the Student's t test.Categorical variables were expressed as proportions and were compared between groups with the Chi-square test or the Fisher's exact test.Statistical analyses were performed using Statistical Package for the Social Sciences for Windows,version 24.0 software(SPSS,Chicago,IL,USA).Differences were considered significant at P<0.05.Results:(1)The success rates of the first 131I ablation for the low and intermediate risk DTC patients between the low and high dose group were 70%and 65.3%respectively,The success rates of the second 131I ablation were 76.7%and 85.3%respectively and the final success rates were 97%and 98.9%respectively.There were not statistically significant difference between the two groups,(all P>0.05).(2)The therapeutic effects of the first 131I ablation were ER(62%),IDR(14%),BIR+SIR(24%)in low dose group and ER(58.2%),IDR(12.2%),BIR+SIR(29.6%)in high dose group.There were not statistically significant difference between the two groups,(all P>0.05).(3)The 131I treatment for the low and intermediate risk DTC patients was safe and reliable.It caused mild side effects(below level 2)in some patients.(4)The incidence of side effects of neck discomfort,nausea,salivary dysfunction,and radioactive gastritis in the low dose group versus high dose group were 17%VS 34.7%,12%VS 28.6%,8%VS 19.4%and 13%VS 27.6%in one week later after the 131I ablation,the differences were statistically significant(all P<0.05).The symptom of nausea and radioactive gastritis in low dose group were lower than the high dose group(3%VS 10.2%,4%VS 16.3%respectively)in one month later after the 131I ablation,the differences were statistically significant(all P<0.05).There was no significant difference between the two groups after 3 months(all P>0.05).(5)The influence of 131I treatment on peripheral blood.The WBC,Neu and LY levels in 5 days,30 days and 60 days of patients in low dose group were higher than patients in high dose group(all P<0.05).It was gradually recovering with time.The levels of WBC,Neu and LY in 60 days after 131I treatment were not different with the levels of WBC,Neu and LY before 131I treatment(all P>0.05).Conclusions:(1)It is safe and reliable to use low dose or high dose 131I treatment for patients with low and intermediate risk DTC patients after thyroidectomy.(2)The successful rate and therapeutic effect of low dose 131I ablation for low and intermediate risk DTC patients after thyroidectomy are equal to high dose 131I ablation.Moreover,low dose 131I ablation causes lower incidence of side effects than high dose.It recommended that low and intermediate risk DTC patients can be treated with low dose 131I ablation after surgery.Part 3:The value of 99mTcO4-SPECT/CT imaging in detection of residual thyroid tissues in patients with differentiated thyroid cancer after surgeryObjectives:To explore the value of 99mTcO4-SPECT/CT imaging in detection of thyroid remnant and extra-thyroid metastases in the neck in patients with differentiated thyroid cancer after surgery.Methods:Samples:The DTC patients treated in nuclear medicine department of our hospital from December 2016 to August 2017.240 DTC patients(68 males and 172 females)were treated with 131I ablation after surgery.The study was reviewed and approved by ethical committee of the hospital.All patients signed the informed consent form of131I treatment for the DTC patients after thyroidectomy.Entry criteria:All patients underwent total or near-total thyroidectomy.The pathology was confirmed as DTC.All patients were suitable for 131I treatment indications.Experimental procedures:All patients were treated with 99mTcO4-SPECT/CT scan before 131I ablation.The 131I whole body scan was performed 5 days after 131I therapy.If it was necessary,neck tomography was performed.Evaluation criteria and observation parameters:The result of 131I thyroid scan was treated as standard.We evaluated the sensitivity,specificity,accuracy,positive predictive value,negative predictive value and the sensitivity of detection of thyroid remnant and extra-thyroid metastases in the neck of the 99mTcO4-SPECT/CT thyroid scan.Results:The sensitivity of detection of thyroid remnant of the 99mTcO4-SPECT/CT thyroid imaging was 83.7%,the specificity was 89.5%,the accuracy was 84.2%,the positive predictive value was 98.9%,and the negative predictive value was 32.1%.The sensitivity of detection of extra-thyroid metastases in the neck of the 99mTcO4-SPECT/CT thyroid scan was 40.2%.Conclusions:(1)99mTcO4-SPECT/CT thyroid imaging has a high sensitivity,specificity,accuracy,and positive predictive value in detection of thyroid remnant for DTC patients.It can be used as replacement for 131I neck scan to value thyroid remnant before 131I treatment,especially for the positive result.(2)99mTcO4-SPECT/CT thyroid imaging is less sensitive than 131I scan in the evaluation of extra-thyroid metastases in the neck. |
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