Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness an...Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.展开更多
Background: The aim of this work was to examine the relationship between the estimated glomerular filtration rate (eGFR) as indicator of renal efficiency potentially related to the ability to release radioactive iodin...Background: The aim of this work was to examine the relationship between the estimated glomerular filtration rate (eGFR) as indicator of renal efficiency potentially related to the ability to release radioactive iodine from the patients bodies and the radioactive iodine whole body effective half-life (WBEHL) defined as the time taken for the administered activity to decay to half of its value for papillary thyroid cancer (PTC) patients undergoing radioactive iodine therapy (RAIT) in a tertiary care medical Centre. Methods: This retrospective observational study included seventy nine patients, sixty females and nineteen males. The patients were divided in two subgroups, those who have WBEHL of less than 11 hours (n = 51) and those with more than 11 (n = 28) hrs based on k-means clustering technique. Results: Analysis of variance (ANOVA) was used to find out if there is a statistically significant difference between the two subgroups Conclusion: There was not a statistically significant difference between the short and the longer WBEHL patients’ groups analyzed in this study. .展开更多
The cumulative evidence over the past decades has shown that the incidence of differentiated thyroid carcinoma(DTC)has exponentially increased.Approximately 10%of patients with DTC exhibit recurrent or metastatic dise...The cumulative evidence over the past decades has shown that the incidence of differentiated thyroid carcinoma(DTC)has exponentially increased.Approximately 10%of patients with DTC exhibit recurrent or metastatic disease,and about two-thirds of the latter will be defined as refractory to radioactive iodine(RAIR)treatment.Since this condition implies 10-year survival rates less than 10% after detection,using available treatments,such as systemic and targeted therapies,have become increasingly relevant.The initiation of these treatments aims to reach stabilization,tumor volume reduction,and/or symptom improvement and it should be decided by highly specialized endocrinologists/oncologists on the basis of patient’s features.Considering that despite enlarged progression-free survival was proven,multikinase inhibitors remain non-curative,their benefits last for a limited time and the side effects potentially cause harm and quality of life reduction.In this context,molecular testing of cancer cells provides a promising spectrum of targeted therapies that offer increased compatibility with individual patient needs by improving efficacy,progression free survival,overall survival and adverse events profile.This review article aims to provide a summary of the current therapeutic strategies in advanced RAIR-DTC,including approved target therapies as well as those for off-label use,RAI resensitization agents,and immunotherapy.展开更多
Background and Objectives: Following the initial management, some patients with differentiated thyroid cancer (DTC) develop a state of high thyroglobulin (Tg) and Negative Iodine Scintigraphy. The predisposing factors...Background and Objectives: Following the initial management, some patients with differentiated thyroid cancer (DTC) develop a state of high thyroglobulin (Tg) and Negative Iodine Scintigraphy. The predisposing factors and outcome of this condition are unclear. In this study, our objectives were to analyze the characteristics of patients with high Tg level and negative Iodine scintigraphy and to determine the predictive factors for development of high Tg and negative scintigraphy. Patients and Methods: Retrospective study of 34 patients undergoing treatment for DTC, followed in the Nuclear Medicine department of the University Hospital—Sahloul Sousse between 1990 and 2006 and having a high Tg and negative Iodine scintigraphy. Fourteen patients had Tg between 2 and 10 ng/ml, 16 had Tg between 11 and 100 ng/ml and 4 patients had Tg more than 100 ng/ml. Results: There were 25 women and 9 men. The mean age was 51.65 years. In 94.1% of cases, the tumor was papillary carcinoma. Follicular tumors accounted for only 5.9%. The mean nodule size was3.26 cm. Capsular invasion was seen in 47.1% cases. The locoregional invasion was found in 35.3%. The lymph node extension was found in 84.8% of patients having lymph node surgery. Lymph node involvement was observed in 92.8% of patients with papillary cancer but it was found in 7.2% of patients with follicular cancers. Lymph node invasion was unilateral in 28.6% (N1a) and bilateral, contralateral or mediastinal in 71.4% (N1b). Initial level of Tg was as follows: 7 patients had Tg between 2 and 10 ng/ml, 14 patients had Tg between 11 and 100 ng/ml and 12 had Tg more than 100 ng/ml. The mean number of radioactive Iodine cure was 11.08 for patients with Tg more than 100 ng/ml with a significant difference (P = 0.001). Conclusion: Among epidemiological, pathological and clinical characteristics, lymph node invasion is the most frequent parameter found in patients with a DTC with high Tg level and negative Iodine scintigraphy.展开更多
To monitor the extent and the duration of lymphocyte subset changes in patients with thyroid carcinoma undergoing therapeutic 131I administration, the percentage of lymphocyte subsets were serially analyzed before and...To monitor the extent and the duration of lymphocyte subset changes in patients with thyroid carcinoma undergoing therapeutic 131I administration, the percentage of lymphocyte subsets were serially analyzed before and after 131I treatment. In patients who received 1850 MBq of 131I for ablation of thyroid remnants, only for NK cells and B cells showed a significant reduction. In patients received 3700 MBq of 131I for treatment of local lymph node me-tastases, NK cells, B cells and CD4+ were found decreased. In patients received 7400 MBq of 131I for treatment of distant metastases, NK cells, B cells and CD4+ and CD8+ were all affected. However, there is no significant reduc-tion compared to the baseline in the percentage of all lymphocyte subsets three months after 131I treatment. The re-sults show that the sensitivity of lymphocytes to 131I internal radiation depends upon lymphocyte phenotype and 131I activity. The immunosuppression effects are temporary and reversible.展开更多
BACKGROUND Hyponatremia is a common clinical electrolyte disorder.However,the association between hyponatremia and acute hypothyroidism is unclear.Acute hypothyroidism is usually seen in patients who undergo preparati...BACKGROUND Hyponatremia is a common clinical electrolyte disorder.However,the association between hyponatremia and acute hypothyroidism is unclear.Acute hypothyroidism is usually seen in patients who undergo preparation for radioactive iodine therapy.AIM To analyze the incidence and influencing factors of hyponatremia in a condition of iatrogenic acute hypothyroidism in patients with differentiated thyroid cancer(DTC)before ^(131)I treatment.METHODS The study group consisted of 903 DTC patients who received ^(131)I treatment.The clinical data before and after surgery,as well as on the day of ^(131)I treatment were analyzed.According to the blood sodium level before ^(131)I treatment,patients were divided into the non-hyponatremia group and hyponatremia group.Correlations between serum sodium levels before ^(131)I treatment and baseline data were analyzed.Univariate analysis and binary logistic regression were performed to identify the influencing factors of hyponatremia.RESULTS A total of 903 patients with DTC,including 283(31.3%)males and 620(68.7%)females,with an average age of 43.8±12.7 years,were included in this study.The serum sodium levels before surgery and ^(131)I treatment were 141.3±2.3 and 140.5±2.1 mmol/L,respectively(P=0.001).However,the serum sodium levels in males and females before ^(131)I treatment were lower than those before surgery.Patients aged more than 60 years and less than 60 years also showed decreased serum sodium levels before ^(131)I treatment.In addition,the estimated glomerular filtration rate(eGFR)in males and females decreased before ^(131)I treatment compared with those before surgery(P=0.001).Moreover,eGFR in patients over 60 years and under 60 years decreased before ^(131)I treatment,when compared with that before surgery.There were no significant differences in serum potassium,calcium,albumin,hemoglobin,and blood glucose in patients before surgery and ^(131)I treatment(P>0.05).Among the 903 patients,23(2.5%)were diagnosed with hyponatremia before ^(131)I treatment,including 21 cases(91.3%)of mild hyponatremia and 2 cases(8.7%)of moderate hyponatremia.Clinical data showed that patients with mild hyponatremia had no specific clinical manifestations,while moderate hyponatremia cases were mainly characterized by fatigue and dizziness,which were similar to neurological symptoms caused by hypothyroidism and were difficult to distinguish.Correlation analysis showed a correlation between serum sodium before ^(131)I treatment and the preoperative level(r=0.395,P=0.001).There was no significant correlation between blood sodium and thyroid-stimulating hormone(TSH)levels and urine iodine before ^(131)I treatment(r=0.045,P=0.174;r=0.013,P=0.697).Univariate analysis showed that there were significant differences in age,sex,history of diuretic use,distant metastasis,preoperative blood sodium,blood urea nitrogen(BUN),eGFR,TSH and urinary iodine between the two groups(all P<0.05).Logistic regression analysis showed that factors such as history of diuretic use,distant metastases,preoperative sodium and BUN were all influencing factors of hyponatremia.The Hosmer and Lemeshow test(c2=2.841,P=0.944)suggested a high fit of the model.Omnibus tests of model coefficients indicated the overall significance of the model in this fitted model(P<0.05).Preoperative serum sodium was a significant factor associated with pre-^(131)I therapy hyponatremia(OR=0.763;95%CI:0.627-0.928;P=0.007).CONCLUSION The incidence of hyponatremia induced by ^(131)I treatment preparation was not high.Preparation for radioactive iodine therapy was not a risk factor for the development of hyponatremia in thyroid cancer patients.展开更多
基金supported by the Project on InterGovernmental International Scientific and Technological Innovation Cooperation in National Key Projects of Research and Development Plan (No. 2019YFE0106400)the National Natural Science Foundation of China (No. 81771875)。
文摘Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.
文摘Background: The aim of this work was to examine the relationship between the estimated glomerular filtration rate (eGFR) as indicator of renal efficiency potentially related to the ability to release radioactive iodine from the patients bodies and the radioactive iodine whole body effective half-life (WBEHL) defined as the time taken for the administered activity to decay to half of its value for papillary thyroid cancer (PTC) patients undergoing radioactive iodine therapy (RAIT) in a tertiary care medical Centre. Methods: This retrospective observational study included seventy nine patients, sixty females and nineteen males. The patients were divided in two subgroups, those who have WBEHL of less than 11 hours (n = 51) and those with more than 11 (n = 28) hrs based on k-means clustering technique. Results: Analysis of variance (ANOVA) was used to find out if there is a statistically significant difference between the two subgroups Conclusion: There was not a statistically significant difference between the short and the longer WBEHL patients’ groups analyzed in this study. .
文摘The cumulative evidence over the past decades has shown that the incidence of differentiated thyroid carcinoma(DTC)has exponentially increased.Approximately 10%of patients with DTC exhibit recurrent or metastatic disease,and about two-thirds of the latter will be defined as refractory to radioactive iodine(RAIR)treatment.Since this condition implies 10-year survival rates less than 10% after detection,using available treatments,such as systemic and targeted therapies,have become increasingly relevant.The initiation of these treatments aims to reach stabilization,tumor volume reduction,and/or symptom improvement and it should be decided by highly specialized endocrinologists/oncologists on the basis of patient’s features.Considering that despite enlarged progression-free survival was proven,multikinase inhibitors remain non-curative,their benefits last for a limited time and the side effects potentially cause harm and quality of life reduction.In this context,molecular testing of cancer cells provides a promising spectrum of targeted therapies that offer increased compatibility with individual patient needs by improving efficacy,progression free survival,overall survival and adverse events profile.This review article aims to provide a summary of the current therapeutic strategies in advanced RAIR-DTC,including approved target therapies as well as those for off-label use,RAI resensitization agents,and immunotherapy.
文摘Background and Objectives: Following the initial management, some patients with differentiated thyroid cancer (DTC) develop a state of high thyroglobulin (Tg) and Negative Iodine Scintigraphy. The predisposing factors and outcome of this condition are unclear. In this study, our objectives were to analyze the characteristics of patients with high Tg level and negative Iodine scintigraphy and to determine the predictive factors for development of high Tg and negative scintigraphy. Patients and Methods: Retrospective study of 34 patients undergoing treatment for DTC, followed in the Nuclear Medicine department of the University Hospital—Sahloul Sousse between 1990 and 2006 and having a high Tg and negative Iodine scintigraphy. Fourteen patients had Tg between 2 and 10 ng/ml, 16 had Tg between 11 and 100 ng/ml and 4 patients had Tg more than 100 ng/ml. Results: There were 25 women and 9 men. The mean age was 51.65 years. In 94.1% of cases, the tumor was papillary carcinoma. Follicular tumors accounted for only 5.9%. The mean nodule size was3.26 cm. Capsular invasion was seen in 47.1% cases. The locoregional invasion was found in 35.3%. The lymph node extension was found in 84.8% of patients having lymph node surgery. Lymph node involvement was observed in 92.8% of patients with papillary cancer but it was found in 7.2% of patients with follicular cancers. Lymph node invasion was unilateral in 28.6% (N1a) and bilateral, contralateral or mediastinal in 71.4% (N1b). Initial level of Tg was as follows: 7 patients had Tg between 2 and 10 ng/ml, 14 patients had Tg between 11 and 100 ng/ml and 12 had Tg more than 100 ng/ml. The mean number of radioactive Iodine cure was 11.08 for patients with Tg more than 100 ng/ml with a significant difference (P = 0.001). Conclusion: Among epidemiological, pathological and clinical characteristics, lymph node invasion is the most frequent parameter found in patients with a DTC with high Tg level and negative Iodine scintigraphy.
基金Supported by the Science and Technology Development Fund of Shanghai (No: 024119053)
文摘To monitor the extent and the duration of lymphocyte subset changes in patients with thyroid carcinoma undergoing therapeutic 131I administration, the percentage of lymphocyte subsets were serially analyzed before and after 131I treatment. In patients who received 1850 MBq of 131I for ablation of thyroid remnants, only for NK cells and B cells showed a significant reduction. In patients received 3700 MBq of 131I for treatment of local lymph node me-tastases, NK cells, B cells and CD4+ were found decreased. In patients received 7400 MBq of 131I for treatment of distant metastases, NK cells, B cells and CD4+ and CD8+ were all affected. However, there is no significant reduc-tion compared to the baseline in the percentage of all lymphocyte subsets three months after 131I treatment. The re-sults show that the sensitivity of lymphocytes to 131I internal radiation depends upon lymphocyte phenotype and 131I activity. The immunosuppression effects are temporary and reversible.
文摘BACKGROUND Hyponatremia is a common clinical electrolyte disorder.However,the association between hyponatremia and acute hypothyroidism is unclear.Acute hypothyroidism is usually seen in patients who undergo preparation for radioactive iodine therapy.AIM To analyze the incidence and influencing factors of hyponatremia in a condition of iatrogenic acute hypothyroidism in patients with differentiated thyroid cancer(DTC)before ^(131)I treatment.METHODS The study group consisted of 903 DTC patients who received ^(131)I treatment.The clinical data before and after surgery,as well as on the day of ^(131)I treatment were analyzed.According to the blood sodium level before ^(131)I treatment,patients were divided into the non-hyponatremia group and hyponatremia group.Correlations between serum sodium levels before ^(131)I treatment and baseline data were analyzed.Univariate analysis and binary logistic regression were performed to identify the influencing factors of hyponatremia.RESULTS A total of 903 patients with DTC,including 283(31.3%)males and 620(68.7%)females,with an average age of 43.8±12.7 years,were included in this study.The serum sodium levels before surgery and ^(131)I treatment were 141.3±2.3 and 140.5±2.1 mmol/L,respectively(P=0.001).However,the serum sodium levels in males and females before ^(131)I treatment were lower than those before surgery.Patients aged more than 60 years and less than 60 years also showed decreased serum sodium levels before ^(131)I treatment.In addition,the estimated glomerular filtration rate(eGFR)in males and females decreased before ^(131)I treatment compared with those before surgery(P=0.001).Moreover,eGFR in patients over 60 years and under 60 years decreased before ^(131)I treatment,when compared with that before surgery.There were no significant differences in serum potassium,calcium,albumin,hemoglobin,and blood glucose in patients before surgery and ^(131)I treatment(P>0.05).Among the 903 patients,23(2.5%)were diagnosed with hyponatremia before ^(131)I treatment,including 21 cases(91.3%)of mild hyponatremia and 2 cases(8.7%)of moderate hyponatremia.Clinical data showed that patients with mild hyponatremia had no specific clinical manifestations,while moderate hyponatremia cases were mainly characterized by fatigue and dizziness,which were similar to neurological symptoms caused by hypothyroidism and were difficult to distinguish.Correlation analysis showed a correlation between serum sodium before ^(131)I treatment and the preoperative level(r=0.395,P=0.001).There was no significant correlation between blood sodium and thyroid-stimulating hormone(TSH)levels and urine iodine before ^(131)I treatment(r=0.045,P=0.174;r=0.013,P=0.697).Univariate analysis showed that there were significant differences in age,sex,history of diuretic use,distant metastasis,preoperative blood sodium,blood urea nitrogen(BUN),eGFR,TSH and urinary iodine between the two groups(all P<0.05).Logistic regression analysis showed that factors such as history of diuretic use,distant metastases,preoperative sodium and BUN were all influencing factors of hyponatremia.The Hosmer and Lemeshow test(c2=2.841,P=0.944)suggested a high fit of the model.Omnibus tests of model coefficients indicated the overall significance of the model in this fitted model(P<0.05).Preoperative serum sodium was a significant factor associated with pre-^(131)I therapy hyponatremia(OR=0.763;95%CI:0.627-0.928;P=0.007).CONCLUSION The incidence of hyponatremia induced by ^(131)I treatment preparation was not high.Preparation for radioactive iodine therapy was not a risk factor for the development of hyponatremia in thyroid cancer patients.
