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Objective:To investigate the significance of B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation in the prediction of response to apatinib treatment in advanced radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC). Methods:Twenty patients (10 males, 10 females, age: 51.5(46.3, 65.0) years) with advanced RAIR-DTC from Peking Union Medical College Hospital between March 2016 and March 2023 were retrospectively enrolled, and all patients were treated with apatinib and underwent genetic sequencing (including BRAF V600E and telomerase reverse transcriptase (TERT) promoter). The serological and imaging data, progression-free survival (PFS) and overall survival (OS) data were collected during apatinib treatment. The Kaplan-Meier survival analysis (log-rank test) was performed, and Mann-Whitney U test were used to analyze the differences of duration of response (DOR) between mutation group and wild-type group. Then univariate and multivariate Cox regression analyses were conducted. Results:The PFS (35.3 vs 9.2 months, χ2=7.53, P=0.006) and DOR (25.8(7.4, 35.2) vs 8.2(2.5, 13.4) months, U=23.00, P=0.046) of the BRAF V600E mutation group were longer than those of the wild-type group. Univariate Cox regression analysis showed that the BRAF V600E mutation group had better PFS benefit (hazard ratio ( HR)=0.22 (95% CI: 0.06-0.72), P=0.013), and the risk of disease progression or death in patients with lung metastasis and bone or brain metastasis was 3.06(95% CI: 1.10-8.54, P=0.033) times higher than that in patients with lung metastasis alone. Further, multivariate cox regression analysis showed that only BRAF V600E mutation was an independent predictor of PFS ( HR=0.23 (95% CI: 0.07-0.80), P=0.021), suggesting that RAIR-DTC patients with BRAF V600E mutation might have better efficacy of apatinib. There was no significant difference in PFS ( χ2=1.34, P=0.247) and OS ( χ2=0.19, P=0.664) between TERT promoter mutation group and wild-type group. Conclusion:RAIR-DTC patients with BRAF V600E mutation have longer PFS and DOR after apatinib treatment than those with BRAF V600E wild-type, suggesting that BRAF V600E may be a potential biomarker to guide tyrosine kinase inhibitor (TKI) therapy and help to refine TKI treatment indications.
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Objective:To investigate the value of cellular immune status before initial 131I treatment for predicting treatment response in young and middle-aged patients with papillary thyroid cancer (PTC). Methods:From March 2018 to April 2019, 150 young and middle-aged patients with PTC (46 males, 104 females, age (40.0±9.8) years) who underwent total thyroidectomy and neck lymph node dissection in the Affiliated Hospital of Qingdao University were enrolled retrospectively. All patients underwent radioablation 1-2 months after operation, and the serum lymphocyte subsets (CD3 + , CD4 + , CD8 + , CD4/CD8) as well as natural killer (NK) cells were detected 1 d before the initial 131I treatment. Patients were divided into excellent response (ER) group and non-ER group according to the response of 6-12 months after 131I treatment. Clinicopathological characteristics, preablative stimulated thyroglobulin (psTg), initial 131I dose and lymphocyte subsets that might affect the response to 131I treatment were analyzed (independent-sample t test, Mann-Whitney U test, χ2 test, multiple logistic regression analysis). ROC curve analysis was used to evaluate the predictive value of significant factors for non-ER. Results:Of 150 patients, 84 cases were in ER group (56.00%), and 66 cases (44.00%) were in non-ER group. Age ( z=-2.86, P=0.004), M stage ( χ2=13.64, P<0.001), psTg ( z=-8.94, P<0.001), initial 131I dose ( z=-7.60, P<0.001), CD4 + ( t=2.50, P=0.014), CD4/CD8 ( z=-2.22, P=0.027) of the two groups were significantly different. Multivariate analysis showed that psTg (odds ratio ( OR)=1.27, 95% CI: 1.16-1.40, P<0.001) and CD4/CD8 ( OR=0.39, 95% CI: 0.15-0.99, P=0.048) were independent factors for predicting 131I treatment response. The cut-off values of psTg and CD4/CD8 for predicting non-ER were 6.78 μg/L and 1.67, respectively. Conclusions:Cellular immune status before initial 131I treatment may predict treatment response in young and middle-aged patients with PTC. It indicates non-ER response when Tg is higher than 6.78 μg/L and CD4/CD8 is lower than 1.67.
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Objective:To evaluate the efficacy by using domestic recombinant human thyroid-stimulating hormone (rhTSH) in patients with differentiated thyroid cancer (DTC) before or after 131I therapy. Methods:From May 2019 to November 2020, a total of 24 patients with DTC (5 males, 19 females, median age 41 years) in Peking Union Medical College Hospital and Affiliated Tumor Hospital of Zhengzhou University were enrolled into the open-label, dose escalation phase Ⅰ study. All patients were divided into 4 domestic rhTSH dose groups: 0.9 mg×1 d (group A), 0.9 mg×2 d (group B), 1.8 mg×1 d (group C), 1.8 mg×2 d (group D) in succession, with 6 patients in each group. Each patient underwent rhTSH phase and thyroid hormone withdrawal (THW) phase. The end point included safety, tolerability, the quality of life (hypothyroidism symptom and sign score (Billewicz score), profile of mood states (POMS)), effectiveness (thyroid-stimulating hormone (TSH) and thyroglobulin (Tg) levels, diagnostic whole-body scan (Dx-WBS)) and pharmacokinetic characteristics (peak time, peak concentration) of rhTSH. Paired t test and Wilcoxon signed rank test were used for statistical analysis. Results:There were no dose-limiting toxicities, serious adverse events, or no grade ≥3 adverse events reported. The quality of life in rhTSH phase was significantly better than those in THW phase, including the lower Billewicz score (-53.00(-53.00, -53.00) vs -39.50(-47.00, -23.00); S=119.50, P<0.001) and the lower POMS score (91.92±12.06 vs 99.67±19.13; t=0.95, P=0.025). Serum TSH level was increased from 0.04(0.02, 0.11) mU/L (baseline) to 150.00(105.20, 173.31) mU/L 24 h after the last rhTSH administration, which was increased along with the elevation of rhTSH doses. In the THW phase, patients′ TSH levels were≥30 mU/L after 23 d (median) of THW, with the median of 73.51(57.22, 106.22) mU/L. Median Tg level of baseline was 0.10(0.10, 0.41) μg/L, which reached a peak of 0.85(0.12, 3.01) μg/L at 48 h after rhTSH administration. The peak Tg level in the THW phase was 0.88(0.15, 8.04) μg/L. The Dx-WBS consistency rate between rhTSH and THW phase was 95.8%(23/24). Conclusion:rhTSH is a safe and effective method to stimulate the serum Tg level and radioiodine uptake in patients undergoing post-operation or post- 131I assessment for DTC, as well as maintain a higher quality of life in comparison to THW phase.
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Objective:To analyze the relationship between serologically biochemical response and the disease progression trend and prognosis evaluated by traditional structural imaging in patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) treated by apatinib.Methods:A retrospective study was performed on apatinib-treated (phase Ⅱ) patients ( n=19; 9 males, 10 females; age 46.0 (41.0, 57.5) years) with locally advanced/metastatic RAIR-DTC in Peking Union Medical College Hospital from March 2016 to June 2022. The relationships between serum thyroglobulin (Tg) and response evaluation criteria in solid tumors (RECIST) 1.1 structural imaging efficacy evaluation and disease progression trend were analyzed. The relationships between change of Tg after dose adjustment and the change of maximum diameter of target lesions in structure imaging were also discussed. Mann-Whitney U test and Wilcoxon signed-rank test were used to analyze the data. Results:During the median 49.41 months follow-up, the baseline Tg was 363.20(13.08, 2 490.50) μg/L. The Tg time-to-response was 0.47(0.47, 0.98) months, which was 1.80 (1.30, 1.90) months for RECIST 1.1. After 2, 4 and 8 weeks of initial treatment, the median Tg of the whole cohort decreased by 38.68%, 64.70% and 78.94%, respectively. After 8 weeks, the reducing degree of maximum diameter of target lesions was 33.48%. According to the best response, patients were divided into two groups: partial response (PR) group ( n=15) and stable disease (SD) group ( n=4). The median decreasing degree of Tg in PR group and that in SD group were 87.00% and 28.79%, and the reducing degree of maximum diameter of target lesions in corresponding groups were 45.00% and 21.22%. According to the final efficacy evaluation, patients were further divided into two groups: progressive disease (PD) group ( n=13) and non-PD (including PR and SD) group ( n=5). The median increasing degree of Tg in PD group was higher than that in non-PD group (381.55% vs 175.43%; U=10.00, P=0.037). The increasing degree of Tg and that of the maximum diameter of target lesions were 167.31% and 2.14% after the 1st adjustment, which were 231.06% and 9.73% after the 2nd adjustment. The differences of changes in Tg and maximum diameter of target lesions before and after the 1st dose adjustment were statistically significant ( z values: -3.06 and -2.23, P values: 0.002 and 0.026). Conclusion:During the apatinib treatment of RAIR-DTC, Tg can reflect the therapeutic effect of apatinib earlier than traditional imaging (RECIST 1.1), indicating the disease progression trend more sensitively.
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Objective:To explore the value of preablative stimulated thyroglobulin (ps-Tg) in predicting distant metastasis (DM) at the time of 131I therapy in children and adolescents with differentiated thyroid cancer (DTC). Methods:From January 2016 to March 2020, 54 children and adolescents who underwent total thyroidectomy due to DTC in Peking Union Medical College Hospital were retrospectively reviewed and divided into 2 groups according to the presence of DM or not: M0 group( n=29, 10 males, 19 females, age (16.3±3.8) years) and M1 group( n=25, 13 males, 12 females, age (12.4±4.3) years). Independent-sample t test, χ2 test (or Fisher′s exact test) and Mann-Whitney U test were used to analyze the general characteristics between the two groups. According to status of regional lymph node (RLN) at the time of 131I therapy, the two groups were further divided into M1RLN+ ( n=8) and M1RLN-( n=17), M0RLN+ ( n=5) and M0RLN-( n=24) subgroups. Mann-Whitney U test was used to analyze the different ps-Tg levels between M0 and M1, M1RLN+ and M1RLN-, as well as M0RLN+ and M0RLN-groups. The receiver operating characteristic (ROC) curve analysis was employed to obtain a cut-off value of ps-Tg as a predictor of DM. Results:Patients with DM tended to have higher ps-Tg level (medians: 406.80 μg/L vs 7.90 μg/L, U=690.000, P<0.001), younger age ( t=-3.559, P=0.001), larger tumor size ( t=3.523, P=0.001), more advanced T stage ( U=506.500, P=0.010) and more multifocality( P=0.013) in comparison with those without DM. Though ps-Tg did not significantly differ between M1RLN+ group and M1RLN-group ( U=98.500, P>0.05) or between M0RLN+ group and M0RLN-group ( U=63.000, P>0.05), the two RLN+ groups tended to hold higher medians than the two RLN-groups (18.05 vs 5.71 μg/L; 1 698.50 vs 216.40 μg/L). In order to avoid the possible influence on the ps-Tg cut-off value, 13 RLN+ samples were removed, and the area under the ROC curve was 0.946 (95% CI: 0.883-1.000). The ps-Tg level of 55.87 μg/L was established as the optimal cut-off value to distinguish M0RLN- from M1RLN-, with the sensitivity and specificity of 14/17 and 95.8%(23/24), respectively. Conclusion:Ps-Tg holds a high predictive value in identifying DM, which may be of great help in avoiding inadequate 131I treatment in children and adolescents with metastatic DTC ignored by radiological examinations.
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Objective:To evaluate 131I adjuvant therapy in B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutant patients with non-distant metastatic papillary thyroid cancer (PTC). Methods:From January 2008 to January 2019, a total of 181 PTC patients (65 males, 116 females, age: (38.9±11.8) years) with non-distant metastases from Peking Union Medical College Hospital were retrospectively enrolled. All patients received only one time 131I therapy with complete clinicopathological information, data of follow-up (median time: 63 months) and assessment of response to therapy. Patients were divided into mutant and wild type group in terms of BRAF V600E status or ablation group (1.1 GBq) and adjuvant therapy group (3.7-5.5 GBq) in terms of different 131I dosage. Clinicopathological features and the response to therapy were compared between different groups by using independent-sample t test, Mann-Whitney U test and χ2 test. Results:The levels of preablative stimulated thyroglobulin (ps-Tg) in the BRAF V600E mutant type group ( n=150) was significantly higher than that in the wild type group ( n=31; 6.32(0.90, 8.70) vs 3.92(0.40, 4.40) μg/L; z=-2.413, P=0.016), however, there were no significant differences in other clinicopathological characteristics (including age, sex, tumor size, multifocality, capsule invasion and N staging) between the two groups ( t=-0.663, z=-1.151, χ2 values: 0.003-1.491, all P>0.05) and the therapeutic response was also not different between the two groups( χ2=1.094, P=0.778). Of 81 patients who received 131I adjuvant therapy, the ps-Tg level of BRAF V600E mutant type group ( n=69) was higher than that of the wild type group( n=12; 8.70(1.30, 11.80) vs 3.40(0.30, 4.50) μg/L; z=-2.194, P=0.028), while the therapeutic response was not different between the two groups ( χ2=1.792, P=0.617). Compared with BRAF V600E mutant patients received 131I ablation ( n=81), BRAF V600E mutant patients received 131I adjuvant therapy ( n=69) had larger tumors (1.52(0.95, 2.00) vs 1.21(0.60, 1.50) cm; z=-2.728, P=0.006), more advanced N staging ( χ2=11.460, P=0.003) and higher ps-Tg level (8.70(1.30, 11.80) vs 4.34(0.50, 5.30) μg/L; z=-3.314, P=0.001), but the therapeutic response was not different between the two groups ( χ2=6.478, P=0.091). Conclusion:131I adjuvant therapy may improve the longer-term response to therapy in BRAF V600E mutant PTC patients with lager tumors, more advanced N staging and higher ps-Tg level.
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Background@#Excessive delivery of free fatty acids (FFAs) to the liver promotes steatosis and insulin resistance (IR), with IR defined as reduced glucose uptake, glycogen synthesis and anti-lipolysis stimulated by normal insulin levels. Whether the associations between FFAs and diabetes development differ between patients with and without nonalcoholic fatty liver disease (NAFLD) remains unclear. @*Methods@#Consecutive subjects (2,220 NAFLD subjects and 1,790 non-NAFLD subjects according to ultrasound imaging) were enrolled from the First Affiliated Hospital of Sun Yat-sen University between 2009 and 2019. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. @*Results@#There was an approximate J-shaped relationship between FFA levels and HOMA-IR in the NAFLD group. Higher FFA concentration quartiles were associated with higher risks of IR (odds ratio [OR], 9.24; 95% confidence interval [CI], 6.43 to 13.36), prediabetes (OR, 10.48; 95% CI, 5.66 to 19.39), and type 2 diabetes mellitus (T2DM; OR, 19.43; 95% CI, 12.75 to 29.81) in the NAFLD group but not in the non-NAFLD group. The cut-off points for the FFA levels increased in a stepwise manner in discriminating IR, prediabetes and T2DM (573, 697, and 715 μmol/L) in the NAFLD group but not in non-NAFLD individuals. @*Conclusion@#A distinct dose-dependent relationship of FFA levels was found with IR, prediabetes and T2DM in NAFLD patients. Screening serum FFA levels in NAFLD patients would be valuable in preventing diabetes development.
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Background@#Excessive delivery of free fatty acids (FFAs) to the liver promotes steatosis and insulin resistance (IR), with IR defined as reduced glucose uptake, glycogen synthesis and anti-lipolysis stimulated by normal insulin levels. Whether the associations between FFAs and diabetes development differ between patients with and without nonalcoholic fatty liver disease (NAFLD) remains unclear. @*Methods@#Consecutive subjects (2,220 NAFLD subjects and 1,790 non-NAFLD subjects according to ultrasound imaging) were enrolled from the First Affiliated Hospital of Sun Yat-sen University between 2009 and 2019. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. @*Results@#There was an approximate J-shaped relationship between FFA levels and HOMA-IR in the NAFLD group. Higher FFA concentration quartiles were associated with higher risks of IR (odds ratio [OR], 9.24; 95% confidence interval [CI], 6.43 to 13.36), prediabetes (OR, 10.48; 95% CI, 5.66 to 19.39), and type 2 diabetes mellitus (T2DM; OR, 19.43; 95% CI, 12.75 to 29.81) in the NAFLD group but not in the non-NAFLD group. The cut-off points for the FFA levels increased in a stepwise manner in discriminating IR, prediabetes and T2DM (573, 697, and 715 μmol/L) in the NAFLD group but not in non-NAFLD individuals. @*Conclusion@#A distinct dose-dependent relationship of FFA levels was found with IR, prediabetes and T2DM in NAFLD patients. Screening serum FFA levels in NAFLD patients would be valuable in preventing diabetes development.
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Poor dietary habit is an important cause of the global prevalence of metabolic associated fatty liver disease (MAFLD), and the adjustment of dietary pattern is the cornerstone of MAFLD management. In recent years, a large number of new dietary intervention methods have been proposed and applied in the treatment of MAFLD, including calorie restrict diet, low-carbohydrate diet, low-glycemic index diet, low free sugar diet, intermittent fasting pattern, high protein diet, and Mediterranean diet, and these new methods have different effects in clinical practice. This article introduces the treatment concepts and practical methods of these new dietary treatment strategies and the evidence of their benefits in the treatment of MAFLD in China and globally, so as to provide a new perspective for clinicians to guide patients to achieve individualized nutritional therapy.
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Thyroid cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow- up(ESMO: European Society for Medical Oncology)has been published in December 2019, aiming for providing physicians with the best available evidence on particular issues and recommendations for the best care, and providing cost-effective strategies that will minimize the overtreatment risks. In this article, we focused on the differentiated thyroid cancer (DTC) without distant metastases to interpret the ESMO guidelines in the following aspects: diagnosis and pathology/molecular biology, risk of persistent or recurrent disease, radioiodine therapy and long-term follow-up, and compared the ESMO guidelines with American Thyroid Association guidelines (2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer), together with the related consensuses and recent researches, in order to review the progress in radioiodine therapy.
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Objective:To investigate the correlation between 131I uptake and therapeutic efficacy in metastatic differentiated thyroid carcinoma (DTC). Methods:The clinical data of 138 patients with metastatic DTC (42 males, 96 females, age range: 8-74 years) treated with 131I in nuclear medicine departments of 31 centers all over China were retrospectively analyzed. The lesional 131I uptake was quantitatively analyzed with target-to-nontarget (T/NT) ratio through the regions of interest in metastatic lesions confirmed by either planar or tomographic 131I SPECT/CT imaging. The efficacies of 131I treatment on the metastatic DTC were divided into complete remission (CR), partial remission (PR), stable disease (SD) and progress disease (PD) based on the change of the lesion diameter before and after the treatment. Factors which may affect therapeutic efficacy were assessed by the univariate (Kruskal-Wallis rank sum test, χ2 test and one-way analysis of variance) and binary logistic regression analyses. The receiver operating characteristic (ROC) curve of lesional T/NT ratio to predict the ineffectiveness of 131I therapy was performed. Results:A total of 1 165 efficacies were evaluated. The planar imaging results ( n=653) showed that there was no statistically significant difference of T/NT ratio among CR, PR, SD and PD groups ( χ2=4.15, P>0.05). The tomographic imaging results ( n=512) suggested CR, PR, SD and PD in 7.6%(39/512), 65.8%(337/512), 22.9%(117/512), and 3.7%(19/512) of individuals, respectively, and the T/NT ratio among the four groups was significantly different ( χ2=30.46, P<0.01). The univariate analysis also showed that age, stimulated thyroglobulin(sTg), 131I dose were the factors affecting therapeutic efficacy ( F or χ2 values: 2.561, 7.095 and 8.799, all P<0.05). Furthermore, binary logistic regression analysis revealed that older patients (odds ratio ( OR)=1.034, P=0.022) or patients with lower lesional T/NT ( OR=1.086, P=0.006) had a higher probability of ineffectiveness. The area under ROC curve for T/NT ratio to predict ineffectiveness was 0.726, and the cut-off value was 6.2, with a sensitivity of 78.7%(107/136) and a specificity of 73.1%(275/376). Conclusions:131I therapy is an effective treatment for metastatic DTC. The age at the time of metastatic diagnosis and the lesional T/NT ratio are independent influential factors for ineffectiveness of 131I therapy. When the leisonal T/NT ratio is lower than 6.2, the inefficiency of 131I is higher.
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Objective:To explore the significance of serum thyroglobulin (Tg) in the decision-making of response to 131I therapy and subsequent treatment for distant metastatic differentiated thyroid cancer (DM-DTC). Methods:Between January 2018 and December 2019, a total of 62 papillary thyroid cancer (PTC) patients (20 males and 42 females, age: (38.1±15.9) years) with pulmonary metastasis from Peking Union Medical College Hospital were retrospectively analyzed. Patients were divided into two groups (non-radioactive iodine (RAI)-avid group and RAI-avid group) according to the post-treatment whole body scan (Rx-WBS). The serum Tg response to 131I therapy including Tg change and Tg change speed was compared between two groups, and the relationship between serum Tg change speed and structural progression was explored by binary logistic regression analysis. The Tg response to different treatment schemes ( 131I treatment or follow-up) was compared in non-RAI-avid group. χ2 test and Mann-Whitney U test were used to compare data between different groups. Receiver operating characteristic (ROC) curve analysis was used to find the best threshold of Tg change speed to predict the structural progress. Results:After 131I treatment, increased Tg level was found in 60.0% (15/25) patients in non-RAI-avid group ( n=25), while only 21.6%(8/37) patients in RAI-avid group ( n=37; χ2=9.417, P=0.002). Non-RAI-avid group showed an overall increased Tg trend, with a speed of 0.05(-0.16, 0.15) μg·L -1·month -1, while RAI-avid group showed a general decreased Tg trend, with a speed of -0.18(-1.95, 0.01) μg·L -1·month -1 ( U=265.000, P=0.005). A significant correlation between Tg change speed and structural response (odds ratio ( OR)=53.005, P<0.001) was found. When Tg change speed was more than 0.135 μg·L -1·month -1, structural progression could be well predicted with the sensitivity of 87.5% and specificity of 97.1%. 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 Tg change and Tg change speed ( χ2=0.071, U=394.000; both P>0.05). Conclusions:The serum Tg monitoring can be more sensitive in evaluating the therapeutic response to 131I for DM-DTC patients in whom response evaluation criteria in solid tumors (RECIST) might not be sensitive enough to reflect the minor change. For patients with non-RAI-avidity, Tg evaluation will offer more sensitive evidence to tailor the necessity of further 131I treatment.
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The retained functionality of the sodium iodide symporter (NIS) expressed in differentiated thyroid cancer (DTC) cells allows the further utilization of post-surgical radioactive iodine (RAI) therapy, which is an effective treatment for reducing the risk of recurrence, and even the mortality, of DTC. Whereas, the dedifferentiation of DTC could influence the expression of functional NIS, thereby reducing the efficacy of RAI therapy in advanced DTC. Genetic alternations (such as BRAF and the rearranged during transfection [RET]/papillary thyroid cancer [PTC] rearrangement) have been widely reported to be prominently responsible for the onset, progression, and dedifferentiation of PTC, mainly through activating the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling cascades. These genetic alternations have been suggested to associate with the reduced expression of iodide-handling genes in thyroid cancer, especially the NIS gene, disabling iodine uptake and causing resistance to RAI therapy. Recently, novel and promising approaches aiming at various targets have been attempted to restore the expression of these iodine-metabolizing genes and enhance iodine uptake through in vitro studies and studies of RAI-refractory (RAIR)-DTC patients. In this review, we discuss the regulation of NIS, known mechanisms of dedifferentiation including the MAPK and PI3K pathways, and the current status of redifferentiation therapy for RAIR-DTC patients.
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Humanos , Técnicas In Vitro , Iodo , Transporte de Íons , Isótopos , Mortalidade , Proteínas Quinases , Recidiva , Iodeto de Sódio , Glândula Tireoide , Neoplasias da Glândula Tireoide , TransfecçãoRESUMO
Radioiodine-131(131I) therapy as one of the post-surgical targeted therapies has been proven as an effective treatment modality in reducing the risk of recurrence and mortality in intermediate and high risk differentiated thyroid cancer (DTC). With increasing evidence over recent years, improvements in the management of DTC have been observed. In this review, several points and their influences on DTC decision making are discussed, including the purpose of 131I therapy, evaluating system for risks and on-going response to therapy, as well as the significance of molecular features such as thyroglobulin, molecular pathology and nuclear medicine molecular imaging.
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Objective:To continuously evaluate the response of differentiated thyroid cancer(DTC)after radioiodine therapy,and to an-alyze influencing factors for excellent response. Methods: Data of 237 patients with non-distant metastatic DTC treated in Peking Union Medical College Hospital were retrospectively analyzed,and the changes in response were evaluated(excellent response,ER;biochemical incomplete response,BIR;and structure incomplete response,SIR)2 years after receiving the 131I therapy.The responses of different recurrence-risk stratification and TNM stages were contrasted,and the influencing factors to ER were analyzed by multiple-factor analysis.Results:The percentage of the responses obtained 3 months and 2 years after 131I therapy were(3 months/2 years)as follows:54.9%/73.0%,33.3%/18.1%,11.8%/6.0%,and 0/3.4%.Of the initial IR patients,45.6% were observed to transfer into ER and 28.6% of the BIR patients are confirmed cervical recurrence by pathology.Recurrence-risk stratification and ER rate were negatively correlated(r=0.973,P=0.147);however,TNM stage and response showed no evident correlation.The size of tumor and the number of lymph node metastasis were the main influencing factors in obtaining ER(P=0.008,0.007,respectivtly).Conclusion:The rate of ER in non-metastasis DTC patients increased gradually after receiving 131I therapy.Approximately half of initial IR patients reached ER two years after treatment,and the patients with small diameter of tumor and less lymph node invasion tend to obtain ER.
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Objective To compare two recurrence-risk stratification software (RSS),which could evaluate the recurrence-risk in patients with differentiated thyroid carcinoma (DTC) intelligently.Methods Based on 2009 American Thyroid Association (ATA) guidelines and clinical guidelines for 131I therapy of DTC patients in China (2014),two RSS (RSS1 and RSS2) were designed.From January 2013 to January 2016,1 043 non-metastasis DTC patients (386 males,657 females;average age (46.4±10.5) years) in Peking Union Medical College Hospital were involved to be risk-stratified,and the results were evaluated by ATA response evaluation system.x2 test was used to analyze the data.Results With 2 years' (median) follow-up,the recurrence rates in low,intermediate and high recurrence-risk groups evaluated by RSS1 were 2.8％(1/36),4.7％ (34/725) and 42.9％ (121/282),and those were 0(0/29),3.7％ (26/698) and 41.1％(130/316) evaluated by RSS2.The recurrence rate was lower in low-risk group evaluated by RSS2 than that by RSS1,but there was no significant difference (x2=3.046,P＞0.05).More patients with recurrence were divided into high-risk group evaluated by RSS2,but the recurrence rates of 2 high-risk groups evaluated by RSS1 and RSS2 were not significantly different (x2 =0.082,P＞0.05).Conclusion RSS1 and RSS2 could predict recurrence-risk effectively,and RSS2 could classify more recurrent patients into high-risk group.
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With the increasing of incidence,differentiated thyroid carcinoma (DTC) has become a global concern.Over the recent decades,the guidelines for the management of DTC has been kept updating along with the development of molecular biology and improvement of diagnosis and treatment approaches.Here we focus on the updates regarding nuclear medicine management of DTC in American Thyroid Association (ATA) and National Cancer Comprehensive Network (NCCN) guidelines.A brief interpretation is related from the roles of following perspectives with regards to the evaluation before radioactive iodine therapy and during follow-up,including the value of recurrence risk stratification,thyroglobulin (Tg),molecular pathology,nuclear medicine imaging and ongoing evaluation system.
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Objective To investigate the efficacy of thyroid ablation with low dose (1 110 MBq) 131 I for non-distant metastases differentiated thyroid carcinoma (DTC) and its probable influence factors.Methods A total of 183 DTC patients (48 males,135 females,average age:(39.75±10.14) years) treated by thyroid ablation with 1 110 MBq 131I from January 2015 to December 2016 were respectively observed.All patients underwent diagnostic whole body scan (Dx-WBS) and the stimulated thyroglobulin (sTg) was measured 6-9 months after thyroid ablation.According to the results,patients were divided into successful ablation group (G1) and unsuccessful group (G2).Clinical and pathological characteristics of 2 groups were compared by two-sample t test,Mann-Whitney u test andx2 test.Logistic regression was used to identify the influence factors for efficacy of 131I ablation,and the cutoff value was determined by receiver operating characteristic (ROC) curve analysis.Results There were 156 patients in G1 and 27 patients in G2.The successful ablation rate was 85.25％(156/183).Comparing with patients in G2,patients in G1 showed higher thyroid stimulating hormone (TSH) before ablation and lower sTg.The TSH level was 137.94(124.21,150.00) and 74.91(55.57,98.18) mU/L respectively (u=6.458,P＜0.05),and sTg was 1.80(0.69,5.20) and 22.30(4.49,32.20) μg/L respectively (u=-6.174,P＜0.05).Logistic regression showed that TSH,sTg and T stage before ablation were independent predictors for efficacy of 131I ablation (odds ratios:0.357-0.944).The optimal cutoff values of TSH and sTg identified by ROC curve analysis were 122.98 mU/L and 13.78 μg/L.Conclusions Low-dose 131I is effective enough for ablation treatment in non-distant metastases DTC patients with low T stage and low sTg(＜ 13.78 μg/L).High TSH (＞ 122.98 mU/L) before ablation may facilitate the efficacy of 131I ablation.
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The prevalence of thyroid nodules, especially differentiated thyroid cancer, has increased during the past decades. With the consideration of increasing prevalence of the diseases, American Thyroid Association (ATA) updated the guidelines for adult patients with thyroid nodules and differentiated thyroid carcinoma (DTC) in 2015. The aim of the new guidelines was to minimize potential harm from overtreatment in majority of patients at low risk for diseasespecific mortality and morbidity while appropriately treat and monitor those patients at higher risk. The updates of contents in new ATA guidelines are interpreted in this article, including the contents about screening, diagnosis and treatment plan of nodules, initial surgical treatment of DTC, the evaluation and treatment of DTC after surgery, follow-up and diagnosis and treatment of recurrence, persistence, and distant metastasis of DTC.
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Surgery, selective radioiodine therapy and thyroid stimulating hormone suppressive therapy are the standard treatment modalities for differentiated thyroid cancer (DTC). After therapy, most DTC patients could get good prognosis. However, some patients with distant metastasis lose the ability to concentrate radioiodine at early time or during the treatment, and develop radioiodine-refractory DTC (RAIR-DTC). These patients progress quickly and have high mortality. Looking for effective treatments for these patients has been the hot spot in research of thyroid carcinoma. In this paper, we summarized the recent advances in the diagnosis and treatment of RAIR-DTC, hoping to early identify these patients and buy time for early intervention of other possible beneficial treatments such as targeted therapy and radiotherapy.
