Transcriptome and metabolome sequencing identifies glutamate and LPAR1 as potential factors of anlotinib resistance in thyroid cancer.

OBJECTIVE: To explore the mechanism of anlotinib resistance in thyroid carcinoma. METHODS: We constructed an anlotinib-resistant thyroid carcinoma cell line and observed the effect of drug resistance on the functional activity of these cell lines. Transcriptome sequencing and metabolomic sequencing combined with biosynthesis analysis were used to explore and screen possible drug resistance regulatory pathways. RESULTS: Through transcriptomic sequencing analysis of drug-resistant cell lines, it was found that the differentially expressed genes of drug-resistant strains were enriched mainly in the interleukin 17, transforming growth factor-ß, calcium, peroxisome proliferator activated receptor, and other key signaling pathways. A total of 354 differentially expressed metabolic ions were screened using liquid chromatography-mass spectrometry/mass spectrometry to determine the number of metabolic ions in the drug-resistant strains. The results of the Venn diagram correlation analysis showed that glutamate is closely related to multiple pathways and may be an important regulatory factor of anlotinib resistance in thyroid carcinoma. In addition, eight common differentially expressed genes were screened by comparing the gene expression profiling interactive analysis database and sequencing results. Further quantitative real time polymerase chain reaction verification, combined with reports in the literature, showed that LPAR1 may be an important potential target. CONCLUSION: This is the first study in which the drug resistance of thyroid cancer to anlotinib was preliminarily discussed. We confirmed that anlotinib resistance in thyroid cancer promotes the progression of malignant biological behavior. We conclude that glutamate may be a potential factor for anlotinib resistance in thyroid cancer and that LPAR1 is also a potentially important target.

Trends of the prevalence rate of central lymph node metastasis and multifocality in patients with low-risk papillary thyroid carcinoma after delayed thyroid surgery.

Background: Active surveillance has been an option for patients with low-risk papillary thyroid carcinoma (PTC). However, whether delayed surgery leads to an increased risk of local tumor metastasis remain unclear. We sought to investigate the impact of observation time on central lymph node metastasis (CLNM) and multifocal disease in patients with low-risk PTC. Methods: Patients who were diagnosed with asymptomatic low-risk PTC, and with a pathological maximum tumor size ≤1.5 cm by were included. The patients were classified into observation group and immediate surgery group, and subgroup analyses were conducted by observation time period. The prevalence of CLNM, lymph node (LN) involved >5, multifocal PTC and bilateral multifocal PTC were considered as outcome variables. The changing trend and risk ratio of prevalence over observation time were evaluated by Mann-Kendall trend test and Logistics regression. Results: Overall, 3,427 and 1,860 patients were classified to the observation group and immediate surgery group, respectively. Trend tests showed that decreasing trends both on the prevalence of CLNM and LN involved >5 over the observation time, but the difference was not statistically significant, and the prevalence of multifocal PTC and bilateral multifocal PTC showed the significant decreasing trends. After adjustment, multivariate analysis showed no statistically significant difference between observed and immediate surgery groups in the four outcome variables. Conclusion: In patients with subclinical asymptomatic low-risk PTC, observation did not result in an increased incidence of local metastatic disease, nor did the increased surgery extent in patients with delayed surgery compared to immediate surgery. These findings can strengthen the confidence in the active surveillance management for both doctors and patients.

Anlotinib in Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid Carcinoma: A Randomized, Double-Blind, Multicenter Phase II Trial.

PURPOSE: Alhough antiangiogenic agents are the bedrock of treatment for radioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC), novel antiangiogenic agents with optimized features like greater target-binding affinities and more favorable pharmacokinetics profile are needed. This phase II randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of anlotinib, a multikinase inhibitor, for RAIR-DTC. PATIENTS AND METHODS: Patients (ages between 18 and 70 years) with pathologically confirmed locally advanced or metastatic RAIR-DTC were enrolled and randomly received 12 mg anlotinib once daily or placebo on day 1 to 14 every 3 weeks. Patients on placebo were allowed to receive open-label anlotinib after disease progression. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and safety. RESULTS: Between September 2015 and August 2018, 76 and 37 patients randomly received anlotinib and placebo, respectively. Patients receiving anlotinib had a significantly longer median PFS [40.5 months, 95% confidence interval (CI), 28.3-not estimable (NE) versus placebo 8.4 months, 95% CI, 5.6-13.8; HR = 0.21, 95% CI, 0.12-0.37, P < 0.001], meeting the primary endpoint. OS was still immature, with a trend of benefit with anlotinib (HR = 0.57, 95% CI, 0.29-1.12). All patients in the anlotinib group experienced adverse events (AE); 8 (10.5%) discontinued treatment due to AEs. CONCLUSIONS: Anlotinib demonstrated promising efficacy and favorable tolerance in the treatment of locally advanced or metastatic RAIR-DTC, supporting further research to establish its role in the treatment of this serious disease.

TPO as an indicator of lymph node metastasis and recurrence in papillary thyroid carcinoma.

The objective of this study was to investigate the expression of thyroid peroxidase (TPO) in papillary thyroid carcinoma (PTC) and to preliminarily investigate its value as a marker of lymph node metastasis and recurrence in patients with PTC. Clinical data of PTC patients and TPO expression were collected from The Cancer Genome Atlas (TCGA) database for analysis. We recruited 230 consecutive PTC patients from the Department of Thyroid Surgery of the First Affiliated Hospital of Kunming Medical University, collected their clinicopathological data, and also performed immunohistochemical analysis of TPO expression on their thyroid specimens to validate the results of bioinformatics analysis. In addition, the construction of protein-protein interaction networks was performed too. Functional enrichment analysis and immuno-infiltration analysis characterized the pathways in which TPO genes may be involved. Data mining based on the TCGA database showed that TPO expression in PTC tissues was significantly lower than in paired normal thyroid tissues. The expression level of TPO in PTC tissues correlated with tumor lymph node metastasis and recurrence. Follow-up data from our center also validated the difference in TPO expression and its relationship with lymph node metastasis in PTC patients. Functional enrichment analysis showed that TPO function was significantly associated with signaling pathways related to amino acid metabolism, gene expression regulation and tumorigenesis. TPO expression was also significantly associated with immune infiltration. Our study showed that reduced TPO expression was significantly associated with lymph node metastasis and recurrence in patients with PTC, and we validated this result in our central cohort. These data suggest that TPO may serve as a prognostic indicator for PTC.

Neoadjuvant therapy with anlotinib in a locally advanced and pulmonary metastasis PTC patient harboring TERT promoter and BRAFV600E mutations: a case report.

A 71-year-old woman with recurrent papillary thyroid carcinoma (PTC) was referred to our hospital. A computed tomography scan revealed extensive recurrence in the neck, invading sternocleidomastoid muscle, internal jugular vein, sternal end of the clavicle, strap muscle and skin; and lateral compartment and subclavian lymph nodes were also involved. Multiple pulmonary micrometastases also noticed. The tumor was considered unresectable; however, the patient was unwilling to accept highly invasive surgery. Therefore, we initiated neoadjuvant therapy with anlotinib, 12mg p.o. daily with a 2-week on/1-week off regimen. The tumor shrunk to resectable state after 4 cycles of treatment, and after 3 weeks of withdrawal, successful surgical resection without gross tumor residual was performed. Pathology confirmed as classic PTC harboring coexistent TERT promoter and BRAFV600E mutations by NGS. After anlotinib therapy, apoptosis induction was observed, and proliferation increased, which was due to three weeks of anlotinib withdraw. Structual recurrence was recorded at 6 months after operation due to no further treatment was taken. Our finding suggests that anlotinib could represent as a good treatment option for patients with locally advanced (with or without distant metastasis) PTC; Anlotinib treatment resulted in sufficient reduction of the tumor mass to enable total thyroidectomy and radioactive iodine treatment, providing long-term control of the disease.

Single inferior parathyroid autotransplantation during total thyroidectomy with bilateral central lymph node dissection for papillary thyroid carcinoma: a retrospective cohort study.

BACKGROUND: Management of the inferior parathyroid gland using total thyroidectomy (TT) with central lymph node dissection (CLND) is still controversial. Therefore, we evaluated the safety and effectiveness of single inferior parathyroid autotransplantation. METHODS: The clinical data of patients with papillary thyroid carcinoma (PTC) who underwent TT with bilateral CLND from January 2018 to December 2020 were collected. Quality of life (QoL) was assessed using the Chinese version of the EORTC QLQ-C30 and THYCA-QOL. The patients were divided into an autotransplantation group and a preservation group according to whether a single inferior parathyroid gland was transplanted. The incidence of permanent hypoparathyroidism, the number of resected central lymph nodes (CLNs), the rate of recurrence reoperation, the rate of radioactive iodine (RAI) treatment, and the QoL score were compared between the two groups. RESULTS: A total of 296 patients were included in the study; there were 99 patients in the autotransplantation group and 197 in the preservation group. The incidence of permanent hypoparathyroidism was 3.0% (3/99) and 4.6% (9/197) in the autotransplantation and preservation groups, respectively (P = 0.532). The median number of resected CLNs was 12 (8-17) and 10 (6-14) in the autotransplantation and preservation groups, respectively (P = 0.015). No reoperations were performed for patients with CLN recurrence, and the rates of lateral lymph node (LLN) recurrence reoperation were 2.0% (2/99) and 3.6% (7/197) in the autotransplantation and preservation groups, respectively (P = 0.473). The RAI treatment rates were 12.1% (12/99) and 22.3% (44/197) in the autotransplantation and preservation groups, respectively (P = 0.034). A total of 276 questionnaires were recovered, including 84 in the autotransplantation group and 192 in the preservation group. The QoL of the two groups of patients is similar (P > 0.05). CONCLUSION: Single inferior parathyroid autotransplantation during thyroidectomy can be used to prevent permanent hypoparathyroidism and can enable more extensive CLND.

Association of Body Mass Index With Clinicopathological Features of Papillary Thyroid Carcinoma: A Retrospective Study.

OBJECTIVE: We examined the effect of body mass index (BMI) on clinicopathological features of papillary thyroid carcinoma (PTC). METHODS: The clinical data of 4476 patients with PTC who underwent surgical treatment were retrospectively analyzed. According to the different BMI of patients, it can be divided into underweight (BMI < 18.5 kg/m2), normal weight (18.5 ≤ BMI < 24.0 kg/m2), overweight (24 ≤ BMI < 28 kg/m2), and obese (BMI ≥ 28 kg/m2). Spearman correlation analysis was performed to assess the relationship between the BMI and the size of PTC tumor. Multivariate binary logistic regression analysis was performed to estimate the association of overweight and obesity with clinicopathological features of PTC. RESULTS: There was a positive correlation between the BMI and PTC tumor size (r = 0.087, P < .001). As compared with normal weight patients with PTC, overweight and obese patients with PTC had a greater risk of bilaterality (odds ratio [OR] = 1.295, OR = 1.669), multifocality (OR = 1.273, OR = 1.617), extrathyroidal extension (OR = 1.560, OR = 2.477), T (3 + 4) stage (OR = 1.482, OR = 2.392), and recurrence risk (intermediate-high risk) (OR = 1.215, OR = 1.718) (P < .05 for all). As compared with normal weight patients with papillary thyroid microcarcinoma (PTMC), overweight and obese patients with PTMC had a greater risk of bilaterality (OR = 1.341, OR = 1.737), multifocality (OR = 1.244, OR = 1.640), extrathyroidal extension (OR = 1.992, OR = 2.080), T (3 + 4) stage (OR = 1898, OR = 2.039), and recurrence risk (intermediate-high risk) (OR = 1.458, OR = 1.536) (P < .05 for all). CONCLUSION: Overweight and obesity were significantly associated with aggressive clinicopathological features of PTC and PTMC. The impact of overweight and obesity should be considered when choosing treatment decisions for PTC and PTMC.

Safety and effectiveness of carbon nanoparticles suspension-guided lymph node dissection during thyroidectomy in patients with thyroid papillary cancer: a prospective, multicenter, randomized, blank-controlled trial.

Objective: This study aimed to evaluate the effectiveness and safety of carbon nanoparticles-guided lymph node dissection during thyroidectomy in patients with papillary thyroid cancer(PTC). Methods: Clinical trials consisted of two subgroups: unilateral lobectomy (UL; n=283) and total thyroidectomy (TT; n=286). From each subgroup, the patients were randomly assigned to two groups: the carbon nanoparticle group and control group. Primary endpoints included parathyroid hormone (PTH) levels, number of lymph nodes (LNs) detected, number of tiny lymph nodes detected, and recognition and retention of the parathyroid glands. Secondary endpoint was recognition and protection of the recurrent laryngeal nerve. Results: A total of 569 patients with PTC were recruited. There were no statistically significant differences in demographics between the carbon nanoparticles and control groups (P > 0.05). In the UL subgroup, there were no significant differences in PTH levels between the two groups at preoperative, intraoperative, and postoperative day one, and postoperative month one (P>0.05). There was no significant difference in the serum Ca2+ levels between the two groups preoperatively and at postoperative month one (P>0.05). The number of lymph nodes dissected in the carbon nanoparticles group was significantly higher than that in the control group (P<0.0001). The detection rate of tiny lymph nodes in the carbon nanoparticles group was higher than that in the control group (P=0.0268). In the TT subgroup, there was no significant difference in PTH levels between the two groups at preoperative, intraoperative, and postoperative day one (P>0.05). However, the mean PTH level in the carbon nanoparticles group was significantly higher than that of the control group at postoperative month one (P=0.0368). There was no significant difference in the serum Ca2+ levels between the two groups preoperatively and at postoperative month one (P>0.05). There were no significant differences between the two groups in the number of dissected LNs (P>0.05) or the detection rate of tiny lymph nodes (P>0.05). No drug-related AE and complications due to the injection of carbon nanoparticles were recorded in this study. There were no significant differences between the two groups in terms of parathyroid preserved in situ and recurrent laryngeal nerve injury in the UL and TT subgroups. Conclusions: Carbon nanoparticles demonstrated efficacy and safety in thyroidectomy. The application of carbon nanoparticles could significantly facilitate the identification and clearance of LNs and the optimum preservation of parathyroid function. Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2300068502.

Neoadjuvant therapy with anlotinib in a locally advanced and pulmonary metastasis PTC patient harboring TERT promoter and BRAFV600E mutations: a case report

SUMMARY A 71-year-old woman with recurrent papillary thyroid carcinoma (PTC) was referred to our hospital. A computed tomography scan revealed extensive recurrence in the neck, invading sternocleidomastoid muscle, internal jugular vein, sternal end of the clavicle, strap muscle and skin; and lateral compartment and subclavian lymph nodes were also involved. Multiple pulmonary micrometastases also noticed. The tumor was considered unresectable; however, the patient was unwilling to accept highly invasive surgery. Therefore, we initiated neoadjuvant therapy with anlotinib, 12mg p.o. daily with a 2-week on/1-week off regimen. The tumor shrunk to resectable state after 4 cycles of treatment, and after 3 weeks of withdrawal, successful surgical resection without gross tumor residual was performed. Pathology confirmed as classic PTC harboring coexistent TERT promoter and BRAFV600E mutations by NGS. After anlotinib therapy, apoptosis induction was observed, and proliferation increased, which was due to three weeks of anlotinib withdraw. Structual recurrence was recorded at 6 months after operation due to no further treatment was taken. Our finding suggests that anlotinib could represent as a good treatment option for patients with locally advanced (with or without distant metastasis) PTC; Anlotinib treatment resulted in sufficient reduction of the tumor mass to enable total thyroidectomy and radioactive iodine treatment, providing long-term control of the disease.

Anlotinib in patients with medullary thyroid carcinoma with negative prognostic factors: A sub-analysis based on the ALTER01031 study.

Background: Medullary thyroid carcinoma (MTC) is a rare type of thyroid cancer; however, it accounted for 13.4% of the disease-specific mortalities. ALTER01031 (NCT02586350) was a randomised, placebo-controlled phase 2b trial that evaluated the efficacy and safety of anlotinib in locally advanced or metastatic MTC. This post hoc analysis aimed to evaluate the efficacy and safety of anlotinib in older patients and those with bone metastases using ALTER01031. Methods: In ALTER01031, anlotinib significantly prolonged the median progression-free survival (PFS) from 11.1 months to 20.7 months compared with placebo in the whole population. Patients who were older (≥ 50 years) or had bone metastases were selected. PFS and overall survival (OS) were estimated and compared between patients receiving anlotinib or placebo in each subgroup. A sub-analysis of tumour response and safety was also performed. Results: Patients with older age or bone metastases experienced rapid disease progression as the median PFS was 6.8 months and 7.0 months respectively in the placebo group. Anlotinib significantly improved the median PFS to 17.5 months (P = 0.002) and 20.7 months (P = 0.029) with hazard ratio (HR) of 0.31 (95% CI, 0.15-0.68) and 0.44 (95% CI, 0.20-0.94) compared with placebo. Significant benefit in OS was observed in patients with older age after a longer follow-up (HR = 0.47 [95% CI, 0.22-0.99], P = 0.041). The safety profile of these subgroups was similar to that of the entire population. Conclusion: This sub-analysis demonstrated significant survival benefits and favourable safety of anlotinib in patients with MTC who had old age or bone metastases, supporting the feasibility of anlotinib in these patients.

The impact of the initial operation of PTC in children on recurrence: 9-year experience in a single center.

PURPOSE: To summarize the treatment experience of single-center children with PTC and to explore the influence of initial surgery on the recurrence/metastasis of papillary thyroid carcinoma (PTC) in children. METHODS: A retrospective analysis of PTC case data of children (≤ 18 years old) who were admitted to and received surgical treatment in the First Affiliated Hospital of Kunming Medical University from January 2012 to December 2020. RESULTS: A total of 64 children with PTC were included, including 45 cases (70.31%) with a single lesion, and 19 cases (29.69%) with multiple lesions (≥ 2 lesions). Fifteen patients relapsed. Univariate analysis found that gender, thyroidectomy scope, central lymph node dissection, and lateral lymph node dissection were risk factors affecting reoperation; multi-factor analysis showed that central lymph node dissection was an independent risk factor affecting reoperation. According to Kaplan-Meier analysis, central lymph node dissection, total thyroidectomy (TT), lobectomy (LT), and disease-free survival (DFS) were statistically significant (p = 0.000, p = 0.000). CONCLUSION: At the time of diagnosis of PTC in children, the rate of lymph node metastasis in the central and lateral cervical regions is high. The vast majority of children with PTC should be treated with TT, and LT is chosen for a small number of patients. CND should be routinely lined.

Errate: Role of Ca²âº in Inhibiting Ischemia-Induced Apoptosis of Parathyroid Gland Cells in New Zealand White Rabbits.

In Figure 1A, the images of CG 24h group and Sham 72h group are duplicated, where the picture of Sham 72h group is correct, now the authors have corrected the picture of CG 24h group. In Figure 2A, the images of CG 72h and CSG 72h groups are duplicated, the images of CG 168h and CSG 168h groups are duplicated，where the pictures of CG 168h and CSG 72h groups are correct, now the authors have corrected the pictures of CG 72h and CSG 168h groups. In Figure 3B, the images of CG 24h group and CSG 72h group are duplicated, where the picture of CSG 72h group is correct, now the authors have corrected the picture of CG 24h group. Reference: Wei-han Cao, Yan-jun Su, Nian-qiu Liu, Ying Peng, Chang Diao, Ruo-chuan Cheng: Role of Ca²âº in Inhibiting Ischemia-Induced Apoptosis of Parathyroid Gland Cells in New Zealand White Rabbits. Med Sci Monit, 2020; 26: e920546. DOI: 10.12659/MSM.920546.

A Mathematical Model to Assess the Effect of Residual Positive Lymph Nodes on the Survival of Patients With Papillary Thyroid Microcarcinoma.

Background: Active surveillance (AS) has been considered the first-line management for patients with clinical low-risk papillary thyroid microcarcinoma (PTMC) who often have lymph node micrometastasis (m-LNM) when diagnosed. The "low-risk" and "high prevalence of m-LNM" paradox is a potential barrier to the acceptance of AS for thyroid cancer by both surgeons and patients. Methods: Patients diagnosed with PTMC who underwent thyroidectomy with at least one lymph node (LN) examined were identified from a tertiary center database (n = 5,399). A ß-binomial distribution was used to estimate the probability of missing nodal disease as a function of the number of LNs examined. Overall survival (OS) probabilities of groups with adequate and inadequate numbers of LNs examined were estimated using the Kaplan-Meier method in the Surveillance, Epidemiology, and End Results (SEER) database (n = 15,340). A multivariable model with restricted cubic splines was also used to verify the association of OS with the number of LNs examined. Results: The risk of residual m-LNM (missed nodal disease) ranged from 31.3% to 10.0% if the number of LNs examined ranged from 1 and 7 in patients with PTMC. With 7 LNs examined serving as the cutoff value, the intergroup comparison showed that residual positive LNs did not affect OS across all patients and patients aged ≥55 years (P = 0.72 and P = 0.112, respectively). After adjusting for patient and clinical characteristics, the multivariate model also showed a slight effect of the number of LNs examined on OS (P = 0.69). Conclusions: Even with the high prevalence, OS is not significantly compromised by persistent m-LNM in the body of patients with low-risk PTMC. These findings suggest that the concerns of LNM should not be viewed as an obstacle to developing AS for thyroid cancer. For patients with PTMC who undergo surgery, prophylactic central LN dissection does not provide a survival benefit.

Surgical treatment of pediatric and adolescent papillary thyroid cancer: a retrospective study of 54 patients in a single center

Abstract Objective: In 2015, American Thyroid Association (ATA) issued the first version of Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer. The purpose of this study is to evaluate whether the ATA pediatric guidelines recommended surgical approach for the patient can be applied to surgical treatment of pediatric PTC in China. Method: From April 2012 to December 2020, clinical data of children (≤18 years) with PTC consecutively admitted and treated with initial surgery in the study's department were retrospectively reviewed. Results: The authors found that the central lymph node metastasis (CLNM) rate was significantly higher than that in the lateral neck (83.33 % vs 62.96%, χ2 = 5.704, p = 0.017) .The lymph node metastasis rate was significantly lower in cN1b (-) patients than in cN1b (+) patient (55.00% vs 100.00%, χ2 = 15.263, p = 0.000); Meanwhile, the CLNM and LLNM rates of ipsilateral were significantly higher than those of contralateral central compartment (83.33༅vs 57.41༅%, χ2 = 8.704, p = 0.003). Lymph nodes of 51 lateral lymph node dissection (LND) were analyzed, which revealed the LNM rate of cN1b (-) patients was significantly lower than that of cN1b (+) patients (55.00% vs. 100.00%, χ2 = 15.263, p = 0.000). Conclusion: Children and adolescents have a higher rate of lymph node metastasis at the time of diagnosis. TT should be conducted in the majority of children with PTC. CND should be routinely performed; therapeutic LND is recommended for children with cN1b (+).

Surgical treatment of pediatric and adolescent papillary thyroid cancer: a retrospective study of 54 patients in a single center.

OBJECTIVE: In 2015, American Thyroid Association (ATA) issued the first version of Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer. The purpose of this study is to evaluate whether the ATA pediatric guidelines recommended surgical approach for the patient can be applied to surgical treatment of pediatric PTC in China. METHOD: From April 2012 to December 2020, clinical data of children (≤18 years) with PTC consecutively admitted and treated with initial surgery in the study's department were retrospectively reviewed. RESULTS: The authors found that the central lymph node metastasis (CLNM) rate was significantly higher than that in the lateral neck (83.33 % vs 62.96%, χ2 = 5.704, p = 0.017) .The lymph node metastasis rate was significantly lower in cN1b (-) patients than in cN1b (+) patient (55.00% vs 100.00%, χ2 = 15.263, p = 0.000); Meanwhile, the CLNM and LLNM rates of ipsilateral were significantly higher than those of contralateral central compartment (83.33༅vs 57.41༅%, χ2 = 8.704, p = 0.003). Lymph nodes of 51 lateral lymph node dissection (LND) were analyzed, which revealed the LNM rate of cN1b (-) patients was significantly lower than that of cN1b (+) patients (55.00% vs. 100.00%, χ2 = 15.263, p = 0.000). CONCLUSION: Children and adolescents have a higher rate of lymph node metastasis at the time of diagnosis. TT should be conducted in the majority of children with PTC. CND should be routinely performed; therapeutic LND is recommended for children with cN1b (+).

Can Active Surveillance Management be Developed for Patients With Low-Risk Papillary Thyroid Microcarcinoma? A Preliminary Investigation in a Chinese Population.

OBJECTIVE: Active surveillance (AS) has been shown to be a safe approach that can effectively block transition from overdiagnosis to overtreatment in patients with low-risk papillary thyroid microcarcinoma (PTMC). This study aimed to determine whether the AS approach can be implemented in China and investigate the population characteristics of Chinese patients who underwent AS. METHODS: The epidemiologic and clinical characteristics as well as patient adherence were evaluated in 115 patients who underwent AS management as an alternative to immediate surgery for low-risk (or highly suspected) PTMC. RESULTS: The mean patient age was 41.8 ± 10.3 years, with 41.7% and 4.4% of the patients aged <40 and ≥60 years, respectively. The median baseline diameter of index tumors was 4 (range, 3-6) mm, with 73.0% of the tumors being ≤5 mm. A total of 84.4% of the patients had a junior college, college, or graduate degree, and 83.5% were employed by the government, public institutions, companies, or technical posts. After a median 25-month follow-up, a tumor growth of ≥3 mm occurred in 3 patients (2.6%), and no new lymph node metastasis occurred. Surgery was performed in 4 patients because of patient preferences rather than because of disease progression. There was satisfactory adherence in 109 patients (94.8%) in a simulated ideal medical environment. CONCLUSION: The AS approach can be used as an alternative to low-risk PTMC management in China. Given the difference in epidemiologic and clinical characteristics, Chinese institutions should fully consider the features of the Chinese population while developing candidate criteria, surveillance intervals, and follow-up strategies for AS.

A multicenter, prospective study to observe the initial management of patients with differentiated thyroid cancer in China (DTCC study).

BACKGROUND: To assess the gaps between the initial management of patients with differentiated thyroid cancer (DTC) in real clinical practice and the recommendations of the 2012 Chinese DTC guidelines. METHODS: This multicenter, prospective study was conducted at nine tertiary hospitals across China. Eligible patients were those having intermediate or high-risk DTC after first-time thyroidectomy. During 1 year of follow-up, comprehensive medical records were collected and summarized using descriptive statistics. RESULTS: Of 2013 patients, 1874 (93.1%) underwent standard surgery according to the guidelines (including total lobectomy plus isthmusectomy and total/near total thyroidectomy), and 1993 (99.0%) underwent lymph node dissection; only 56 (2.8%) had postoperative complications. Overall, 982/2013 patients (48.8%) received radioactive iodine (RAI) therapy after thyroidectomy. Of all enrolled patients, 61.4% achieved the target serum thyroid-stimulating hormone level, with a median time to target of 234.0 days (95% CI: 222.0-252.0). At 1 year of follow-up, proportions of patients with excellent response, incomplete structural response, biochemical incomplete response, and indeterminate response were 34.6, 11.2, 6.6, and 47.5%, respectively; recurrence or metastasis occurred in 27 patients (1.3%). During the overall study period, 209 patients (10.4%) had at least one adverse event: 65.1% of cases were mild, 24.9% moderate, and 10.1% severe. CONCLUSIONS: This was the first large-scale prospective study of how patients with DTC in China are treated in actual practice. Initial DTC management is generally safe and adheres to the 2012 Chinese guidelines but could be improved, and the level of guideline adherence did not produce the anticipated treatment response at 1 year of follow-up.

The active surveillance management approach for patients with low risk papillary thyroid microcarcinomas: is China ready?

Due to exponential increases in incidences, low risk papillary thyroid microcarcinoma (PTMC) has become a clinical and social issue in recent years. An active surveillance (AS) management approach is an alternative to immediate surgery for patients with low risk PTMC. With decreased doubts about the safety and validity due to evidence from a large number of studies, the AS approach has become increasingly popular worldwide. However, Chinese thyroid surgeons still lag behind other countries in their knowledge of clinical practices and research related to AS. To promote the implementation of AS in China, thyroid surgeons should understand the implications, advantages, and disadvantages of management approaches for AS, and should also consider the willingness of Chinese patients, the impact on the medical billing system, and the enthusiasm of doctors. Thus, a management approach for AS based on the Chinese population should be developed to reduce the risk of disease progression and enhance patient adherence. Herein, we summarize the recent research achievements and deficiencies in AS approaches, and describe the initial experiences regarding AS in the Chinese population, in order to assist Chinese thyroid surgeons in preparing for AS management in the era of PTMC precision medicine.

Risk factors for central lymph node metastasis in the cervical region in papillary thyroid carcinoma: a retrospective study.

BACKGROUND: To investigate the influence of different risk factors on central lymph node metastasis (CLNM) in the cervical region in patients with papillary thyroid carcinoma (PTC). METHODS: This retrospective study included 2586 PTC patients. Potential risk factors were identified by univariate analysis, and the relationships between these factors and CLNM were ascertained by multivariable analysis. A scoring system was constructed, and the optimal cut-off value was determined. RESULTS: On univariate analysis, sex, age, tumor diameter, multifocality, capsule invasion, vascular invasion, total number of lymph nodes in the central region, and serum thyroid peroxidase antibody (TPOAb) concentration were identified as potential risk factors for CLNM in the cervical region, whereas nerve invasion, thyroid-stimulating hormone concentration, and thyroglobulin antibody (TgAb) concentration were not. Multivariable analysis indicated that male sex, young age, large tumor diameter, multifocality, vascular invasion, a large number of central lymph nodes, and a low TPOAb concentration were significant risk factors. From these factors, a preoperative CLNM risk assessment scale was constructed for predicting CLNM in the cervical region for PTC patients. CONCLUSION: Male sex, young age, large tumor diameter, multifocality, vascular invasion, a large number of central lymph nodes, and a low TPOAb concentration were positively correlated with CLNM in the cervical region in PTC patients. The preoperative CLNM risk assessment scale based on these risk factors is expected to offer accurate preoperative assessment of central lymph node status in PTC patients.

Case Report: Anlotinib Therapy in a Patient With Recurrent and Metastatic RAIR-DTC Harboring Coexistent TERT Promoter and BRAFV600E Mutations.

We describe a case of recurrent and metastatic radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) treated with anlotinib in this report. The patient was randomized to placebo initially, after disease progressed at C8 (C is the treatment cycle), the patient was referred to the open label therapy of anlotinib, 12 mg p.o. daily with a 2-week on/1-week off regimen. Partial response was achieved at C2 with anlotinib treatment. To date, over 37 months of progression-free survival (PFS) has been achieved. Adverse effects were tolerable and manageable in this patient. Molecular characterization revealed coexistent C228T mutation of TERT promoter and BRAFV600E mutations. Favorable clinical outcome in this patient suggests that anlotinib might provide a novel effective therapeutic option for patients with RAIR-DTC. TERT and BRAFV600E mutations may represent as biomarker for predicting salutary effects of anlotinib.