Time Kinetics and prognosis roles of calcitonin after surgery for medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a malignant tumor with low incidence. Currently, most studies have focused on the prognostic risk factors of MTC, whatever, time kinetic and risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) are yet to be elucidated. METHODS: A retrospective study was conducted for 190 MTC patients. Risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) were analyzed. The predictors of calcitonin normalization time (CNT) and biochemical persistent/recurrent time (BPT) were identified. Further, the prognostic roles of CNT and BPT were also demonstrated. RESULTS: The 5- and 10-year DFS were 86.7% and 70.2%, respectively. The 5- and 10-year OS were 97.6% and 78.8%, respectively. CN was achieved in 120 (63.2%) patients, whereas BP was presented in 76 (40.0%) patients at the last follow up. After curative surgery, 39 (32.5%) and 106 (88.3%) patients achieved CN within 1 week and 1 month. All patients who failed to achieve CN turned to BP over time and 32/70 of them developed structural recurrence. The median time of CNT and BPT was 1 month (1 day to 84 months) and 6 month (3 day to 63months), respectively. LNR > 0.23 and male gender were independent predictors for CN and BP. LNR > 0.23 (Hazard ratio (HR), 0.24; 95% CI,0.13-0.46; P < 0.01) and male gender (HR, 0.65; 95% CI, 0.42-0.99; P = 0.045) were independent predictors for longer CNT. LNR > 0.23 (HR,5.10; 95% CI,2.15-12.11; P < 0.01) was still the strongest independent predictor followed by preoperative serum Ctn > 1400ng/L (HR,2.34; 95% CI,1.29-4.25; P = 0.005) for shorter BPT. In survival analysis, primary tumor size > 2 cm (HR, 5.81; 95% CI,2.20-15.38; P < 0.01), CNT > 1 month (HR, 5.69; 95% CI, 1.17-27.61; P = 0.031) and multifocality (HR, 3.10; 95% CI, 1.45-6.65; P = 0.004) were independent predictor of DFS. CONCLUSION: Early changes of Ctn after curative surgery can predict the long-term risks of biochemical and structural recurrence, which provide a useful real-time prognostic information. LNR significantly affect the time kinetic of biochemical prognosis. Tumor burden and CNT play a crucial role in MTC survival, the intensity of follow-up must be tailored accordingly.

Efficacy and safety of pralsetinib in patients with advanced RET fusion-positive non-small cell lung cancer.

BACKGROUND: Pralsetinib is a potent, selective RET inhibitor targeting oncogenic RET alterations. As part of the global, phase 1/2 ARROW trial (NCT03037385), the efficacy and safety of pralsetinib in Chinese patients with advanced RET fusion-positive non-small cell lung cancer (NSCLC) were evaluated. METHODS: Adult patients with advanced, RET fusion-positive NSCLC with or without prior platinum-based chemotherapy were enrolled into two cohorts receiving 400-mg once-daily oral pralsetinib. Primary end points were objective response rates assessed by blinded independent central review and safety. RESULTS: Of 68 patients enrolled, 37 had received prior platinum-based chemotherapy (48.6% with ≥3 prior systemic regimens) and 31 were treatment-naïve. As of March 4, 2022 (data cutoff), of the patients with measurable lesions at baseline, a confirmed objective response was observed in 22 (66.7%; 95% confidence interval [CI], 48.2-82.0) of 33 pretreated patients, including 1 (3.0%) complete response and 21 (63.6%) partial responses; and in 25 (83.3%; 95% CI, 65.3-94.4) of 30 treatment-naïve patients, including two (6.7%) complete responses and 23 (76.7%) partial responses. Median progression-free survival was 11.7 months (95% CI, 8.7-not estimable) in pretreated patients and 12.7 months (95% CI, 8.9-not estimable) in treatment-naïve patients. The most common grade 3/4 treatment-related adverse events in 68 patients were anemia (35.3%) and decreased neutrophil count (33.8%). Eight (11.8%) patients discontinued pralsetinib because of treatment-related adverse events. CONCLUSION: Pralsetinib showed robust and durable clinical activity with a well-tolerated safety profile in Chinese patients with RET fusion-positive NSCLC. CLINICAL TRIAL REGISTRATION: NCT03037385.

Multi-omics profiling of papillary thyroid microcarcinoma reveals different somatic mutations and a unique transcriptomic signature.

BACKGROUND: Papillary thyroid microcarcinoma (PTMC) incidence has significantly increased, and some cases still exhibit invasive traits. The entire molecular landscape of PTMC, which can offer hints for the etiology of cancer, is currently absent. METHODS: We compared our findings with those for PTMC in the TCGA by analyzing the largest study at the current stage of whole exome sequencing and RNA-sequencing data from 64 patients with PTMC. Then, we systematically demonstrated the differences between the two PTMC subtypes based on multi-omics analyses. Additionally, we created a molecular prediction model for the PTMC subtypes and validated them among TCGA patients for individualized integrative assessment. RESULTS: In addition to the presence of BRAF mutations and RET fusions in the TCGA cohort, we also discovered a new molecular signature named PTMC-inflammatory that implies a potential response to immune intervention, which is enriched with AFP mutations, IGH@-ext fusions, elevated immune-related genes, positive peroxidase antibody, and positive thyroglobulin antibody. Additionally, a molecular prediction model for the PTMC-inflammatory patients was created and validated among TCGA patients, while the prognosis for these patients is poor. CONCLUSIONS: Our findings comprehensively define the clinical and molecular features of PTMC and may inspire new therapeutic hypotheses.

The survival outcomes of prophylactic lateral neck dissection for medullary thyroid carcinoma, a retrospective cohort study.

OBJECTIVES: The purpose of this study was to evaluate the benefits of prophylactic lymph node dissection in medullary thyroid carcinoma (MTC) patients without radiographically lateral neck metastases. DESIGN: Retrospective cohort study. SETTING: Tianjin Medical University Cancer Institute and Hospital. PARTICIPANTS: Patients who underwent primary surgery for MTC between 2011 and 2019 and without structural disease of the lateral neck preoperatively. MAIN OUTCOME MEASURES: Locoregional recurrence, disease-free survival (DFS), and overall survival (OS) were examined. RESULTS: The patients were divided into two groups: the central lymph node dissection (CLND) only group and the prophylactic lateral lymph node dissection (PLND) group, which included CLND and ipsilateral lateral lymph node dissection (LLND). A total of 89 patients were included: 71 patients in the CLND group and 18 patients in the PLND group. Although there were no significant differences in age, gender, multifocality, capsule invasion or TNM stage between the two groups, the tumour size and preoperative median calcitonin levels were different. The recurrence rate was 4.2% for the CLND group and 5.6% for the PLND group (p > 0.05). DFS among the CLND and PLND groups was 95.4% and 94.4%, and OS among the groups was 100% and 94.1% (p > 0.05) at 5 years. The biochemical cure rates were similar. CONCLUSIONS: PLND in the absence of structural disease of the lateral neck preoperatively is not associated with improved survival in patients with sporadic MTC.

Indoleamine 2,3-dioxygenase 2 immunohistochemical expression in medullary thyroid carcinoma: implications in prognosis and immunomodulatory effects.

BACKGROUND: The linkage between IDO2 expression and cancer progression is still unclear, particularly in medullary thyroid carcinoma (MTC). Our purpose is to unveil the potential correlations between IDO2 status, clinical-pathological parameters, patients' prognosis, and the possible immunomodulatory functions in MTC. METHODS: Immunohistochemical expression levels of IDO2 were evaluated in the resected MTC surgical specimens and corresponding lymph nodes. CD4 + T cell infiltration was also evaluated by immunohistochemical analysis in the MTC tissues. The association of the IDO2 expression level with clinicopathologic characteristics, overall survival (OS)/recurrence-free survival (RFS), and CD4 + T cell infiltration were retrospectively investigated. RESULTS: High expression of IDO2 is closely associated with more aggressive clinicopathological features, such as multifocality, ETE, a higher pT stage and especially a higher pN stage. Moreover, a significant difference in RFS was observed between the IDO2-high and IDO2-low groups. IDO2 expression of lymph node tissues was significantly related to the metastasis status. Furthermore, we found that IDO2 expression is negatively correlated with CD4 + T cell infiltrations in MTC tissues. CONCLUSION: The expression level of IDO2 is associated with aggressive characteristics and is predictive of poor prognosis in patients with MTC. Also, an interesting observation is that IDO2 involvement in MTC showed a moderate sexual dimorphism, of which female patients tend to be more affected by IDO2 status. Moreover, our results showed the potential immunomodulatory functions of IDO2. The close relationship between IDO2 and CD4 + T cell infiltration in the MTC microenvironment, together with its potential prognostic implications, makes it possible for IDO2 to serve as an alternative drug target in cancer immunotherapy and as a new prognostic tool.

Surgical selection and prognostic analysis in patients with unilateral sporadic medullary thyroid carcinoma.

PURPOSE: The extent of thyroid surgery and cervical lymph node dissection of unilateral sporadic medullary thyroid carcinoma (sMTC) is still controversial, and the aim of this study was to investigate whether hemithyroidectomy was adequate as a locally curative surgery for patients with unilateral sMTC. METHODS: This study is a retrospective case series of patients with sMTC who underwent curative total thyroidectomy or hemithyroidectomy in our institution from January 2011 to December 2019. RESULTS: In total, 129 patients who met the inclusion criteria were enrolled including 49 (38.0%) patients who underwent total thyroidectomy and 80 (62.0%) patients who underwent hemithyroidectomy. About 80 (62.0%) patients achieved a biochemical cure (BC), whereas there was no significant difference between two groups in biochemical cure rate (61.2% versus 62.5%, P = 0.885). A logistic regression analysis showed a strong negative correlation between the factors of preoperative calcitonin level and pTNM stage and biochemical cure. In the log-rank test, no significant difference in OS (P = 0.314) and DFS (P = 0.409) was found between the two surgical groups. Lateral cervical lymph node metastasis and pTNM stage were significant prognostic factors affecting DFS in univariate analysis; moreover, absence of biochemical cure, tumor size ≥ 4 cm and lateral cervical lymph node metastasis were independent risk factors of unilateral sMTC patients in our analysis. CONCLUSION: For patients with unilateral sMTC, hemithyroidectomy was adequate as a locally curative surgery, because the patients underwent total thyroidectomy did not benefit more from it in the aspects of BC/OS/RFS, while the postoperative increasing incidence rate of postoperative hypocalcemia could not improve patients' quality of life.

Tumor Biology is King: Secondary Tumors of the Thyroid From 2 Medical Centers in China.

BACKGROUND: We studied the clinical characteristics, diagnosis, treatment, and prognosis of secondary tumors of the thyroid (STTs) and analyzed this rare phenomenon based on our clinical experience. METHODS: We reviewed 16 000 malignant thyroid tumors diagnosed at 2 medical centers in China from 1978 to 2018, including 55 patients with STTs. RESULTS: The most frequent primary tumor sites included lung (21.8%), gastrointestinal (18.2%), breast (14.5%), and kidney (12.7%). The median age at STT diagnosis was 56 years. The time from diagnosis of primary tumor to metastases to the thyroid ranged from 0 to 108 months, with the longest interval being for renal cell carcinoma (RCC; mean: 49 months). There were 22 cases of single metastatic foci and 33 cases of multiple metastatic foci. At the time of STT diagnosis, 42 patients had multiple organ metastases and 13 patients had only thyroid metastases. Thyroid function was examined in 50 patients, including 23 with Hashimoto's thyroiditis. Metastases were diagnosed histologically and confirmed by negative immunohistochemistry for thyroid markers. Twenty-one patients were treated with resection, including total thyroidectomy in 14 and unilateral lobectomy in 7. Thirty-four patients were treated without resection, but 2 were treated with tracheotomy. The median survival time of all patients with metastasis was 10 months (range: 1-96 months). Patients with primary RCC had the best prognosis (median survival time: 52 months), followed by patients with breast cancer (33 months). Patients who underwent thyroid surgery had a better prognosis than patients without thyroid surgery. Patients with single metastatic foci or single organ metastases had a better prognosis than patients with multiple metastatic foci or multiple organ metastases. CONCLUSIONS: Metastasis to the thyroid is a rare clinical phenomenon, and sometimes a diagnosis of STT is difficult; so, we need to pay more attention to it. While prognosis appears to be related to surgery or some characteristics of metastatic spread, these data suggest it is more complex. Tumor biology is king; in fact, prognosis was mainly related to the biological behavior of the primary tumor. We cannot only opt for surgery; thus, case selection is important, and the treatment strategy for STT patients should be determined individually according to their specific biological behaviors.

Visual Interpretability in Computer-Assisted Diagnosis of Thyroid Nodules Using Ultrasound Images.

BACKGROUND The number of studies on deep learning in artificial intelligence (AI)-assisted diagnosis of thyroid nodules is increasing. However, it is difficult to explain what the models actually learn in artificial intelligence-assisted medical research. Our aim is to investigate the visual interpretability of the computer-assisted diagnosis of malignant and benign thyroid nodules using ultrasound images. MATERIAL AND METHODS We designed and implemented 2 experiments to test whether our proposed model learned to interpret the ultrasound features used by ultrasound experts to diagnose thyroid nodules. First, in an anteroposterior/transverse (A/T) ratio experiment, multiple models were trained by changing the A/T ratio of the original nodules, and their classification, accuracy, sensitivity, and specificity were tested. Second, in a visualization experiment, class activation mapping used global average pooling and a fully connected layer to visualize the neural network to show the most important features. We also examined the importance of data preprocessing. RESULTS The A/T ratio experiment showed that after changing the A/T ratio of the nodules, the accuracy of the neural network model was reduced by 9.24-30.45%, indicating that our neural network model learned the A/T ratio information of the nodules. The visual experiment results showed that the nodule margins had a strong influence on the prediction of the neural network. CONCLUSIONS This study was an active exploration of interpretability in the deep learning classification of thyroid nodules. It demonstrated the neural network-visualized model focused on irregular nodule margins and the A/T ratio to classify thyroid nodules.

Ensemble Deep Learning Model for Multicenter Classification of Thyroid Nodules on Ultrasound Images.

BACKGROUND Thyroid nodules are extremely common and typically diagnosed with ultrasound whether benign or malignant. Imaging diagnosis assisted by Artificial Intelligence has attracted much attention in recent years. The aim of our study was to build an ensemble deep learning classification model to accurately differentiate benign and malignant thyroid nodules. MATERIAL AND METHODS Based on current advanced methods of image segmentation and classification algorithms, we proposed an ensemble deep learning classification model for thyroid nodules (EDLC-TN) after precise localization. We compared diagnostic performance with four other state-of-the-art deep learning algorithms and three ultrasound radiologists according to ACR TI-RADS criteria. Finally, we demonstrated the general applicability of EDLC-TN for diagnosing thyroid cancer using ultrasound images from multi medical centers. RESULTS The method proposed in this paper has been trained and tested on a thyroid ultrasound image dataset containing 26 541 images and the accuracy of this method could reach 98.51%. EDLC-TN demonstrated the highest value for area under the curve, sensitivity, specificity, and accuracy among five state-of-the-art algorithms. Combining EDLC-TN with models and radiologists could improve diagnostic accuracy. EDLC-TN achieved excellent diagnostic performance when applied to ultrasound images from another independent hospital. CONCLUSIONS Based on ensemble deep learning, the proposed approach in this paper is superior to other similar existing methods of thyroid classification, as well as ultrasound radiologists. Moreover, our network represents a generalized platform that potentially can be applied to medical images from multiple medical centers.

Assessment of the prognostic value and N1b changes of the eighth TNM/AJCC staging system for differentiated thyroid carcinoma.

BACKGROUND: The aim of this study was to evaluate the prognostic veracity for disease-specific survival (DSS) of the eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control tumor-node-metastasis staging system (TNM-8) compared with the seventh edition (TNM-7) in a Chinese population of patients with differentiated thyroid carcinoma (DTC) and to evaluate the impact of N1b redefinition and reclassification on prediction of survival. METHODS: A total of 569 DTC patients who underwent thyroid surgery in two Chinese hospitals were included in analysis to assess the predictive accuracy and N1b changes of TNM-8. Data from the Surveillance, Epidemiology and End Results (SEER) program were applied to validate the findings on N1b changes of TNM-8. Unadjusted DSS was calculated using the Kaplan-Meier method. Multivariable Cox proportional hazards models were used to evaluate the association of stage and lymph node metastasis (LNM) status with survival. The proportion of variation explained (PVE), Akaike information criterion (AIC), and Bayesian information criterion (BIC) were evaluated to compare model performance. RESULTS: When TNM-8 was applied, 39.7% of patients were downstaged relative to TMN-7. In comparison of TNM-7 and TMN-8, the PVE was 18.68% and 22.33%, the AIC was 704.22 and 680.50, and the BIC was 702.98 and 679.24, respectively. In 569 Chinese patients with DTC, levels I-V LNM was significantly related to poorer DSS compared with N0 and level VI LNM. Among patients aged ≥ 55 years, those with levels I-V and VII LNM had significantly worse DSS than those with N0 and Level VI LNM. In the SEER dataset, patients with levels I-V and VII LNM had significantly worse DSS compared with those with N0 and Level VI LNM, especially in older patients (age ≥ 55 years). CONCLUSIONS: TNM-8 staged a significant number of Chinese patients into lower stages and improved the accuracy of predicting DSS compared with TNM-7. However, changes in lateral LNM definition and classification of TNM-8 have a significant prognostic implication for patients with DTC, especially older patients (≥ 55 years). Our data suggest that a modified TNM staging system would be more useful for predicting mortality and determining a proper treatment strategy in patients with DTC.

Diagnosis of thyroid cancer using deep convolutional neural network models applied to sonographic images: a retrospective, multicohort, diagnostic study.

BACKGROUND: The incidence of thyroid cancer is rising steadily because of overdiagnosis and overtreatment conferred by widespread use of sensitive imaging techniques for screening. This overall incidence growth is especially driven by increased diagnosis of indolent and well-differentiated papillary subtype and early-stage thyroid cancer, whereas the incidence of advanced-stage thyroid cancer has increased marginally. Thyroid ultrasound is frequently used to diagnose thyroid cancer. The aim of this study was to use deep convolutional neural network (DCNN) models to improve the diagnostic accuracy of thyroid cancer by analysing sonographic imaging data from clinical ultrasounds. METHODS: We did a retrospective, multicohort, diagnostic study using ultrasound images sets from three hospitals in China. We developed and trained the DCNN model on the training set, 131 731 ultrasound images from 17 627 patients with thyroid cancer and 180 668 images from 25 325 controls from the thyroid imaging database at Tianjin Cancer Hospital. Clinical diagnosis of the training set was made by 16 radiologists from Tianjin Cancer Hospital. Images from anatomical sites that were judged as not having cancer were excluded from the training set and only individuals with suspected thyroid cancer underwent pathological examination to confirm diagnosis. The model's diagnostic performance was validated in an internal validation set from Tianjin Cancer Hospital (8606 images from 1118 patients) and two external datasets in China (the Integrated Traditional Chinese and Western Medicine Hospital, Jilin, 741 images from 154 patients; and the Weihai Municipal Hospital, Shandong, 11 039 images from 1420 patients). All individuals with suspected thyroid cancer after clinical examination in the validation sets had pathological examination. We also compared the specificity and sensitivity of the DCNN model with the performance of six skilled thyroid ultrasound radiologists on the three validation sets. FINDINGS: Between Jan 1, 2012, and March 28, 2018, ultrasound images for the four study cohorts were obtained. The model achieved high performance in identifying thyroid cancer patients in the validation sets tested, with area under the curve values of 0·947 (95% CI 0·935-0·959) for the Tianjin internal validation set, 0·912 (95% CI 0·865-0·958) for the Jilin external validation set, and 0·908 (95% CI 0·891-0·925) for the Weihai external validation set. The DCNN model also showed improved performance in identifying thyroid cancer patients versus skilled radiologists. For the Tianjin internal validation set, sensitivity was 93·4% (95% CI 89·6-96·1) versus 96·9% (93·9-98·6; p=0·003) and specificity was 86·1% (81·1-90·2) versus 59·4% (53·0-65·6; p<0·0001). For the Jilin external validation set, sensitivity was 84·3% (95% CI 73·6-91·9) versus 92·9% (84·1-97·6; p=0·048) and specificity was 86·9% (95% CI 77·8-93·3) versus 57·1% (45·9-67·9; p<0·0001). For the Weihai external validation set, sensitivity was 84·7% (95% CI 77·0-90·7) versus 89·0% (81·9-94·0; p=0·25) and specificity was 87·8% (95% CI 81·6-92·5) versus 68·6% (60·7-75·8; p<0·0001). INTERPRETATION: The DCNN model showed similar sensitivity and improved specificity in identifying patients with thyroid cancer compared with a group of skilled radiologists. The improved technical performance of the DCNN model warrants further investigation as part of randomised clinical trials. FUNDING: The Program for Changjiang Scholars and Innovative Research Team in University in China, and National Natural Science Foundation of China.

TERT promoter mutation in primary papillary thyroid carcinoma lesions predicts absent or lower 131 i uptake in metastases.

Genetic mutations play important roles in not only development of papillary thyroid carcinoma (PTC) but also determination of its properties. The radioactive iodine refractory (RAIR) state is a harbinger of poor outcomes for PTC. We used various statistical models to investigate the significance of TERT promoter, BRAF, and RAS mutations in distinguishing the RAIR state and their associations with 131 I uptake. Mutations were examined in primary lesions of 33 RAIR cases and 34 age- and sex-matched 131 I-treated cases with disease-free status. Thyrotropin-stimulated thyroglobulin (sTg) change, 131 I uptake ability, and RAIR categories were evaluated in the RAIR cases. The prevalence of TERT mutation in the RAIR group was 24.24% (8/33), which was significantly higher than that in the disease-free group (0/34). BRAF mutation showed a similar high prevalence in both the RAIR group (69.70%) and disease-free group (64.71%). Among the eight TERT mutation-positive cases, six carried both TERT and BRAF mutations. RAS mutation was detected in only one disease-free case and in two RAIR cases. Despite a significantly higher prevalence of TERT mutations in the RAIR group, only tumor size and N1b lymph node involvement were independently associated with RAIR status. In the RAIR group, all patients carrying a TERT mutation showed maximum or increased sTg. Multivariate analyses demonstrated that the TERT mutation was associated with decreased 131 I uptake and the RAIR categories of absent or weaker 131 I uptake. TERT mutation constitutes a novel genetic biomarker indicating absent or weaker 131 I-avid lesions in RAIR PTC patients. It is worth evaluating the TERT status in all DTC patients undergoing 131 I therapy. © 2019 IUBMB Life, 2019.

Impact of major different variants of papillary thyroid microcarcinoma on the clinicopathological characteristics: the study of 1041 cases.

BACKGROUND: The incidence of papillary thyroid microcarcinoma (PTMC) has been increasing globally in the past few decades. PTMC does not have a distinctive morphology that results in differences in biological behavior. The aim of this study was to classify PTMCs according to the morphological features and explore the relationship with clinicopathological characteristics. Additionally, we sought to evaluate whether different variants of PTMC can be an independent predictor for lymph mode metastasis when considering other risk factors. METHODS: Between December 2014 and December 2015, 1041 PTMC cases undergoing surgical resection at Tianjin Medical University Cancer Institute and Hospital were reviewed retrospectively. Statistical analysis was performed to investigate the independent factors for lymph node metastasis in PTMC. RESULTS: Conventional variant PTMC (CPTMC), follicular variant PTMC (FPTMC), and encapsulated variant PTMC (EnPTMC) were major variants in PTMC, collectively accounting for 96.7% of the entire PTMC cohort.There were significant differences in clinicopathological characteristics among the three major variants. The frequency of aggressive parameters was significantly different among the three variants, including tumor size, minimal extrathyroidal extension (minimal ETE), and lymph node metastasis (all P < 0.05), being highest in CPTMC, lowest in EnPTMC, and intermediate in FPTMC. FPTMC (OR = 0.642, P = 0.003) and EnPTMC (OR = 0.540, P = 0.041) were independent protective factors for lymph node metastasis (LNM). In contrast, male gender (OR = 1.836, P = 0.000), age less than 45 years (OR = 1.457, P = 0.009), tumor size greater than 0.5 cm (OR = 1.453, P = 0.007), calcification (OR = 1.465, P = 0.016), minimal ETE (OR = 1.801, P = 0.001), and multifocality (OR = 1.721, P = 0.000) were independent risk factors for LNM. CONCLUSIONS: The present study demonstrates the distinct biological behaviors of the three major PTMC variants and establishes an aggressive order of CPTMC â‰« FPTMC > EnPTMC. It is necessary to take into consideration variant-related risks and other independent predictors for the determination of lymphadenectomy in patients with PTMC.

Loss of PTEN Expression Is Associated With High MicroRNA 24 Level and Poor Prognosis in Patients With Tongue Squamous Cell Carcinoma.

PURPOSE: The aim of this study was to detect the relationship between phosphatase and tensin homolog deletion on chromosome 10 (PTEN) and microRNA 24 (miR-24) and correlate PTEN expression with important clinical parameters of patients with tongue squamous cell carcinoma (TSCC). MATERIALS AND METHODS: In this retrospective case series, all TSCC patients treated at Tianjin Medical University Cancer Institute and Hospital between March 2005 and October 2011 were retrospectively reviewed. Demographic information and clinical data (histologic type, clinical stage, tumor differentiation, and so on) were collected. The miR-24 level was detected by quantitative reverse transcription-polymerase chain reaction. The PTEN level was analyzed by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction. Data analyses were performed by Spearman correlation analysis, Pearson χ2 test, and paired t test. Kaplan-Meier curves, log-rank analyses, and a Cox proportional hazards model were used to evaluate the prognostic value of PTEN. RESULTS: A total of 90 patients (aged 59.4 ± 9.5 years, 53 men and 37 women) were identified. Loss of PTEN expression was detected in 27 of 90 tumors (30%)" in both occurrences [corrected]. The PTEN messenger RNA level was negatively correlated with the miR-24 level (r = -0.569, P < .01). PTEN expression also was negatively correlated with the miR-24 level (r = -0.621, P < .01). Furthermore, PTEN expression was significantly lower in cancer tissues than in adjacent normal tissues, and its expression was negatively correlated with clinical stage (P < .01) and positively correlated with differentiation (P < .05) in TSCC patients. In addition, the Kaplan-Meier curve indicated that loss of PTEN expression resulted in poor survival of TSCC patients (P < .01). Multivariate analysis indicated that PTEN expression level and clinical stage may be independent prognostic factors for TSCC patients. CONCLUSIONS: This study suggested that PTEN expression was negatively correlated with the miR-24 level in TSCC. The loss of PTEN expression may serve as a predictor of unfavorable prognosis for TSCC patients.

Efficacy and safety of selpercatinib in treating RET-altered MTC: A single-arm meta-analysis.

Background: Selpercatinib is effective in the treatment of RET-altered medullary thyroid carcinoma (MTC). This study aimed to evaluate the efficacy and safety of selpercatinib in the treatment of patients with RET-altered MTC. Methods: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched from their inception to April 5, 2024. Outcomes included complete response (CR), partial response (PR), stable disease (SD), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). We carried out a meta-analysis of these studies and exploratory subgroup analyses. The effect sizes for all pooled results were presented as 95% confidence intervals with upper and lower limits. Results: The pooled CR, PR, and SD rates for all patients were 10%, 59%, and 26%, respectively. The pooled ORR in all patients was 70%, while the pooled ORR in pre-treated and non-pre-treated groups were 67% and 70%, respectively. The pooled DCR in all patients was 95%, while the pooled DCR in pre-treated and non-pre-treated groups were 96% and 95%, respectively. The most common AEs associated with selpercatinib were hypertension, alanine aminotransferase (ALT) increased and aspartate aminotransferase (AST) increased. Conclusion: Selpercatinib offers significant benefits to patients with RET-altered MTC with assessable CR, PR, SD, ORR, and grade 3-4 AEs; however, treatment-related AEs should be considered.

Analysis of Surgical Outcomes in Endoscopic-Assisted Lateral Neck Dissection.

BACKGROUND: Currently, endoscopic-assisted lateral neck dissection (EALND) is performed to reduce postoperative scarring of the anterior neck. This study aimed to compare surgical outcomes between EALND and conventional open lateral neck dissection (COLND) for papillary thyroid carcinoma (PTC) with lateral lymph node metastases (LNM). METHODS: The study reviewed 103 PTC patients who were classified on the basis of surgical type and statistically compared using propensity score matching analysis. RESULTS: The mean operation time is longer, and the cost of surgery is higher in the EALND group than COLND group (all p < 0.05). The numbers of retrieved and positive level II LNs, the rate of level II LNs detection between two groups do not differ significantly (all p > 0.05). The incidence of postoperative neck numbness is lower, and patients are more satisfied with postoperative neck scarring in the EALND group than COLND group (all p < 0.05). The common complications of two groups are transient recurrent laryngeal nerve injury and transient hypoparathyroidism. CONCLUSIONS: EALND is safe and feasible compared with COLND. The incision is more aesthetically satisfactory, which makes EALND a surgical approach for PTC patients with lateral LNM. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2221-2227, 2024.

Predictive and prognostic value of aurora kinase A combined with tumor-infiltrating lymphocytes in medullary thyroid carcinoma.

Background: Aurora kinase A (AURKA) and tumor-infiltrating lymphocytes (TILs) are both known to play an essential role in tumorigenesis. However, the expression and prognostic value of the AURKA and TILs in medullary thyroid carcinoma (MTC) have not yet been investigated. Patients and methods: Surgical specimens and clinical data of 137 patients diagnosed with MTC were collected. AURKA expression and TILs infiltration were quantified by immunohistochemistry and hematoxylin-eosin staining. Subsequently, the prognostic value of AURKA expression and TIL infiltration in MTC was evaluated. Results: AURKA was highly expressed in patients with multifocal tumor, cervical lymph node metastasis, and an advanced TNM stage, indicating a high probability of recurrence. AURKA further exhibited a positive correlation with TILs (R = 0.44, P < 0.001). High expression of AURKA combined with a low numbers of TILs (AURKAhigh/TILslow) was identified as an independent prognostic factor for biochemical recurrence (odds ratio: 4.57, 95% confidence interval: 1.54-14.66, P < 0.01) and recurrence-free survival (hazard ratio: 3.64, 95% confidence interval: 1.52-8.71, P < 0.001). The combination of AURKA and TILs apparently improves the prognostic value for biochemical recurrence (area under the curve: 0.751) and structural recurrence (area under the curve: 0.836) of MTC. Notably, AURKAhigh/TILslow demonstrated a high value for prediction of distant or unresectable locoregional recurrence, with an overall accuracy of 86.9%. Conclusion: AURKAhigh is associated with the MTC malignancy. The combination of AURKAhigh/TILslow was identified as novel independent prognostic marker in MTC, predicting incurable disease recurrence with high accuracy.

An Inducible CRISPR-dCas9-Based Transcriptional Repression System for Cancer Therapy.

Gene therapy has been adapted for improving malignant tumor treatment. However, pharmacotherapies targeting cancer remain limited and are generally inapplicable for rare disease patients. Oleanolic acid (OA) is a plant-derived triterpenoid that is frequently used in Chinese medicine as a safe but slow-acting treatment for many disorders. Here, the congruent pharmacological activities of OA and CRISPR-dCas9 in targeting AURKA or KDM1A and improving disease-specific prognosis and used a synthetic-biology-inspired design principle to engineer a therapeutic gene circuit that enables a concerted action of both drugs are utilized. In particular, the OA-triggered CRISPR-dCas9 transcriptional repression system rapidly and simultaneously attenuated lung and thyroid cancer. Collectively, this work shows that rationally engineered synthetic gene circuits are capable of treating multifactorial diseases in a synergistic manner by multiplexing the targeting efficiencies of single therapeutics.

Changes of biochemical factors and the effect on recurrence of medullary thyroid carcinoma after surgery.

Objective: Medullary thyroid carcinoma (MTC) is a rare malignancy secreting calcitonin (Ctn). We aimed to analyze the relationship between Ctn levels at different time points in patients with MTC, and evaluate its predictive effect on recurrence. Methods: A retrospective study of patients diagnosed with MTC in a large medical center were conducted in northern China. The interrelationships between preoperative Ctn, normalization of postoperative serum Ctn at the first month (NPS), and long-term biochemical cure as well as their predicting roles on structural recurrence were assessed. Results: A total of 212 patients were included in this study. The median follow-up time was 59.5 months. The 5- and 10-year cumulative disease-free survival rates were 81.5 % and 66.8 %, respectively. NPS (OR: 216.33, 95 % CI: 28.69-1631.09, P < 0.001) and absence of structural recurrence (OR: 61.71, 95 % CI: 3.90-975.31; P = 0.003) were associated with biochemical cure. Non-biochemical cure (OR: 28.76; 95 % CI: 2.84-290.86; P = 0.004, HR: 14.63, 95 % CI: 2.27-94.07, P = 0.005), larger tumor size (OR: 8.79, 95 % CI: 2.12-36.40, P = 0.003, HR: 5.41, 95 % CI: 2.04-14.37, P = 0.001), and multifocality (OR: 4.02, 95 % CI: 1.06-15.17, P = 0.040, HR: 3.00, 95 % CI: 1.18-7.60, P = 0.021) were unfavorable independent predictors of structural recurrence and disease-free survival. For sporadic MTC confined to the thyroid lobe, there was no difference in biochemical or structural prognosis between the different surgeries in the subgroup analysis. Conclusions: NPS, rather than preoperative Ctn, predicted long-term biochemical cure for MTC. Non-biochemical cure, larger tumor burden including larger tumor size and multifocality at initial surgery, served as worse prognostic predictors.

Multidimensional data analysis revealed thyroiditis-associated TCF19 SNP rs2073724 as a highly ranked protective variant in thyroid cancer.

BACKGROUND: Thyroid cancer represents the most prevalent malignant endocrine tumour, with rising incidence worldwide and high mortality rates among patients exhibiting dedifferentiation and metastasis. Effective biomarkers and therapeutic interventions are warranted in aggressive thyroid malignancies. The transcription factor 19 (TCF19) gene has been implicated in conferring a malignant phenotype in cancers. However, its contribution to thyroid neoplasms remains unclear. RESULTS: In this study, we performed genome-wide and phenome-wide association studies to identify a potential causal relationship between TCF19 and thyroid cancer. Our analyses revealed significant associations between TCF19 and various autoimmune diseases and human cancers, including cervical cancer and autoimmune thyroiditis, with a particularly robust signal for the deleterious missense variation rs2073724 that is associated with thyroid function, hypothyroidism, and autoimmunity. Furthermore, functional assays and transcriptional profiling in thyroid cancer cells demonstrated that TCF19 regulates important biological processes, especially inflammatory and immune responses. We demonstrated that TCF19 could promote the progression of thyroid cancer in vitro and in vivo and the C>T variant of rs2073724 disrupted TCF19 protein binding to target gene promoters and their expression, thus reversing the effect of TCF19 protein. CONCLUSIONS: Taken together, these findings implicate TCF19 as a promising therapeutic target in aggressive thyroid malignancies and designate rs2073724 as a causal biomarker warranting further investigation in thyroid cancer.