Pralsetinib as neoadjuvant therapy for RET-Altered differentiated thyroid cancer: Two case reports.

BACKGROUND: 5-10% of thyroid cancers are at locally advanced stage. Neoadjuvant targeted therapy will likely create surgical opportunities for these patients with unresectable or borderline resectable tumors. Pralsetinib, a RET inhibitor, has been approved for advanced or metastatic RET-altered thyroid cancer. However, there is no evidence on the efficacy of pralsetinib as neoadjuvant therapy in locally advanced RET-altered thyroid cancer. CASE REPORT: Two patients with locally advanced pappilary thyroid carcinoma (PTC) were treated with pralsetinib (400 mg daily) to reduce tumor size and increase the chance of R0 resection. Both PTCs, characterized by RET-fusion, underwent successful R0 resection without major surgical complications after 4-months neoadjuvant pralsetinib. CONCLUSION: There is a potential for pralsetinib as a neoadjuvant treatment in PTC with RET-fusion.

BRAFV600E/p-ERK/p-DRP1(Ser616) Promotes Tumor Progression and Reprogramming of Glucose Metabolism in Papillary Thyroid Cancer.

Background: Papillary thyroid cancer (PTC) with the BRAFV600E mutation is associated with a poorer prognosis. BRAF inhibitors may demonstrate limited efficacy due to emerging drug resistance. The Warburg effect may have cancer therapeutic implications. It is not known if the BRAFV600E mutation is associated with altered glucose metabolism in PTC. Methods: This study examined the effect of BRAFV600E and dynamin-related protein 1 (DRP1) on various cellular processes in PTC cells, including cell proliferation, migration, invasion, mitochondrial fission, glucose metabolism, reactive oxygen species (ROS) generation, and apoptosis. We used RT-qPCR to assess the expression of key glycolytic enzymes in thyroid cancer tissues. Additionally, the regulatory interaction between BRAFV600E and DRP1 was investigated through Western blot and immunohistochemical staining. We further evaluated the impact of DRP1 in PTC and the inhibitory effects of dabrafenib and 2-deoxy-d-glucose (2-DG) in vitro and in vivo. Results: We found that the BRAFV600E mutation significantly augments aerobic glycolysis while suppressing oxidative phosphorylation in PTC. We identified the BRAFV600E/p-ERK/p-DRP1(Ser616) signaling pathway as a critical mediator in PTC progression. First, the BRAFV600E/p-ERK/p-DRP1(Ser616) signaling pathway enhances cell proliferation by upregulating hexokinase 2 expression and thereby increasing aerobic glycolysis. Second, it inhibits apoptosis by promoting mitochondrial fission and reducing ROS levels. Moreover, we demonstrated that the combination therapy of 2-DG and dabrafenib markedly impedes the progression of BRAFV600E-positive PTC. Conclusion: The BRAFV600E/p-ERK/p-DRP1(Ser616) signaling pathway plays a pivotal role in glucose metabolism reprogramming, contributing to the aggressiveness and progression of BRAFV600E-positive PTC. Our findings suggest that a combined therapeutic approach using 2-DG and dabrafenib has the potential to improve the outcome of PTC patients with BRAFV600E.

A multicenter prospective study of lateral neck lymph node mapping in papillary thyroid cancer.

Background: Despite the high incidence of lateral neck lymph node (LN) metastasis in papillary thyroid cancer (PTC), the management of the lateral neck remains controversial. We aimed to map the draining LNs in the lateral neck using carbon nanoparticles and explore its potential in neck evaluation. Methods: We conducted a multicenter, prospective study in PTC patients who had non-palpable yet suspicious metastatic lateral LNs on ultrasound and/or computed tomography (CT) but could not be confirmed by fine needle aspiration. Carbon nanoparticle suspension was injected peritumorally into the thyroid and modified lateral neck dissection was subsequently performed. Results: A total of 154 patients were enrolled for analysis. And 5,070 lateral LNs were removed, of which 1,079 (21.3%) were dyed. The median of dyed LNs was 6 per case (range, 1-33). The distribution of dyed LNs in neck compartments was IV > III > IIA > IIB/V, independent of tumor size, location, multifocality or microscopic extra-thyroidal extension (ETE). Compared with undyed LNs, the probabilities of metastasis in dyed LNs were significantly increased in compartment III, IV, V, and II-V (III: 29.3% vs. 15.4%, P<0.001; IV: 26.3% vs. 14.5%, P<0.001; V: 16.7% vs. 3.3%, P=0.005; II-V: 26.3% vs. 10.0%, P<0.001). The relative risks of metastasis in dyed LNs compared with undyed LNs were 1.90, 1.82, 5.04 and 2.62 in compartment III, IV, V, and II-V, respectively. Conclusions: It was the first prospective multicenter study to map the lateral neck LNs with carbon nanoparticles, which could help surgeons visualize the suspicious LNs during surgery. Instead of unguided LN biopsy, this method has a potential role in lateral neck assessment for indeterminate lateral LNs in PTC.

The Efficacy and Safety of Surufatinib Combined with Anti PD-1 Antibody Toripalimab in Neoadjuvant Treatment of Locally Advanced Differentiated Thyroid Cancer: A Phase II Study.

BACKGROUND: Surgery is the primary treatment for locally advanced differentiated thyroid cancer (DTC). However, some locally advanced patients are not candidates for R0/1 resection. There is limited evidence of neoadjuvant treatment in locally advanced DTC. Surufatinib targets multiple kinases, which is efficient, tolerable, and safe in patients with radioiodine-refractory DTC. In addition, surufatinib plus toripalimab (an anti-PD-1 antibody) showed encouraging antitumor activity in advanced solid tumors. This study was designed to evaluate the efficacy and safety of surufatinib plus toripalimab in locally advanced DTC in the neoadjuvant setting. METHODS: In this single-arm, phase II study, patients with pathologically confirmed unresectable or borderline resectable DTC were eligible and received a combination of 250 mg of surufatinib (orally daily) with 240 mg of toripalimab (intravenous, every 3 weeks). Treatment continued until satisfied for curative surgery, disease progression, withdrawal of consent, unacceptable toxicity, or investigator decision. Primary endpoint was objective response rate (ORR). Secondary endpoints included R0/1 resection rate, adverse events (AEs), etc. RESULTS: Ten patients were enrolled and received at least 4 cycles of treatment. The ORR was 60%. Nine patients received R0/1 resections after neoadjuvant treatment. The median best percentage change in the sum of the target lesion diameter was 32%. Most adverse events (AEs) were grade 1 or 2. CONCLUSIONS: Surufatinib in combination with toripalimab as neoadjuvant therapy for locally advanced DTC was feasible, and the majority of patients achieved R0/1 resection. It represents a new option for locally advanced DTC and needs further investigation.

Using a CT-based scale to evaluate disease extension and the resectability of locally advanced thyroid cancer.

OBJECTIVES: To establish a computed tomography (CT)-based scale to evaluate the resectability of locally advanced thyroid cancer. METHODS: This twin-centre retrospective study included 95 locally advanced thyroid cancer patients from the 1st centre as the training cohort and 31 patients from the 2nd centre as the testing cohort, who were categorised into the resectable and unresectable groups. Three radiologists scored the CT scans of each patient by evaluating the extension to the recurrent laryngeal nerve (RLN), trachea, oesophagus, artery, vein, soft tissue, and larynx. A 14-score scale (including all comprised structures) and a 12-score scale (excluding larynx) were developed. Receiver-operating characteristic (ROC) analysis was used to evaluate the performance of the scales. Stratified fivefold cross-validation and external verification were used to validate the scale. RESULTS: In the training cohort, compromised RLN (p < 0.001), trachea (p = 0.001), oesophagus (p = 0.002), artery (p < 0.001), vein (p = 0.005), and soft tissue (p < 0.001) were predictors for unresectability, while compromised larynx (p = 0.283) was not. The 12-score scale (AUC = 0.882, 95%CI: 0.812-0.952) was not inferior to the 14-score scale (AUC = 0.891, 95%CI: 0.823-0.960). In subgroup analysis, the AUCs of the 12-score scale were 0.826 for treatment-naïve patients and 0.976 for patients with prior surgery. The 12-score scale was further validated with a fivefold cross-validation analysis, with an overall accuracy of 78.9-89.4%. Finally, external validation using the testing cohort showed an AUC of 0.875. CONCLUSIONS: The researchers built a CT-based 12-score scale to evaluate the resectability of locally advanced thyroid cancer. Validation with a larger sample size is required to confirm the efficacy of the scale. CLINICAL RELEVANCE STATEMENT: This 12-score CT scale would help clinicians evaluate the resectability of locally advanced thyroid cancer. KEY POINTS: • The researchers built a 12-score CT scale (including recurrent laryngeal nerve, trachea, oesophagus, artery, vein, and soft tissue) to evaluate the resectability of locally advanced thyroid cancer. • This scale has the potential to help clinicians make treatment plans for locally advanced thyroid cancer.

Different clinicopathologic features predispose to different patterns of distant metastasis with heterogeneous short-term prognosis in patients with differentiated thyroid cancer.

BACKGROUND: Limited studies have focused on the associated clinicopathologic features and short-term prognostic impacts of metastatic patterns at initial diagnosis in differentiated thyroid cancer (DTC). METHODS: Overall, 530 individuals with distant DTC diagnosed between 2010 and 2014 were identified from Surveillance, Epidemiology, and End Results (SEER) database. Multinomial logistic regression model was used to assess the clinicopathologic factors influencing the pattern of distant metastasis. Kaplan-Meier method and multivariable Cox regression were used to estimate the short-term effects of metastatic patterns on overall (OS) and thyroid cancer-specific survival (TCSS). RESULTS: Fifty, 111, 263, 59 and 47 patients presented with distant lymph node (LN)-only, bone-only, lung-only, bone plus lung, and liver and/or brain metastases (Mets), respectively. Regional lymph node metastasis (LNM) and follicular histotype were the only confirmed risk factors for distant LN-only Mets and bone-only Mets, respectively. Larger tumour size, extrathyroidal extension (ETE) and papillary histotype were associated with lung-only Mets. Synchronous bone and lung Mets were more likely to occur in older patients. In addition, patients with distant LN-only Mets had hardly any negative effect on OS and TCSS, whereas those with synchronous bone and lung or liver/brain Mets predicted unfavourable short-term outcomes, regardless of whether they received total thyroidectomy and radioisotopes. CONCLUSIONS: Different clinicopathologic factors predispose to different patterns of metastases with profound short-term survival differences among DTC patients. Our findings may help to determine effective pretreatment screening for aggressive metastatic patterns at initial diagnosis, and thus to provide additional treatment or access of clinical trials for these patients.

The Efficacy and Safety of Anlotinib in Neoadjuvant Treatment of Locally Advanced Thyroid Cancer: A Single-Arm Phase II Clinical Trial.

Background: Surgery is the primary treatment for locally advanced thyroid cancer. For some cases, R0/R1 resection could not be achieved at initial diagnosis and neoadjuvant treatment would be an option. Anlotinib is a multitarget tyrosine kinase inhibitor, which demonstrated antitumor activity in radioiodine-refractory differentiated thyroid cancer and medullary thyroid cancer. We aimed to evaluate the efficacy and safety of anlotinib in locally advanced thyroid cancer in the neoadjuvant setting. Methods: This single-arm phase II study investigated the efficacy and safety of anlotinib (12 mg orally daily, 2 weeks on/1 week off) for 2-6 cycles in patients with locally advanced thyroid cancer in the neoadjuvant setting. The key eligibility criteria included age 14-80 years old; locally advanced thyroid cancer that would benefit from surgery, and at least one measurable lesion. Operable patients received surgery after neoadjuvant treatment. The primary endpoint was objective response rate (ORR). Results: A total of 13 patients were enrolled and received an average of 3.5 cycles of anlotinib treatment. The ORR of anlotinib was 76.9% (95% confidence interval: 46.2-95.0%). The R0/R1 resection rate in the intent-to-treat population was 61.5% and in the per-protocol population was 72.7%. The median time to response was 61.5 days, and the disease control rate at 18 weeks was 92.3%. No patients had blood transfusion or tracheotomy. Most adverse events (AEs) were grade 1 or 2 and tended to discontinue when neoadjuvant treatment ceased. Common AEs of all grades were hypertension (76.9%), hypertriglyceridemia (69.2%), proteinuria (53.8%), thyrotropin increase (53.8%), cholesterol elevation (53.8%), and hand-foot syndrome (38.5%). Conclusions: Anlotinib demonstrated antitumor activity in the neoadjuvant treatment and the majority of patients achieved R0/R1 resection. AEs were consistent with the known anlotinib AE profile. These results suggest that anlotinib neoadjuvant treatment represents a new option for locally advanced thyroid cancer. Clinical Trial Registration Number: NCT04309136.

Mammary analog secretory carcinoma of the thyroid gland: A rare cancer harboring TRK fusion.

Mammary analog secretory carcinoma (MASC), or secretory carcinoma of the thyroid is an extremely rare disease harboring ETV6-NTRK3 gene fusion with TRK activation. Here we report the twelfth case of MASC of the thyroid worldwide. A 36-year-old female was diagnosed with poor-differentiated thyroid carcinoma (PDTC). Pathology consultant and immunochemical workups showed the tumor cells were negative for TTF1, TG, PAX8, positive for S100, Vimentin, GATA-3, and focally positive for mammaglobin. Fluorescence in situ hybridization (FISH) assay using a dual-color break-apart probe showed ETV6 translocation t(12p13) (ETV6) was present and established the diagnosis of MASC. Next-generation sequencing (NGS) of a 47-gene panel identified exon 1-5 of ETV6 gene were fused with exons 15-19 of NTRK3 gene. The patient experienced three loco-regional recurrences within 12 months and eventually developed inoperable local disease as well as bilateral lung metastasis. She is currently receiving anti-TRK treatment with a follow-up time of 33 months. A literature review of MASC in the thyroid was also conducted.

Mitotically associated long non-coding RNA is a tumor promoter in anaplastic thyroid cancer.

BACKGROUND: Patients with anaplastic thyroid cancer (ATC), which is among the deadliest of all cancers, often have a poor response to traditional therapies. Currently, the role of long non-coding RNAs (lncRNAs) in ATC carcinogenesis is unclear. In this study, we analyzed the lncRNA expression profile of ATC with the aim of identifying potential molecular targets for treatment of the disease. METHODS: Whole transcriptome sequencing of three ATC and two normal thyroid (NT) samples was performed, and the lncRNA expression profile of ATC was analyzed. Original data as well as datasets deposited in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were used for clinical validation. Cell proliferation, Transwell, and apoptosis assays were performed using ATC cell lines. Gene Ontology (GO) and gene set enrichment analyses (GSEA) were performed to determine the dysregulated pathways. RESULTS: Whole transcriptome sequencing revealed 182 lncRNAs to be differentially expressed in ATC. One of the lncRNAs, mitotically associated long non-coding RNA (MANCR; LINC00704), was significantly overexpressed in ATC cell lines and patient samples compared with NT and papillary thyroid cancer (PTC). MANCR depletion in ATC cells significantly inhibited cancer cell proliferation and invasion, and induced apoptosis. By further analyzing the transcriptome data, we identified 451 genes co-expressed with MANCR. GO and GSEA showed that the top dysregulated pathways were related to mitosis and cell cycle. CONCLUSIONS: MANCR is a tumor promoter in ATC, and its role in carcinogenesis is possibly associated with cell cycle regulation. Because MANCR expression is minimal in most normal tissues, it may serve as a potential target in the future treatment of ATC.

Prognostic Nomograms for Predicting Overall Survival and Cancer-Specific Survival of Patients with Major Salivary Gland Mucoepidermoid Carcinoma.

Background: The aim of this study was to develop and validate prognostic nomograms predicting overall (OS) and cancer-specific survival (CSS) of patients with major salivary gland (MaSG) mucoepidermoid carcinoma (MEC). Methods: 1398 MaSG-MEC patients were identified from the Surveillance, Epidemiology and End Results (SEER) database. They were randomly and equally divided into a training cohort (n=699) and a validation cohort (n=699). The best subsets of covariates were identified to develop nomograms predicting OS and CSS based on the smallest Akaike Information Criterion (AIC) value in the multivariate Cox models. The nomograms were internally and externally validated by the bootstrap resampling method. The predictive ability was evaluated by Harrell's Concordance Index (C-index). Results: For the training cohort, eight (age at diagnosis, tumor grade, primary site, surgery, radiation, T, N and M classification) and seven predictors (all the above factors except primary site) were selected to create the nomograms estimating the 3- and 5- year OS and CSS, respectively. C-index indicated better predictive performance of the nomograms than the 7th AJCC staging system, which was confirmed by both internal (via the training cohort: OS: 0.888 vs 0.785, CSS: 0.938 vs 0.821) and external validation (via the validation cohort: OS: 0.844 vs 0.743, CSS: 0.882 vs 0.787). The calibration plots also revealed good agreements between the nomogram-based prediction and observed survival. Conclusions: We have proposed and validated the nomograms predicting OS and CSS of MaSG-MEC. They are proved to be of higher predictive value than the AJCC staging system and may be adopted in future clinical practice.

Association Between Programmed Death-Ligand 1 Expression and Clinicopathological Characteristics, Structural Recurrence, and Biochemical Recurrence/Persistent Disease in Medullary Thyroid Carcinoma.

Background: Expression of the programmed death-ligand 1 (PD-L1) in medullary thyroid carcinoma (MTC) has been rarely reported. In this study, we evaluated PD-L1 positivity in MTC and analyzed its correlation with clinicopathological characteristics, structural recurrence (SR), and biochemical recurrence/persistent disease (BcR/BcPD). We also evaluated the prevalence of PD-L1 expression in patients developing distant or unresectable locoregional recurrence. Methods: In total, 201 consecutive MTC patients who underwent initial surgery in our institution from January 2006 to December 2015 were included. PD-L1 expression was evaluated by immunohistochemical staining and was considered positive in case of a combined positive score ≥1. The association of PD-L1 positivity with clinicopathological characteristics, structural recurrence-free survival (SRFS), and BcR/BcPD was retrospectively investigated. Results: The median follow-up length of the entire cohort was 73 months. We observed positive PD-L1 staining in 29 (14.4%) patients who were more likely to have a larger tumor size (p = 0.002), lymph node metastases (p = 0.036), and advanced TNM staging (p = 0.019). The five-year SRFS of the PD-L1-negative and PD-L1-positive groups was 85.4% and 57.9% (p = 0.001). Multivariate Cox analysis showed that PD-L1 positivity was independently associated with SR (hazard ratio = 2.19 [95% confidence interval (CI) 1.01-4.77], p = 0.047). Furthermore, multivariate logistic analysis showed that PD-L1 positivity was significantly associated with BcR/BcPD (odds ratio = 3.16 [CI 1.16-8.66], p = 0.025). During the study period, 20 patients developed distant or unresectable locoregional recurrence, among whom 8 (40%) were PD-L1 positive, which was much higher than in the entire MTC population. Conclusions: Using a large cohort of MTC patients, we demonstrate that PD-L1 positivity is associated with aggressive clinicopathological features and is independently predictive of SR and BcR/BcPD. Furthermore, a higher rate of PD-L1 expression in patients with incurable recurrence has been observed. Therefore, immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1)/PD-L1 pathway may be a potential therapeutic strategy to treat advanced MTC.

Anatomic extent of lymph node metastases as an independent prognosticator in node-positive major salivary gland carcinoma: A study of the US SEER database and a Chinese multicenter cohort.

BACKGROUND: We aimed to explore whether the anatomic extent of lymph node metastases (AE-LNM) could independently predict prognosis of node-positive major salivary gland carcinoma (MaSGC). METHODS: A total of 376 pathologically node-positive MaSGC patients were identified from the Surveillance, Epidemiology and End Results database and constituted the training cohort. Using the X-Tile program, these patients were divided into three groups based on AE-LNM degrees. Discrimination of overall survival (OS) and disease-specific survival (DSS) was evaluated and compared with the 8th American Joint Committee on Cancer (AJCC) pN classification. The results were externally validated by 220 patients in a Chinese multicenter cohort (Validation cohort). RESULTS: Using the training cohort, AE-LNM was divided into Extent 1 (spread to parotid LNs or level I), Extent 2 (spread to level II-IV) and Extent 3 (spread to level V or bilateral LNs or rare LNs). Regarding both OS and DSS, the AE-LNM model revealed clear separation of survival curves, while the pN classification failed to discriminate the prognosis of pN1 and pN2 patients. When we incorporated both the AE-LNM model and AJCC pN classification into the same multivariate Cox analyses, AE-LNM was still an independent prognostic factor, while the AJCC pN classification lost its significance. These results were externally validated by the validation cohort. CONCLUSION: AE-LNM is an independent nodal prognosticator for node-positive MaSGC and may have improved discriminative ability over the current AJCC pN classification. Integration of anatomic extent of LNM into the current AJCC N classification could be considered.

An Update of the Appropriate Treatment Strategies in Anaplastic Thyroid Cancer: A Population-Based Study of 735 Patients.

BACKGROUND: Anaplastic thyroid cancer (ATC) responds poorly to conventional therapies and requires a multidisciplinary approach to manage. The aim of the current study is to explore whether aggressive treatment is beneficial, especially the appropriate extent of surgery in ATC. METHODS: Patients diagnosed with ATC from 2004 to 2014 were identified from the Surveillance, Epidemiology, and End Results (SEER) database and included in our study. RESULTS: A total of 735 ATC patients were identified. The two-year overall survival (OS) rates for stage IVA, IVB, and IVC patients were 36.5%, 15.6%, and 1.4%, respectively. By directly comparing eight treatment modalities, we found that surgery + radiotherapy (RT) ± chemotherapy was the most effective treatment strategy. surgery + chemotherapy and RT + chemotherapy had comparable results (hazard ratio (HR) = 1.461, 95% confidential interval (CI): 0.843-2.531, P = 0.177). Multivariate Cox regression analysis also showed increased mortality risk in patients with increased age (HR = 1.022, P < 0.001), tumor extension to adjacent structures (HR = 1.649, P = 0.013), and distant metastasis (HR = 2.041, P < 0.001), while surgery + RT (HR = 0.600, P = 0.004) and chemotherapy (HR = 0.692, P = 0.010) were independently associated with improved OS. Further analysis revealed that patients undergoing total/near-total thyroidectomy (TT) had superior OS to those receiving less than TT (P < 0.001). In subgroup analysis, the benefit of TT remained significant in patients with tumors larger than 4.0 cm (HR = 0.776, 95% CI: 0.469-0.887, P = 0.007), with adjacent structure extension (HR = 0.642, 95% CI: 0.472-0.877, P = 0.005), including trachea and major vessels, but not in patients with early phase local disease such as tumor ≤ 4.0 cm or tumor within the thyroid or with minimal extrathyroidal extension. Patients with very locally advanced disease or distant metastasis could not benefit from TT as well. CONCLUSIONS: In operable cases, surgery + RT ± chemotherapy was the optimal treatment modality. Otherwise, RT + chemotherapy was the appropriate strategy. However, TT was not beneficial for very early stage or metastatic ATC.

Lingual ectopic papillary thyroid carcinoma: Two case reports and review of the literature.

Ectopic thyroid occurs when it is not located on the normal thyroid compartment. While 90% of the ectopic thyroids were located at the base of the tongue, only 1% were lingual thyroid carcinoma (LTC). Only 56 LTC cases have been reported so far. Here we reported two cases of LTC. Patient 1 was a 47-year-old female with LTC and co-current sub-hyoid ectopic thyroid. She experienced major hematemesis and dyspnea requiring emergent tracheotomy. Patient 2 was a 61-year old female who was presented with LTC with multiple lymph node metastasis and bilateral lung metastasis. Both of the patients' lingual masses were removed via trans-submaxillary excisions. Pathology revealed ectopic papillary thyroid carcinoma. Then they were treated with radio-active iodine (RAI). These patients had full recovery and there were no complications. A review of literature was also presented.

Association between breast cancer and thyroid cancer: A study based on 13 978 patients with breast cancer.

BACKGROUND: Thyroid cancer (TC) is one of the most commonly seen secondary malignancy in breast cancer (BC) survivors. MATERIALS AND METHODS: A retrospective study was conducted in BC patients in our center from 1999 to 2013. Patients were divided into BC-TC group and BC-alone group. RESULTS: In total, 13 978 BC patients were identified, among whom 247 (1.8%) had TC. The standardized incidence ratio (SIR) of TC was 4.48 compared with Chinese females, and up to 98.0% of cases were thyroid papillary carcinomas. A family history of malignancy was the only independent risk factor (odds ratio = 1.457, P = 0.025) for development of TC in patients with BC. We also identified inferior survival in patients with synchronous versus metachronous BC-TC (P = 0.016). Synchronous BC-TC (risk ratio = 5.597, P = 0.018) was an independent prognostic factor for inferior RFS. CONCLUSIONS: We observed high co-occurrence of TC in patients with BC. There might be different mechanisms behind synchronous and metachronous BC-TC.

Prognostic value of primary tumor surgery in minor salivary-gland carcinoma patients with distant metastases at diagnosis: first evidence from a SEER-based study.

PURPOSE: The prognostic value of primary tumor surgery (PTS) in minor salivary-gland carcinoma (MiSGC) with distant metastasis (DM) at diagnosis has never been investigated. In this study, we aimed to provide the first evidence. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was employed to identify MiSGC patients with DM at diagnosis. The prognostic value of PTS was evaluated by Kaplan-Meier methods, log-rank analyses, and multivariate Cox proportional-hazard regression models. RESULTS: Of the 152 eligible patients included in our study, 50 (32.9%) had undergone PTS. Kaplan-Meier analyses showed that the PTS group had >20% increase in 1- and 2-year overall survival (OS) and cancer-specific survival (CSS) compared with their counterparts without PTS (PTS group vs no-PTS group, 1-year OS 66.1% vs 43.9%, 1-year CSS 69.9% vs 44.9%, 2-year OS 56.6% vs 24.2%, 2-year CSS 59.9% vs 25.7%). Compared with the no-PTS group, multivariate analyses also demonstrated a significantly decreased risk of overall mortality (HR 0.601, 95% CI 0.379-0.952; P=0.031) and cancer-specific mortality (HR 0.547, 95% CI 0.336-0.891; P=0.015) in the PTS group. Subgroup multivariate analyses revealed patients with T1-T3 oropharynx, nasal cavity, or paranasal sinus primary MiSGC, especially adenoid cystic carcinoma, might benefit from PTS (all P<0.05). CONCLUSION: PTS is associated with improved survival in highly selected MiSGC patients and may be considered in future clinical practice. However, prospective studies with larger sample size are still necessary to validate our findings.

Central Lymph Node Status has Significant Prognostic Value in the Clinically Node-Negative Tall-Cell Variant of Papillary Thyroid Cancer Regardless of T-Staging and Radioactive Iodine Administration: First Evidence From a Population-Based Study.

BACKGROUND: The prognostic value of central lymph node (CLN) status in papillary thyroid cancer (PTC) remains controversial. This study aimed to provide the first evidence on this issue for the aggressive tall-cell variant (TCV) subtype. METHODS: The study identified TCV patients from the Surveillance, Epidemiology, and End Results database. The Kaplan-Meier method, log-rank test, and multivariate Cox regression models were used for analysis. RESULTS: Of the 744 patients included, 404 were recorded as N0, which were pathologically or only clinically confirmed. Overall survival (OS) and cancer-specific survival (CSS) did not differ significantly between the N0 and pN1a patients (p > 0.05). To investigate the reason, the N0 patients were subdivided according to the number of examined lymph nodes (ELN). The patients with a N0 diagnosis confirmed by two or more ELNs (N0-e2+) showed significantly better outcomes than the pN1a patients and their N0 counterparts without ELN (N0-e0) (p < 0.05), whereas the N0-e0 and pN1a groups demonstrated comparable outcomes in both the log-rank and multivariate analyses (p > 0.05). Moreover, the subgroup analyses showed that even among the patients with early T-staging (T1-T2) or receipt of radioactive iodine (RAI) therapy, the N0-e0 patients still demonstrated compromised OS compared with the N0-e2+ group (p < 0.05). CONCLUSION: The cN0 patients without ELN (N0-e0) had outcomes similar to those of the pN1a patients, but showed a poorer OS than the N0-e2+ group regardless of T-staging and RAI administration, suggesting that occult CLN metastases might act as a negative prognosticator in cN0 TCV. Therefore, prophylactic central neck dissection might be considered for biopsy-proven cN0 TCV patients. Prospective studies are expected to further validate our conclusions.

Trends and clinicopathological predictors of axillary evaluation in ductal carcinoma in situ patients treated with breast-conserving therapy.

The aim of this study was to investigate the trends of axillary lymph node evaluation in ductal carcinoma in situ (DCIS) patients treated with breast-conserving therapy (BCT) and to identify the clinicopathological predictors of axillary evaluation. DCIS patients treated with BCT in 2006-2015 at our institute were retrospectively included in the analysis. Patients were categorized into three groups: sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND), and non-evaluation. Univariate and multivariate logistic regression analyses were performed to identify factors that predicted axillary evaluation. A total of 315 patients were identified, among whom 135 underwent SLNB, and 15 underwent ALND. The proportion of patients who underwent axillary evaluation increased from 33.0% in 2006-2010 to 53.8% in 2011-2015 (P < 0.001), however, no patients had lymph node metastasis based on final pathology. In multivariate analysis, high-grade tumor favored axillary evaluation (OR = 4.376, 95% CI:1.410-13.586, P = 0.011); while excision biopsy favored no axillary evaluation compared with other biopsy methods (OR = 0.418, 95% CI: 0.192-0.909, P = 0.028). Subgroup analysis of patients treated in 2011-2015 revealed that high-grade tumor (OR = 5.898, 95% CI: 1.626-21.390, P = 0.007) and palpable breast lump (OR = 2.497, 95% CI: 1.037-6.011, P = 0.041) were independent predictors of axillary lymph node evaluation. Despite the significant decrease in ALND and a concerning overuse of SLNB, we identified no axillary lymph node metastasis, which justified omitting axillary evaluation in these patients. High-grade tumor, palpable lump, and biopsy method were independent predictors of axillary evaluations. Excision biopsy of suspicious DCIS lesions may potentially preclude the invasive component of the disease and help to avoid axillary surgery.

A prospective study of breast anthropomorphic measurements, volume and ptosis in 605 Asian patients with breast cancer or benign breast disease.

OBJECTIVES: The current study aims to summarize breast anthropomorphic measurement features in Chinese patients with breast diseases and to investigate their potential correlations with demographic factors. MATERIALS AND METHODS: Fifteen breast anthropomorphic parameters of 605 Chinese female patients were collected prospectively. Breast ptosis status was scaled by two methods and breast volume was calculated according to a modified formula of BREAST-V. RESULTS: Among 1210 breasts, the average breast volume was 340.0±109.1 ml (91.8-919.2 ml). The distance from the nipple to the inframammary fold was 7.5±1.6 cm in the standing position. The width of the breast base was 14.3±1.4 cm (8.5-23.5 cm). The incidence of breast ptosis was 22.8% (274/1204), of which 37 (23.5%) and 79 (31.7%) women had severe ptosis assessed by different criteria. Increased height (OR[odds ratio] = 1.500, P<0.001), post-menopausal status (OR = 1.463, P = 0.02), increased BMI, breastfeeding for 7-12 months (OR = 1.882, P = 0.008) and more than one year (OR = 2.367, P = 0.001) were risk factors for an increased breast volume. Post-menopausal status (OR = 2.390, P<0.001 and OR = 2.621, P<0.001 for different scales), BMI≥24.7 kg/m2 (OR = 3.149, P<0.001 and OR = 2.495, P = 0.002), breastfeeding for 7-12 months (OR = 4.136, P = 0.004 and OR = 4.010, P = 0.002), and breastfeeding for more than one year (OR = 6.934, P<0.001 and OR = 6.707, P<0.001) were independent risk factors for breast ptosis. CONCLUSIONS: The current study provides anthropomorphic measurements data of Chinese women with breast diseases, which are useful for cosmetic and reconstructive breast surgery decisions. Post-menopausal status, increased BMI, and breastfeeding for more than six months were independent risk factors for both increased breast volume and breast ptosis.

Surgical management of breast cancer in China: A 15-year single-center retrospective study of 18,502 patients.

The aim of the study was to review the surgical trends in breast cancer treatment in China over the past 15 years and to explore the possible factors related to the choice of surgical modality.The medical records of 18,502 patients with unilateral early stage breast cancer who underwent surgery from January 1999 to December 2013 at our institute were retrospectively reviewed. The utilization of different surgical modalities and the associated clinicopathological factors were analyzed. Furthermore, the prognostic role of surgical modality was also evaluated.The median patient age was 50.0 years. According to the pTNM staging system, 12.5% of the patients were classified as stage 0; 30.2% as stage I; 40.0% as stage II; and 17.3% as stage III. In total, 9.3% of the patients could not be staged. Overall, 67.1% of the breast cancer cases were estrogen receptor (ER) positive. The pattern of breast cancer surgery has changed tremendously over the past 15 years (P < 0.001). The pattern of mastectomy has shifted from radical mastectomy to modified radical mastectomy and simple mastectomy + sentinel lymph node biopsy. A total of 81.7% of the patients underwent mastectomy without immediate reconstruction, 15.2% underwent breast-conserving surgery (BCS), and 3.7% received immediate breast reconstruction after mastectomy. Age, TNM staging, and pathological characteristics greatly affected the choice of surgical modality. The 5-year recurrence-free survival (RFS) rates for the mastectomy, BCS, and reconstruction groups were 87.6%, 93.2%, and 91.7%, respectively (P < 0.001); the RFS rate was likely affected by distant recurrence instead of loco-regional recurrence. We also identified improved RFS over time, stratified by surgical modality and tumor stage. Multivariate Cox-regression analysis revealed that time of treatment, tumor stage, tumor grade, LVI status, and ER status were independent prognostic factors for RFS in our cohort, whereas surgical modality was not.Mastectomy remains the most prevalent surgical modality used to manage early stage breast cancer in China, although the utilization of BCS has increased in the past decade. However, surgical management was not a prognostic factor for RFS. The selection of appropriate patients depended on the assessment of multiple clinicopathological factors, which is essential for making surgical decisions.