Thyroid Gland Papillary Carcinoma

The detection of BRAF fusions and their many partners was enabled by the Afirma XA exome-enriched RNASeq panel. Although BRAF fusions occurred in only 0.2% of thyroid nodules, they were GSC-Suspicious and lacked typical BRAF/RAS mutations. Interestingly, expression signatures associated with malignancy varied by fusion partner.

P2, N=79, Terminated, Grupo Espanol de Tumores Neuroendocrinos | Trial completion date: Dec 2025 --> Nov 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jul 2025 --> Nov 2024; In compliance with current legislation applicable to Clinical Trials, following the instructions of the Spanish Agency for Medicines and Health Products.

P=N/A, N=900, Recruiting, The First Affiliated Hospital of Dalian Medical University; The First Affiliated Hospital of Dalian Medical University

P=N/A, N=256, Not yet recruiting, hunan cancer hospital; hunan cancer hospital

P=N/A, N=480, Not yet recruiting, Qilu Hospital of Shandong University; Qilu Hospital of Shandong University

P1, N=474, Not yet recruiting, Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

P1, N=25, Recruiting, DeuterOncology | Trial completion date: Apr 2025 --> Dec 2026 | Trial primary completion date: Oct 2024 --> Dec 2025

Combining the lymphocyte features in and around the tumor yielded a statistically significantly improvement in prognostic performance (HR = 3.17 (95% CI: 3.02, 3.32)) on training and were independently evaluated against 62 patients outside TCGA-THCA with HR = 2.44 (95% CI: 2.19, 2.69). Multivariable Cox-regression analysis on the validation set revealed that the density of peritumoral and intratumoral lymphocytes were prognostic independent of histological subtype with a C-index = 0.815.

The prognosis of papillary thyroid carcinoma (PTC) is highly dependent on gene mutations and pathologic features.The common gene mutations in PTC include BRAF V600E,RET/PTC rearrangement,and RAS mutations.These mutations have been suggested to be associated with an increased risk of recurrence,poorer efficacy of postoperative radioactive iodine therapy,and reduced survival.The pathologic subtypes of PTC include classic,follicular,tall cell,hobnail,columnar cell,diffuse sclerosing,solid/trabecular,oncocytic,Warthin-like,clear cell,and spindle cell subtypes,which have different aggressiveness and linked with varied clinical prognosis.Therefore,detecting the gene mutations and pathologic subtypes of PTC is of great importance for therapeutic regimen selection and prognosis evaluation.Ultrasound imaging with non-invasiveness,convenience,and high resolution has become the primary examination method for the diagnosis and treatment of thyroid cancer.This paper reviews the correlations of gene mutations and pathologic subtypes with the ultrasound features of PTC,aiming to give new insights into the application of ultrasound imaging in predicting gene mutations and pathologic subtypes of PTC before surgery as well as provide new ideas for accurate assessment of preoperative prognosis.

This Indian study identified novel somatic mutations and fusion genes in PTC, revealing a distinct genomic landscape with implications in precision diagnostics and personalized therapies. NGS with intraoperative live sampling shows promise in prognostication and therapeutic optimization of advanced/metastatic PTC cases.

P=N/A, N=1200, Recruiting, Ohio State University Comprehensive Cancer Center | Trial completion date: Dec 2023 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2026

However, for papillary thyroid carcinoma, sensitivity in Bethesda categories V and VI was 86% in non-AIT patients but decreased to 61.5% in AIT patients. These findings emphasize the importance of considering surgical intervention in pediatric patients with Bethesda III-VI cytology, particularly in those with AIT.

Lastly, inhibiting NOD1 showed significant anti-PTC activity in vitro. Our results suggest that pyroptosis-related genes can be used for PTC diagnosis, and NOD1 could be a promising therapeutic target.

The present study constructed a pyroptosis-related gene signature that could predict the prognosis of PTC. Additionally, this signature was correlated with tumor immunity.

P2, N=30, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

Thyroid GuidePx reliably identifies a low-risk subgroup (early type 1 and early type 2 papillary thyroid cancers) for which conservative procedures would be appropriate. Tall cell variants in this subgroup are uncommon (1.2%), and none of the tall cell variants in this subgroup recurred. Type 3 papillary thyroid cancers have greater recurrence rates in both early and advanced papillary thyroid cancers. Tall cell variant appears to further increase recurrence in this subgroup.

The findings reveal a crucial role of XPR1 in PTC progression and prognosis via the BRAF-ERK1/2-P53 signaling pathway, providing potential therapeutic targets for treating PTC.

Higher TAS2R14 expression correlated with better progression-free survival in patients (p<0.05). T2R activation by bitter agonists induces apoptosis and higher TAS2R expression is associated with survival, suggesting potential therapeutic relevance in thyroid cancer management.

The BRAFV600E and TERT-p double mutation in PTC was significantly associated with relatively old age, larger tumor size, lobulated configuration in tumor margin, papillary excrescences on the cut surface, solid-cut surface, ETE, and high Ki-67 LI. These features are suggestive of the presence of the double mutation and should be analyzed at the molecular level in patients with PTC.

Neoadjuvant use of tyrosine kinase inhibitors seems extremely effective in downstaging surgically unresectable differentiated thyroid cancers to achieve R0 resection while avoiding unnecessary surgical morbidities. A multidisciplinary approach with early genomic profiling to guide personalized neoadjuvant use of tyrosine kinase inhibitors is essential. Prospective studies are urgently needed to define the potential role of neoadjuvant tyrosine kinase inhibitors in advanced thyroid cancer management.

Serum circ_0001955, Tg, and TgAb value, and their combination may have diagnostic value in predicting recurrence. Serum circ_0001955 levels in patients with PTC after radical thyroidectomy and iodine 131 thyroidectomy may help predict recurrence.

The loss of claudin-1 and claudin-4 characterized more aggressive cancers. Several studies have shown the benefits of targeting claudins in cancers, but their implementation into clinical practice requires further trials.

Drug retention rates were also high, and disease activation and function improved compared to baseline. Therefore, secukinumab could be a safe and effective option for this patient group.

TRAb enhances angiogenesis and upregulates PROX1 expression in HUVECs, suggesting a novel possible mechanism for goiter formation in GD.

Using public databases, RNA sequencing, and bioinformatics, we discovered that E2 stimulates the ERα/KRT19 signaling axis to stimulate PTC proliferation, migration, and invasion.

Allo-aca treatment reduced the number of metastatic lung nodules formed by thyroid cancer cells in nude mice and reduced the diameter of metastatic lesions. ADSCs upregulate MMP-2 levels of thyroid cancer cells through exocrine leptin, thereby promoting cancer cell migration, which may be one of the key mechanisms by which obesity increases the invasiveness of thyroid cancer.

Preoperative calcitonin can be helpful in the diagnostic workup of thyroid nodules. Due to different treatment strategies, precise histological differentiation of potential lymph node metastasis is essential.

The overexpression of circTIAM1 is associated with the malignant progression of PTC. A high level of circTIAM1 promotes the malignancy of PTC cells via the miR-338-3p/LASP1 axis.

TCCRP is a rare entity, which carries an excellent prognosis. A proper diagnosis is essential to conduct the best treatment next to a careful follow-up due to the ambiguous natural history of this rare entity.

P1/2, N=4, Terminated, Istari Oncology, Inc. | N=15 --> 4 | Trial completion date: May 2025 --> Jun 2024 | Recruiting --> Terminated | Trial primary completion date: May 2025 --> Apr 2024; business decision

While the identification of NIFTP represents a significant advancement in thyroid cancer diagnosis, challenges remain in refining preoperative diagnostic tools and establishing optimal long-term follow-up strategies. The objective of this review is to provide a comprehensive overview of NIFTP, including its histopathological characteristics, molecular profile, clinical presentation, diagnostic criteria, management strategies, and future research directions.

Additionally, we analyzed the performance of single-protein/gene receiver operating characteristic in differentiating the invasive encapsulated follicular variant of papillary thyroid carcinoma from others within The Cancer Genome Atlas projects, which yielded an AUC > 0.5. We demonstrated that integration of high-throughput proteomics with machine learning can effectively differentiate the invasive encapsulated follicular variant of papillary thyroid carcinoma from other follicular pattern thyroid tumors.

P2, N=30, Recruiting, Massachusetts General Hospital | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Mar 2024 --> Mar 2025

A high density of infiltrated CD163+ TAMs predicts recurrence in correlation with low LMR and circulating monocyte accumulation. Thus, TAMs should be considered when assessing advanced PTC.

The predictive model developed in this study effectively predicts lymph node metastasis risk in PTC patients by incorporating ultrasound features, demographic characteristics, and serum parameters. However, including the BRAF V600 E mutation does not significantly improve the model's diagnostic performance.

We conclude that AS can be an acceptable approach and is safe and effective in Latin America, although more prospective studies are needed to consolidate this strategy in our region. Adequate infrastructure, follow-up, and patient education, as well as multidisciplinary healthcare teams trained in conducting AS must be ensured for successful results.

EGFR gene mutations were found in 16 (29%) and KRAS or NRAS alterations in 8 (14%) of the 54 tumors analyzed. We described herein seven non-hotspot/novel variants in the BRAF gene, highlighting their potential role in expanding our understanding of FCDTC genetics.

The frequent occurrence of fusion mutations and their associations with certain clinicopathological metrics highlight the importance of integrating molecular profiling into routine PTC management. Early detection of fusion mutations can inform surgical decisions and therapeutic strategies, potentially improving clinical outcomes.

Moreover, Dicer1 overexpression led to decreased proliferation, invasion, and increased apoptosis. Our findings deepen the understanding of Dicer1's role in thyroid cancer, demonstrating that both complete elimination and overexpression of Dicer1 inhibit thyroid oncogenesis, highlighting Dicer1 as a promising target for novel therapeutic strategies.

This study demonstrated that resveratrol inhibits thyroid papillary carcinoma cell proliferation and reduces poor prognostic BRAF and ERK mRNA and protein expressions, while increasing NIS mRNA and protein expression suggesting a redifferentiating effect. More studies are needed to evaluate resveratrol as a novel therapeutic agent in the treatment of papillary thyroid cancer.

Silencing these genes inhibited tumor cell functions and enhanced CD8+ T cell activity, both in vitro and in vivo. CLDN1 and EGFR are crucial in PTC, linked to tumor invasiveness, EMT, and immune suppression, presenting them as potential therapeutic targets.

Our data demonstrate high feasibility of [18F]SiTATE PET/CT in a small cohort of patients with MTC and DTC. The use of [18F]SiTATE may overcome logistical disadvantages of 68Ga-based tracers and facilitate SSTR-targeted PET/CT imaging of thyroid carcinoma.