Thyroid Gland Hurthle Cell Carcinoma

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.

Moreover, IDH2 is significantly overexpressed in OCA compared to OA highlighting its potential as a biomarker for differential diagnosis of oncocytic tumors and malignancy. These findings improve the understanding of oncocytic thyroid tumors molecular pathology and suggest IDH2 as a valuable marker for clinical management.

To our knowledge, this is the largest study to date comparing the clinical application of abnormalities found on molecular testing for FTC and OTC. It further demonstrates the distinct clinicopathological and molecular characteristics of OTC.

However, they did not affect clinical outcomes, possibly due to short follow-up. Reflex testing for this genetic alteration in miFTCs and miOTCs could be justified regardless of tumor size, though the clinical benefit remains uncertain.

P2, N=79, Active, not recruiting, Grupo Espanol de Tumores Neuroendocrinos | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jul 2024 --> Jul 2025

P4, N=50, Active, not recruiting, Eisai Pharmaceuticals India Pvt. Ltd | Trial completion date: Aug 2024 --> Dec 2024 | Trial primary completion date: Aug 2024 --> Dec 2024

P2, N=115, Active, not recruiting, Fudan University | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

Biopsy and molecular testing provided diagnostic accuracy and informed treatment. Individualized approaches are essential for better outcomes, especially in aggressive subtypes, balancing the risks and benefits of intervention.

P4, N=50, Active, not recruiting, Eisai Pharmaceuticals India Pvt. Ltd | Trial completion date: May 2024 --> Aug 2024 | Trial primary completion date: May 2024 --> Aug 2024

P2, N=60, Completed, Academic and Community Cancer Research United | Active, not recruiting --> Completed

Hence, this brief investigative series study is of particular diagnostic interest because it prompts pathologists to use the term adenoma when a solitary oncocytic nodule is encountered, regardless of the established criteria for the diagnosis of adenoma. This viewpoint leads to the possible need for the reevaluation of the histological criteria of adenomas when it comes to oncocytic lesions in order to gain a common diagnostic approach and nomenclature among pathologists and overcome any controversies in such cases.

P2, N=21, Recruiting, City of Hope Medical Center

This study represents the largest molecularly defined cohort of non-oncocytic thyroid carcinomas with columnar cell morphology. These tumors represent a genetically and behaviorally heterogeneous group of neoplasms, some of which have RAS-like or follicular neoplasm-like genetics, some of which have BRAF-p.V600E-like or classic papillary thyroid carcinoma-like genetics, and some of which remain unclear. Noninvasive or minimally invasive tumors showed an indolent course compared to those with angioinvasion, gross extrathyroidal growth, or high-grade morphology. Consideration could be given to reclassification of this neoplasm outside of the subtyping of papillary thyroid carcinoma in light of its genetic diversity, distinct morphology, and clinical behavior more closely aligned with follicular thyroid neoplasms.

P2/3, N=504, Active, not recruiting, University College, London | Trial primary completion date: Dec 2023 --> Dec 2024

Due to disease progression, lenvatinib was initiated...Zoledronic acid was initiated for the treatment of the skeletal metastases, and palliative external beam radiation (2000 cGy in 5 fractions) was administered to the sternal lesion to alleviate the bone pain... The NBN gene encodes for the protein nibrin, a member of the MRE11/RAD50 complex that is involved in DNA repair. PVs in NBN are commonly identified in non-thyroidal malignancies such as breast and lung carcinomas. While NBN PVs are rarely reported in DTCs, as per our knowledge, this is the first described case of OTC with a PV in NBN as the molecular driver, manifesting with an aggressive disease course.

The WHO 5th thus emphasizes the importance of classifying tumors based on both genetic abnormalities and histomorphology. This approach aids in achieving accurate pathological diagnosis and facilitates the early selection of appropriate treatment options, including molecular targeted therapies.

P2, N=63, Active, not recruiting, National Cancer Institute (NCI)

P2, N=27, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2024 --> Sep 2024 | Trial primary completion date: Jan 2024 --> Sep 2024

FLCN alterations are exceedingly rare in TCa with an incidence of pathogenic changes below 1%. However, FLCN may exceptionally serve as a key driver mutation in TCa, based on our index patient. Identification of FLCN mutations may be clinically important due to possible presence of a germline mutation predisposing to renal tumors and potential responsiveness to immune checkpoint inhibitors.

However, despite the merits of these discoveries, we acknowledge that 5hmC currently cannot segregate minimally invasive from widely invasive tumors, although 5hmC levels were lower in wi-FPTCs. Further research is needed to explore the potential clinical implications of 5hmC in thyroid tumors.

P2, N=115, Active, not recruiting, Fudan University | Trial completion date: Dec 2023 --> Jun 2024 | Trial primary completion date: Apr 2023 --> Dec 2023

Oncocytic thyroid tumors with papillary features can span a spectrum from benign hyperplastic, to encapsulated neoplastic, to invasive malignant lesions. Owing to their papillary features, it is important not to confuse them for other types of thyroid tumors, such as oncocytic papillary thyroid carcinoma.

The frequency of subclonal mutations in ATCs was significantly higher than in PTCs (43% vs 25%, p#60;0.01) and PDTCs (43% vs 22%, p#60;0.01). Metastatic TCs are enriched in clinically informative genetic alterations such as RET translocations, BRAF hotspot mutations and NF1 biallelic losses that may be explored therapeutically.

The CaSR is differentially expressed on parathyroid tissue making it a feasible target for parathyroid imaging. False positives might be anticipated with medullary and Hürthle cell cancers.

P2, N=57, Completed, Academic and Community Cancer Research United | Active, not recruiting --> Completed

P2, N=120, Active, not recruiting, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Aug 2023 --> Aug 2024

In this study, CNAs were associated with Hurthle cell morphology on thyroid FNA and benign adenomas upon surgical follow-up. Therefore, if the only finding of a positive ThyroSeq v3 GC result is a CNA, conservative management can be considered if clinically indicated.

Y-biologics Inc would like to thank all the participating patients, dedicated clinical trial investigators and their team members who have helped to bring this novel therapy to the clinic. This research was supported by Korea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare (HN21C1391, Republic of Korea).

Conclusions Here we demonstrate the preclinical efficacy of a CSPG4-CAR T cell-based immunotherapy for the treatment of ATC. Our findings provide the rationale to design clinical studies for ATC patients not responding to currently available therapies, and patients with BRAF wild type tumors who are not eligible for treatment with the Dabrafenib/Trametinib combination, the only FDA-approved treatment for ATC.

The prevalence of thyroid cancer among transgender female veterans was 0. 341% (95% CI: 0. 223% ‐ 0.

In clinical practice, long term follow up of hurthle cell carcinomas and a need for multidisciplinary team approach is critical for the management of these complex tumors. Our patient continues to receive imaging and biochemical surveillance.

PD‐L1 expression varies significantly among different histological subtypes of TC highlighting the critical importance of patient selection for PD‐L1 based immunotherapies. Higher levels of suppressive immune markers may underly more aggressive clinical phenotypes in BRAF‐mutated‐TCs.

OC patients displayed a significant inverse relationship between SSTR2 and TSHR expression that was not seen in OA patients. This may be a key relationship that can be utilized to prognosticate and treat OCs.

P2, N=30, Recruiting, Memorial Sloan Kettering Cancer Center

The sensitivity and specificity for 5hmC immunohistochemistry (IHC) to detect mutated cases were 10% and 100% (RM236) and 20% and 89% (4D9). Therefore, 5hmC IHC is not a sensitive marker for detecting TERT promoter mutations in follicular thyroid tumors.

We demonstrate in cultured cells and a PDX model that small molecule inhibitors of lactate dehydrogenase selectively induce an ATP crisis and cell death in HTC. This work demonstrates that complex I loss exposes fermentation as a therapeutic target in HTC and has implications for other tumors bearing mutations that irreversibly damage mitochondrial respiration.

Rescuing complex I redox activity with the yeast NADH dehydrogenase (NDI1) in HCC cells diminishes ferroptosis sensitivity, while inhibiting complex I in normal thyroid cells augments ferroptosis induction. Our work demonstrates unmitigated lipid peroxide stress to be an HCC vulnerability that is mechanistically coupled to the genetic loss of mitochondrial complex I activity.

The authors found the immune microenvironment in HCC to be depleted. This immunosuppression is associated with a global LOH from haploidization and uniparental disomy, resulting in whole chromosome losses across the genome.

CNA patterns were different between the histopathological subgroups (p<0.001). By applying the structured interpretation and considerations provided by the current study, CNA-LOH analysis using an NGS panel that is feasible for daily practice may be of great added value to the widespread application of molecular diagnostics in the diagnosis and risk stratification of OCN.

P4, N=50, Active, not recruiting, Eisai Pharmaceuticals India Pvt. Ltd | Trial completion date: Dec 2022 --> May 2024 | Trial primary completion date: Dec 2022 --> May 2024

P1, N=20, Recruiting, The First Affiliated Hospital of Xiamen University | Phase classification: P2 --> P1