Thymic Carcinoma

The tumorigenic role of SNAI1 through the PIK3R2/p-EphA2 axis was preliminarily validated in TETs. A potential therapeutic strategy for TETs may involve the inhibition of SNAI1.

The tumor was diagnosed to be thymic squamous cell carcinoma because the immunostaining for CD5 and CD117 was positive. The same type of carcinoma was recognized as a small nodule during the previous lung cancer surgery, and it is considered to represent a synchronous double cancer.

Treatment includes cholinesterase inhibitors and immunotherapy agents, with extended thymectomy serving as an effective surgical option for drug-resistant cases. Minimally invasive approaches (video-assisted thoracoscopic surgery or robot-assisted thoracoscopic surgery) have demonstrated comparable oncological outcomes to sternotomy, highlighting their effectiveness and reliability.

P2, N=66, Active, not recruiting, SWOG Cancer Research Network | Trial primary completion date: Dec 2024 --> Mar 2025

P=N/A, N=0, Withdrawn, Travera Inc | N=630 --> 0 | Not yet recruiting --> Withdrawn

No difference in the methylation levels of the investigated genes was seen among TM stages and subtypes. No changes in blood methylation levels of the investigated genes were seen among TET subtypes. The present study confirms GHSR, ELF3, IL1RN and RAG1 as TET epigenetic biomarkers.

P2, N=30, Recruiting, Dwight Owen | Suspended --> Recruiting

Whole exome sequencing revealed loss of function mutations in TP53, STK11, PBRM1, SMAD3, FN1, NTRK1, and FANCD2, as well as gain of function mutations in MTOR, BCL11A and COL1A1, along with amplification of CCND3 and MDM2. This mutational landscape halfway between thymic carcinoma (TP53, PBRM1) and hepatoid variant carcinoma of other sites (STK11) suggests that, at some point during carcinogenesis, a switch occurred from an epithelial thymic phenotype to a hepatoid-like one.

P1/2, N=88, Completed, Vanderbilt-Ingram Cancer Center | Active, not recruiting --> Completed | Trial completion date: Jul 2025 --> Apr 2024

P2, N=647, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Jul 2024

P4, N=400, Not yet recruiting, Xi'an Jiaotong University Second Affiliated Hospital; Xi'an Jiaotong University Second Affiliated Hospital

The pooled estimated expression level of PD-L1 is 0.71 ([0.59-0.81]). This systematic review provides an overview of the gene alteration landscape and PD-L1 expression levels in TETs, discovers several potential confounding factors that may contribute to the high heterogeneity, and facilitates deeper investigations into the elucidation of the molecular landscape of TETs.

Additionally, an interactive immune environment in TETs is identified that correlates with the infiltration of abnormal FOXI1+ CFTR- ionocytes. Collectively, the data broaden the knowledge of TET cellular ecosystems, providing a basis for tackling histopathological diagnosis and related treatment.

A WB and immunohistochemistry staining comparison of primary and disseminated lesions of TETs using surgical specimens showed upregulated expression of ACTN4, β-catenin, and Slug proteins in disseminated lesions. In summary, our study suggests ACTN4 is associated with malignant potential characteristics such as invasion and dissemination in TETs via the β-catenin/Slug pathway.

Our findings revealed prognostic biomarkers such as TP53/CDKN2A and potential therapeutic targets such as KIT. Because thymic carcinoma is extremely rare, sharing molecular profiling data could provide valuable insights into the molecular mechanisms driving the development of these tumors.

These results indicate that IHC of both YAP1(N) and YAP1(C) is recommended to obtain staining patterns almost unique to MT. The biological significance of YAP1 in high-grade TETs warrants further investigation.

TROP2 expression in thymic carcinoma was confirmed by both RNA-seq and IHC, with high expression observed in IHC for intensity (76.9%) and proportion. TROP2 could be a potential target in thymic carcinoma.

P2, N=55, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jun 2024 --> Jun 2025

Lenvatinib combined with pembrolizumab is a potential standard treatment in pre-treated advanced B3-thymoma and thymic carcinoma. Toxicity profile is manageable but close monitoring is advised.

P2, N=66, Active, not recruiting, SWOG Cancer Research Network | Trial completion date: Nov 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Dec 2024

Immune checkpoint inhibitors (ICIs) are ongoing under evaluation in the advanced or metastatic diseases despite the challenges related to the very low tumor mutation burden (TMB) and the high incidence of immune-related adverse events in TETs. In this regard, predictive impact of tissue biomarkers expression such as programmed cell death ligand-1 (PD-L1), and other emerging biomarkers, as well as their optimal and shared interpretation are currently under evaluation in order to predict response rates to ICIs in TETs.

Lenvatinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, is approved as a drug therapy for thymic carcinoma (TC); however, although it is a molecular targeted therapy, there are no obvious predictors of therapeutic efficacy...Furthermore, the pathological stage was the only factor significantly associated with OS in multivariate analysis. The results of the present study suggest the possibility that the indications for VEGF inhibitor therapy could be extended to type B3 thymoma.

INSM1 positivity in lymphoepithelial carcinoma of the thymus may represent a pitfall for diagnosis, particularly in small biopsy samples. Awareness of this finding may be of importance to avoid misdiagnosis of neuroendocrine malignancy.

Some studies have revealed the molecular characteristics of thymic carcinoma, although the results of these studies have shown a different pattern of gene alterations. The further accumulation of data would be helpful in revealing the genomic landscape and establishing molecular-targeted therapies.

P2, N=34, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed

Cytokines showed a causal relationship with benign and malignant thymic tumors. Interleukin-12 subunit beta is a common cytokine that affects malignant and benign thymic tumors.

P1, N=74, Recruiting, VM Oncology, LLC | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Dec 2025

The cases in this series highlight a tumor that is different from conventional thymic carcinoma and that has the morphological and immunohistochemical features commonly seen in adenoid cystic carcinomas with high-grade transformation. Correct diagnosis is essential for patient management.

P2, N=18, Recruiting, Georgetown University | Trial completion date: Jul 2025 --> Dec 2026 | Trial primary completion date: Jul 2025 --> Apr 2026

Carcinoma showing thymus-like elements has recently been reported in the salivary gland. Similar to thymic carcinoma, tumor cells are positive for CD5 and are accompanied by T lymphocytes.

P3, N=172, Recruiting, Fudan University

This article reviews the current understanding of the biological function and clinical significance of LOXL1-AS1 in human cancers. These findings suggest that LOXL1-AS1 may be both a reliable biomarker and a potential therapeutic target for cancers.

P2, N=56, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Jul 2024

P2, N=18, Recruiting, Georgetown University | Not yet recruiting --> Recruiting

This case report contributes to the growing understanding of thymic basaloid carcinoma, a rare and potentially aggressive thymic carcinoma subtype. It emphasizes the necessity for precise surgical techniques and enhanced diagnostic acumen among cardiothoracic surgeons and oncologists.

GFH018 monotherapy presented a favorable safety profile without cardiac toxicity or bleeding. Modest efficacy warrants further studies, including combination strategies.

However, the application of these revolutionary treatments for thymic cancers is limited to their use for the management of recurrent thymic carcinoma because of the risk of immune toxicity. In this paper, we review the current uses of immunotherapy for the management of thymic epithelial tumors and highlight potential strategies to improve safety and broaden the application of these treatments for patients with thymic cancers.

P1/2, N=88, Active, not recruiting, Vanderbilt-Ingram Cancer Center | Trial primary completion date: Jul 2024 --> Feb 2024

P2, N=34, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Feb 2024 --> Jul 2023

P2; Recruiting --> Suspended

P2, N=43, Active, not recruiting, MedSIR | Recruiting --> Active, not recruiting

P=N/A, N=1020, Recruiting, Erasmus Medical Center