Thymic Carcinoma

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

P2, N=95, Terminated, Jiangsu Alphamab Biopharmaceuticals Co., Ltd | The overall safety of KN046 is good, and no new safety signals have been found. The decision to terminate this study was made due to the adjustment of the sponsor's development strategy.

We reviewed the latest treatments for thymic epithelial tumors. If new therapeutic agents such as ICIs and molecular-targeted drugs are developed, this review suggests that surgery will become more important not only as therapy but also as part of multidisciplinary treatment that includes tissue collection.

The SUVmax and CYFRA 21-1 levels are significant indicators for the diagnosis of thymic carcinoma. Combining these indicators resulted in a more accurate diagnosis of thymic malignancies, which could facilitate the decision-making process for determining the optimal treatment strategies.

The classically described ivory-white gross appearance of the tumor, histomorphology of thick bands dividing the tumor into lobules, squamous cell differentiation, tight whorls of cells resembling Hassall's corpuscle, and areas showing dense lymphocytic infiltration, together with an immunoprofile of CD5, Ckit, Tumor protein 63 (p63), and B-cell lymphoma 2 gene (bcl2) positivity, helped in diagnosing this rare entity. Though classically ITC is said to have a good prognosis, cases with spread to adjacent organs and lymph node metastasis may not have an indolent course.

MTB advised molecular-guided treatment options in 32 situations, for 17 PM and 15 TET patients (75% clinical trial option, 22% off-label drug or compassionate use, 3% early access program). Molecular testing and MTB discussion were feasible for patients with rare thoracic cancers and allowed the broadening of treatment options for 30% of the cases.

P2, N=18, Not yet recruiting, Georgetown University

Targeted therapies, and ongoing clinical trials show promising results, addressing challenges rooted in the scarcity of actionable mutations and limited genomic understanding. International collaborations and data-sharing initiatives are crucial for breakthroughs in TETs research.

Vorolanib plus nivolumab had a manageable safety profile and may have clinical benefits in various thoracic malignancies. The disease control rate in thymic malignancies warrants further assessment.

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

Novel combination therapy strategies are also undergoing evaluation, with the goal of augmenting efficacy and understanding the toxicity while expanding the biomarkers of efficacy and safety. With advances in technology to improve target identification and drug delivery, old targets may become new opportunities, and the subsequently developed drugs may find their place in the treatment of thymic tumors.

P2, N=38, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Jan 2024 --> Dec 2024

P1, N=74, Recruiting, VM Oncology, LLC | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

Anti-angiogenic drugs and immune checkpoint inhibitors targeting the PD-1/PD-L1 axis have shown promising results for the treatment of unresectable tumors. Since thymic carcinomas are frankly aggressive tumors, this report presents insights into their oncogenic drivers, categorized under the established hallmarks of cancer.

Thymic carcinomas might be characterized by unique neuroendocrine differentiation and loss of identity as thymic epithelial cells. Future studies investigating the role of HDAC9 and NFATC1 in thymic epithelium are warranted to explore their potential as therapeutic targets in TETs.

P2, N=43, Recruiting, MedSIR | Trial completion date: Oct 2023 --> Jan 2026 | Trial primary completion date: Jun 2023 --> Jun 2024

We highlight the critical role of platinum-based chemotherapy agents as a primary treatment modality in advanced thymic carcinoma, underscoring the efficacy of platinum as a first-line option for recurrent disease, even in cases previously treated with platinum. Additionally, our findings indicate that CD5 positivity could be associated with improved PFS, suggesting its potential as a prognostic marker.

Seven studies assessed the clinical efficacy of sunitinib and five studies the use of apatinib and/or anlotinib. The current evidence suggests that the most active agent is lenvatinib, whereas sunitinib could be proposed as an acceptable second-line therapy for TC. Further research concerning the combination of immune checkpoint inhibitors with anti-angiogenic drugs is warranted.

PAX1 IHC has a moderate-to-high sensitivity for thymic epithelial neoplasms; however, the wide staining variability and fixation effects may lead to difficulty with consistent interpretation. This marker is unlikely to supplant the role of PAX8 in diagnostic practice, but it may be a useful addition to immunohistochemistry panels when evaluating for thymic primary tumors.

Circulating serum LDH level may serve as a non-invasive biomarker for the diagnosis and prognosis of TET. The relationship between LDH expression and immune cell infiltration merits further regarding its application in companion diagnosis for immunotherapy.

We profiled the mutational features of 47 Chinese patients with thymic malignancy of diverse pathologic phenotypes to uncover the integrated genomic landscape of these rare tumors, and identified the pathology-specific mutational patterns, prognostic signatures, and potential therapeutic targets for TCs and TNENs.

Our results confirm that CD5 and CD117 co-expression support a diagnosis of ITTC. All tumors in this cohort were DNA MMR-proficient and were not associated with Epstein-Barr virus (EBV) infection. A high CPS for PD-L1 suggests that immune checkpoint inhibitor therapy may be worthy of further exploration in patients with ITTC.

In conclusion, the findings in this study support the potential use of CD5 immunohistochemistry for distinguishing salivary CASTLE from other histological types of salivary gland tumors. Aberrant CD5 expression in this tumor may be linked to the tumor microenvironment.

P2; Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Jul 2023 --> Dec 2024

To the best of our knowledge, this is the largest cohort in which genomic alterations, TMB and MSI status of TETs were investigated. Potential targets for treatment previously unbeknownst in TETs are identified in this study, entailing newfound opportunities to advance therapeutic development.

Despite study heterogeneity, this review shows that ICI could be a therapeutic option for selected patients with TET that are not amenable to curative radical treatment after first-line chemotherapy.

P2, N=34, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Jan 2025 --> Dec 2023 | Trial primary completion date: Jan 2025 --> Dec 2023

P2, N=35, Recruiting, National Cancer Center, Japan | Not yet recruiting --> Recruiting

These molecules could potentially increase the effects of ICIs, particularly inducing a durable response. CD80/CD86 and MHC-II can be predictive biomarkers of ICIs in TETs, promoting the development of drugs for such TETs.

YAP1 C-terminus immunohistochemistry is a highly sensitive and specific ancillary marker that distinguishes metaplastic thymoma from its mimics. BA-FISH assays could not effectively detect YAP1::MAML2 fusions due to the proximity of the two genes. Loss of YAP1 C-terminus expression is a reliable surrogate for the detection of YAP1::MAML2 fusions in metaplastic thymoma.

Thymic malignancies treated with PBT appear to have favorable outcomes, especially in the adjuvant setting, in this cohort representing the largest series of such patients.

To be determined.

In this largest single-institution analysis of IMPT/PBS experience, we note extremely low incidence of grade 3+ acute or late toxicity with excellent local control and overall survival. No marginal failures were noted. In a patient population at high risk of cardiopulmonary radiation toxicities, IMPT/PBS should be strongly explored as a possible treatment option.