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Journal of Thoracic Oncology : Official... Mar 2023Thymic epithelial tumors are rare and are classified as thymoma, thymic carcinoma, and thymic neuroendocrine tumors. The objective of this systematic review was to... (Review)
Review
INTRODUCTION
Thymic epithelial tumors are rare and are classified as thymoma, thymic carcinoma, and thymic neuroendocrine tumors. The objective of this systematic review was to evaluate the treatment options for patients with thymic epithelial tumors.
METHODS
This systematic review was developed by Ontario Health (Cancer Care Ontario)'s Program in Evidence-Based Care and by the Lung Cancer Disease Site Group. MEDLINE, EMBASE, and the Cochrane Library were searched for studies comparing surgical, radiotherapy, or systemic treatments against any combination of these treatments in patients with thymic epithelial tumors. Meta-analyses were conducted with clinically homogenous studies.
RESULTS
A total of 106 studies were included, mainly from observational studies. There was an overall survival benefit with postoperative radiotherapy for patients with thymic carcinoma (hazard ratio = 0.65, 95% confidence interval: 0.47-0.89) and for patients with thymoma (hazard ratio = 0.70, 95% confidence interval: 0.59-0.82), especially for those with a high risk for mortality. Patients with thymic carcinoma or thymoma had a response to chemotherapy. Selection bias affected the results for studies that evaluated neoadjuvant chemotherapy or minimally invasive surgical techniques. Furthermore, the overall survival benefit found for adjuvant chemotherapy may have been confounded by the administration of postoperative radiotherapy.
CONCLUSIONS
For patients with thymoma or thymic carcinoma, the literature is of low quality and subject to bias. There were overall survival benefits with postoperative radiotherapy. The results of this systematic review were used to inform treatment recommendations in a clinical practice guideline. Future large-scale prospective studies that control for confounders are needed.
Topics: Humans; Thymoma; Prospective Studies; Lung Neoplasms; Thymus Neoplasms; Neoplasms, Glandular and Epithelial
PubMed: 36343922
DOI: 10.1016/j.jtho.2022.10.016 -
Journal of Thoracic Oncology : Official... May 2022Thymic carcinomas are rare malignancies that in general arise in the prevascular (anterior) mediastinum. These tumors are usually invasive, often present at advanced... (Review)
Review
Thymic carcinomas are rare malignancies that in general arise in the prevascular (anterior) mediastinum. These tumors are usually invasive, often present at advanced stages, and typically behave aggressively. Studies are hampered by the paucity of these tumors, the large variety of carcinoma subtypes, and the lack of unique morphologic and immunophenotypic features. Despite these challenges, advances in diagnostic imaging, surgical approaches, systemic therapies, and radiation therapy techniques have been made. The WHO classification of thymic epithelial tumors has been updated in 2021, and the eighth tumor nodal metastasis staging by the American Joint Committee on Cancer/Union for International Cancer Control included thymic carcinomas in 2017. Molecular alterations that provide more insight into the pathogenesis of these tumors and that potentially permit use of novel targeted therapies are increasingly being identified. New approaches to radiation therapy, chemotherapy, and immunotherapy are under evaluation. International societies, including the International Thymic Malignancy Interest Group, European Society of Thoracic Surgeons, and Japanese, Chinese, and Korean thymic associations, have been critical in organizing and conducting multi-institutional clinical studies. Herein, we review contemporary multidisciplinary perspectives in diagnosis and management of thymic carcinoma.
Topics: Humans; Lung Neoplasms; Neoplasm Staging; Neoplasms, Glandular and Epithelial; Public Opinion; Thymoma; Thymus Neoplasms
PubMed: 35227908
DOI: 10.1016/j.jtho.2022.01.021 -
The Lancet. Oncology Mar 2018Treatment options are limited for patients with thymic carcinoma. These aggressive tumours are not typically associated with paraneoplastic autoimmune disorders, and...
BACKGROUND
Treatment options are limited for patients with thymic carcinoma. These aggressive tumours are not typically associated with paraneoplastic autoimmune disorders, and strong PD-L1 expression has been reported in thymic epithelial tumours. We aimed to assess the activity of pembrolizumab, a monoclonal antibody that targets PD-1, in patients with advanced thymic carcinoma.
METHODS
We completed a single-arm phase 2 study of pembrolizumab in patients with recurrent thymic carcinoma who had progressed after at least one line of chemotherapy. This was a single-centre study performed at Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA. Key inclusion criteria were an Eastern Cooperative Oncology Group performance status of 0-2, no history of autoimmune disease or other malignancy requiring treatment or laboratory abnormality, and adequate organ function. Patients received 200 mg of pembrolizumab every 3 weeks for up to 2 years. The primary objective of the study was the proportion of patients who had achieved a response assessed with Response Evaluation Criteria in Solid Tumors version 1.1. Analysis was per protocol, in all eligible patients. The study is registered with ClinicalTrials.gov, number NCT02364076, and is closed to accrual; we report the final analysis.
FINDINGS
41 patients were enrolled from March 12, 2015, to Dec 16, 2016, of whom 40 were eligible and evaluable and one was excluded because of elevated liver enzymes at screening. The median follow-up was 20 months (IQR 14-26). The proportion of patients who achieved a response was 22·5% (95% CI 10·8-38·5); one (3%) patient achieved a complete response, eight (20%) patients achieved partial responses, and 21 (53%) patients achieved stable disease. The most common grade 3 or 4 adverse events were increased aspartate aminotransferase and alanine aminotransferase (five [13%] patients each). Six (15%) patients developed severe autoimmune toxicity, including two (5%) patients with myocarditis. There were 17 deaths at the time of analysis, but no deaths due to toxicity.
INTERPRETATION
Pembrolizumab is a promising treatment option in patients with thymic carcinoma. Because severe autoimmune disorders are more frequent in thymic carcinoma than in other tumour types, careful monitoring is essential.
FUNDING
Merck & Co.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; District of Columbia; Female; Humans; Male; Middle Aged; Thymoma; Thymus Neoplasms; Time Factors; Treatment Outcome
PubMed: 29395863
DOI: 10.1016/S1470-2045(18)30062-7 -
Journal of Thoracic Oncology : Official... Nov 2022The aim of this guideline was to provide recommendations for the most effective therapy for patients with thymic epithelial tumors, including thymoma, thymic carcinoma,... (Review)
Review
INTRODUCTION
The aim of this guideline was to provide recommendations for the most effective therapy for patients with thymic epithelial tumors, including thymoma, thymic carcinoma, and thymic neuroendocrine tumors (NETs). This guideline is intended to be used by all health care professionals managing patients with thymic epithelial tumors.
METHODS
The guideline was developed by Ontario Health (Cancer Care Ontario)'s Program in Evidence-Based Care and by the Lung Cancer Disease Site Group through a systematic review of the evidence, expert consensus, and formal internal and external reviews.
RESULTS
Evidence-based recommendations were developed to improve the management of patients with thymic epithelial tumors. The guideline includes recommendations for surgical, radiation, and systemic treatments for patients with thymoma, thymic carcinoma, and thymic NETs separated by stage of disease using the TNM staging system. Recommendations for patients with thymic NETs were endorsed from the 2021 National Comprehensive Cancer Network Neuroendocrine and Adrenal Tumors Guideline.
CONCLUSIONS
This guideline reflects the new staging system for patients with thymoma and thymic carcinoma and includes supporting evidence from the best available studies.
Topics: Humans; Thymoma; Lung Neoplasms; Thymus Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasm Staging; Neuroendocrine Tumors; Retrospective Studies
PubMed: 36031176
DOI: 10.1016/j.jtho.2022.08.007 -
Oncology Reports Jun 2021Due to the lack of specific symptoms in early thymic epithelial tumours (TETs), patients are mostly in the advanced stage at the time of presentation. The aim of the...
Due to the lack of specific symptoms in early thymic epithelial tumours (TETs), patients are mostly in the advanced stage at the time of presentation. The aim of the present study was to explore the mechanism by which the long noncoding RNA (lncRNA) LOXL1‑AS1 affects thymoma and thymic carcinoma progression by targeting the miR‑525‑5p‑ axis. Bioinformatics was used to analyse the process of LOXL1‑AS1 targeting miR‑525‑5p‑ and its expression characteristics in TET. The relationships between LOXL1‑AS1, miR‑525‑5p, and prognosis were analysed. The dual luciferase reporter assay was applied to verify targeting. The gene was knocked down or overexpressed by plasmid transfection. Cell counting kit 8 (CCK‑8) assay, flow cytometry and Transwell assay were used to detect cell viability, apoptosis and invasion ability, respectively. Proteins and RNAs were examined by western blot analysis and qPCR, respectively. A tumour‑burdened assay was used to perform verification. LOXL1‑AS1 and were overexpressed in thymoma and thymic carcinoma; high levels of LOXL1‑AS1 and were associated with poor prognosis, and there was a significant positive correlation between their levels. Downregulation of miR‑525‑5p expression was also associated with poor prognosis of patients. Clinical trials also demonstrated the same trends. miR‑525‑5p inhibited the expression of protein by targeting the 3'‑untranslated region (UTR) of mRNA. LOXL1‑AS1 promoted the expression of as a sponge targeting miR‑525‑5p. Animal experiment results also showed that knockdown of miR‑525‑5p promoted cancer by promoting the expression of . In conclusion, LOXL1‑AS1 and are highly expressed in thymoma and thymic carcinoma; miR‑525‑5p is expressed at low levels in thymoma and thymic carcinoma; and downregulation of miR‑525‑5p is associated with poor prognosis. In summary, this study demonstrates that LOXL1‑AS1 acts as a sponge that targets miR‑525‑5p to promote expression, thereby promoting the growth and invasion and inhibiting apoptosis of thymoma and thymic carcinoma cells.
Topics: 3' Untranslated Regions; Animals; Apoptosis; Cell Line, Tumor; Computational Biology; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; HSP70 Heat-Shock Proteins; Humans; Mice; MicroRNAs; Mitochondrial Proteins; Neoplasm Invasiveness; Prognosis; RNA, Long Noncoding; Survival Rate; Thymectomy; Thymoma; Thymus Gland; Thymus Neoplasms; Xenograft Model Antitumor Assays
PubMed: 33907842
DOI: 10.3892/or.2021.8068 -
International Journal of Molecular... Apr 2022Thymic Epithelial Neoplasms (TENs) represent the most common tumors of the thymus gland. Epigenetic alterations are generally involved in initiation and progression of... (Review)
Review
Thymic Epithelial Neoplasms (TENs) represent the most common tumors of the thymus gland. Epigenetic alterations are generally involved in initiation and progression of various cancer entities. However, little is known about the role of epigenetic modifications in TENs. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The search terms thymoma, thymic carcinoma, thymic epithelial neoplasm, epigenetics, DNA methylation, HDAC and miRNA were employed and we were able to identify forty studies focused on TENs and published between 1997 and 2021. Aberrant epigenetic alterations seem to be involved in the tumorigenesis of thymomas and thymic carcinomas, with numerous studies reporting on non-coding RNA clusters and altered gene methylation as possible biomarkers in different types of TENs. Interestingly, Histone Deacetylase Inhibitors have shown potent antitumor effects in clinical trials, thus possibly representing effective epigenetic therapeutic agents in TENs. Additional studies in larger patient cohorts are, nevertheless, needed to verify the clinical utility and safety of novel epigenetic agents in the treatment of patients with TENs.
Topics: Epigenesis, Genetic; Humans; MicroRNAs; Neoplasms, Glandular and Epithelial; Thymoma; Thymus Neoplasms
PubMed: 35409405
DOI: 10.3390/ijms23074045 -
Endocrine Journal Nov 2022Intrathyroidal thymic carcinoma (ITTC) is a rare malignancy of the thyroid. It is thought to originate from ectopic thymic tissue or embryonic thymic rest, in, or...
Intrathyroidal thymic carcinoma (ITTC) is a rare malignancy of the thyroid. It is thought to originate from ectopic thymic tissue or embryonic thymic rest, in, or adjacent to, the thyroid. We analyzed the backgrounds, clinicopathological features, and prognosis of 20 patients with ITTC, treated at our hospital. Thirteen of the 15 patients (86%) who underwent ultrasonography were diagnosed as malignant, based on imaging findings. 16 of the 17 patients (93%) who underwent cytology, were diagnosed or suspected to be malignant. Locally curative surgery (thyroidectomy and lymph node dissection) was performed for 19 patients. Large tumor size (>4 cm) was positively related to pathological node metastasis (p = 0.0389). Fourteen patients, including nine Ex-positive patients, underwent adjuvant external beam radiotherapy (EBRT) of the neck after surgery. Two patients showed recurrence of thyroid bed after and neither of them underwent adjuvant EBRT after surgery. Two patients who underwent EBRT showed recurrences of the lateral nodes (level V and level II), but they were easily dissected by re-operation. Ten- and 20-year local recurrence-free survival rates were 84.9% and 60.6%, respectively. To date, four patients showed distant recurrence, and 10- and 20-year distant recurrence-free survival rates were 75.0% and 75.0%, respectively. Our findings indicate that 1) the prognosis of ITTC is generally favorable, and 2) large tumor size is significantly related to lymph node metastasis. Two patients showing recurrence of the central region did not undergo EBRT; thus, further comparative studies are desirable to elucidate whether EBRT can prevent significant local recurrence.
Topics: Humans; Carcinoma, Papillary; Thyroid Neoplasms; Thymoma; Thyroidectomy; Prognosis; Thymus Neoplasms; Neoplasm Recurrence, Local; Neck Dissection; Retrospective Studies
PubMed: 35768280
DOI: 10.1507/endocrj.EJ22-0141 -
The Cochrane Database of Systematic... Aug 2013Thymic carcinoma or advanced thymoma is a rare cancer of the thymus gland that tends to be aggressive and infiltrate neighbouring organs, making total resection very... (Review)
Review
BACKGROUND
Thymic carcinoma or advanced thymoma is a rare cancer of the thymus gland that tends to be aggressive and infiltrate neighbouring organs, making total resection very difficult. Induction or adjuvant chemotherapy, or both, are often used in a multimodality approach to treat people affected by this condition, but the effectiveness of chemotherapy for thymic carcinoma or advanced thymoma remains uncertain.
OBJECTIVES
To assess the role of chemotherapy in adults with thymic carcinoma or advanced thymoma.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2012, Issue 7), MEDLINE (accessed via Ovid from 1966 to July 2012), EMBASE (accessed via Ovid, from 1980 to July 2012), Latin American and Caribbean Literature on Health Sciences (LILACS), the Chinese Biological Medicine Database (CBM, 1978 to July 2012), China National Knowledge Infrastructure (CNKI, 1980 to July 2012) and the Chinese scientific periodical database VIP Information (VIP, 1989 to July 2012). There was no language restriction in searching for studies.
SELECTION CRITERIA
We planned to include randomised controlled trials (RCTs) of trials using chemotherapy (either single-agent or combination chemotherapy plus surgery, radiotherapy or not) for thymic carcinoma and/or advanced thymoma. We planned to include all adults (aged 18 years and over) diagnosed with thymic carcinoma and/or with Masaoka stage III or IV thymic tumours. The intended primary outcomes were overall survival (OS) and progression-free survival (PFS).
DATA COLLECTION AND ANALYSIS
Two review authors independently evaluated the search results according to the inclusion and exclusion criteria. There were no studies identified for inclusion and therefore no data extraction was completed.
MAIN RESULTS
No RCTs were eligible for inclusion in this review. We report details of excluded prospective studies in an additional table and try to provide some useful evidence regarding current practice.
AUTHORS' CONCLUSIONS
There were no RCTs eligible for inclusion in this review. In current practice the most common regimen for adult patients with thymic carcinoma or advanced thymoma is cisplatin-based chemotherapy. Considering the condition is rare, it is suggested that an international group is set up to organise and evaluate prospective collection of data from cohorts of patients to inform current clinical practice.
Topics: Adult; Antineoplastic Agents; Humans; Prospective Studies; Thymoma; Thymus Neoplasms
PubMed: 23970462
DOI: 10.1002/14651858.CD008588.pub2 -
Head and Neck Pathology Sep 2022Ectopic thymic carcinomas are rarely diagnosed in the thyroid gland, let alone in extrathyroid tissues. In the currently available literature, only five cases of... (Review)
Review
Ectopic thymic carcinomas are rarely diagnosed in the thyroid gland, let alone in extrathyroid tissues. In the currently available literature, only five cases of extrathyroidal malignancies with thymic differentiation have been reported as arising in the major salivary glands. A 69-year-old female presented with a slow-growing palpable mass in the left parotid gland. Fine needle aspiration biopsy suggested metastatic cancer, whereas core needle biopsy revealed high-grade squamous cell carcinoma. The patient underwent left radical parotidectomy with selective ipsilateral lymph node dissection and subsequent radiation therapy. The surgical specimen was taken for histopathological examination. Microscopically, the tumor resembled thymic carcinoma. It was composed of large nests of squamoid cells with smooth contours, focally with a syncytial growth pattern, and accompanied by abundant lymphocytes with reactive lymphoid follicles. This appearance resembled a micronodular thymic carcinoma with lymphoid hyperplasia. Moreover, the tumor displayed expression of squamous markers (p40 and p63) and markers of thymic carcinoma (CD5 and CD117). Therefore, the final diagnosis of intrasalivary thymic carcinoma was rendered. The molecular analysis including next-generation sequencing demonstrated no variants of the strong, potential, or unknown clinical significance. The patient remains disease-free at 1-year follow-up. In the current case, we comprehensively present a clinical, microscopic, molecular, and radiological picture of CD5-positive squamous cell carcinoma of the parotid. We postulate that similar cases should be designated as intrasalivary thymic carcinoma analogically to similar thyroid tumors. Our case and the limited literature data indicate they should be distinguished from conventional squamous cell carcinoma of major salivary glands due to their rather favorable prognosis.
Topics: Aged; Carcinoma, Squamous Cell; Female; Humans; Thymoma; Thymus Neoplasms; Thyroid Neoplasms
PubMed: 34807356
DOI: 10.1007/s12105-021-01394-6 -
Cancer Apr 2023Thymic epithelial tumors (TETs) are a rare group of malignancies arising from the thymus. Surgery remains the foundation of treatment for patients with early-stage... (Review)
Review
Thymic epithelial tumors (TETs) are a rare group of malignancies arising from the thymus. Surgery remains the foundation of treatment for patients with early-stage disease. Limited treatment options are available for the treatment of unresectable, metastatic, or recurrent TETs and are associated with modest clinical efficacy. The emergence of immunotherapies in the treatment of solid tumors has generated significant interest in understanding their role in TET treatment. However, the high rates of comorbid paraneoplastic autoimmune disorders, particularly in thymoma, have tempered expectations regarding the role of immune-based therapies. Clinical studies of immune checkpoint blockade (ICB) in thymoma and thymic carcinoma have revealed higher frequencies of immune-related adverse events (IRAEs) and limited efficacy. Despite these setbacks, the growing understanding of the thymic tumor microenvironment and systemic immune system has advanced the understanding of these diseases and provided opportunities for novel immunotherapy modalities. Ongoing studies are evaluating numerous immune-based treatments in TETs with the goal of improving clinical efficacy and mitigating IRAE risk. This review will provide insight into the current understanding of the thymic immune microenvironment, outcomes of previous ICB studies, and review treatments currently being explored for the management of TET.
Topics: Humans; Thymoma; Thymus Neoplasms; Neoplasms, Glandular and Epithelial; Immunotherapy; Immune Checkpoint Inhibitors; Tumor Microenvironment
PubMed: 36808725
DOI: 10.1002/cncr.34678