-
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 -
International Journal of Biological... 2023As the most common malignancy from mediastinum, the metabolic reprogramming of thymoma is important in its development. Nevertheless, the connection between the...
As the most common malignancy from mediastinum, the metabolic reprogramming of thymoma is important in its development. Nevertheless, the connection between the metabolic map and thymoma development is yet to be discovered. Thymoma was categorized into three subcategories by unsupervised clustering of molecular markers for metabolic pathway presentation in the TCGA dataset. Different genes and functions enriched were demonstrated through the utilization of metabolic Gene Ontology (GO) analysis. To identify the main contributors in the development of thymic malignancy, we utilized Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The prognosis of thymoma was evaluated by screening the essential pathways and genes using GSVA scores and machine learning classifiers. Furthermore, we integrated the transcriptomics findings with spectrum metabolomics investigation, detected through LC-MS/MS, in order to establish the essential controller network of metabolic reprogramming during thymoma progression. The thymoma prognosis is related to glycosphingolipid biosynthesis-lacto and neolacto series pathway, of what high B3GNT5 indicate poor survival. The investigation revealed that glycosphingolipid charts have a significant impact on metabolic dysfunction and could potentially serve as crucial targets in the clinical advancement of metabolic therapy.
Topics: Humans; Thymoma; Chromatography, Liquid; Tandem Mass Spectrometry; Thymus Neoplasms; Cluster Analysis
PubMed: 37781041
DOI: 10.7150/ijbs.83468 -
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 -
BMJ Case Reports Aug 2019Thymoma-associated multiorgan autoimmunity is a relatively new term to describe the rare paraneoplastic syndrome that complicates thymoma, which can involve the thyroid,...
Thymoma-associated multiorgan autoimmunity is a relatively new term to describe the rare paraneoplastic syndrome that complicates thymoma, which can involve the thyroid, liver and intestine in addition to the skin. The pathology often indicates a graft-versus-host-like pattern commonly observed in recipients of an allogeneic haematopoietic cell transplant. We report a case of type B2 and B3 thymoma with invasion to the lung and pleura in a patient who presented with oral lichen planus and graft-versus-host-like erythroderma. The cutaneous lesions improved after complete resection of the thymoma in combination with systemic glucocorticoids, which was subsequently complicated by cytomegalovirus pneumonitis.
Topics: Autoimmune Diseases; Combined Modality Therapy; Glucocorticoids; Humans; Image-Guided Biopsy; Lichen Planus, Oral; Lung; Male; Middle Aged; Neoplasm Invasiveness; Pleura; Thymoma; Thymus Neoplasms
PubMed: 31377716
DOI: 10.1136/bcr-2018-229163 -
Cells Apr 2022Myasthenia gravis (MG) is a rare autoimmune disease mediated by antibodies against components of the neuromuscular junction, particularly the acetylcholine receptor... (Review)
Review
Myasthenia gravis (MG) is a rare autoimmune disease mediated by antibodies against components of the neuromuscular junction, particularly the acetylcholine receptor (AChR). The thymus plays a primary role in AChR-MG patients. In early-onset AChR-MG and thymoma-associated MG, an interferon type I (IFN-I) signature is clearly detected in the thymus. The origin of this chronic IFN-I expression in the thymus is not yet defined. IFN-I subtypes are normally produced in response to viral infection. However, genetic diseases called interferonopathies are associated with an aberrant chronic production of IFN-I defined as sterile inflammation. Some systemic autoimmune diseases also share common features with interferonopathies. This review aims to analyze the pathogenic role of IFN-I in these diseases as compared to AChR-MG in order to determine if AChR-MG could be an acquired interferonopathy.
Topics: Autoantibodies; Graft vs Host Disease; Humans; Myasthenia Gravis; Receptors, Cholinergic; Thymoma; Thymus Neoplasms
PubMed: 35406782
DOI: 10.3390/cells11071218 -
Zhongguo Fei Ai Za Zhi = Chinese... Mar 2020Thymoma is a potential malignant disease with a recurrence rate of 10% to 30% after complete resection. There is no agreement on the treatment strategy and standard for... (Review)
Review
Thymoma is a potential malignant disease with a recurrence rate of 10% to 30% after complete resection. There is no agreement on the treatment strategy and standard for recurrent thymoma. The treatment methods include reoperation, chemotherapy, radiotherapy, targeted therapy and immunotherapy. In this article, we review the previous literature and summarize the indications, efficacy and prognosis of different treatments for recurrent thymoma, so as to provide some reference for treatment criteria for recurrent thymoma.
Topics: Humans; Prognosis; Thymoma
PubMed: 32102138
DOI: 10.3779/j.issn.1009-3419.2020.03.11 -
Scientific Reports Feb 2019Thymoma represents the most common anterior mediastinal compartment neoplasm, originating from the epithelial cell population in the thymus. Various histological types...
Thymoma represents the most common anterior mediastinal compartment neoplasm, originating from the epithelial cell population in the thymus. Various histological types of thymoma feature different clinical characteristics. Furthermore, thymoma is frequently associated with autoimmune disorders, esp. myasthenia gravis (MG). However, the underlying molecular tumourigenesis of thymoma remains largely unknown. The goal of our current study is to demonstrate the underlying genetic abberations in thymoma, so as to understand the possible cause of MG in thymoma patients. By using CapitalBio mRNA microarray analysis, we analyzed 31 cases of thymoma including 5 cases of type AB thymoma, 6 B1-type cases, 12 B2-type cases, 5 B2B3-type cases and 3 type-B3 cases. 6 cases of thymoma were not associated with myasthenia gravis, while 25 cases were with myasthenia gravis. By comparisons between thymoma and the paratumoral tissues, differentially expressed genes were identified preliminarily. Among them, 292 genes increased more than 2-fold, 2 genes more than 5-fold. On the other hand, 596 genes were decreased more than 2-fold, 6 genes more than 20-fold. Interestingly, among these genes upregulated more than 2-fold, 6 driver genes (FANCI, NCAPD3, NCAPG, OXCT1, EPHA1 and MCM2) were formerly reported as driver oncogenes. This microarray results were further confirmed through real-time PCR. 8 most dysregulated genes were verified: E2F2, EPHA1, CCL25 and MCM2 were upregulated; and IL6, FABP4, CD36 and MYOC were downregulated. Supervised clustering heat map analysis of 2-fold upregulated and 2-fold downregulated genes revealed 6 distinct clusters. Strikingly, we found that cluster 1 was composed of two type-B2 thymoma; and cluster 6 was three type-B2/B3 thymoma. KEGG database analysis revealed possible genetic mechanisms of thymoma and functional process. We further compared gene expression pattern between thymoma with and without MG, and found 5 genes were upregulated more than 2-fold, more than 30 genes were downregulated more than 2-fold. KEGG analysis revealed 2 important signaling pathways with more than 2-fold upregulated genes (TGF- beta signaling pathway and HTLV-I signaling pathway) as differially functioning between MG positive and negative thymomas. Real-time PCR analysis confirmed that CCL25 was upregulated; and MYC, GADD45B, TNFRSF12 downregulated in thymoma with MG. Our study thus provided important genetic information on thymoma. It shed light on the molecular bases for analyzing the functional process of thymoma and finding potential biomarkers for pathological categorizing and treatment. Our work may provide important clues in understanding possible causes of MG in thymoma patients.
Topics: Adult; Aged; Biomarkers; Cluster Analysis; Epithelial Cells; Female; Humans; Male; Microarray Analysis; Middle Aged; Myasthenia Gravis; RNA, Messenger; Thymoma; Thymus Gland; Thymus Neoplasms
PubMed: 30787364
DOI: 10.1038/s41598-019-38878-z -
Journal of Thoracic Oncology : Official... Feb 2023
Topics: Humans; Lung Neoplasms; Thymus Neoplasms; Thymoma; Neoplasms, Glandular and Epithelial
PubMed: 36682839
DOI: 10.1016/j.jtho.2022.11.029 -
Radiotherapy and Oncology : Journal of... Jun 2023Surgery is the first-line treatment for patients with thymoma associated with myasthenia gravis (MG); however, the value of radiotherapy among these patients remains... (Review)
Review
INTRODUCTION
Surgery is the first-line treatment for patients with thymoma associated with myasthenia gravis (MG); however, the value of radiotherapy among these patients remains debatable. Herein, we examined the impact of postoperative radiotherapy (PORT) on the efficacy and prognosis of patients with thymoma and MG.
METHODS
This retrospective cohort study included 126 patients with thymoma and MG who were enrolled in the Xiangya Hospital clinical database between 2011 and 2021. Demographic and clinical data were collected including sex, age, histologic subtype, Masaoka-Koga staging, primary tumor, lymph node, metastasis (TNM) staging, and therapeutic modalities. To evaluate short-term MG symptom improvement following PORT, we examined changes in the quantitative myasthenia gravis (QMG) scores within 3 months post-treatment. Minimal manifestation status (MMS) was the main endpoint for assessing long-term improvement in MG symptoms. Overall survival (OS) and disease-free survival (DFS) were primary endpoints to determine the impact of PORT on prognosis.
RESULTS
Effects of PORT on MG symptoms: QMG scores significantly differed between the non-PORT and PORT groups (χ2 = 6.300, p = 0.012). The median time to achieve MMS was significantly shorter in the PORT group than that in the non-PORT group (2.0 years vs. 4.4 years; p = 0.031). Multivariate analysis revealed that radiotherapy was associated with a reduced time to achieve MMS (hazard ratio [HR] 1.971, 95% confidence interval [CI]:1.102-3.525, p = 0.022). Effects of PORT on DFS and OS: The 10-year OS rate of the entire cohort was 90.5%, whereas OS rates for the PORT and non-PORT groups were 94.4 and 85.1%, respectively. The 5-year DFS rates for the whole cohort, PORT group, and non-PORT group were 89.7, 95.8, and 81.5%, respectively. PORT was associated with improved DFS (HR 0.139, 95% CI: 0.037-0.533, p = 0.004). In the high-risk histologic subgroup (type B2, B3), patients who received PORT had better OS (p = 0.015) and DFS (p = 0.0053) than those who did not receive PORT. PORT was associated with improved DFS (HR 0.232, 95% CI: 0.069-0.782, p = 0.018) in Masaoka-Koga stages II, III, and IV disease.
CONCLUSIONS
Overall, our findings indicate that PORT positively impacts thymoma patients with MG, particularly those with a higher histologic subtype and Masaoka-Koga staging.
Topics: Humans; Thymoma; Retrospective Studies; Neoplasm Staging; Thymus Neoplasms; Prognosis; Myasthenia Gravis
PubMed: 36990391
DOI: 10.1016/j.radonc.2023.109644