Postoperative radiotherapy for thymic epithelial tumors: a narrative review
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ABSTRACT:
SUBMITTER: Kishi N
PROVIDER: S-EPMC11330913 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Background and objectiveThymic epithelial tumors (TETs) are frequently diagnosed at an advanced stage, highlighting the importance of understanding the treatment strategies for these cases. Surgical intervention after chemotherapy or chemoradiotherapy presents specific challenges and underscores the crucial role of perioperative management. This study aimed to explore the perioperative management and postoperative outcomes in patients with locally advanced TETs.MethodsRelevant studies published between 2000 and 2022 were identified through PubMed searches using a combination of the following terms: "Locally advanced TETs", "Thymoma", "Thymic cancer", "Surgery", "Induction therapy", and "Postoperative outcomes". We analyzed available data to describe the perioperative management and postoperative outcomes of locally advanced TETs.Key content and findingsSurgical outcomes after induction therapy for locally advanced TETs were analyzed for 18 references (total n=646) between 2000 and 2022. The primary objective of induction therapy for locally advanced TETs is complete tumor resection. In recent years, many medical centers have adopted systemic chemotherapy and chemoradiation for the treatment of thymoma and thymic carcinoma, respectively. During surgical intervention, resecting the surrounding organs, such as the lungs, pericardium, and phrenic nerves, is a common practice. Additionally, there may be cases wherein vascular resection of the superior vena cava (SVC) and innominate veins is necessary. Techniques and strategies for revascularization without complications are crucial in these situations. The incidence of postoperative complications varied significantly, ranging from 4.8% to 42%. However, perioperative mortality is typically reported to be approximately 0%, with only two reports showing mortality rates of 1.8% and 9.0%.ConclusionsThe short-term postoperative outcomes of surgical treatment following induction therapy for locally advanced TETs were generally deemed acceptable. However, incomplete resection may occur, particularly when the tumor invades the pulmonary artery or aorta. Hence, careful evaluation the indications for surgery is crucial, considering the patient's overall condition and treatment response.
| S-EPMC10839523 | biostudies-literature
Project description: Not available
| S-EPMC10915418 | biostudies-literature
Project description:Thymic epithelial tumors (TETs) are rare thoracic tumors, often requiring multimodal approaches. Surgery represents the first step of the treatment, possibly followed by adjuvant radiotherapy (RT) and, less frequently, chemotherapy. For unresectable tumors, a combination of chemotherapy and RT is often used. Currently, the optimal dose for patients undergoing radiation is not clearly defined. Current guidelines on RT are based on studies with a low level of evidence, where 2D RT was widely used. We aim to shed light on the optimal radiation dose for patients with TETs undergoing RT through a systematic review of the recent literature, including reports using modern RT techniques such as 3D-CRT, IMRT/VMAT, or proton-therapy. A comprehensive literature search of four databases was conducted following the PRISMA guidelines. Two investigators independently screened and reviewed the retrieved references. Reports with < 20 patients, 2D-RT use only, median follow-up time < 5 years, and reviews were excluded. Two studies fulfilled all the criteria and therefore were included. Loosening the follow-up time criteria to > 3 years, three additional studies could be evaluated. A total of 193 patients were analyzed, stratified for prognostic factors (histology, stage, and completeness of resection), and synthesized according to the synthesis without meta-analysis (SWIM) method. The paucity and heterogeneity of eligible studies led to controversial results. The optimal RT dose neither for postoperative, nor primary RT in the era of modern RT univocally emerged. Conversely, this overview can spark new evidence to define the optimal RT dose for each TETs category.
| S-EPMC8960904 | biostudies-literature
Project description:The emergence of immunotherapy as a modern pillar of cancer treatment has changed the treatment landscape for various cancers. Immune checkpoint inhibitors directed at programed death-1 (PD-1) or its ligand (PD-L1), in particular, have found widespread clinical applications and have resulted in durable responses and an improvement in survival of patients with advanced or metastatic disease. Tumor cell PD-L1 expression and tumor mutation burden (TMB) are biomarkers of response and efforts are underway to identify other biomarkers that might predict benefit with these drugs. Most patients tolerate immunotherapy well, although a subset of patients develop immune-mediated toxicity due to excessive immune stimulation. Thymic epithelial tumors (TETs) have a unique biology which can predispose to development of autoimmune paraneoplastic disease, especially in patients with thymoma. Due to defects in immunological self-tolerance, the use of immunotherapy in TET patients is associated with an increased risk of immune-mediated adverse events, which can be potentially life-threatening. Development of biomarkers of response and toxicity is particularly important for the treatment of TETs since it is important to identify patients who might benefit from treatment and be at low risk for development of severe immune toxicity. The use of immunotherapy in patients with autoimmune disorders and those who have previously experienced immune-mediated toxicity is currently an area of active research. Various risk mitigation strategies are under evaluation in prospective clinical trials, including trials of immune checkpoint inhibitors in patients with thymic cancers.
| S-EPMC8445513 | biostudies-literature
Project description:Thymic epithelial tumours (TETs) represent a rare disease, yet they are the most common tumours of the anterior mediastinum. Due to the rare occurrence of TETs, evidence on optimal treatment is limited. Surgery is the treatment of choice in the management of TETs, while the role of postoperative radiotherapy (PORT) remains unresolved. PORT remains debated for thymomas, especially in completely resected stage II tumours, for which PORT may be more likely to benefit in the presence of aggressive histology (WHO subtype B2, B3) or extensive transcapsular invasion (Masaoka-Koga stage IIB). For stage III thymoma, evidence suggests an overall survival (OS) benefit for PORT after complete resection. For incompletely resected thymomas stage II or higher PORT is recommended. Thymic carcinomas at any stage with positive resection margins should be offered PORT. Radiotherapy plays an important role in the management of unresectable locally advanced TETs. Induction therapy (chemotherapy or chemoradiation) followed by surgery may be useful for locally advanced thymic malignancies initially considered as unresectable. Chemotherapy only is offered in patients with unresectable, metastatic tumours in palliative intent, checkpoint inhibitors may be promising for refractory diseases. Due to the lack of high-level evidence and the importance of a multidisciplinary approach, TETs should be discussed within a multidisciplinary team and the final recommendation should reflect individual patient preferences.
| S-EPMC8107733 | biostudies-literature
Project description:Thymic epithelial tumors (TETs), including thymomas and thymic carcinomas, are rare malignancies arising from the thymus gland. The optimal management requires a multidisciplinary approach. Standard first-line systemic treatment involves cytotoxic chemotherapeutic regimens; however, alternative options for systemic treatment are required. Current research focuses on the unique profile of immune-related pathogenic mechanisms of TETs, involving an overlap with certain autoimmune phenotypes, as well as on determining the landscape of oncogenic molecular alterations and the role of tumor angiogenesis. The aim of the present review is to summarize the current clinical investigation on immunotherapy and targeted agents in the management of TETs. Regarding immune checkpoint inhibitors, efficacy results are promising in certain subsets of patients; however, caution is required concerning their toxicity. Anti-angiogenic agents, mainly potent small-molecule inhibitors, have demonstrated antitumor activity in TETs, whereas other targeted agents, including KIT inhibitors and epigenetic agents, are associated with encouraging, yet still modest results for unselected populations, in the absence of predictive biomarkers. Future research should focus on identifying predictive biomarkers for patients with TETs, and should implement multicenter collaborations and appropriate clinical trials tailored for rare tumor types.
| S-EPMC9877504 | biostudies-literature
Project description:This review article comprehensively examines the diagnostic approach to thymic epithelial tumors (TETs) and other mediastinal masses, focusing on imaging modalities and differential diagnosis. Beginning with a discussion on traditional and contemporary classification systems for mediastinal tumors, including the Japanese Association for Research on the Thymus (JART) and International Thymic Interest Group (ITMIG) classifications, it highlights the shift towards computed tomography (CT)-based categorizations. Emphasis is placed on the importance of distinguishing between solid and cystic lesions in the anterior mediastinum, with detailed insights into imaging characteristics and histological features of various TET subtypes such as thymomas, thymic carcinomas, and thymic neuroendocrine tumors (NETs). The review also elucidates common differential diagnoses, including lymphomas and germ cell tumors, providing guidance on key imaging findings and considerations for accurate diagnosis. Furthermore, it underscores the significance of patient background and blood tests in differential diagnosis, discussing age-related prevalence patterns and tumor marker assessment. After addressing the diagnostic challenges posed by thymic cysts offering insights into their radiological features, management considerations, and potential complications, this review extends to other rare mediastinal lesions highlighting the need for a comprehensive evaluation for accurate identification and management of these tumors. Finally, as illustrative examples, we present six cases highlighting various aspects of anterior mediastinal tumors, including TET. These cases provide valuable insights into the diagnostic challenges, imaging characteristics, and management considerations encountered in clinical practice. The cases presented herein do not all illustrate typical images, courses, and diagnoses. However, they each contain significant implications. Thus, we present them with the belief that they will aid in understanding the intricate nuances of image diagnosis in actual clinical practice.
| S-EPMC11330907 | biostudies-literature
Project description:Background Radiotherapy (RT) for thymic epithelial tumors (TET) is indicated postoperatively for advanced/aggressive disease or incomplete resection, or as primary treatment in inoperable patients. In selected patients, proton therapy spares better normal tissues compared to standard photon treatment, and therefore has a high potential to reduce toxicity. The aim of this study is to compare photon and proton plans regarding doses and normal tissue complication probability (NTCP), as a validated surrogate for toxicity. Methods Patients with TET referred for radiotherapy from 08.2019–03.2022 were included. Intensity-modulated proton therapy (IMPT) and volumetric-arc photon therapy (VMAT) plans were compared for mean doses to the lungs (MLD), heart (MHD) and esophagus (MED) (using Wilcoxon signed ranks test), and normal tissue complication probability (NTCP) with endpoints radiation pneumonitis (grade ≥2), cardiac toxicity (major coronary events), acute dysphagia (grade ≥2) and since 03.2022 secondary breast cancer. VMAT plans consisted typically of 2–3 partial 6 MV arcs in the anterior region, and the dose was prescribed to the PTV. IMPT plans were typically administered with 3 or 4 anterior and anterior-oblique beams, using robust optimization. Results Twenty-four TET-patients had a VMAT-IMPT comparison (17 thymoma/4 thymic carcinoma) with Masaoka-Koga stages IIA–IVB. Mean age was 61 years. Average MLD, MHD and MED decreased significantly with IMPT (from 9.4 to 5.4 Gy, from 9.0 tot 6.6 Gy and from 7.4 to 2.0 Gy, respectively). Average NTCP-values for radiation pneumonitis, cardiac toxicity and dysphagia all decreased with IMPT compared to VMAT from 11.6% to 7.1%, from 16.3% to 14.6% and from 15.5% to 3.4%, respectively. Average NTCP-difference favoring proton therapy was 4.5% (range, 0.6% to 15.9%) for radiation pneumonitis, 1.7% (−0.1% to 4.9%) for cardiac toxicity and 12.1% (−0.3% to 43.4%) for dysphagia. Seventeen patients (71%) had a significantly lower NTCP with IMPT for at least one of the endpoints and qualified for reimbursement; 13 of these were treated with protons at our centre. Conclusions IMPT significantly reduced mean doses to lungs, heart and esophagus in all patients compared with VMAT, resulting in a significant reduction of NTCP for at least one endpoint in 71% of patients.
| S-EPMC9792829 | biostudies-literature
Project description:Thymic epithelial tumors (TETs) arise from the epithelial cells of the thymus and consist in the 1% of all adult malignancies, despite the fact that they are the most common lesions of the anterior mediastinum. TETs can be divided mainly into thymomas, thymic carcinomas, and the rarest ad aggressive neuroendocrine forms. Despite the surgical resection is quite resolving, the diagnosis of TETs is complicated by the absence of symptoms and the clinical presentation aggravated by several paraneoplastic disorders, including myasthenia gravis. Thus, the heterogeneity of TETs prompts the search for molecular biomarkers that could be helpful for tumor characterization and clinical outcomes prediction. With these aims, several researchers investigated the epigenetic profiles of TETs. In this manuscript, we narratively review the works investigating the deregulation of epigenetic mechanisms in TETs, highlighting the need for further studies combining genetic, epigenetic, and expression data to better characterize the different molecular subtypes and identify, for each of them, the most relevant epigenetic biomarkers of clinical utility.
| S-EPMC9856807 | biostudies-literature
Project description:Despite their rarity, thymic epithelial tumors (TETs) have attracted much interest over the years, leading to an impressive number of histological and staging classifications. At present, TETs are divided by the WHO classification into four main subtypes: type A, type AB, and type B thymomas (subdivided into B1, B2, and B3), and thymic carcinomas, going from the more indolent to the most aggressive ones. Among many debated staging proposals, the TNM and the Masaoka-Koga staging systems have been widely accepted and used in routine practice. The four-tiered histological classification is symmetrically mirrored by the molecular subgrouping of TETs, which identifies an A-like and an AB-like cluster, with frequent GTF2I and HRAS mutations; an intermediate B-like cluster, with a T-cell signaling profile; and a carcinoma-like cluster comprising thymic carcinomas with frequent CDKN2A and TP53 alterations and a high tumor molecular burden. Molecular investigations have opened the way to tailored therapies, such as tyrosine kinase inhibitors targeting KIT, mTOR, and VEGFR, and immune-checkpoints that have been adopted as second-line systemic treatments. In this review, we discuss the crucial events that led to the current understanding of TETs, while disclosing the next steps in this intriguing field.
| S-EPMC9964105 | biostudies-literature