Radiotherapy for thymic epithelial tumours: a review.
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ABSTRACT:
SUBMITTER: Suveg K
PROVIDER: S-EPMC8107733 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC11330913 | biostudies-literature
Project description:Background and objectivesThe treatment of unresectable thymic epithelial tumours (TETs) remains controversial. Here, we present the efficacy and safety of induction therapy followed by surgery for unresectable TET.MethodsEighty-one patients with unresectable TETs treated with induction therapy followed by surgery were selected from a retrospective review of consecutive TETs from January 2005 to January 2021. Clinicopathological data were analyzed to assess tumour responses, resectability, adverse events, progression-free survival (PFS) and overall survival (OS).ResultsInduction therapy produced a major tumour response rate of 69.1%, a tumour response grade (TRG) 1-3 rate of 84.0% and an R0 resection rate of 74.1%. The most common toxic effects were all-grade neutropenia (35.8%) and anaemia (34.6%). The 10-year OS and PFS rates were 45.7% and 35.2%. Multivariate analysis showed that ypTNM stage, ypMasaoka stage, complete resection, and TRG were significant independent prognostic factors. Exploratory research revealed that different induction modalities and downstaging of T, N, M, TNM, or Masaoka classifications did not significantly alter the pooled hazard ratio for survival.ConclusionsInduction therapy followed by surgery is well tolerated in patients with unresectable TETs, with encouraging R0 resection rates. Multimodality management provides good control of tumors for unresectable TET patients.
| S-EPMC8766658 | biostudies-literature
Project description:Thymic epithelial tumours represent a wide range of anatomical, clinical, histological and molecular malignant entities that may be aggressive and difficult to treat. The histopathological classification distinguishes thymomas from thymic carcinomas. Thymomas may be associated with autoimmune disorders. The management of thymic epithelial tumours is a paradigm of co-operation between clinicians, surgeons and pathologists, from establishing the diagnosis to organising the multimodal therapeutic strategy. Surgery is the mainstay of the curative-intent treatment, as complete resection represents the most significantly favourable prognostic factor on overall survival. In case of invasion of intra-thoracic structures and/or dissemination to the pleura and the pericardium, precluding complete resection to be achieved, primary chemotherapy has been used to reduce the tumour burden, possibly allowing subsequent surgery and/or radiotherapy. Novel strategies are needed, especially for refractory, recurrent tumours and thymic carcinomas, which carry a poor prognosis. Personalised approaches are currently being developed, as potentially "druggable" molecular targets are emerging from recent integrated genomic analyses. Along with the large variety of questions relative to the treatment strategy, thymic epithelial tumours represent a model of therapeutic implementation and achievement in orphan thoracic oncology, showing how the advent of new results induces new questions, as well as diversifies further clinical research directions and international collaborative initiatives.
| S-EPMC9487428 | 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:Thymic epithelial tumours (TET) represent a heterogeneous group of rare malignancies that include thymomas and thymic carcinoma. Treatment of TET is based on the resectability of the tumour. If this is considered achievable upfront, surgical resection is the cornerstone of treatment. Platinum-based chemotherapy is the standard regimen for advanced TET. Due to the rarity of this disease, treatment decisions should be discussed in specific multidisciplinary tumour boards, and there are few prospective clinical studies with new strategies. However, several pathways involved in TET have been explored as potential targets for new therapies in previously treated patients, such as multi-tyrosine kinase inhibitors with antiangiogenic properties and immune checkpoint inhibitors (ICI). One third of patient with thymoma present an autoimmune disorders, increasing the risk of immune-related adverse events and autoimmune flares under ICIs. In these guidelines, we summarize the current evidence for the therapeutic approach in patients with TET and define levels of evidence for these decisions.
| S-EPMC8817662 | biostudies-literature
Project description:Simple Summary The biology of thymic epithelial tumours (TETs), including thymomas and thymic carcinomas, and particularly the extent of molecular dysregulation, is poorly understood. Through next-generation sequencing of 15 genes implicated in common solid tumours in 53 TETs, we found a larger number of single nucleotide variants (SNVs) in thymic carcinomas than thymomas. About 30% of thymic carcinomas had at least one somatic pathogenic gene variant in TP53, ERBB2, KIT, or KRAS, whereas variants of uncertain clinical significance in KIT, ERBB2, and FOXL2 were found exclusively in thymomas. The presence of somatic pathogenic variants was non-significantly associated with shorter disease-free survival in thymic carcinoma patients. No somatic pathogenic or likely pathogenic SNV was found in thymomas. Importantly, we also evaluated germline SNVs, adding to the number of known genetic alterations in TETs and thereby enhancing our molecular understanding of these neoplasms. Abstract A better understanding of the molecular pathogenesis of thymic epithelial tumours (TETs) could revolutionise their treatment. We evaluated thymomas and thymic carcinomas by next-generation sequencing (NGS) of somatic or germline single nucleotide variants (SNVs) in genes commonly mutated in solid tumours. In total, 19 thymomas and 34 thymic carcinomas were analysed for nonsynonymous SNVs in 15 genes by targeted NGS (reference genome: hg19/GRCh37). Ten SNVs in TP53 (G154V, R158P, L194H, R267fs, R273C, R306 *, Q317 *), ERBB2 (V773M), KIT (L576P), and KRAS (Q61L) considered somatic and pathogenic/likely pathogenic were detected in 10 of 34 (29.4%) thymic carcinomas. No somatic SNVs confirmed as pathogenic/likely pathogenic were found in thymomas. Rare SNVs of uncertain or unknown functional and clinical significance, to our knowledge not reported previously in TETs, were found in ERBB2 (S703R), KIT (I690V), and FOXL2 (P157S) in 3 of 19 (16%) thymomas. The most frequent germline SNVs were TP53 P72R (94% TETs), ERBB2 I655V (40% TETs), and KIT M541L (9% TETs). No significant difference in median disease-free survival (DFS) was found between thymic carcinoma patients with and without pathogenic SNVs (p = 0.190); however, a trend toward a longer DFS was observed in the latter (16.0 vs. 30.0 months, respectively). In summary, NGS analysis of TETs revealed several SNVs in genes related to the p53, AKT, MAPK, and K-Ras signalling pathways. Thymic carcinomas showed greater genetic dysregulation than thymomas. The germline and rare SNVs of uncertain clinical significance reported in this study add to the number of known genetic alterations in TETs, thus extending our molecular understanding of these neoplasms. Druggable KIT alterations in thymic carcinomas have potential as therapeutic targets.
| S-EPMC9324890 | 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: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:BackgroundNo standard treatment exists for refractory or relapsed advanced thymic epithelial tumours. We investigated the efficacy of cixutumumab, a fully human IgG1 monoclonal antibody targeting the insulin-like growth factor 1 receptor in thymic epithelial tumours after failure of previous chemotherapy.MethodsBetween Aug 25, 2009, and March 27, 2012, we did a multicentre, open-label, phase 2 trial in patients aged 18 years or older with histologically confirmed recurrent or refractory thymic epithelial tumours. We enrolled individuals who had progressed after at least one previous regimen of platinum-containing chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had measurable disease and adequate organ function. Eligible patients received intravenous cixutumumab (20 mg/kg) every 3 weeks until disease progression or development of intolerable toxic effects. The primary endpoint was the frequency of response, analysed on an intention-to-treat basis. We also did pharmacodynamic studies. This trial is registered with ClinicalTrials.gov, number NCT00965250.Findings49 patients were enrolled (37 with thymomas and 12 with thymic carcinomas) who received a median of eight cycles of cixutumumab (range 1-46). At the final actuarial analysis when follow-up data were updated (Nov 30, 2012), median potential follow-up (from on-study date to most current follow-up date) was 24·0 months (IQR 17·3-36·9). In the thymoma cohort, five (14%) of 37 patients (95% CI 5-29) achieved a partial response, 28 had stable disease, and four had progressive disease. In the thymic carcinoma cohort, none of 12 patients (95% CI 0-26) had a partial response, five had stable disease, and seven had progressive disease. The most common grade 3-4 adverse events in both cohorts combined were hyperglycaemia (five [10%]), lipase elevation (three [6%]), and weight loss, tumour pain, and hyperuricaemia (two each [4%]). Nine (24%) of 37 patients with thymoma developed autoimmune conditions during treatment (five were new-onset disorders), the most common of which was pure red-cell aplasia. Two (4%) patients died; one was attributed to disease progression and the other to disease-related complications (respiratory failure, myositis, and an acute coronary event), which could have been precipitated by treatment with cixutumumab.InterpretationCixutumumab monotherapy is well-tolerated and active in relapsed thymoma. Development of autoimmunity during treatment needs further investigation.FundingDivision of Cancer Treatment and Diagnosis at the National Cancer Institute (National Institutes of Health), ImClone Systems.
| S-EPMC3954701 | biostudies-literature
Project description:ObjectivesSurgery for thymic epithelial tumours (TETs) with pleural involvement is infrequently performed. Thus, the value of surgical therapy for primary or recurrent TETs with pleural involvement is not sufficiently defined yet.MethodsTwelve institutions contributed retrospective data on 152 patients undergoing surgery (1977-2014) on behalf of the ESTS Thymic Working group. Outcome measures included overall (OS), cause-specific (CSS) and disease-free (DFS) survival as well as freedom from recurrence (FFR).ResultsIn 70.4% of cases, pleural involvement was present at the time of primary intervention, whereas 29.6% had surgery for recurrent disease involving the pleura. Pleural involvement resulted from thymomas (88.8%) and thymic carcinomas (11.2%). Forty extrapleural pneumonectomies (EPPs), 23 total pleurectomies (TPs), and 88 local pleurectomies (LPs) were performed (completeness of resection in 76.8%). OS for the entire patient population at 1, 3, 5 and 10 years was 96.4%, 91.0%, 87.2% and 62.7%, respectively. There was no statistically significant difference regarding FFR and OS for patients with local or advanced disease undergoing EPP, TP or LP. Thymic carcinomas in comparison with thymomas had a negative impact on OS [hazard ratio 6.506, P = 0.002], CSS and FFR. Incomplete resections predicted worse OS [hazard ratio 6.696, P = 0.003].ConclusionsComplete resection remains the mainstay of treatment for TETs with pleural involvement. Study populations treated with EPP, TP and LP had similar survival that may be factual as observed, but in the presence of selection bias, we can further conclude from the results that EPP, TP and LP are equally effective procedures. Procedural choice depends upon the extent of tumour distribution. EPPs, TPs and LPs performed within a multimodality setting seem to be efficient procedures for local control of disease, as they yield excellent results regarding OS, DFS, CSS and FFR.
| S-EPMC5848821 | biostudies-literature