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ESMO Open Jun 2023Thymic malignancies are rare intrathoracic tumors, which may be aggressive and difficult to treat. They represent a therapeutic challenge in the advanced/metastatic...
BACKGROUND
Thymic malignancies are rare intrathoracic tumors, which may be aggressive and difficult to treat. They represent a therapeutic challenge in the advanced/metastatic setting, with limited treatment options after the failure of first-line platinum-based chemotherapy. They are frequently associated with autoimmune disorders that also impact oncological management.
MATERIALS AND METHODS
NIVOTHYM is an international, multicenter, phase II, two-cohort, single-arm trial evaluating the activity and safety of nivolumab [240 mg intravenously (i.v.) q2 weeks] alone or with ipilimumab (1 mg /kg i.v. q6 weeks) in patients with advanced/relapsed type B3 thymoma or thymic carcinoma, after exposure to platinum-based chemotherapy. The primary endpoint is progression-free survival rate at 6 months (PFSR-6) based on RECIST 1.1 as per independent radiological review.
RESULTS
From April 2018 to February 2020, 55 patients were enrolled in 15 centers from 5 countries. Ten patients (18%) had type B3 thymoma and 43 (78%) had thymic carcinoma. The majority were male (64%), and the median age was 58 years. Among the 49 eligible patients who started treatment, PFSR-6 by central review was 35% [95% confidence interval (CI) 22% to 50%]. The overall response rate and disease control rate were 12% (95% CI 5% to 25%) and 63% (95% CI 48% to 77%), respectively. Using the Kaplan-Meier method, median progression-free survival and overall survival by local assessment were 6.0 (95% CI 3.1-10.4) months and 21.3 (95% CI 11.6-not estimable) months, respectively. In the safety population of 54 patients, adverse events (AEs) of grade 1/2 were observed in 22 (41%) patients and grade 3/4 in 31 (57%) patients. Treatment-related AEs of grade 4 included one case of neutropenia, one case of immune-mediated transaminitis, and two cases of myocarditis.
CONCLUSIONS
Nivolumab monotherapy demonstrated an acceptable safety profile and objective activity, although it has been insufficient to meet its primary objective. The second cohort of NIVOTHYM is currently ongoing to assess the combination of nivolumab plus ipilimumab.
Topics: Humans; Male; Female; Middle Aged; Nivolumab; Ipilimumab; Thymoma; Thymus Neoplasms; Progression-Free Survival
PubMed: 37285717
DOI: 10.1016/j.esmoop.2023.101576 -
Journal of Thoracic Oncology : Official... Oct 2010The role of radiotherapy in the treatment of thymoma and thymic carcinoma has been evaluated by many investigators over the past two decades. The low incidence of these... (Review)
Review
The role of radiotherapy in the treatment of thymoma and thymic carcinoma has been evaluated by many investigators over the past two decades. The low incidence of these neoplasms has limited most published studies to small series spanning long time intervals or population-based studies. The exact indications and protocols for the use of radiotherapy as a part of the multidisciplinary approach to thymoma and thymic carcinoma are still unclear. However, a review of recent literature shows potential benefits for certain patients based on stage and grade of disease as well as the extent of surgical resection.
Topics: Clinical Trials as Topic; Humans; Thymoma; Thymus Neoplasms; Treatment Outcome
PubMed: 20859128
DOI: 10.1097/JTO.0b013e3181f20ec4 -
Frontiers in Immunology 2023Thymic epithelial tumors (TETs) are a rare and diverse group of neoplasms characterized by distinct molecular signatures. This review delves into the complex molecular... (Review)
Review
Thymic epithelial tumors (TETs) are a rare and diverse group of neoplasms characterized by distinct molecular signatures. This review delves into the complex molecular networks of TETs, highlighting key aspects such as chromosomal abnormalities, molecular subtypes, aberrant gene mutations and expressions, structural gene rearrangements, and epigenetic changes. Additionally, the influence of the dynamic tumor microenvironment on TET behavior and therapeutic responses is examined. A thorough understanding of these facets elucidates TET pathogenesis, offering avenues for enhancing diagnostic accuracy, refining prognostic assessments, and tailoring targeted therapeutic strategies. Our review underscores the importance of deciphering TETs' unique molecular signatures to advance personalized treatment paradigms and improve patient outcomes. We also discuss future research directions and anticipated challenges in this intriguing field.
Topics: Humans; Thymoma; Thymus Neoplasms; Neoplasms, Glandular and Epithelial; Prognosis; Tumor Microenvironment
PubMed: 37849766
DOI: 10.3389/fimmu.2023.1264325 -
Scientific Reports Mar 2023In recent years, thoracoscopic and robotic surgical procedures have increasingly replaced median sternotomy for thymoma and thymic carcinoma. In cases of partial...
In recent years, thoracoscopic and robotic surgical procedures have increasingly replaced median sternotomy for thymoma and thymic carcinoma. In cases of partial thymectomy, the prognosis is greatly improved by ensuring a sufficient margin from the tumor, and therefore intraoperative fluorescent imaging of the tumor is especially valuable in thoracoscopic and robotic surgery, where tactile information is not available. γ-Glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) has been applied for fluorescence imaging of some types of tumors in the resected tissues, and here we aimed to examine its validity for the imaging of thymoma and thymic carcinoma. 22 patients with thymoma or thymic carcinoma who underwent surgery between February 2013 and January 2021 were included in the study. Ex vivo imaging of specimens was performed, and the sensitivity and specificity of gGlu-HMRG were 77.3% and 100%, respectively. Immunohistochemistry (IHC) staining was performed to confirm expression of gGlu-HMRG's target enzyme, γ-glutamyltranspeptidase (GGT). IHC revealed high GGT expression in thymoma and thymic carcinoma in contrast to absent or low expression in normal thymic parenchyma and fat tissue. These results suggest the utility of gGlu-HMRG as a fluorescence probe for intraoperative visualization of thymomas and thymic carcinomas.
Topics: Humans; Thymoma; Thymus Neoplasms; gamma-Glutamyltransferase; Optical Imaging; Fluorescent Dyes
PubMed: 36882498
DOI: 10.1038/s41598-023-30753-2 -
Thoracic Cancer Dec 2022Thymic epithelial tumors (TET) are a group of rare neoplasms of the anterior mediastinum comprising thymomas and thymic carcinomas. The carcinogenesis of TET is mostly... (Review)
Review
Thymic epithelial tumors (TET) are a group of rare neoplasms of the anterior mediastinum comprising thymomas and thymic carcinomas. The carcinogenesis of TET is mostly unknown. Many studies, mostly retrospective case series, have tried to establish prognostic factors in TET. TET is a very heterogeneous group of tumors with many subtypes for which diagnosis and treatment remains a very challenging task. Despite the disparities among retrospective studies, there are some prognostic factors that are more pertinent such as the completeness of resection, TNM stage and the Masaoka-Koga classification. On the other hand, the identification of different genetic pathways that result in the pathogenesis of TET represents a fascinating field of study that could possibly lead to the development of new targeted therapies. The aim of this review is to discuss the different prognostic factors and genetic markers of TET. The meticulous use of national and international databases could provide sufficient number of patients in order to draw more valid conclusions.
Topics: Humans; Prognosis; Retrospective Studies; Genetic Markers; Neoplasm Staging; Thymus Neoplasms; Thymoma; Neoplasms, Glandular and Epithelial
PubMed: 36349433
DOI: 10.1111/1759-7714.14725 -
Lung Cancer (Amsterdam, Netherlands) Feb 2023Thymic carcinoma (TC) is a rare cancer and patients failing initial chemotherapy (relapse/refractory) face limited therapeutic options given no approved options or... (Meta-Analysis)
Meta-Analysis Review
Thymic carcinoma (TC) is a rare cancer and patients failing initial chemotherapy (relapse/refractory) face limited therapeutic options given no approved options or consensus standard of care. This study aimed to identify and summarize clinical outcomes of all regimens evaluated in clinical trials of relapsed or refractory patients. Interventional trials enrolling advanced TC patients who failed first-line chemotherapy and reported outcomes in this group were eligible for inclusion in our systemic literature review (SLR). Between-study heterogeneity was assessed to determine the feasibility of pooling specific studies and treatments. Objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and duration of response (DOR) endpoints were of interest for meta-analysis. Nineteen trials were identified in the SLR. Three trials with one or two TC patients were removed from our assessment to reduce publication bias. Response rates among studies with at least ten TC patients varied from 9 % to 38 %. Pooled ORRs in patients receiving S-1 (46 patients), sunitinib (46 patients), or pembrolizumab (66 patients) were 28 %, 24 %, and 21 %, respectively. Prolonged duration of response with pembrolizumab was observed with a pooled median of 23.8 months (95 % confidence interval [CI]: 12, not reached). Median PFS of five months or greater was reported in patients treated with sunitinib, lenvatinib, pembrolizumab, capecitabine + gemcitabine, everolimus, or S-1. Median OS of 20 months or greater was reported in trials evaluating S-1 or pembrolizumab; this endpoint was not reached in trials evaluating lenvatinib, regorafenib, or sunitinib. Generalizability of treatment effects is challenging in the research of rare diseases and meta-analysis of clinical outcomes may help to increase precision and relevance of results to the larger TC population. Our study found limited treatment options upon relapse, demonstrating a need for further investigations into novel therapeutics and well-powered clinical trials to better inform on optimal treatments.
Topics: Humans; Sunitinib; Thymoma; Platinum; Neoplasm Recurrence, Local; Lung Neoplasms; Thymus Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36638588
DOI: 10.1016/j.lungcan.2023.01.003 -
American Society of Clinical Oncology... 2014The rarity of thymic malignancies prevents us from performing large randomized clinical trials. As a result, systemic treatment decisions are often guided by a small... (Review)
Review
The rarity of thymic malignancies prevents us from performing large randomized clinical trials. As a result, systemic treatment decisions are often guided by a small amount of prospective trial data, retrospective series, and individual case reports. In recent years, we have begun to unravel the molecular biology of thymic tumors. It is becoming more apparent as a result of gene expression profiling and genomic clustering studies that the subclassifications of type A, AB, B1, B2, B3, and thymic carcinoma have different molecular features that may be clinically relevant. Genomic profiling distinguishes type B3 thymoma and thymic carcinoma as distinct entities from type A and type B2 thymoma. Furthermore, type B2 thymomas can be separated from other subgroups in that it has a more distinct lymphocytic component than the other groups where epithelial cells predominate. Next generation RNA sequencing has recently identified a large microRNA cluster on chromosome 19q13.42 in types A and AB thymomas, which is absent in type B thymomas and thymic carcinomas. This cluster has been shown to result in activation of the phosphoinositide 3-kinase (PI3K)/AKT pathway, which suggests a possible role for PI3K inhibitors in these subtypes. The presence of KIT mutations in thymic carcinomas is also well described. Herein we discuss the chemotherapeutic and targeted treatment options for advanced thymic malignancies and highlight important advances in our understanding of the molecular biology of these rare tumors.
Topics: Antineoplastic Agents; Chromosomes, Human, Pair 19; ErbB Receptors; Gene Expression Regulation, Neoplastic; Humans; Molecular Targeted Therapy; Neoplasm Staging; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-kit; Thymoma; Thymus Neoplasms; Vascular Endothelial Growth Factor A
PubMed: 24857125
DOI: 10.14694/EdBook_AM.2014.34.e367 -
Polish Journal of Pathology : Official... 2020Thymic epithelial tumours are rare malignancies of the anterior superior mediastinum. Several studies have analysed the presence of c-KIT mutations in thymic...
Thymic epithelial tumours are rare malignancies of the anterior superior mediastinum. Several studies have analysed the presence of c-KIT mutations in thymic carcinoma. Immunohistochemical c-KIT expression and mutations in exons 8, 9, 11, 13, 14, 17, and 18 of the KIT gene and in the promoter region of the TERT gene (chr5, 1,295,228C>T/A and 1,295,250C>T) were analysed by PCR based direct sequencing using representative formalin-fixed paraffin-embedded tumour samples of 18 thymic carcinomas. Of 18 patients, 4 test samples were excluded from the study due to inadequate DNA quality. Of 14 patients with thymic carcinomas, KIT and TERT mutation was not detected in any samples. C-KIT expression was associated with nearly a worse overall survival (median time 24.160-49.840, log-rank, p = 0.05). We showed that squamous cell carcinomas led to worse survival than other subtypes. As expected, TNM stage II was significantly correlated with better OS (p = 0.015). Thymic carcinoma is characterised by a KIT-positive and CD5-positive staining pattern. We report a worse overall survival for patients with c-kit expressing tumours. These data suggest a negative prognostic role for c-kit expression especially within the first 5 years.
Topics: Carcinoma, Squamous Cell; Humans; Mutation; Proto-Oncogene Proteins c-kit; Thymoma; Thymus Neoplasms
PubMed: 32729302
DOI: 10.5114/pjp.2020.97019 -
Clinics (Sao Paulo, Brazil) Dec 2015The role of chemotherapy in treating advanced thymic carcinoma is unclear. The purpose of the current study was to investigate the efficacy of chemotherapy and the...
OBJECTIVE
The role of chemotherapy in treating advanced thymic carcinoma is unclear. The purpose of the current study was to investigate the efficacy of chemotherapy and the prognostic factors for patients with advanced thymic carcinoma.
METHODS
A retrospective review of the medical records of 86 patients treated with chemotherapy for advanced thymic carcinoma was conducted between 2000 and 2012 at our institution. The clinical characteristics, chemotherapy regimens and prognostic factors were analyzed. Survival curves were plotted using the Kaplan-Meier method and the Cox proportional hazard model was used for multivariate analysis.
RESULTS
Of the 86 patients, 56 were male and 30 were female. The median survival time was 24.5 months. For the first-line chemotherapy treatment, the objective response rate was 47.7% and the disease control rate was 80.2%. The median progression-free survival for all patients was 6.5 months for first-line chemotherapy. No significant differences in progression-free survival were observed among the different chemotherapy regimens. Multivariate analyses revealed that the prognostic factors for overall survival included performance status (p=0.043), histology grade (p=0.048), and liver metastasis (p=0.047).
CONCLUSION
Our results suggest that there is no difference in efficacy between multiagent and doublet regimens. The prognosis of patients with advanced thymic carcinoma can be predicted based on histological grade, liver metastasis and performance status.
Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Male; Middle Aged; Prognosis; Retrospective Studies; Thymoma; Thymus Neoplasms; Time Factors; Treatment Outcome
PubMed: 26735216
DOI: 10.6061/clinics/2015(12)03 -
Cancer Medicine Sep 2022Front-line platinum-base chemotherapy for advanced thymoma and thymic carcinoma (TC) improves resectability and prolongs patients' overall survival (OS). In this study,...
BACKGROUND
Front-line platinum-base chemotherapy for advanced thymoma and thymic carcinoma (TC) improves resectability and prolongs patients' overall survival (OS). In this study, we evaluated patients' outcomes given different front-line regimens: cisplatin, doxorubicin, and cyclophosphamide (CAP); cisplatin and etoposide (EP); or cisplatin and paclitaxel (TP).
MATERIALS AND METHODS
We retrospectively evaluated the medical records of patients with advanced thymoma and TC who were treated at our medical center between 2005 and 2015. We investigated objective response rates (ORRs), progression-free survival (PFS), and OS after undergoing different front-line regimens.
RESULTS
Among the 108 enrolled patients, 37 (34%) had thymoma and 71 (66%) had TC; 45 received CAP, 36 received EP, and 27 received TP regimens. The ORRs of patients receiving CAP, EP, and TP were 51%, 50%, and 41%, respectively. For patients with stage III and IVA disease, the median PFS after CAP, EP, and TP were 34.5, 26.4, and 18.0 months (p = 0.424), respectively, and the 5-year OS rates were 84.9%, 70.6%, and 60.0% (p = 0.509). In patients with stage IVB disease, the median PFS were 9.4, 8.2, and 11.6 months after undergoing CAP, EP, and TP (p = 0.173), respectively, and the 5-year OS rates were 41.1%, 39.1%, and 14.3% (p = 0.788). TC pathology subtype and liver metastasis were associated with poor OS. Three patients with stage IVB TC had an OS of more than 5 years.
CONCLUSION
Different front-line chemotherapy regimens may provide similar long-term PFS and OS in patients with advanced thymoma and TC. In addition to TC and liver metastasis were associated with poor OS, other potential prognostic factors are warranted for studying.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclophosphamide; Doxorubicin; Etoposide; Humans; Liver Neoplasms; Paclitaxel; Platinum; Retrospective Studies; Thymoma; Thymus Neoplasms
PubMed: 35348307
DOI: 10.1002/cam4.4711