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Journal of Thoracic Oncology : Official... Feb 2023Thymic epithelial tumors (TETs) are rare but are the most common tumors of the anterior mediastinum. Platinum-based combination chemotherapy is the standard of care for...
INTRODUCTION
Thymic epithelial tumors (TETs) are rare but are the most common tumors of the anterior mediastinum. Platinum-based combination chemotherapy is the standard of care for such tumors and is associated with a 50% to 90% objective response rate (ORR) in metastatic disease. Nevertheless, there is no standard chemotherapeutic option after failure of platinum-based combination chemotherapy. Genetic alterations associated with the cell cycle, including pRB, p16, and cyclin D1, are most often observed in TETs. On the basis of these results, we conducted a phase 2 trial to evaluate the efficacy and safety of palbociclib in patients with recurrent or refractory advanced TETs.
METHODS
This is a phase 2, multicenter, open-label, single-arm study of palbociclib monotherapy in patients with recurrent or metastatic advanced TETs who failed one or more cytotoxic chemotherapies. The patients received 125 mg of oral palbociclib daily for 21 days, followed by a 7-day break. The primary end point was progression-free survival (PFS). The secondary end points were ORR, duration of response, overall survival, and safety.
RESULTS
Between August 2017 and October 2019, a total of 48 patients were enrolled. The median number of previous chemotherapies was one (range: one to four), and 21 (43.7%) of 48 patients received thymectomy. By the WHO classification, the patients were type A (n = 1), type B1 (n = 2), type B2 (n = 8), type B3 (n = 13), thymic carcinoma (n = 23), and unknown (n = 1). With a median follow-up of 14.5 months (range: 0.8-38.2), the median number of cycles of palbociclib monotherapy was 10 (range: 1-40). The ORR was 12.5% (four partial responses in thymoma and two partial responses in thymic carcinoma). The PFS at 6 months was 60.2%, and the median PFS was 11.0 months (95% confidence interval: 4.6-17.4). The median overall survival was 26.4 months (95% confidence interval: 17.4-35.4). The most common treatment-related adverse events of any grade were neutropenia (62.5%), anemia (37.5%), and thrombocytopenia (29.1%), and the most common grade 3/4 treatment-related hematologic adverse event was neutropenia (41.7%). Neutropenia above grade 3 was reversible, and there were no cases with neutropenic fever.
CONCLUSIONS
Palbociclib monotherapy was well tolerated and had encouraging efficacy in patients with TETs who failed platinum-based combination chemotherapy.
Topics: Humans; Thymoma; Lung Neoplasms; Thymus Neoplasms; Neoplasms, Glandular and Epithelial; Neutropenia; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36307042
DOI: 10.1016/j.jtho.2022.10.008 -
Thoracic Cancer Jun 2021Thymomas are the most common type of anterior mediastinal tumors. Calcification is sometimes observed in thymomas using computed tomography (CT), and it is more frequent...
BACKGROUND
Thymomas are the most common type of anterior mediastinal tumors. Calcification is sometimes observed in thymomas using computed tomography (CT), and it is more frequent in invasive thymomas than in noninvasive thymomas. However, the significance of calcification in thymomas remains unknown. This study aimed to evaluate the significance of calcification in thymomas on invasiveness to surrounding organs and investigate the characteristics of thymoma cases with calcification at our institution.
METHODS
We included thymoma patients treated at our institution between 2000 and 2016, and evaluated their characteristics, including demographics, calcification on CT, histology, Masaoka stage, and myasthenia gravis status. The patients were categorized into calcification (C) and noncalcification (NC) groups.
RESULTS
Among 51 included patients, 11 (21.6%) had calcification. A higher proportion of group C patients had World Health Organization histological type B2 and B3 tumors (high-risk) than type A, AB, and B1 tumors (low-risk; p = 0.0477). The number of patients with Masaoka stages III and IV were significantly higher in the C group than in the NC group (p < 0.0001). The C group patients had significantly higher rates of invasion to the mediastinal pleura, pericardium, lung, phrenic nerve, and chest wall and pleural dissemination than the NC group patients.
CONCLUSIONS
Calcification reflects invasiveness of tumors to surrounding organs and tissues, and may thus predict thymoma stage and histologically high-risk thymomas. Calcification in thymomas may also predict the pathological stage and help decide therapeutic methods and surgical approaches to treat thymomas based on the calcification status according to CT findings.
Topics: Calcinosis; Female; Humans; Male; Middle Aged; Neoplasm Invasiveness; Thymoma
PubMed: 33955164
DOI: 10.1111/1759-7714.13964 -
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 -
Interactive Cardiovascular and Thoracic... Jun 2022Thymomectomy is gaining consensus over complete thymectomy in early-stage thymoma without myasthenia gravis. This is due both to the difficulty of establishing...
OBJECTIVES
Thymomectomy is gaining consensus over complete thymectomy in early-stage thymoma without myasthenia gravis. This is due both to the difficulty of establishing prospective and randomized controlled studies and to the lack of well-defined selection criteria. This bicentric, retrospective propensity score-matched study aims at comparing oncological outcomes, measured in terms of overall survival and thymoma-related survival, in patients undergoing either thymomectomy or complete thymectomy.
METHODS
We retrospectively analysed medical records of patients with clinical early-stage (I and II) thymoma undergoing thymomectomy or complete thymectomy. Exclusion criteria were the presence of myasthenia gravis, clinical advanced tumours and thymic carcinoma. A propensity score-matching analysis was applied to reduce potential preoperative selection biases such as comorbidity (Charlson score), tumour maximal diameter and surgical approach (open versus minimal). All variables were dichotomized.
RESULTS
A total of 255 patients were enrolled from 2 different Hospitals, 126 underwent complete thymectomy and 129 a thymomectomy. Disease-free and thymoma-related survivals showed a 5-year rate of 87.7% and 96.0% and a 10-year rate of 82.2% and 91.9%, respectively. Propensity score-matching analysis selected a total of 176 patients equally divided between the 2 groups. No difference was found for both disease-free (P = 0.11) and thymoma-related (P = 0.37) survival in the 2 groups of resection. Multivariable Cox regression analysis showed that histology (P < 0.001), residual disease (P < 0.001) and adjuvant chemotherapy (P < 0.001) were the only predictors of shorter disease-free survival. Whereas there was no evidence to confirm that disease-free and thymoma-related survivals were influenced by resection extent.
CONCLUSIONS
Thymomectomy is an adequate surgical resection for non-myasthenic thymoma, achieving disease-free and thymoma-related survivals comparable to those after complete thymectomy.
Topics: Humans; Myasthenia Gravis; Neoplasm Staging; Propensity Score; Prospective Studies; Retrospective Studies; Thymectomy; Thymoma; Thymus Neoplasms
PubMed: 35723542
DOI: 10.1093/icvts/ivac167 -
Cancer Medicine Jun 2023In this study, relationships between clinicopathologic characteristics and progression-free survival (PFS) of patients after thymomectomy were analyzed to provide...
BACKGROUND
In this study, relationships between clinicopathologic characteristics and progression-free survival (PFS) of patients after thymomectomy were analyzed to provide valuable suggestions regarding the treatment of thymoma.
METHODS
Data from 187 thymoma patients undergoing surgery at Beijing Tongren Hospital between January 1, 2006, and December 31, 2015, were retrospectively reviewed. We explored the risk factors for PFS among sex, age, thymoma-associated MG, completeness of resection, histologic type and TNM stage, and investigated their interrelationship.
RESULTS
Among the 187 patients, 18 patients (9.63%) had tumor recurrence/metastasis, and all of whom had in situ recurrence or pleural metastasis, and most of them (10 of 18 patients) had MG symptoms that reappeared or were aggravated. Fifteen patients (8.02%) died, and myasthenic crisis was a leading cause. Based on Cox regression analysis, only age (HR = 3.16; 95% CI: 1.44-6.91; p = 0.004) and the completeness of resection (HR = 9.03; 95% CI: 2.58-31.55; p = 0.001) were independent risk factors for PFS. Furthermore, we found that the completeness of resection was related to the histologic type (p = 0.009) and TNM stage (p < 0.001) by Fisher's exact test.
CONCLUSIONS
The results of this cohort study remind us that we should pay attention to the reappearance or aggravation of MG after thymoma resection, because it is the leading cause of death and may indicate tumor progression. Furthermore, completeness of resection was related to the histologic type and TNM stage, but it was the independent risk factors of thymoma. Therefore, R0 resection is critical to the prognosis of thymoma.
Topics: Humans; Thymoma; Retrospective Studies; Cohort Studies; Neoplasm Staging; Neoplasm Recurrence, Local; Thymus Neoplasms; Prognosis; Risk Factors
PubMed: 37156630
DOI: 10.1002/cam4.6043 -
Scientific Reports Feb 2023To determine the prognostic CT features in patients with untreated thymic epithelial tumors (TETs). Clinical data and CT imaging features of 194 patients with...
To determine the prognostic CT features in patients with untreated thymic epithelial tumors (TETs). Clinical data and CT imaging features of 194 patients with pathologically confirmed TETs were retrospectively reviewed. The subjects included 113 male and 81 female patients between 15 and 78 years of age, with a mean age of 53.8 years. Clinical outcomes were categorized according to whether relapse, metastasis or death occurred within 3 years after the first diagnosis. Associations between clinical outcomes and CT imaging features were determined using univariate and multivariate logistic regression analyses, while the survival status was analyzed by Cox regression. In this study, we analyzed 110 thymic carcinomas, 52 high-risk thymomas and 32 low-risk thymomas. Percentages of poor outcome and patient death in thymic carcinomas were much higher than those in patients with high-risk and low-risk thymomas. In the thymic carcinomas groups, 46 patients (41.8%) experienced tumor progression, local relapse or metastasis and were categorized as having poor outcomes; vessel invasion and pericardial mass were confirmed to be independent predictors by logistic regression analysis (p < 0.01). In the high-risk thymoma group, 11 patients (21.2%) were categorized as having poor outcomes, and the CT feature pericardial mass was confirmed to be an independent predictor (p < 0.01). In survival analysis, Cox regression showed that CT features of lung invasion, great vessel invasion, lung metastasis and distant organ metastasis were independent predictors for worse survival in the thymic carcinoma group (p < 0.01), while lung invasion and pericardial mass were independent predictors for worse survival in high-risk thymoma group. No CT features were related to poor outcome and worse survival in the low-risk thymoma group. Patients with thymic carcinoma had poorer prognosis and worse survival than those with high-risk or low-risk thymoma. CT can serve as an important tool for predicting the prognosis and survival of patients with TETs. In this cohort, CT features of vessel invasion and pericardial mass were related to poorer outcomes in those with thymic carcinoma and pericardial mass in those with high-risk thymoma. Features including lung invasion, great vessel invasion, lung metastasis and distant organ metastasis indicate worse survival in thymic carcinoma, whereas lung invasion and pericardial mass indicate worse survival in high-risk thymoma.
Topics: Humans; Male; Female; Middle Aged; Thymoma; Prognosis; Retrospective Studies; Neoplasm Recurrence, Local; Thymus Neoplasms; Neoplasms, Glandular and Epithelial; Lung Neoplasms
PubMed: 36801902
DOI: 10.1038/s41598-023-30041-z -
Annals of Medicine 2023Metaplastic thymoma (MT) is a very uncommon thymoma type, with biphasic differentiation as one of its histological characteristics. This histological pattern, however,...
BACKGROUND
Metaplastic thymoma (MT) is a very uncommon thymoma type, with biphasic differentiation as one of its histological characteristics. This histological pattern, however, can also be mistaken for type A thymoma and the A component in type AB thymoma.
METHODS
Postoperative specimens were collected from five MT and four type A thymomas with a retrospective analysis involving immunohistochemistry, fluorescence hybridization (FISH) and next-generation sequencing (NGS).
RESULTS
The histological morphology of the MT overlapped with that of the type A thymoma. With immunostains, the former's spindle cell components expressed vimentin and EMA, but not CD20. In MT, 3/5 cases had the nuclear expression of YAP1. The spindle cell component of the type A thymoma was found to express CD20. In all five cases of MT, FISH detection revealed fusion, which was not found in any type A thymoma cases. NGS sequencing confirmed rearrangement in all five cases of MT, and mutations in and were also found in two cases, respectively. c.74146970 T > A mutations were found in all cases of type A thymoma, and and mutations were found in two cases, but no rearrangement was evident.
CONCLUSIONS
For the diagnosis and differential diagnosis of challenging cases, the rearrangement and mutation were both significant molecular events specific to MT and type A thymoma, respectively.
Topics: Humans; Diagnosis, Differential; Thymoma; In Situ Hybridization, Fluorescence; Retrospective Studies; Mutation; Thymus Neoplasms; Transcription Factors, TFIII; Transcription Factors, TFII; Trans-Activators
PubMed: 37489594
DOI: 10.1080/07853890.2023.2237040 -
Journal of B.U.ON. : Official Journal... 2021Thymic epithelial tumors represent 0.2-1.5% among all malignant neoplasms. They are slow-growing tumors with an overall recurrence rate around 10% and 90% of them are... (Review)
Review
Thymic epithelial tumors represent 0.2-1.5% among all malignant neoplasms. They are slow-growing tumors with an overall recurrence rate around 10% and 90% of them are located in the anterior mediastinum. In this review we focused on the classification, histopathology, molecular pathology and prognosis of thymic epithelial tumors, mainly thymoma and thymic carcinoma.
Topics: Carcinoma; Humans; Neoplasms, Glandular and Epithelial; Prognosis; Thymoma; Thymus Neoplasms
PubMed: 34564969
DOI: No ID Found -
Cancer Medicine Mar 2023Immunotherapy has exhibited efficacy in thymic carcinoma patients; however, there are insufficient data to confirm this efficacy in thymoma. The toxicity of...
BACKGROUND
Immunotherapy has exhibited efficacy in thymic carcinoma patients; however, there are insufficient data to confirm this efficacy in thymoma. The toxicity of immunotherapy also remains to be determined.
METHODS
The efficacy and safety of immunotherapy were analyzed in 11 thymoma patients who received PD-1 inhibitors according to a range of relevant indexes including the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and immunotherapy-related adverse events.
RESULTS
The PFS and OS rates for all patients were 12.8 and 56.5 months, respectively. No difference in efficacy was detected between monotherapy and combination therapy (PFS: 12.8 vs 2.2 months, P = 0.787; OS: 73.8 vs 56.5 months, P = 0.367). The ORRs and DCRs for all patients were 27.3% and 90.9%, respectively. The incidence of adverse events was 45.5% among the 11 thymoma patients, including immune-related myocarditis (36.4%), immune-related liver damage (18.2%), and myasthenia gravis (18.2%). In the whole cohort of patients, the rate of adverse events of grade 3 or higher was 36.4%. The rates of adverse events of grade 3 or 4 in B3-type and non-B3-type thymoma patients were 0% and 62.5%, respectively.
CONCLUSIONS
Immunotherapy elicited a response in thymoma patients; however, more attention should be paid to the immune-related adverse events.
Topics: Humans; Thymoma; Thymus Neoplasms; Combined Modality Therapy; Immunotherapy
PubMed: 36394097
DOI: 10.1002/cam4.5357 -
Journal of Thoracic Oncology : Official... Dec 2023A TNM-based system for all types of thymic epithelial tumors was introduced in the eighth edition of the TNM classification of thoracic malignancies. The Thymic Domain...
The International Association for the Study of Lung Cancer Thymic Epithelial Tumors Staging Project: Proposal for a Stage Classification for the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors.
INTRODUCTION
A TNM-based system for all types of thymic epithelial tumors was introduced in the eighth edition of the TNM classification of thoracic malignancies. The Thymic Domain of the Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer, composed of multispecialty international experts, was charged to develop proposals for the ninth edition. This article outlines the proposed definitions for the T, the N, and the M components and their combination into stage groups.
METHODS
A large central database of 11,347 patients with thymic epithelial tumors was assembled thanks to the contribution of the major thymic organizations worldwide and analyses were carried out for the T, the N, and the M components and the stage groups. Overall survival was the outcome measure for patients with completely and incompletely resected tumors, and recurrence for those with complete resection. When the number of patients was sufficient, analyses were performed separately for thymomas, thymic carcinomas, and neuroendocrine thymic tumors.
RESULTS
Tumor size is included in the T1 category as T1a (≤5cm) and T1b (>5 cm); the mediastinal pleura is dropped as a T descriptor; invasion of the lung or phrenic nerve is reclassified as T2 (instead of T3). No changes are proposed for the N and the M components from the eighth edition. The stage groups remain the same.
CONCLUSIONS
The proposed changes for the ninth edition of the TNM classification set the stage for further progress in the future for these rare tumors.
Topics: Humans; Neoplasm Staging; Lung Neoplasms; Prognosis; Myeloma Proteins; Thymus Neoplasms; Thymoma; Neuroendocrine Tumors; Neoplasms, Glandular and Epithelial
PubMed: 37689391
DOI: 10.1016/j.jtho.2023.09.002