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Journal of Surgical Oncology Sep 2023Pleural metastasis has extremely poor prognosis. Resection of pleural implants with infusion of intrathoracic hyperthermic chemotherapy may offer a survival advantage in... (Review)
Review
OBJECTIVES
Pleural metastasis has extremely poor prognosis. Resection of pleural implants with infusion of intrathoracic hyperthermic chemotherapy may offer a survival advantage in selected patients. We evaluated the safety and efficacy of hyperthermic intrathoracic extracorporeal chemotherapy (HITEC) in patients who underwent pleurectomy/decortication (P/D) for secondary malignant pleural disease (SPD).
METHODS
A total of 101 patients were evaluated over 72 months, with 35 patients electing to proceed with P/D and 60 minutes of HITEC with cisplatin at 42°C. Inclusion criteria were adults 18-79 years with unilateral pleural dissemination. Exclusion criteria were patients without control of primary site, extrathoracic metastatic disease, significant comorbidities, and a history of adverse reaction to cisplatin.
RESULTS
Median age was 56 years (36-73); 60% were women. SPD was thymoma in 13, breast cancer in 9, lung cancer in 6, colon cancer in 2, renal cell in 2, and esophageal, anal, and thymic cancers in one each. There was no operative mortality. Postoperative complications occurred in 18 patients (51%). No patient developed renal failure. Median follow-up was 24 months (4-60). The overall survival rate was 61%; 17 patients (49%) developed recurrent disease at a median of 12 months (6-36). There were no recurrences after 36 months Eleven patients (31%) died of metastatic disease at a median of 17 months (7-25).
CONCLUSIONS
Surgical cytoreduction of SPD followed by HITEC with cisplatin was well tolerated. No patient developed cisplatin-related toxicities. Long-term follow-up is warranted to determine survival advantage and refinement of inclusion criteria.
Topics: Adult; Humans; Female; Middle Aged; Male; Cisplatin; Combined Modality Therapy; Pleural Neoplasms; Mesothelioma; Thymus Neoplasms; Pleural Diseases; Hyperthermia, Induced
PubMed: 37409778
DOI: 10.1002/jso.27389 -
Journal of Thoracic Oncology : Official... Oct 2023In 2014, a TNM-based system for thymic epithelial tumors was proposed. The TNM stage classification system was published as a result of a joint project from the... (Review)
Review
The International Association for the Study of Lung Cancer Thymic Epithelial Tumors Staging Project: An Overview of the Central Database Informing Revision of the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors.
INTRODUCTION
In 2014, a TNM-based system for thymic epithelial tumors was proposed. The TNM stage classification system was published as a result of a joint project from the International Association for the Study of Lung Cancer and the International Thymic Malignancy Interest Group for the eighth edition of the American Joint Commission on Cancer and the Union for International Cancer Control stage classification system. The Thymic Domain of the Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer received the mandate to make proposals for the ninth edition of the TNM stage classification.
METHODS
A central thymic database was collected by the Cancer Research And Biostatistics with the contribution of the major thymic associations in the world.
RESULTS
A total of 11,347 patients were collected. Submitting organizations were the following: Japanese Association for Research in the Thymus, European Society of Thoracic Surgeons, Chinese Alliance for Research in Thymoma, Korean Association for Research in the Thymus, International Thymic Malignancy Interest Group, and Réseau tumeurs THYMiques et Cancer. Additional contributions came from centers in the United States, United Kingdom, Turkey, Australia, Spain, and Italy. A total of 9147 cases were eligible for analysis. Eligible cases for analysis came from Asia and Australia (5628 cases, 61.5%), Europe (3113 cases, 34.0%), and North America (406 cases, 4.4%).
CONCLUSIONS
This report provides an overview of the database that has informed the proposals for the updated T, N, and M components and the stage groups for the ninth TNM of malignant tumors.
Topics: Humans; Lung Neoplasms; Neoplasm Staging; Neoplasms, Glandular and Epithelial; Prognosis; Thymus Neoplasms
PubMed: 37702630
DOI: 10.1016/j.jtho.2023.07.008 -
Academic Radiology Apr 2024This study aims to evaluate the feasibility and effectiveness of deep transfer learning (DTL) and clinical-radiomics in differentiating thymoma from thymic cysts.
Development and Validation of Contrast-Enhanced CT-Based Deep Transfer Learning and Combined Clinical-Radiomics Model to Discriminate Thymomas and Thymic Cysts: A Multicenter Study.
RATIONALE AND OBJECTIVES
This study aims to evaluate the feasibility and effectiveness of deep transfer learning (DTL) and clinical-radiomics in differentiating thymoma from thymic cysts.
MATERIALS AND METHODS
Clinical and imaging data of 196 patients pathologically diagnosed with thymoma and thymic cysts were retrospectively collected from center 1. (training cohort: n = 137; internal validation cohort: n = 59). An independent external validation cohort comprised 68 thymoma and thymic cyst patients from center 2. Region of interest (ROI) delineation was performed on contrast-enhanced chest computed tomography (CT) images, and eight DTL models including Densenet 169, Mobilenet V2, Resnet 101, Resnet 18, Resnet 34, Resnet 50, Vgg 13, Vgg 16 were constructed. Radiomics features were extracted from the ROI on the CT images of thymoma and thymic cyst patients, and feature selection was performed using intra-observer correlation coefficient (ICC), Spearman correlation analysis, and least absolute shrinkage and selection operator (LASSO) algorithm. Univariate analysis and multivariable logistic regression (LR) were used to select clinical-radiological features. Six machine learning classifiers, including LR, support vector machine (SVM), k-nearest neighbors (KNN), Light Gradient Boosting Machine (LightGBM), Adaptive Boosting (AdaBoost), and Multilayer Perceptron (MLP), were used to construct Radiomics and Clinico-radiologic models. The selected features from the Radiomics and Clinico-radiologic models were fused to build a Combined model. Receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, calibration, and clinical utility of the models, respectively. The Delong test was used to compare the AUC between different models. K-means clustering was used to subdivide the lesions of thymomas or thymic cysts into subregions, and traditional radiomics methods were used to extract features and compare the ability of Radiomics and DTL models to reflect intratumoral heterogeneity using correlation analysis.
RESULTS
The Densenet 169 based on DTL performed the best, with AUC of 0.933 (95% CI: 0.875-0.991) in the internal validation cohort and 0.962 (95% CI: 0.923-1.000) in the external validation cohort. The AdaBoost classifier achieved AUC of 0.965 (95% CI: 0.923-1.000) and 0.959 (95% CI: 0.919-1.000) in the internal and external validation cohorts, respectively, for the Radiomics model. The LightGBM classifier achieved AUC of 0.805 (95% CI: 0.690-0.920) and 0.839 (95% CI: 0.736-0.943) in the Clinico-radiologic model. The AUC of the Combined model in the internal and external validation cohorts was 0.933 (95% CI: 0.866-1.000) and 0.945 (95% CI: 0.897-0.994), respectively. The results of the Delong test showed that the Radiomics model, DTL model, and Combined model outperformed the Clinico-radiologic model in both internal and external validation cohorts (p-values were 0.002, 0.004, and 0.033 in the internal validation cohort, while in the external validation cohort, the p-values were 0.014, 0.006, and 0.015, respectively). But there was no statistical difference in performance among the three models (all p-values <0.05). Correlation analysis showed that radiomics performed better than DTL in quantifying intratumoral heterogeneity differences between thymoma and thymic cysts.
CONCLUSION
The developed DTL model and the Combined model based on radiomics and clinical-radiologic features achieved excellent diagnostic performance in differentiating thymic cysts from thymoma. They can serve as potential tools to assist clinical decision-making, particularly when endoscopic biopsy carries a high risk.
Topics: Humans; Thymoma; Radiomics; Mediastinal Cyst; Retrospective Studies; Tomography, X-Ray Computed; Machine Learning; Thymus Neoplasms
PubMed: 37949702
DOI: 10.1016/j.acra.2023.10.018 -
Journal of Thoracic Oncology : Official... Dec 2023A TNM-based stage classification system of thymic epithelial tumors was adopted for the eighth edition of the stage classification of malignant tumors. The Thymic Domain...
The International Association for the Study of Lung Cancer Thymic Epithelial Tumor Staging Project: Proposal for the T Component for the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors.
INTRODUCTION
A TNM-based stage classification system of thymic epithelial tumors was adopted for the eighth edition of the stage classification of malignant tumors. The Thymic Domain of the Staging and Prognostics Factor Committee of the International Association for the Study of Lung Cancer developed a new database with the purpose to make proposals for the ninth edition stage classification system. This article outlines the proposed definitions for the T categories for the ninth edition TNM stage classification of thymic malignancies.
METHODS
A worldwide collective database of 11,347 patients with thymic epithelial tumors was assembled. Analysis was performed on 9147 patients with available survival data. Overall survival, freedom-from-recurrence, and cumulative incidence of recurrence were used as outcome measures. Analysis was performed separately for thymomas, thymic carcinomas, and neuroendocrine thymic tumors.
RESULTS
Proposals for the T categories include the following: T1 category is divided into T1a (≤5 cm) and T1b (>5 cm), irrespective of mediastinal pleura invasion; T2 includes direct invasion of the pericardium, lung, or phrenic nerve; T3 denotes direct invasion of the brachiocephalic vein, superior vena cava, chest wall, or extrapericardial pulmonary arteries and veins; and T4 category remains the same as in the eighth edition classification, involving direct invasion of the aorta and arch vessels, intrapericardial pulmonary arteries and veins, myocardium, trachea, or esophagus.
CONCLUSIONS
The proposed T categories for the ninth edition of the TNM classification provide good discrimination in outcome for the T component of the TNM-based stage system of thymic epithelial tumors.
Topics: Humans; Lung Neoplasms; Neoplasm Staging; Vena Cava, Superior; Thymus Neoplasms; Neoplasms, Glandular and Epithelial; Thymoma; Neuroendocrine Tumors; Lung; Prognosis
PubMed: 37634808
DOI: 10.1016/j.jtho.2023.08.024 -
Rozhledy V Chirurgii : Mesicnik... 2024Thoracic surgery is increasingly influenced by the development of minimally invasive approaches which have also influenced surgery in the area of the anterior...
Thoracic surgery is increasingly influenced by the development of minimally invasive approaches which have also influenced surgery in the area of the anterior mediastinum. The previously standard approach to the thymus via partial sternotomy was gradually replaced by the videothoracoscopic approach in most cases. In recent years, robotically assisted surgery has been gaining ground worldwide in this area, as well. The aim of our paper is to provide a comprehensive overview of procedures in the field of the thymus, including their indications, and to share our first experience with robot-assisted thymus surgery. At the 3rd Department of Surgery, since the start of the robot-assisted thymus surgery program, 23 thymectomies have been performed using this approach, of which 17 were performed for thymoma, 3 for myasthenia gravis, and 3 for parathyroid adenoma localized in thymus tissue. From our experience and the available data, it follows that the length of hospitalization, the rate of complications and the resulting effect of robot-assisted procedures is comparable to VTS procedures; however, the robot-assisted surgery also allows for mini-invasive treatment even in significantly obese patients and in patients with advanced thymic tumors who would otherwise be indicated for open thymectomy.
Topics: Humans; Robotic Surgical Procedures; Thymectomy; Thymus Neoplasms; Thymoma; Myasthenia Gravis; Parathyroid Neoplasms; Thymus Gland; Male
PubMed: 38697812
DOI: 10.33699/PIS.2024.103.2.40-47 -
Histopathology Nov 2023Metaplastic thymoma is a rare thymic tumour characterized by Yes Associated Protein 1 (YAP1) and Mastermind Like Transcriptional Coactivator 2 (MAML2) gene fusions...
AIMS
Metaplastic thymoma is a rare thymic tumour characterized by Yes Associated Protein 1 (YAP1) and Mastermind Like Transcriptional Coactivator 2 (MAML2) gene fusions resulting from an intrachromosomal inversion of chromosome 11. Immunohistochemistry with an antibody directed against the C-terminus of YAP1 has shown loss of expression in YAP1-rearranged vascular neoplasms, poromas, and porocarcinomas. This study aimed to validate an anti-YAP1 C-terminal antibody as an ancillary immunohistochemical marker for the diagnosis of metaplastic thymoma.
MATERIALS AND METHODS
Ten metaplastic thymomas were selected for the current study. Fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and reverse transcription-polymerase chain reaction (RT-PCR) analyses were performed to detect YAP1::MAML2 fusions. We then performed immunohistochemistry to detect YAP1 C-terminus expression in 10 metaplastic thymomas, 50 conventional thymomas (10 each of type A thymoma, type AB thymoma, type B1 thymoma, type B2 thymoma, and type B3 thymoma) and seven thymic carcinomas.
RESULTS
All 10 cases showed narrow split signals with a distance of nearly two signal diameters and sometimes had false-negative results in YAP1 and MAML2 break-apart FISH (BA-FISH). Abnormal colocalized signals of the YAP1::MAML2 fusion were observed in all 10 cases using fusion FISH (F-FISH) assays. Eight of 10 cases with adequate nucleic acids were successfully sequenced and all showed YAP1::MAML2 fusions; in two cases the fusions were detected by both DNA and RNA sequencing and in six cases by RNA sequencing only. YAP1::MAML2 fusion transcripts were identified in four cases by RT-PCR. Metaplastic thymoma showed loss of YAP1 C-terminus expression in all 10 (100%) cases. All other thymic neoplasms showed retained YAP1 C-terminus expression.
CONCLUSION
YAP1 C-terminus immunohistochemistry is a highly sensitive and specific ancillary marker that distinguishes metaplastic thymoma from its mimics. BA-FISH assays could not effectively detect YAP1::MAML2 fusions due to the proximity of the two genes. Loss of YAP1 C-terminus expression is a reliable surrogate for the detection of YAP1::MAML2 fusions in metaplastic thymoma.
Topics: Humans; Thymoma; In Situ Hybridization, Fluorescence; Transcription Factors; Thymus Neoplasms; Adaptor Proteins, Signal Transducing; Gene Rearrangement; Trans-Activators
PubMed: 37565303
DOI: 10.1111/his.15024 -
Journal of Clinical Medicine Jan 2024Paraneoplastic Neurological Syndromes (PNS) comprise a diverse group of disorders propagated by immune-mediated effects of malignant tumors on neural tissue.
BACKGROUND
Paraneoplastic Neurological Syndromes (PNS) comprise a diverse group of disorders propagated by immune-mediated effects of malignant tumors on neural tissue.
METHODS
A single-center longitudinal study was performed including consecutive adult patients treated at a tertiary academic hospital between 2015 and 2023 and diagnosed with PNS. PNS were ascertained using the 2004 and the revised 2021 PNS-Care diagnostic criteria.
RESULTS
Thirteen patients who fulfilled the 2004 definite PNS criteria were included. PNS comprise diverse neurological syndromes, with neuromuscular junction disorders (54%) and limbic encephalitis (31%) being predominant. PNS-related antibodies were detected in 85% of cases, including anti-AChR ( = 4), anti-P/Q-VGCC ( = 3), anti-Hu ( = 3), anti-Yo ( = 1), anti-Ma ( = 1), anti-titin ( = 1), anti-IgLON5 ( = 1), and anti-GAD65 ( = 1). Thymoma (31%), small-cell lung cancer (23%), and papillary thyroid carcinoma (18%) were the most frequent tumors. Imaging abnormalities were evident in 33% of cases. Early immunotherapy within 4-weeks from symptom onset was associated with favorable outcomes. At a mean follow-up of 2 ± 1 years, two patients with anti-Hu and anti-Yo antibodies died (18%). Four and three patients fulfilled the 2021 PNS-Care diagnostic criteria for definite and probable PNS, respectively.
CONCLUSIONS
This study highlights the clinical heterogeneity of PNS, emphasizing the need for early suspicion and prompt treatment initiation for optimal outcomes.
PubMed: 38337520
DOI: 10.3390/jcm13030824 -
Journal of Cardiothoracic Surgery Aug 2023Regardless of its rare occurrence, Thymoma remains the most frequently encountered primary tumor of the anterior mediastinum comprising about 50% of all masses in the...
BACKGROUND
Regardless of its rare occurrence, Thymoma remains the most frequently encountered primary tumor of the anterior mediastinum comprising about 50% of all masses in the region. Surgical resection, via thymectomy, remains the mainstay treatment modality. In locally advanced and borderline resectable tumors, neoadjuvant chemotherapy (NACT) may be utilized to increase the chance of R0 resection, raising the question of its efficacy and safety.
METHODS
Demographic and clinical data from patients who presented to a tertiary cancer center between January 2015-October 2021 with a diagnosis of thymoma and underwent curative surgical resection was collected. Computed tomography scan was used to delineate clinical staging, tumor size and to detect post-therapeutic variations in tumor burden. The response evaluation criteria in solid tumors (RECIST) was used to classify the effect of NACT on tumor burden. The pathological response was determined by measuring the percentage of necrotic tissue.
RESULTS
A total of 23 patients were diagnosed with thymoma. Most patients were male with a mean age 46 (± 15) years at diagnosis. The most common clinical stage was stage II with 5 patients (22%). A total of 12 patients had NACT as compared to 11 patients who had upfront surgery. The mean change in tumor volume was 165 cm (p = 0.079) and the change in and maximum diameter was 1.53 ± 1.49 cm (p < 0.01). The effect of NACT on tumor burden based on RECIST criteria was minimal as 8 patients had stable disease. Based on pathological findings, the average necrotic portion of the tumor was 39.5% (p = 0.152). The overall survival rate is 95.65%, mean survival was 115 months (4-125). Recurrence occurred in 5 patients. The NACT group had a higher risk for recurrence (4; 33.3%) with a mean survival of 43.8 months compared to 59.6 months in those who did not receive induction therapy.
CONCLUSIONS
The exact role of induction chemotherapy in locally advanced thymoma patients remains controversial. NACT effect after utilizing radiological and pathological assessment tools was not found to significantly improve oncological outcomes compared to upfront surgery in locally advanced disease, with minimal radiologic and pathologic effect. To further demonstrate the impact of induction chemotherapy, we recommend multicentric collaborative studies.
Topics: Humans; Male; Middle Aged; Female; Thymoma; Neoadjuvant Therapy; Thymus Neoplasms; Mediastinum; Necrosis
PubMed: 37592291
DOI: 10.1186/s13019-023-02357-4 -
European Journal of Nuclear Medicine... Sep 2023The purpose of this study is to compare the ability of [Ga]Ga-DOTA-FAPI-04 PET/CT and [F]FDG PET/CT to stratify the malignancy and invasiveness of thymic epithelial...
PURPOSE
The purpose of this study is to compare the ability of [Ga]Ga-DOTA-FAPI-04 PET/CT and [F]FDG PET/CT to stratify the malignancy and invasiveness of thymic epithelial tumours (TETs).
METHODS
From April 2021 to November 2022, participants with suspected TETs confirmed by histopathology or follow-up imaging were prospectively analysed. All participants underwent [F]FDG and [Ga]Ga-DOTA-FAPI-04 PET/CT within 1 week. Clinical characteristics, CT features, and metabolic parameters (maximum standardized uptake value [SUV] and tumour-to-mediastinum ratio [TMR]) of subjects with different pathological types and stages were compared. The diagnostic capacities of [F]FDG and [Ga]Ga-DOTA-FAPI-04 PET/CT were compared using receiver operating characteristic (ROC) curves and McNemar's test.
RESULTS
Fifty-seven participants were included. [Ga]Ga-DOTA-FAPI-04 PET/CT was superior to [F]FDG PET/CT in differentiating thymomas from thymic carcinomas (TCs) (AUC: 0.99 vs. 0.90, P = 0.02). Logistic regression revealed that SUV (P = 0.04) was a significant predictive factor for TCs. SUV and TMR showed an excellent ability to differentiate low-risk thymomas (types A, AB, and B1), high-risk thymomas (types B2 and B3), and TCs (both P < 0.001). In thymomas, only SUV (P < 0.001), TMR (P < 0.001), and nonsmooth edges (P = 0.02) were significantly higher in the advanced-stage (Masaoka-Koga [MK] stage III/IV) group than in the early-stage group (MK stage I/II). Compared with [F]FDG PET/CT, [Ga]Ga-DOTA-FAPI-04 PET/CT showed significantly higher specificity (67% [46 of 69] vs. 93% [64 of 69], P < 0.001) in the detection of lymph node metastases and higher sensitivity (49% [19 of 39] vs. 97% [38 of 39], P < 0.001) in evaluating distant metastases. Both SUV and TMR were correlated with FAP expression (both r = 0.843, P < 0.001).
CONCLUSION
[Ga]Ga-DOTA-FAPI-04 PET/CT was superior to [F]FDG PET/CT in evaluating the World Health Organization (WHO) classification, MK staging, and metastatic status of TETs.
TRIAL REGISTRATION
ChiCTR2000038080, registration date 2020-09-09, https://www.chictr.org.cn/com/25/showproj.aspx?proj=61192.
Topics: Humans; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Gallium Radioisotopes; Thymoma; Thymus Neoplasms; Quinolines; Neoplasms, Glandular and Epithelial
PubMed: 37316675
DOI: 10.1007/s00259-023-06294-1 -
Journal of Clinical Pathology Jan 2024Micronodular thymoma with lymphoid stroma is a rare subtype of thymoma with characteristic clinical and pathological features. Some of the features, such as indolent...
AIMS
Micronodular thymoma with lymphoid stroma is a rare subtype of thymoma with characteristic clinical and pathological features. Some of the features, such as indolent nature, principally spindle morphology and no significant association to myasthenia gravis, are shared with type A and AB thymoma, which is closely linked to mutation. However, not much is known regarding the molecular genetics of this thymoma subtype. In this study, the mutation status was investigated in 16 cases of micronodular thymoma.
METHODS
16 micronodular thymomas were retrieved and the GTF2I mutation was tested by Sanger sequencing. The clinicopathological findings were documented.
RESULTS
GTF2I c.1271T>A p.(Leu424His) mutation within exon 15 was detected in 14 out of 16 tumours (87.5%). Two patients died of other causes while all others remained alive with no evidence of recurrence during the follow-up period ranging from 19 to 188 months (median: 100 months).
CONCLUSIONS
GTF2I mutation status and presence of spindle cell morphology may indicate that type A and AB thymoma, and micronodular thymoma represent a group biologically distinct from type B thymomas, which generally lack this mutation.
Topics: Humans; Thymoma; Thymus Neoplasms; Mutation; Myasthenia Gravis; Transcription Factors, TFIII; Transcription Factors, TFII
PubMed: 36600564
DOI: 10.1136/jcp-2022-208655