Thymic carcinoma outcomes and prognosis: Results of an international analysis Ahmad, Usman, MD; Yao, Xiaopan, PhD; Detterbeck, Frank, MD ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
2015, January 2015, 2015-Jan, 2015-01-00, 20150101, Letnik:
149, Številka:
1
Journal Article
Recenzirano
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Objectives The objectives of this collaborative study were to characterize patients with thymic carcinoma, their treatment patterns, and association with overall survival (OS) and recurrence-free ...survival (RFS). Methods Clinical, pathologic, treatment, and follow-up information were analyzed. OS and RFS were the primary outcome measures. Results In 1042 cases of thymic carcinoma, 42 (5%) patients had pathologic Masaoka stage I, 138 (17%) had stage II, 370 (45%) had stage III, and 274 (33%) had stage IV disease. Overall, 166 patients (22%) underwent induction chemotherapy and 48 (6%) had preoperative radiation therapy. An R0 resection was performed in 447 cases (61%), R1 in 102 cases (14%), and R2 in 184 cases (25%). Squamous cell carcinoma was the predominant histologic subtype (n = 560; 79%). Adjuvant chemotherapy was administered to 237 (31%) patients, and 449 (60%) received adjuvant radiation therapy. The median OS was 6.6 years (95% confidence interval CI, 5.8-8.3) and the cumulative incidence of recurrence at 5 years was 35% (95% CI, 30%-40%). In univariate analysis, early Masaoka stage, R0 resection, chemotherapy, and radiation therapy were associated with OS. Early Masaoka stage and R0 resection were also associated with RFS. On multivariable analysis, R0 resection and radiation therapy were associated with prolonged OS. Radiation therapy and male gender were associated with prolonged RFS. Conclusions R0 resection and radiation therapy are associated with improved OS, whereas radiation therapy and male gender are associated with longer RFS.
Objective Primary neuroendocrine tumors of the thymus (TNET) are exceedingly rare. We studied a large series of TNET identified through the International Thymic Malignancy Interest Group and the ...European Society of Thoracic Surgeons databases. Methods This was a retrospective multicenter study of patients undergoing operation for TNET between 1984 and 2012. Outcome measures were: overall survival (OS) and cumulative incidence of recurrences (CIR). OS was analyzed using the Kaplan-Meier method and CIR was analyzed using competing risk analysis. Associations with clinical and prognostic factors for OS and CIR were evaluated using the log rank test and Gray test. Results Two hundred five patients with TNET were treated: 25 patients received induction therapy (19 chemotherapy CT and 6 radiotherapy RT). Data about resection status were available in 47% of cases: complete resection was performed in 52 patients (54%). Masaoka-Koga stages I, II, III, and IV were observed in 12, 33, 56, and 47 patients, respectively. Atypical carcinoid was the commonest histologic subtype (71 cases; 40%). One hundred one patients with TNET received adjuvant treatment; 52 patients died and 36 experienced a recurrence. The median OS was 7.5 years; 5-year OS was 68%, and 5-year CIR was 39%. OS was significantly influenced by Masaoka-Koga stage ( P = .02) and completeness of resection ( P = .03). CIR significantly increased in high Masaoka-Koga stages ( P = .04). Histologic subtype was not associated with either OS or CIR. Conclusions Our results confirm the high biologic aggressiveness of these rare neoplasms; pathologic stage and completeness of resection were demonstrated to be strong prognostic factors, whereas histology did not influence patients outcome.
The current staging system for malignant pleural mesothelioma (MPM) is controversial. To plan revisions of this system, the International Association for the Study of Lung Cancer Staging Committee ...developed an international database. Initial analyses focus on patients managed surgically.
Participation was solicited from centers known to have MPM registries. Common data elements were analyzed by the International Association for the Study of Lung Cancer Staging Committee Statistical Center. Survival was analyzed by the Kaplan–Meier method, prognostic factors by log rank and Cox regression model. p Value less than 0.05 was significant.
Data included 3101 patients (15 centers, 4 continents). Demographics: median age 63 years, 79% men, 62.3% epithelioid tumor. Best tumor, node, metastasis (bTNM) stages were: I (11%), II, (21%), III (48%), and IV (20%). Curative-intent surgery was performed in 1494 patients (64.5%). Median survivals by clinical TNM and pathological TNM were similar: stage I, 21 months; stage II, 19 months; stage III, 16 months; and stage IV, 12 months. Median survival by histology: epithelioid 19 months, biphasic 13 months, and sarcomatoid 8 months. By multivariable analyses, significant differences in overall survival were seen for: T4 versus T3 and T3 versus T2 but not T2 versus T1; N0 versus N1 and N2 but not N1 versus N2; stages III and IV versus I but not II versus I; epithelioid histology versus other; age of female versus age of male; and palliative versus curative-intent surgery.
This is the largest international database examining outcomes in surgically managed MPM patients. Survival differences reported from smaller databases are confirmed but suggest the need to revise tumor and node staging.
Abstract Objective This study investigated the prognostic impact of multimodality therapies in locally advanced thymomas. Methods From January 1990 to January 2010, clinicopathological, surgical, and ...oncological features were retrospectively reviewed in a cohort of 370 Masaoka-Koga stage III thymomas (World Health Organization classification A to B3) collected from 37 institutions. A multivariate Cox proportional hazard model was created to identify independent predictors of overall, cancer-specific (CSS), and relapse-free survivals. Furthermore, a propensity score–matching analysis for exposure to adjuvant (AT) therapy was generated. Results Induction therapy and AT were administered to 88 (24.9%) and 245 (69.4%) patients, respectively. Overall, 5- and 10-year overall survival, CSS, and relapse-free survivals were 82.8%, 88.4%, and 80.0%, and 68.9%, 83.3%, and 71.5%, respectively. At multivariable analysis performed in the matched cohort, AT was confirmed as the strongest predictive factor for overall survival (hazard ratio, 2.83; 95% confidence interval, 0.88-9.12; P = .08) and CSS (hazard ratio, 4.70; 95% confidence interval, 1.00-22.2; P = .05). Pathologic T classification (according to International Association for the Study of Lung Cancer and International Thymic Malignancy Interest Group TNM staging proposal) was an independent factor for relapse (hazard ratio, 8.69; 95% confidence interval, 1.08-70.04; P = .04). When CSS was adjusted for T classification, AT confirmed a significant survival advantage for pT3 tumors ( P = .04). On the other hand, for thymomas larger than 5 cm, stratifying for tumor size and AT did not affect 5-year CSS ( P = .17). Conclusions Our results indicate that AT is beneficial for locally advanced thymomas, mainly for specific pathologic features (pT3 or tumor size smaller than 5 cm). Further larger studies are needed to confirm these data.
Background Tumor-infiltrating lymphocytes (TIL) are considered important in anticancer immunosurveillance, although their role has not been clearly established yet. We examined prevalence, ...correlations, and prognostic significance of TIL among our patient population of resected lung neoplasms. Methods From 1993 to 2006, the presence of TIL was retrospectively evaluated in 1,290 patients operated on for primary lung neoplasms. Tumor-infiltrating lymphocytes were defined as those intraepithelial lymphocytes located within the cancer cell nests. Results Tumor-infiltrating lymphocytes were detected in 294 patients (23%). A significant difference was found between prevalence in non–small cell lung carcinomas versus neuroendocrine tumors (290 of 1,208, 24% versus 4 of 82, 5%; p = 0.0001). Prevalence was similar in adenocarcinomas, squamous-cell carcinomas, and large-cell anaplastic carcinomas. Logistic regression analysis indicates that TIL correlate with grading (odds ratio, 1.27; 95% confidence interval, 1.04 to 1.55; p = 0.02), tumor dimension (odds ratio, 0.86; 95% confidence interval, 0.79 to 0.94; p = 0.0008), and vascular invasion (odds ratio, 1.62; 95% confidence interval, 1.21 to 2.16; p = 0.0009). A not significantly better survival in the presence of TIL was observed overall ( p = 0.20), becoming significant in squamous-cell carcinomas ( p = 0.03). In patients with stage I disease, TIL is associated with a significant survival advantage in squamous-cell carcinomas ( p = 0.03). The survival advantage increases with the duration of follow-up and is more evident after 4 to 6 years. Conclusions Tumor-infiltrating lymphocytes are observed in about one fourth of resected lung neoplasms: they are rare in neuroendocrine tumors. Tumor-infiltrating lymphocytes are more frequent in poorly differentiated tumors and in tumors with microscopic vascular invasion. The presence of TIL correlates with an improved survival in squamous cell carcinomas, particularly at early stage. The survival advantage increases with the duration of follow-up.
Malignant pleural mesothelioma (MPM) is a highly aggressive disease with limited therapeutic options. Histological subtype remains among the most reliable prognostic factors, because the epithelioid ...subtype associated with the best prognosis and the sarcomatoid subtype with the worst. The biphasic subtype has an intermediate prognosis, but its definitive histological diagnosis may be challenging owing to the difficulty of assessing the neoplastic nature of the stromal component. Recent data identified BRCA1-associated protein 1 gene (BAP1) as one of the most frequently mutated genes in MPM. Immunohistochemical testing for BRCA1-associated protein 1 (BAP1) has been proposed to be predictive for the detection of BAP1 mutation in neoplastic cells. The aim of the present study was to define the diagnostic usefulness of immunohistochemical determination of BAP1 in MPM, with clinicopathological correlation.
A series of 143 MPMs were investigated for BAP1 protein expression in correlation with clinical and pathological data, including with a newly proposed nuclear grade. A pilot series of 20 selected cases were also investigated for BAP1 mutational status.
Negative nuclear staining for BAP1 occurred in 62% of MPMs (including 27% with a cytoplasmic pattern) and was significantly associated with the presence of BAP1 mutation, epithelioid subtype, and a better prognosis. In a subgroup of cases, the pattern of expression of BAP1 in stromal cells supported their distinction as reactive versus neoplastic, thus helping achieve the correct classification of biphasic histological subtype.
We showed that BAP1 protein determination is a diagnostic tool to correctly distinguish biphasic MPM from epithelial subtypes with an atypical/activated reactive stroma and an independent prognostic parameter in MPM.
The International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee-Thymic Domain conducted a web-based cross-sectional survey to assess the acceptance of the TNM ...thymic staging system in the thoracic community.
A 50-item, web-based questionnaire was circulated among the members of the major thymic organizations worldwide from September to December 2018. The survey consisted of six sections (general information; overall perception of the TNM system; pretreatment staging; T category; N category; and perioperative treatments).
In total, 217 responses were collected from 37 countries in four continents. The TNM classification was considered useful by 78% of the responders (N = 169); the Masaoka-Koga staging system was being used by 87% of the responders (N = 189). With regard to the T category, most responders (mostly surgeons) felt that the capsular and mediastinal pleural involvements should be considered separate T categories. As for the N category, 48% of the responders (N = 105) used the International Thymic Malignancies Interest Group/International Association for the Study of Lung Cancer thymic nodal map, and lymph node dissection (N1/N2) was performed for 50%/21% thymomas and 66%/41% thymic carcinomas. While analyzing the results by the three continents (Europe, Asia, and Americas), responders in Asia were found to report the largest use of the TNM system, the greatest attention to the N category, and the best participation in international thymic databases.
The survey indicates that the Union for International Cancer Control/American Joint Committee on Cancer TNM stage classification of thymic tumors is gaining acceptance among the scientific community. The present results will guide the work of the Staging and Prognostic Factors Committee-Thymic Domain for the revision of the ninth edition of the TNM stage classification of thymic tumors.
Abstract Thymic epithelial tumors (thymomas, thymic carcinomas and neuroendocrine tumors – NETs) are rare primary mediastinal neoplasms, recently classified as orphan diseases. Their rarity might ...explain the fact that currently, no official staging system has been defined by the Union Internationale Contre le Cancer (UICC) and the American Joint Commission on Cancer (AJCC). However, the appropriate staging of these tumors has been matter of debate and several proposals have been published over the years, but very few have received a clinical validation. Recently an international database for thymic malignancies has been provided by the International Thymic Malignancy Interest Group (ITMIG); one of its aims is to accomplish a new and evidence based staging system, to allow progress in clinical management in thymic tumors. This paper will review the history of proposed staging systems, comparing resemblances and differences, being a sort of starting point for the development of a new widely accepted clinical staging system.
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.
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.
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.
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.
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