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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 -
Frontiers in Immunology 2021Good syndrome is a rare adult-onset immunodeficiency characterized by thymoma and hypogammaglobulinemia. Its clinical manifestations are highly heterogeneous, ranging... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Good syndrome is a rare adult-onset immunodeficiency characterized by thymoma and hypogammaglobulinemia. Its clinical manifestations are highly heterogeneous, ranging from various infections to autoimmunity.
OBJECTIVE
This study was to summarize patient characteristics, identify prognostic factors and define clinical subgroups of Good syndrome.
METHODS
A systematic literature review was conducted to include patients with Good syndrome identified in PubMed, Embase and Cochrane databases between January 2010 and November 2020. Logistic and Cox regressions were used to identify prognostic factors impacting outcomes. Clinical subgroups were defined by multiple correspondence analysis and unsupervised hierarchical clustering. A decision tree was constructed to characterize the subgroup placement of cases.
RESULTS
Of 162 patients included in the current study, the median age at diagnosis was 58 years and 51% were male. Type AB was the most common histological subtype of thymoma, and infections as well as concurrent autoimmune disorders were identified in 92.6% and 51.2% patients, respectively. Laboratory workup showed typical findings of combined immunodeficiency. Thymoma status (odds ratio [OR] 4.157, confidence interval [CI] 1.219-14.177, = 0.023), infections related to cellular immunity defects (OR 3.324, 95% CI 1.100-10.046, = 0.033), infections of sinopulmonary tract (OR 14.351, 95% CI 2.525-81.576, = 0.003), central nerve system (OR 6.403, 95% CI 1.205-34.027, = 0.029) as well as bloodstream (OR 6.917, 95% CI 1.519-31.505, = 0.012) were independent prognostic factors. The 10-year overall survival was 53.7%. Cluster analysis revealed three clinical subgroups with distinct characteristics and prognosis (cluster 1, infections related to cellular immunity defects; cluster 2, infections related to other immunity defects; cluster 3, infections related to humoral and phagocytic immunity defects). A decision tree using infection types (related to humoral and cellular immunity defects) could place patients into corresponding clusters with an overall correct prediction of 72.2%.
CONCLUSIONS
Infection type and site were the main prognostic factors impacting survival of patients with Good syndrome. We identified three subgroups within Good syndrome associated with distinct clinical features, which may facilitate the study of underlying pathogenesis as well as development of targeted therapy.
Topics: Autoimmunity; Disease Management; Disease Susceptibility; Global Health; Humans; Immunologic Deficiency Syndromes; Neoplasms, Second Primary; Odds Ratio; Phenotype; Population Surveillance; Prognosis; Symptom Assessment
PubMed: 34113351
DOI: 10.3389/fimmu.2021.679556 -
Thoracic Cancer Jan 2022Surgical resection of the thymus is indicated in the presence of primary thymic diseases such as thymoma. Video-assisted thoracoscopic surgery (VATS) and robot-assisted... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Surgical resection of the thymus is indicated in the presence of primary thymic diseases such as thymoma. Video-assisted thoracoscopic surgery (VATS) and robot-assisted thoracic surgery (RATS) offer a minimally invasive approach to thymectomy. However, there is no clear conclusion whether RATS can achieve an equal or even better surgical effect when compared with VATS in treatment of thymoma. We performed this meta-analysis to explore and compare the outcomes of RATS versus VATS for thymectomy in patients with thymoma.
METHODS
PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Medline, and Web of Science databases were searched for full-text literature citations. The quality of the articles was evaluated using the Newcastle-Ottawa Scale and the data analyzed using Review Manager 5.3 software. Fixed or random effect models were applied according to heterogeneity. Subgroup analysis was conducted.
RESULTS
A total of 11 studies with 1418 patients, of whom 688 patients were in the RATS group and 730 in the VATS group, were involved in the analysis. Compared with VATS, RATS was associated with less blood loss in operation, lower volume of drainage, fewer postoperative pleural drainage days, shorter postoperative hospital stay, and fewer postoperative complications. There was no significant difference in operative time and patients with or without myasthenia gravis between the two groups.
CONCLUSIONS
RATS has more advantages over VATS, indicating that RATS is better than VATS in terms of postoperative recovery. We look forward to more large-sample, high-quality randomized controlled studies published in the future.
Topics: Humans; Robotic Surgical Procedures; Thoracic Surgery, Video-Assisted; Thymectomy; Thymoma; Thymus Neoplasms
PubMed: 34806328
DOI: 10.1111/1759-7714.14234 -
Journal of Cancer Research and Clinical... Feb 2015Thymic malignancies, comprising thymoma and thymic carcinoma, are rare. Consequently, optimal chemotherapy for advanced thymic malignancies remains controversial.... (Review)
Review
PURPOSE
Thymic malignancies, comprising thymoma and thymic carcinoma, are rare. Consequently, optimal chemotherapy for advanced thymic malignancies remains controversial. Platinum-based chemotherapy is currently the consensus treatment based on the results of single-arm phase II trials and retrospective investigations. However, comparison of cisplatin-based and carboplatin-based chemotherapy has yet to be undertaken; the effectiveness of the addition of anthracycline also remains uncertain.
METHODS
In the present study, clinical trials and retrospective data regarding platinum-based chemotherapy were analyzed. The endpoint was the response rate to each chemotherapy. For advanced thymoma, we compared platinum with anthracycline-based chemotherapy and platinum with non-anthracycline-based chemotherapy. For advanced thymic carcinoma, anthracycline-based versus non-anthracycline-based chemotherapy and carboplatin-based versus cisplatin-based chemotherapy were compared. This analysis included a retrospective study of response of advanced thymic carcinoma to irinotecan and cisplatin in our institution.
RESULTS
The response rate for the 314 patients from 15 studies with advanced thymoma, including both prospective and retrospective data, was 69.4% [95% confidence interval (CI) 63.1-75.0%] for platinum with anthracycline-based chemotherapy and 37.8% (95% CI 28.1-48.6%; p < 0.0001) for platinum with non-anthracycline-based chemotherapy. The response rates after anthracycline-based and non-anthracycline-based chemotherapy for advanced thymic carcinoma were similar (41.8 vs. 40.9%; p < 0.91), whereas the response rates after cisplatin-based and carboplatin-based chemotherapy for advanced thymic carcinoma differed significantly (53.6 vs. 32.8%; p = 0.0029) in 206 patients from 10 studies.
CONCLUSIONS
Platinum with anthracycline-based chemotherapy is an optimal combination for advanced thymoma. For advanced thymic carcinoma, cisplatin-based chemotherapy may be superior to carboplatin-based chemotherapy.
Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cisplatin; Clinical Trials as Topic; Humans; Prognosis; Thymus Neoplasms
PubMed: 25146529
DOI: 10.1007/s00432-014-1800-6 -
Journal of Thoracic Oncology : Official... Jan 2016Complete resection is the standard of care for treatment of thymic malignancies. The use of minimally invasive surgery remains controversial. We searched online... (Comparative Study)
Comparative Study Meta-Analysis Review
Complete resection is the standard of care for treatment of thymic malignancies. The use of minimally invasive surgery remains controversial. We searched online databases and identified studies from 1995 to 2014 that compared minimally invasive to open thymectomy for thymic malignancies. Study end points included operative blood loss, operative time, respiratory complications, cardiac complications, length of hospital stay, R0 resection, and recurrence. We summarized outcomes across studies using random-effects meta-analysis to account for study heterogeneity. We calculated ORs for binary outcomes and standardized mean differences for continuous outcomes. We calculated incidence rate ratios for the number of recurrences, accounting for total person-time observed in each study. Of 516 potential reference studies, 30 with a total of 2038 patients met the inclusion criteria. Patients with Masaoka stage I or II thymic malignancy constituted 94.89% of those in the minimally invasive surgery (MIS) group and 78.62% of those in open thymectomy (open) group. Mean tumor size was 4.09 cm (MIS) versus 4.80 (open). Of the 1355 MIS cases, 32 were converted to open cases. Patients in the MIS group had significantly less blood loss; however, no significant differences in operating time, respiratory complications, cardiac complications, or overall complications were identified. Length of stay was shorter for patients in the MIS group. When patients with Masaoka stage I and II thymic malignancy only were analyzed, there was no difference in rate of R0 resection or overall recurrence rate. One postoperative death occurred in the open group. The results of this unadjusted meta-analysis of published reports comparing minimally invasive with open thymectomy suggest that in selected patients with thymic malignancy, minimally invasive thymectomy is safe and can achieve oncologic outcomes similar to those of open thymectomy.
Topics: Humans; Minimally Invasive Surgical Procedures; Risk Assessment; Thymectomy; Thymoma; Thymus Neoplasms
PubMed: 26762737
DOI: 10.1016/j.jtho.2015.08.004 -
Clinical Immunology (Orlando, Fla.) Jun 2010Good syndrome (GS) is a rare association of thymoma and immunodeficiency first described more than 50 years ago. However, this syndrome still remains a mystery to... (Review)
Review
Good syndrome (GS) is a rare association of thymoma and immunodeficiency first described more than 50 years ago. However, this syndrome still remains a mystery to clinicians. We systematically reviewed all the clinical, laboratory and immunologic findings from 152 patients with Good syndrome. The syndrome has a worldwide distribution and approximately half of the cases (47%) have been described in Europe. The diagnosis of thymoma preceded the diagnosis of hypogammaglobulinemia, infection, or diarrhea in 42% of patients whereas in 38% of patients the diagnoses were made almost simultaneously within 2 months of each other. We found significant mortality in patients with this syndrome (44.5%). Astute clinical acumen and increased awareness about the clinical and immunological profile of this syndrome may increase early recognition of this syndrome and prevent mortality. Further studies are needed to elucidate this clinical entity.
Topics: Humans; Immunologic Deficiency Syndromes; Thymoma; Thymus Neoplasms
PubMed: 20149753
DOI: 10.1016/j.clim.2010.01.006 -
Medical Science Monitor : International... Aug 2015The association between PTPN22 R620W polymorphism and risk of myasthenia gravis (MG) remains controversial. Therefore, we did this meta-analysis to investigate this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The association between PTPN22 R620W polymorphism and risk of myasthenia gravis (MG) remains controversial. Therefore, we did this meta-analysis to investigate this association.
MATERIAL AND METHODS
We did a comprehensive search in PubMed, Medline, Embase, CNKI (China National Knowledge Infrastructure), and Wanfang electronic databases to retrieve relevant articles. The overall effect was measured by odds ratios (ORs) with its 95% confidence intervals (CIs). Statistical analyses were conducted with STATA software.
RESULTS
Overall, a total of 7 case-control studies with 2802 cases and 3730 controls were finally included in this review. PTPN22 R620W polymorphism was significantly associated with an increased risk of MG (OR=1.57; 95% CI, 1.34-1.82; I(2)=31%). In the subgroup analysis, thymoma patients were significantly associated with risk of MG (OR=1.59; 95% CI, 1.28-1.98; I(2)=0%). However, non-thymoma patients with this polymorphism did not have increased MG risk (OR=1.36; 95% CI, 0.86-2.15; I(2)=77%). In addition, PTPN22 R620W polymorphism showed increased early-onset myasthenia gravis (EOMG) risk (OR=2.38; 95% CI, 1.52-3.71; I(2)=0%).
CONCLUSIONS
This meta-analysis shows a significant association between PTPN22 R620W polymorphism and MG risk.
Topics: Genetic Predisposition to Disease; Humans; Myasthenia Gravis; Polymorphism, Genetic; Protein Tyrosine Phosphatase, Non-Receptor Type 22
PubMed: 26318187
DOI: 10.12659/MSM.894307 -
Interactive Cardiovascular and Thoracic... Mar 2022Our goal was to evaluate the effect of thymectomy on the progression of thymolipomatous myasthenia gravis.
OBJECTIVES
Our goal was to evaluate the effect of thymectomy on the progression of thymolipomatous myasthenia gravis.
METHODS
An electronic search performed across PubMed, MEDLINE and Web of Science databases included all article types. We included 15 series comprising 36 cases that met specific criteria, including case reports or case series related to thymolipoma with a myasthenia gravis association, where thymectomy was cited as the primary intervention with postoperative reporting of the prognosis and articles written in the English language.
RESULTS
Our study included 17 men (47.2%) and 19 women (52.8%). Tumour sizes varied between 34 × 18 × 7 cm and 2.8 × 2.3 × 1.9 cm; the weight of the tumours ranged between 38 and 1780 g (mean 190, standard deviation 341). The surgical approaches were a median sternotomy in 29 patients (80.6%), a thoracotomy in 1 patient (2.8%), video-assisted thoracoscopic surgery in 2 patients (5.6%) and unreported approaches in 4 (11.1%) patients. The disease was entirely resolved with complete, stable remission in 5 patients (13.9%); symptoms were improved in 19 (52.8%) and stable in 10 patients (27.7%). We identified 2 groups of patients according to their improvement post-thymectomy (improved group and group with no change).
CONCLUSIONS
Although the cases were uncontrolled and did not demonstrate strong associations, they do support some hypotheses. We found a significant statistical difference between the 2 groups in terms of age, because younger patients tended to improve to a greater degree post-thymectomy. Also, we found that female patients with thymoma visible on the imaging scans were significantly associated with post-thymectomy myasthenia gravis improvement.
REGISTRATION NUMBER IN PROSPERO
CRD42020173229.
Topics: Female; Humans; Male; Myasthenia Gravis; Thymectomy; Thymoma; Thymus Neoplasms; Treatment Outcome
PubMed: 35362060
DOI: 10.1093/icvts/ivab295 -
The Journal of Thoracic and... Jul 2020Paraneoplastic syndromes associated with thymomas remain incompletely understood. The objective was to examine the association between surgically resected thymomas and...
OBJECTIVE
Paraneoplastic syndromes associated with thymomas remain incompletely understood. The objective was to examine the association between surgically resected thymomas and paraneoplastic syndromes over the past half century.
METHODS
A primary PubMed/MEDLINE search was used to identify published articles describing paraneoplastic syndromes associated with thymomas from 1960 to 2019. A secondary search identified additional articles referenced in the articles found in the primary search. Kaplan-Meier and log-rank test were used for time-to-event data analyses.
RESULTS
From 407 articles describing 507 patients, 123 different paraneoplastic syndromes were associated with thymoma. The 5 most common paraneoplastic syndromes were myasthenia gravis, pure red cell aplasia, lichen planus, Good syndrome, and limbic encephalitis. Complete or partial resolution of paraneoplastic syndrome symptoms after surgery was noted in 76% of patients, of whom 21% had a relapse or new paraneoplastic syndrome onset after surgery. The most common adjunctive therapy associated with resolution of paraneoplastic syndrome was corticosteroids (30%). For all patients after surgery, thymoma recurrence was observed in 17% of cases, whereas recurrence of paraneoplastic syndrome was observed in 34% of cases, and both were observed in approximately 11% of cases. The 5- and 10-year overall survivals were 78% and 66%, respectively. Improved overall survival was associated with patients who had total resolution from paraneoplastic syndrome.
CONCLUSIONS
A comprehensive assessment of publications over the past half century suggests that a multimodal treatment approach that includes surgical resection of thymomas is able to achieve paraneoplastic syndrome resolution in a majority of patients. Onset of new paraneoplastic syndromes after surgery is associated with the recurrence of the first paraneoplastic syndrome, and resolution of paraneoplastic syndrome is associated with improved overall survival.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Neoplasm Recurrence, Local; Paraneoplastic Syndromes; Thymoma; Treatment Outcome; Young Adult
PubMed: 31982129
DOI: 10.1016/j.jtcvs.2019.11.052 -
Archives of Pathology & Laboratory... Jun 2008Evaluation of transcapsular invasion is currently considered very important in the pathologic examination of thymomas. However, recent studies have questioned the... (Meta-Analysis)
Meta-Analysis
CONTEXT
Evaluation of transcapsular invasion is currently considered very important in the pathologic examination of thymomas. However, recent studies have questioned the prognostic value of stratifying thymoma patients into stage I and II disease. Evidence-based pathology promotes the use of systematic reviews of literature and meta-analysis of data to synthesize the results of multiple publications.
OBJECTIVE
To analyze the data in the literature regarding the prognostic importance of transcapsular invasion in thymoma stage I and II.
DESIGN
A systematic review of the English literature was carried out for "thymoma," "stage," and "prognoses." Case reports, case series with fewer than 10 cases, and studies with follow-up periods shorter than 5 years were excluded. Twenty-one retrospective publications reporting the experience with 2451 thymomas were selected for review, including 1419 stage I and 1032 stage II patients. Meta-analysis was performed, and possible publication bias was studied with funnel plots of precision and various statistics.
RESULTS
Meta-analysis yielded no significant differences in disease-free or overall survival rates in stage I and II thymoma patients. Funnel plots of precision and statistical tests such as the Egger regression intercept test showed no significant publication bias.
CONCLUSIONS
The lack of significant differences in the prognosis of patients with stages I and II thymoma suggests that evaluation of transcapsular invasion is of no clinical value in tumors that lack invasion of neighboring organs or the pleura. The data regarding the prognosis of stage II thymoma patients is somewhat heterogenous, with only some individuals having been treated with radiation therapy, suggesting the need for future randomized controlled trials.
Topics: Evidence-Based Medicine; Humans; Prognosis; Thymoma; Thymus Neoplasms
PubMed: 18517274
DOI: 10.5858/2008-132-926-EPATPE