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Acta Oncologica (Stockholm, Sweden) Feb 2018advanced-stage non-small cell lung cancer (NSCLC) is characterized by having limited treatment options and thus a poor prognosis. However, new treatment options, in the... (Review)
Review
BACKGROUND
advanced-stage non-small cell lung cancer (NSCLC) is characterized by having limited treatment options and thus a poor prognosis. However, new treatment options, in the form of targeted agents (TA), have emerged during recent years. This systematic review aims to provide an overview of the accessible literature in PubMed evaluating TA used on NSCLC patients, and the resulting survival outcomes.
METHOD
this systematic literature review was conducted by reviewing all relevant literature in PubMed. Six separate searches were performed: Three searches where controlled entry terms were used and three free text searches. Furthermore, other relevant publications were included manually. A total of seventy-two studies met the search criteria and were thus further analyzed and evaluated.
RESULTS
In the included studies, various TAs and their effect on different molecular targets have been evaluated. Clinical responses vary considerably among the different genetic aberrations. The majority of studies evaluated TA for epidermal growth factor receptor (EGFR) mutations and TA for echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) rearrangements. Studies regarding the use of TA for Rat sarcoma (RAS), rapidly accelerated fibrosarcoma (RAF), ROS proto-oncogene 1 (ROS1) rearrangement, Receptor tyrosine-protein kinase erbB-2 (ERBB2), Phosphatidylinositol 3-kinase (PIK3CA)/v-akt murine thymoma viral oncogene homolog; protein kinase B(AKT)/Phosphatase and tensin homolog deleted on chromosome 10(PTEN), The mammalian target of rapamycin (mTOR), and Mesenchymal-epithelial transition factor (MET) were included as well. In general, studies comparing treatment outcomes in EGFR-mutated patients and EML4-ALK (ALK) rearranged patients after use of either TA or standard chemotherapy, present significant better results after TA.
CONCLUSIONS
This systematic review provides an overview of available literature in PubMed regarding NSCLC and TA. Included studies point toward that TA appears to be a promising therapeutic tool in treating NSCLC patients and use of TA is expected to result in improved treatment outcomes.
Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Molecular Targeted Therapy; Proto-Oncogene Mas
PubMed: 29172833
DOI: 10.1080/0284186X.2017.1404634 -
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 -
European Journal of Cardio-thoracic... Jul 2015Thymectomy has become an increasingly popular procedure for myasthenia gravis. Knowledge of factors associated with a good outcome (remission) or those most likely to... (Review)
Review
Thymectomy has become an increasingly popular procedure for myasthenia gravis. Knowledge of factors associated with a good outcome (remission) or those most likely to benefit from surgery can help clinical decision-making. A systematic review search was conducted in Medline and Embase for English language studies from 1985 through to February 2014. Studies which evaluated variables associated with, or predictive of, remission in adult (≥18 years) myasthenic patients after thymectomy and using multivariable regression models were included. Statistical pooling was not appropriate due to methodological heterogeneity. From 128 potentially relevant studies, 18 reports of 19 studies met the inclusion criteria. Preoperative mild disease classification (i.e. studies reported this variable as Osserman classification 1, 2A or MGFA I-II) showed the most consistent association with remission. Evidence for several other prognostic factors was inconclusive, or no evidence was found. Gender, age and absence of thymoma (or hyperplasia) were not associated with remission following thymectomy. Patients with mild disease preoperatively may have a better chance of remission of MG after thymectomy.
Topics: Adult; Humans; Myasthenia Gravis; Prognosis; Remission Induction; Thymectomy; Treatment Outcome
PubMed: 25108896
DOI: 10.1093/ejcts/ezu309 -
Tumori 2012In the 90s, the introduction of positron emission tomography (PET) represented a milestone in the staging of thoracic tumors. In the last 10 years, PET scan has been... (Review)
Review
AIMS AND BACKGROUND
In the 90s, the introduction of positron emission tomography (PET) represented a milestone in the staging of thoracic tumors. In the last 10 years, PET scan has been widely adopted in thoracic oncology, showing high accuracy in diagnosis and staging and with promising issues in defining prognosis. The aim of this systematic review was to focus on the results and pitfalls of PET scan use in the modern management of chest tumors.
METHODS AND STUDY DESIGN
The literature search was performed on May 2010 in PubMed, Embase, and Cochrane according to PRISMA protocol. The search was restricted to publications in English, using in the same string the word "PET" with 9 different chest tumors; results were then filtered by eliminating technical articles, focusing only on papers in which surgery was considered as a potential diagnostic or therapeutic tool. From 6600 papers initially selected, 99 manuscripts were fully analyzed.
RESULTS
Glucose uptake is a metabolic marker useful in the diagnosis and staging of chest tumors. In lung cancer screening, standard uptake value is helpful in defining the risk of malignancy of isolated pulmonary nodules. The addition of PET scan to conventional staging increases detection of nodal and distant metastases in lung cancer, esophageal cancer and malignant mesothelioma. In thymoma, a close relationship between standard uptake value, histology, and Masaoka stage has been advocated. This link between glucose uptake and prognosis suggests that PET translates biological tumor behavior into clinically detectable findings.
CONCLUSIONS
PET scan has a crucial role in thoracic oncology due to its impact on diagnosis, staging and prognosis. PET scan expresses the biological behavior of tumors, opening interesting perspectives in chest tumor management and improving detection and stage grouping in lung cancer. It anticipates the diagnosis in long-incubating diseases such as mesothelioma and increases biological knowledge of rare diseases, such as thymoma and other mediastinal tumors.
Topics: Early Detection of Cancer; Esophageal Neoplasms; Fluorodeoxyglucose F18; Humans; Lung Neoplasms; Mediastinal Neoplasms; Mesothelioma; Octreotide; Organometallic Compounds; Pleural Neoplasms; Positron-Emission Tomography; Predictive Value of Tests; Prognosis; Radiopharmaceuticals; Solitary Pulmonary Nodule; Thoracic Neoplasms; Thymoma; Thymus Neoplasms
PubMed: 22677982
DOI: 10.1177/030089161209800201 -
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 -
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 -
Lung Cancer (Amsterdam, Netherlands) Jul 2021Pure red cell aplasia (PRCA) is a rare paraneoplastic syndrome observed in 2-5 % of thymomas. Literature reports great variability in its management. Based on an... (Review)
Review
Pure red cell aplasia (PRCA) is a rare paraneoplastic syndrome observed in 2-5 % of thymomas. Literature reports great variability in its management. Based on an illustrative clinical case, we present a systematic literature review whose main objective is to evaluate the therapeutic management of PRCA. The literature search was performed based on the PICO method in the Medline and Scopus databases. The reference clinical case concerns a 51-year-old woman with stage IVa thymoma. After initial response to chemotherapy, a locoregional progression occurred with PRCA development that responded favorably under second line chemotherapy. The patient finally died in a context of bicytopenia with febrile neutropenia. The systematic review covers 135 articles published between 1950 and 2019. Thymectomy alone or in combination with other therapies showed a 31 % complete remission (CR) rate for PRCA of, whereas none was reported with anti-tumor treatments without thymectomy. Among immunomodulatory therapies, cyclosporin gave the highest percentage of CR (74 %). Finally, the combination of thymectomy and immunomodulatory treatments showed a CR rate of 45 %. Thymectomy appeared to be the most effective anti-tumor treatment for PRCA. Immunomodulatory therapies, particularly cyclosporine, are shown effective, but the risk of infectious complications must be considered. The optimal place of anti-tumor and immunomodulatory therapies against PRCA has yet to be determined.
Topics: Female; Humans; Lung Neoplasms; Middle Aged; Red-Cell Aplasia, Pure; Thymectomy; Thymoma; Thymus Neoplasms
PubMed: 34049719
DOI: 10.1016/j.lungcan.2021.05.010 -
Radiotherapy and Oncology : Journal of... Jun 2009With dose escalation and increasing use of concurrent chemoradiotherapy, radiation esophagitis (RE) remains a common treatment-limiting acute side effect in the... (Review)
Review
PURPOSE
With dose escalation and increasing use of concurrent chemoradiotherapy, radiation esophagitis (RE) remains a common treatment-limiting acute side effect in the treatment of thoracic malignancies. The advent of 3DCT planning has enabled investigators to study esophageal dose-volume histogram (DVH) parameters as predictors of RE. The purpose of this study was to assess published dosimetric parameters and toxicity data systematically in order to define reproducible predictors of RE, both for potential clinical use, and to provide recommendations for future research in the field.
MATERIALS AND METHODS
We performed a systematic literature review of published studies addressing RE in the treatment of lung cancer and thymoma. Our search strategy included a variety of electronic medical databases, textbooks and bibliographies. Both prospective and retrospective clinical studies were included. Information relating to the relationship among measured dosimetric parameters, patient demographics, tumor characteristics, chemotherapy and RE was extracted and analyzed.
RESULTS
Eighteen published studies were suitable for analysis. Eleven of these assessed acute RE, while the remainder assessed both acute and chronic RE together. Heterogeneity of esophageal contouring practices, individual differences in information reporting and variability of RE outcome definitions were assessed. Well-described clinical and logistic modeling directly related V(35Gy), V(60Gy) and SA(55Gy) to clinically significant RE.
CONCLUSIONS
Several reproducible dosimetric parameters exist in the literature, and these may be potentially relevant in the prediction of RE in the radiotherapy of thoracic malignancies. Further clarification of the predictive relationship between such standardized dosimetric parameters and observed RE outcomes is essential to develop efficient radiation treatment planning in locally advanced NSCLC in the modern concurrent chemotherapy and image-guided IMRT era.
Topics: Dose-Response Relationship, Radiation; Esophagitis; Humans; Lung Neoplasms; Models, Statistical; Radiation Injuries; Radiotherapy Dosage
PubMed: 18950881
DOI: 10.1016/j.radonc.2008.09.010 -
International Journal of Radiation... Apr 2016To evaluate the survival impact of postoperative radiation therapy (PORT) in stage II to IV thymomas, using systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To evaluate the survival impact of postoperative radiation therapy (PORT) in stage II to IV thymomas, using systematic review and meta-analysis.
METHODS AND MATERIALS
A database search was conducted with EMBASE, PubMed, Web of Science, Cochrane Library, and Ovid from inception to August 2015. Thymic carcinomas were excluded, and studies comparing overall survival (OS) with and without PORT in thymomas were included. The hazard ratios (HRs) of OS were extracted, and a random-effects model was used in the pooled analysis.
RESULTS
Seven retrospective series with a total of 1724 patients were included and analyzed. Almost all of the patients underwent macroscopically complete resection, and thymoma histology was confirmed by the World Health Organization criteria. In the overall analysis of stage II to IV thymomas, OS was not altered with the receipt of PORT (HR 0.79, 95% confidence interval [CI] 0.58-1.08). Although PORT was not associated with survival difference in Masaoka stage II disease (HR 1.45, 95% CI 0.83-2.55), improved OS was observed with the addition of PORT in the discrete pooled analysis of stage III to IV (HR 0.63, 95% CI 0.40-0.99). Significant heterogeneity and publication bias were not found in the analyses.
CONCLUSIONS
From the present meta-analysis of sole primary thymomas, we suggest the potential OS benefit of PORT in locally advanced tumors with macroscopically complete resection, but not in stage II disease. Further investigations with sufficient survival data are needed to establish detailed treatment indications.
Topics: Humans; Neoplasm Staging; Observational Studies as Topic; Postoperative Care; Prognosis; Publication Bias; Radiotherapy, Adjuvant; Retrospective Studies; Survival Analysis; Thymoma; Thymus Neoplasms
PubMed: 27026316
DOI: 10.1016/j.ijrobp.2016.01.007 -
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