title: Systematic review of response rates of sarcomatoid malignant pleural mesotheliomas in clinical trials.
abstract: BACKGROUND
  Malignant pleural mesothelioma is an almost universally fatal malignancy primarily related to asbestos exposure. Based on the differences in immunologic markers and gene expression between histologic subtypes of mesothelioma, and our clinical impression that response rates vary by histology, we decided to examine the reported response rates of mesothelioma subtypes.
  
  
  OBJECTIVE
  Our objective was to compare the response rates of sarcomatoid mesotheliomas to the overall response rates in published clinical trials.
  
  
  METHODS
  We searched PubMed for "mesothelioma" with the clinical trials filter selected. We included articles published between January 1, 2000 and March 20, 2014 in which subjects received first or second line systemic therapy for malignant pleural mesothelioma. Studies investigating multi-modality therapy including surgery were excluded. Response rates [including 95% confidence intervals (95% CI)] were estimated for the entire patient cohort and then separately for subjects with sarcomatoid tumors.
  
  
  RESULTS
  We reviewed 544 publications of which 41 trials met our inclusion criteria. Eleven of these trials did not include patients with sarcomatoid mesothelioma (27% of eligible studies). The remaining 30 publications included 1475 subjects, 1011 with epithelioid tumors (68.5%), 203 with biphasic tumors (13.8%), 137 with sarcomatoid tumors (9.3%) and 124 with unknown subtypes (8.4%). In total, there were 323 responses (21.9%, complete and partial responses, 95% CI: 16.3, 28.8) to systemic therapy across all histological subtypes. In patients with sarcomatoid tumors (n=137) 19 responses were observed. This accounted for 5.9% of all responses and yields a 13.9% (95% CI: 8.6, 21.6) response rate for patients with sarcomatoid tumors. Multiple biases likely affected this systematic review.
  
  
  CONCLUSIONS
  Response rates for different histological subtypes of malignant pleural mesothelioma are infrequently reported. Partial and complete responses to systemic therapies appear to be less common among patients with sarcomatoid tumors.
authors.affiliation: Department of Oncology, Division of Medical Oncology, Mayo Clinic, Rochester, MN, United States. Electronic address: mansfield.aaron@mayo.edu.
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Mansfield
authors.affiliation: Department of Cancer Biostatistics, Levine Cancer Institute Carolinas HealthCare System, Charlotte, NC, United States.
authors.forename: James T
authors.initials: JT
authors.lastname: Symanowski
authors.affiliation: Department of Internal Medicine, Division of Pulmonary Medicine, Mayo Clinic, Rochester, MN, United States.
authors.forename: Tobias
authors.initials: T
authors.lastname: Peikert
mesh_terms: D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D008654:Mesothelioma / Q000628:therapy*; D000086002:Mesothelioma, Malignant; D010997:Pleural Neoplasms / Q000628:therapy*; D016896:Treatment Outcome
keywords: Epithelioid; Mesothelioma; Response rates; Sarcomatoid; Systematic review; Tumor