title: Metabolic response assessment with 18F-FDG-PET/CT is superior to modified RECIST for the evaluation of response to platinum-based doublet chemotherapy in malignant pleural mesothelioma.
abstract: OBJECTIVE
  Efficient monitoring of tumor responsiveness to chemotherapy is essential to mitigate high mortality risks and cytotoxic effects of chemotherapeutics. However, there is no consensus on the most suitable diagnostic technique/parameters for assessing response to chemotherapy in malignant pleural mesothelioma (MPM). We compared the tumor responsiveness of MPM patients as assessed using modified RECIST (mRECIST) criteria and integrated 18F-FDG-PET/CT.
  
  
  METHODS
  Histologically confirmed MPM patients (N=82) who were treated with three cycles of cisplatin and pemetrexed, or carboplatin and pemetrexed, were included. mRECIST and integrated 18F-FDG-PET/CT were used to evaluate MPM tumor response to chemotherapy. Metabolic non-responders were defined as those with a 25% or greater increase in SUVmax compared with the previous value. Time to progression (TTP) and overall survival (OS) were compared between metabolic-responders and non-responders.
  
  
  RESULTS
  After three cycles of chemotherapy, 62(75.6%) of the patients were classified as having SD, 15 (18%) with partial remission (PR), and 5 (6%) with progressive disease (PD), based on mRECIST criteria. The cumulative median OS was 728.0days (95% confidence interval [CI]: 545.9-910.1) and cumulative median TTP was 365.0days (95% CI: 296.9-433.1). For the 82 patients, the disease control rate was 93.9%, whereas the metabolic response rate was only 71.9% (p<0.001). All PD and PR patients were found to be metabolic responders on 18F-FDG-PET/CT; however, among the 62mRECIST SD patients, 18 (29%) were classified as metabolic non-responders. The median TTP for metabolic responders was 13.7 months, while it was 10.0 months for non-responders(p<0.001). Metabolic responders had a trend toward longer OS, although the difference did not reach statistical significance (metabolic responders:33.9 months; non-responders: 21.6 months; p>0.05).
  
  
  CONCLUSIONS
  Several mRECIST-confirmed SD MPM patients may be classified as metabolic non-responders on18F-FDGPET/CT. Metabolic response is significantly correlated with the median TTP, suggesting it should be included in the evaluation of the response to chemotherapy in MPM patients classified as mRECIST SD, to identify non-responders.
authors.affiliation: Department of Respiratory Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kanemura
authors.affiliation: Department of Respiratory Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. Electronic address: kuririn@hyo-med.ac.jp.
authors.forename: Kozo
authors.initials: K
authors.lastname: Kuribayashi
authors.affiliation: Department of Respiratory Medicine, Murakami Memorial Hospital, Asahi University, 3-23 Hashimoto-cho, Gifu 500-8523, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Funaguchi
authors.affiliation: Department of Respiratory Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Shibata
authors.affiliation: Department of Respiratory Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Mikami
authors.affiliation: Department of Radiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Doi
authors.affiliation: Division of Nuclear Medicine and PET center, Department of Radiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kitajima
authors.affiliation: Department of Thoracic Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Seiki
authors.initials: S
authors.lastname: Hasegawa
authors.affiliation: Department of Respiratory Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008654:Mesothelioma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D000068437:Pemetrexed / Q000008:administration & dosage; D010997:Pleural Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D000072078:Positron Emission Tomography Computed Tomography; D019275:Radiopharmaceuticals / Q000378:metabolism*; D066066:Response Evaluation Criteria in Solid Tumors; D016896:Treatment Outcome
chemical_list: D019275:Radiopharmaceuticals; D000068437:Pemetrexed; D019788:Fluorodeoxyglucose F18; D002945:Cisplatin
keywords: Chemotherapy; Malignant pleural mesothelioma; Metabolic response; mRECIST