title: Drug-related pneumonitis during mammalian target of rapamycin inhibitor therapy in patients with neuroendocrine tumors: a radiographic pattern-based approach.
abstract: OBJECTIVE
  The purpose of this study was to investigate the incidence of drug-related pneumonitis during mammalian target of rapamycin (mTOR) inhibitor therapy in patients with neuroendocrine tumours (NET) and characterise radiographic patterns of pneumonitis.
  
  
  METHODS
  Sixty-six patients (39 males, 27 females, age: 22-79 years) with advanced NET treated with mTOR inhibitor, everolimus, were retrospectively studied. Chest computed tomography scans during therapy were reviewed for abnormalities suspicious for drug-related pneumonitis by an independent review of two radiologists. Extent, distributions, and specific findings were evaluated in cases positive for pneumonitis. Radiographic patterns of pneumonitis were classified using the American Thoracic Society/European Respiratory Society classification of interstitial pneumonia.
  
  
  RESULTS
  Drug-related pneumonitis was radiographically detected in 14 patients (21%). Time from the initiation of therapy to pneumonitis was within 6 months of therapy in 10 patients (71%), while it ranged from 1.0 to 27.7 months. Pneumonitis was more common in patients who had never smoked (p=0.03). Lower lungs were more extensively involved than upper and middle lungs. Peripheral and lower distributions were most common (n=8), followed by peripheral and multifocal distributions (n=3). Ground glass and reticular opacities were present in all cases, with consolidation in eight cases. The radiographic pattern of pneumonitis was classified as cryptogenic organising pneumonia (COP) pattern in eight patients, non-specific interstitial pneumonia (NSIP) pattern in five, and hypersensitivity pneumonitis pattern in one patient.
  
  
  CONCLUSIONS
  Drug-related pneumonitis was noted in 21% of the advanced NET patients treated with everolimus. Radiographic pattern of pneumonitis was most commonly COP pattern, followed by NSIP pattern.
authors.affiliation: Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA, 02215, USA. Electronic address: Mizuki_Nishino@DFCI.HARVARD.EDU.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Nishino
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA, 02215, USA; Department of Medicine, Brigham and Women's Hospital, 75 Francis St., Boston, MA, 02215, USA.
authors.forename: Lauren K
authors.initials: LK
authors.lastname: Brais
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA, 02215, USA; Department of Medicine, Brigham and Women's Hospital, 75 Francis St., Boston, MA, 02215, USA.
authors.forename: Nichole V
authors.initials: NV
authors.lastname: Brooks
authors.affiliation: Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA, 02215, USA.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Hatabu
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA, 02215, USA; Department of Medicine, Brigham and Women's Hospital, 75 Francis St., Boston, MA, 02215, USA.
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Kulke
authors.affiliation: Department of Radiology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA, 02215, USA.
authors.forename: Nikhil H
authors.initials: NH
authors.lastname: Ramaiya
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000068338:Everolimus / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy*; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy; D011014:Pneumonia / Q000139:chemically induced* / Q000473:pathology; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus
keywords: Computed tomography; Drug toxicity; Neuroendocrine tumours; Pneumonitis; mTOR inhibitor