title: Drug-Related Pneumonitis During Mammalian Target of Rapamycin Inhibitor Therapy: Radiographic Pattern-Based Approach in Waldenström Macroglobulinemia as a Paradigm.
abstract: BACKGROUND
  This study determined the frequency of drug-related pneumonitis during mammalian target of rapamycin (mTOR) inhibitor therapy in Waldenström macroglobulinemia patients and investigated the imaging characteristics and radiographic patterns of pneumonitis.
  
  
  METHODS
  A total of 40 patients (23 men, 17 women; 43-84 years old) with Waldenström macroglobulinemia treated in 2 trials of the mTOR inhibitor everolimus were retrospectively studied. Chest computed tomography (CT) scans during therapy were reviewed for abnormalities suspicious for drug-related pneumonitis by the consensus of three radiologists, evaluating the extent, distributions, and specific findings. The radiographic patterns of pneumonitis were classified using the American Thoracic Society/European Respiratory Society classification of interstitial pneumonia.
  
  
  RESULTS
  Drug-related pneumonitis was noted in 23 patients (58%). The median time from the initiation of therapy to the onset of pneumonitis was 5.7 months. Lower lungs were involved in all 23 patients, with a higher extent than in the other zones (p < .001). The distribution was peripheral and lower in 11 patients (48%) and mixed and multifocal in 10 (44%). The findings were bilateral in 20 patients (87%). Ground glass opacities (GGOs) and reticular opacities were present in all 23 patients, with consolidation in 12, traction bronchiectasis in 2, and centrilobular nodularity in 1. The pattern of pneumonitis was classified as cryptogenic organizing pneumonia (COP) in 16 (70%) and nonspecific interstitial pneumonia (NSIP) in 7 (30%), with overlapping features of COP and NSIP in 7 patients.
  
  
  CONCLUSIONS
  Drug-related pneumonitis was noted on CT in 58% of Waldenström macroglobulinemia patients treated with mTOR inhibitor therapy. Most common findings were bilateral GGOs and reticular opacities, with or without consolidation, in peripheral and lower lungs, demonstrating COP and NSIP patterns.
  
  
  CONCLUSIONS
  The present study has demonstrated that drug-related pneumonitis during mammalian target of rapamycin (mTOR) inhibitor therapy is highly frequent, occurring in 58% of patients with Waldenström macroglobulinemia. The radiographic patterns of pneumonitis demonstrated cryptogenic organizing pneumonia and nonspecific interstitial pneumonia patterns, with overlapping features in 30% of the patients. The present study describes an initial attempt of a radiographic pattern-based approach to drug-related pneumonitis in the era of molecular targeting therapy, with a cohort of patients with Waldenström macroglobulinemia receiving mTOR inhibitor therapy as a paradigm, which might contribute to further understanding and in-depth interpretation of lung toxicity during novel cancer therapy.
authors.affiliation: Departments of Radiology and Medical Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA Mizuki_Nishino@dfci.harvard.edu.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Nishino
authors.affiliation: Departments of Radiology and Medical Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Erica N
authors.initials: EN
authors.lastname: Boswell
authors.affiliation: Departments of Radiology and Medical Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Hatabu
authors.affiliation: Departments of Radiology and Medical Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Ghobrial
authors.affiliation: Departments of Radiology and Medical Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Nikhil H
authors.initials: NH
authors.lastname: Ramaiya
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000139:chemically induced* / Q000000981:diagnostic imaging*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011859:Radiography; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects* / Q000627:therapeutic use; D008258:Waldenstrom Macroglobulinemia / Q000000981:diagnostic imaging* / Q000188:drug therapy*
chemical_list: D047428:Protein Kinase Inhibitors; D020123:Sirolimus
keywords: Computed tomography; Drug toxicity; Mammalian target of rapamycin inhibitor; Pneumonitis; Waldenström macroglobulinemia; mTOR