title: Pneumothorax as a complication of combination antiangiogenic therapy in children and young adults with refractory/recurrent solid tumors.
abstract: OBJECTIVE
  Antiangiogenic agents show significant antitumor activity against various tumor types. In a study evaluating the combination of sorafenib, bevacizumab, and low-dose cyclophosphamide in children with solid tumors, an unexpectedly high incidence of pneumothorax was observed. We evaluated patient characteristics and risk factors for the development of pneumothorax in patients receiving this therapy.
  
  
  METHODS
  Demographics, clinical course, and radiographic data of 44 patients treated with sorafenib, bevacizumab and cyclophosphamide were reviewed. Risk factors associated with the development of pneumothorax were analyzed.
  
  
  RESULTS
  Pneumothorax likely related to study therapy developed in 11 of 44 (25%) patients of whom 33 had pulmonary abnormalities. Median age of patients was 14.7 years (range, 1.08-24.5). Histologies associated with pneumothorax included rhabdoid tumor, synovial sarcoma, osteosarcoma, Ewing sarcoma, Wilms tumor, and renal cell carcinoma. Cavitation of pulmonary nodules in response to therapy was associated with pneumothorax development (P<0.001). Median time from start of therapy to development of pneumothorax was 5.7 weeks (range, 2.4-31).
  
  
  CONCLUSIONS
  The development of cavitary pulmonary nodules in response to therapy is a risk factor for pneumothorax. As pneumothorax is a potentially life-threatening complication of antiangiogenic therapy in children with solid tumors, its risk needs to be evaluated when considering this therapy.
authors.affiliation: Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Rodrigo B
authors.initials: RB
authors.lastname: Interiano
authors.affiliation: Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Radiology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: M Beth
authors.initials: MB
authors.lastname: McCarville
authors.affiliation: Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Davidoff
authors.affiliation: Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Surgery, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: John
authors.initials: J
authors.lastname: Sandoval
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address: fariba.navid@stjude.org.
authors.forename: Fariba
authors.initials: F
authors.lastname: Navid
mesh_terms: D000293:Adolescent; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D012516:Osteosarcoma / Q000188:drug therapy; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use; D011030:Pneumothorax / Q000139:chemically induced* / Q000175:diagnosis; D012512:Sarcoma, Ewing / Q000188:drug therapy*; D013584:Sarcoma, Synovial / Q000188:drug therapy*; D000077157:Sorafenib; D009396:Wilms Tumor / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D010671:Phenylurea Compounds; D009536:Niacinamide; D000068258:Bevacizumab; D000077157:Sorafenib
keywords: Antiangiogenic; Cavitary pulmonary lesions; Pneumothorax; Solid tumors