title: Aerodigestive fistula formation as a rare side effect of antiangiogenic tyrosine kinase inhibitor therapy for thyroid cancer.
abstract: BACKGROUND
  In the past decade, targeted therapy with antiangiogenic drugs has become standard of care for most types of metastatic, progressive thyroid cancer. While these drugs were thought initially to be less toxic than traditional chemotherapy, they can have rare but serious and fatal toxicities. Once such toxicity that has been reported in other tumor types is upper airway fistula formation, which can be life-threatening.
  
  
  CONCLUSIONS
  Here, we describe three patients treated with antiangiogenic tyrosine kinase inhibitors at two academic institutions who developed aerodigestive fistula. All three patients had risk factors for fistula formation, which included external beam radiation and/or large tumor with invasion of the tracheal wall.
  
  
  CONCLUSIONS
  Fistula formation is a known but rare side effect of antiangiogenic tyrosine kinase inhibitors. Knowledge of the risk factors that may predispose thyroid cancer patients to this serious adverse event is vital prior to prescribing antiangiogenics. Particular caution should be observed when using these drugs in patients undergoing radiation therapy or surgery, or in patients whose tumor is invading vital structures of the neck, as they may be at higher risk of developing this rare complication. In these patients, antiangiogenic tyrosine kinase inhibitors should be used cautiously, patients should be aware of the risk, and physicians should monitor patients for symptoms of fistula.
authors.affiliation: 1 Department of Internal Medicine, University of Texas Health Science Center at Houston , Houston, Texas.
authors.forename: Dean P
authors.initials: DP
authors.lastname: Blevins
authors.forename: Ramona
authors.initials: R
authors.lastname: Dadu
authors.forename: Mimi
authors.initials: M
authors.lastname: Hu
authors.forename: Christina
authors.initials: C
authors.lastname: Baik
authors.forename: Diwakar
authors.initials: D
authors.lastname: Balachandran
authors.forename: William
authors.initials: W
authors.lastname: Ross
authors.forename: Brandon
authors.initials: B
authors.lastname: Gunn
authors.forename: Maria E
authors.initials: ME
authors.lastname: Cabanillas
mesh_terms: D000046:Academic Medical Centers; D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000813:Anilides / Q000009:adverse effects / Q000627:therapeutic use; D003131:Combined Modality Therapy / Q000009:adverse effects; D015507:Drugs, Investigational / Q000009:adverse effects / Q000627:therapeutic use; D004937:Esophageal Fistula / Q000139:chemically induced* / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology; D017809:Fatal Outcome; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D037981:Neck Dissection / Q000009:adverse effects; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use; D011183:Postoperative Complications / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use; D011804:Quinolines / Q000009:adverse effects / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D016156:Respiratory Tract Fistula / Q000139:chemically induced* / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology; D012307:Risk Factors; D000077210:Sunitinib; D013781:Texas / Q000453:epidemiology; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D013965:Thyroidectomy / Q000009:adverse effects; D014138:Tracheoesophageal Fistula / Q000139:chemically induced* / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology
chemical_list: D020533:Angiogenesis Inhibitors; D000813:Anilides; D015507:Drugs, Investigational; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011758:Pyrroles; D011804:Quinolines; C558660:cabozantinib; D020794:Receptor Protein-Tyrosine Kinases; C531958:lenvatinib; D000077210:Sunitinib