title: Antiangiogenic Tyrosine Kinase Inhibitors: Occurrence and Risk Factors of Hemoptysis in Refractory Thyroid Cancer.
abstract: Antiangiogenic tyrosine kinase inhibitors (TKIs) are the mainstay of advanced thyroid cancer (TC) treatment. Concern is rising about TKI-related toxicity.
  
  
  
  To determine the incidence and to investigate the risk factors of hemoptysis in TC patients during TKI treatment.
  
  
  
  We analyzed consecutive TC patients treated with TKI in our center between 2005 and 2013 and performed an independent review of computed tomography scan images for airway invasion assessment. Occurrence of grade 1-2 or grade 3-5 hemoptysis according to Common Terminology Criteria for Adverse Events version 4.03 and risk factors for hemoptysis were investigated.
  
  
  
  A total of 140 patients (89 males; median age, 52 y) with medullary (56%), differentiated (33%), and poorly differentiated (11%) TC were enrolled. Thyroidectomy±neck dissection was performed in 123 patients and neck/mediastinum external-beam radiotherapy in 41 (32% with therapeutic purpose and 68% with adjuvant purpose). Patients received from 1 to 4 lines of TKI (median 1). Median follow-up was 24 months. Airway invasion was found in 65 (46%) cases. Hemoptysis occurred in 9 patients: grade 1-2 in 7 cases (5%) and grade 3-5 in 2 (1.4%) cases (fatal in 1). Hemoptysis was associated with presence of airway invasion (P = .04), poorly differentiated pathology (P = .03), history of therapeutic external-beam radiotherapy (P = .003), and thyroidectomy without neck dissection (P = .02).
  
  
  
  Airway invasion, poorly differentiated pathology, therapeutic external-beam radiotherapy, and thyroidectomy without neck dissection are associated with and increased risk of hemoptysis in TC patients during antiangiogenic TKI treatment. Further research is needed to confirm this data and to sort out interactions between these risk factors. A careful assessment of airway invasion is mandatory before TKI introduction.
authors.affiliation: Departments of Nuclear Medicine and Endocrine Oncology (L.L., S.I., A.B., M.T., D.D., M.S., E.B., S.L.), Radiology (M.D., F.B.), Biostatistics and Epidemiology (I.B.), Medical Biology and Pathology (A.A.G.), Surgery (D.H.), and Department of Radiotherapy (P.B.), Gustave Roussy and University Paris Saclay, 94805 Villejuif, France.
authors.forename: Livia
authors.initials: L
authors.lastname: Lamartina
authors.affiliation: Departments of Nuclear Medicine and Endocrine Oncology (L.L., S.I., A.B., M.T., D.D., M.S., E.B., S.L.), Radiology (M.D., F.B.), Biostatistics and Epidemiology (I.B.), Medical Biology and Pathology (A.A.G.), Surgery (D.H.), and Department of Radiotherapy (P.B.), Gustave Roussy and University Paris Saclay, 94805 Villejuif, France.
authors.forename: S
authors.initials: S
authors.lastname: Ippolito
authors.affiliation: Departments of Nuclear Medicine and Endocrine Oncology (L.L., S.I., A.B., M.T., D.D., M.S., E.B., S.L.), Radiology (M.D., F.B.), Biostatistics and Epidemiology (I.B.), Medical Biology and Pathology (A.A.G.), Surgery (D.H.), and Department of Radiotherapy (P.B.), Gustave Roussy and University Paris Saclay, 94805 Villejuif, France.
authors.forename: M
authors.initials: M
authors.lastname: Danis
authors.affiliation: Departments of Nuclear Medicine and Endocrine Oncology (L.L., S.I., A.B., M.T., D.D., M.S., E.B., S.L.), Radiology (M.D., F.B.), Biostatistics and Epidemiology (I.B.), Medical Biology and Pathology (A.A.G.), Surgery (D.H.), and Department of Radiotherapy (P.B.), Gustave Roussy and University Paris Saclay, 94805 Villejuif, France.
authors.forename: F
authors.initials: F
authors.lastname: Bidault
authors.affiliation: Departments of Nuclear Medicine and Endocrine Oncology (L.L., S.I., A.B., M.T., D.D., M.S., E.B., S.L.), Radiology (M.D., F.B.), Biostatistics and Epidemiology (I.B.), Medical Biology and Pathology (A.A.G.), Surgery (D.H.), and Department of Radiotherapy (P.B.), Gustave Roussy and University Paris Saclay, 94805 Villejuif, France.
authors.forename: I
authors.initials: I
authors.lastname: Borget
authors.affiliation: Departments of Nuclear Medicine and Endocrine Oncology (L.L., S.I., A.B., M.T., D.D., M.S., E.B., S.L.), Radiology (M.D., F.B.), Biostatistics and Epidemiology (I.B.), Medical Biology and Pathology (A.A.G.), Surgery (D.H.), and Department of Radiotherapy (P.B.), Gustave Roussy and University Paris Saclay, 94805 Villejuif, France.
authors.forename: A
authors.initials: A
authors.lastname: Berdelou
authors.affiliation: Departments of Nuclear Medicine and Endocrine Oncology (L.L., S.I., A.B., M.T., D.D., M.S., E.B., S.L.), Radiology (M.D., F.B.), Biostatistics and Epidemiology (I.B.), Medical Biology and Pathology (A.A.G.), Surgery (D.H.), and Department of Radiotherapy (P.B.), Gustave Roussy and University Paris Saclay, 94805 Villejuif, France.
authors.forename: A
authors.initials: A
authors.lastname: Al Ghuzlan
authors.affiliation: Departments of Nuclear Medicine and Endocrine Oncology (L.L., S.I., A.B., M.T., D.D., M.S., E.B., S.L.), Radiology (M.D., F.B.), Biostatistics and Epidemiology (I.B.), Medical Biology and Pathology (A.A.G.), Surgery (D.H.), and Department of Radiotherapy (P.B.), Gustave Roussy and University Paris Saclay, 94805 Villejuif, France.
authors.forename: D
authors.initials: D
authors.lastname: Hartl
authors.affiliation: Departments of Nuclear Medicine and Endocrine Oncology (L.L., S.I., A.B., M.T., D.D., M.S., E.B., S.L.), Radiology (M.D., F.B.), Biostatistics and Epidemiology (I.B.), Medical Biology and Pathology (A.A.G.), Surgery (D.H.), and Department of Radiotherapy (P.B.), Gustave Roussy and University Paris Saclay, 94805 Villejuif, France.
authors.forename: P
authors.initials: P
authors.lastname: Blanchard
authors.affiliation: Departments of Nuclear Medicine and Endocrine Oncology (L.L., S.I., A.B., M.T., D.D., M.S., E.B., S.L.), Radiology (M.D., F.B.), Biostatistics and Epidemiology (I.B.), Medical Biology and Pathology (A.A.G.), Surgery (D.H.), and Department of Radiotherapy (P.B.), Gustave Roussy and University Paris Saclay, 94805 Villejuif, France.
authors.forename: M
authors.initials: M
authors.lastname: Terroir
authors.affiliation: Departments of Nuclear Medicine and Endocrine Oncology (L.L., S.I., A.B., M.T., D.D., M.S., E.B., S.L.), Radiology (M.D., F.B.), Biostatistics and Epidemiology (I.B.), Medical Biology and Pathology (A.A.G.), Surgery (D.H.), and Department of Radiotherapy (P.B.), Gustave Roussy and University Paris Saclay, 94805 Villejuif, France.
authors.forename: D
authors.initials: D
authors.lastname: Deandreis
authors.affiliation: Departments of Nuclear Medicine and Endocrine Oncology (L.L., S.I., A.B., M.T., D.D., M.S., E.B., S.L.), Radiology (M.D., F.B.), Biostatistics and Epidemiology (I.B.), Medical Biology and Pathology (A.A.G.), Surgery (D.H.), and Department of Radiotherapy (P.B.), Gustave Roussy and University Paris Saclay, 94805 Villejuif, France.
authors.forename: M
authors.initials: M
authors.lastname: Schlumberger
authors.affiliation: Departments of Nuclear Medicine and Endocrine Oncology (L.L., S.I., A.B., M.T., D.D., M.S., E.B., S.L.), Radiology (M.D., F.B.), Biostatistics and Epidemiology (I.B.), Medical Biology and Pathology (A.A.G.), Surgery (D.H.), and Department of Radiotherapy (P.B.), Gustave Roussy and University Paris Saclay, 94805 Villejuif, France.
authors.forename: E
authors.initials: E
authors.lastname: Baudin
authors.affiliation: Departments of Nuclear Medicine and Endocrine Oncology (L.L., S.I., A.B., M.T., D.D., M.S., E.B., S.L.), Radiology (M.D., F.B.), Biostatistics and Epidemiology (I.B.), Medical Biology and Pathology (A.A.G.), Surgery (D.H.), and Department of Radiotherapy (P.B.), Gustave Roussy and University Paris Saclay, 94805 Villejuif, France.
authors.forename: S
authors.initials: S
authors.lastname: Leboulleux
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006469:Hemoptysis / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D018714:Radiotherapy, Adjuvant; D012307:Risk Factors; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000532:radiotherapy / Q000601:surgery; D013965:Thyroidectomy; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases