Anti-angiogenic Tyrosine Kinase Inhibitors: occurrence and risk factors of hemoptysis in refractory thyroid cancer

BACKGROUND: Anti-angiogenic Tyrosine Kinase Inhibitors (TKI) are the mainstay of advanced thyroid cancer (TC) treatment. Concern is rising about TKI-related toxicity. OBJECTIVE: to determine the incidence and to investigate the risk factors of hemoptysis in TC patients during TKI treatment. METHODS: We analyzed consecutive TC patients treated with TKI in our center between 2005 and 2013 and performed an independent review of CT-scan images for airway invasion assessment. Occurrence of grade 1-2 or grade 3-5 hemoptysis according to CTCAE version 4.03 and risk factors for hemoptysis were investigated. RESULTS: 140 patients (89 males, median age: 52 years) with medullary (56%), differentiated (33%) and poorly differentiated TC (11%) were enrolled. Thyroidectomy±neck dissection was performed in 123 patients and neck/mediastinum external-beam radiotherapy (EBRT) 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 one). Hemoptysis was associated with presence of airway invasion [p= 0.04], poorly differentiated pathology [0.03], history of therapeutic EBRT [p= 0.003] and thyroidectomy without neck dissection [p= 0.02]. CONCLUSION: Airway invasion, poorly differentiated pathology, therapeutic EBRT and thyroidectomy without neck dissection are associated with and increased risk of hemoptysis in TC patients during anti-angiogenic 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.