Locally unresectable differentiated thyroid cancer: outcomes and perspectives.

PURPOSE: Differentiated thyroid cancer (DTC) patients with an unresectable primary tumor cannot benefit from curative surgery, and radioiodine treatment for locoregional and distant disease is not possible with the thyroid gland still in place. Due to local invasion, these patients cannot be included in clinical trials, so that treatment options are limited. The aim of this study was to describe the characteristics and the prognosis of patients with these locally unresectable DTC. PATIENTS AND METHODS: A retrospective and multicentric analysis of consecutive cases of unresectable DTC diagnosed between 2000 and 2015 was performed. RESULTS: The study population consisted in 22 patients, 13 females (59%); median age: 77 years (range: 52-91). Thyroid tumors were papillary in six, follicular in seven, Hürthle cell in one and poorly differentiated in eight patients. Patients were treated with external beam radiation therapy (EBRT) (57%), locoregional therapy of distant metastases (41%), cytotoxic chemotherapy (38%) and tyrosine kinase inhibitors (TKIs) (33%). TKI treatment resulted in median disease control duration of 7 months with a grade 3-4 toxicity rate of 44%. Only one patient had a total thyroidectomy after neo-adjuvant EBRT. The 1, 3 and 5-year cumulative survival rate was 81%, 27.7% and 21.5%, respectively. The cause of death was DTC in 11 cases (local progression in 7), and to other causes in 7 cases; no patient died from treatment toxicity. CONCLUSIONS: Clinical trials and approved treatments are lacking for unresectable DTC. TKI treatment may allow prolonged disease control with acceptable toxicity.

Thermal-ablation of vertebral metastases prevents adverse events in patients with differentiated thyroid carcinoma.

PURPOSE: To evaluate a strategy that used thermal-ablation of vertebral metastases (VM) to prevent vertebral related events (VRE) in patients with differentiated thyroid cancer (DTC). METHODS: This single center study retrospectively reviewed records and post-operative imaging of all DTC patients treated with thermal-ablation for asymptomatic VMs. Rate of local tumor control at first post-operative imaging, 12 and 24 months after thermal-ablation and rate of VREs at 12 and 24 months among the treated VMs were reported. New VMs that occurred during the follow-up and were not considered for additional thermal-ablation were moniroted and VREs were reported. RESULTS: Thermal-ablation was used to achieve local control of 41 VMs in 28 patients. Median post-treatment follow-up was 22 months [range: 12-80] and the mean delay for first post-operative imaging was 2 months [range: 0.6-7.5]. Local control at first post-operative imaging, 12 and 24 months was achieved in 87.8%, 82.9% and 75.6%, respectively. Among the treated VMs the rates of VRE was 7.3% at 2 years, significantly lower if local control was achieved at first post-operative imaging than if it was not (0% vs 30%, p = 0.011, OR = 0.184 [95%CI = 0.094-0.360]). After thermal-ablation procedures, 19 news VMs occurred in 11 patients (39.2%) with a median interval of 8 months [range 1-26] and remained untreated. Among these untreated VMs, the rate of VREs at 2 years was significantly higher compared to the treated VMs: (36.8% vs. 7.3%, p = 0.008, OR = 0.135, [95%CI = 0.030-0.607]). CONCLUSION: local tumor control of VMs using thermal-ablation decreases the risk of VREs in DTC patients.

Antiangiogenic Tyrosine Kinase Inhibitors: Occurrence and Risk Factors of Hemoptysis in Refractory Thyroid Cancer.

BACKGROUND: Antiangiogenic tyrosine kinase inhibitors (TKIs) 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 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. RESULTS: 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). CONCLUSION: 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.