Time Until Partial Response in Metastatic Adrenocortical Carcinoma Long-Term Survivors

A partial response (PR) has been proposed as a surrogate for overall survival in advanced adrenocortical carcinoma (ACC). The primary endpoint of the study was to characterize the time until a PR in patients with metastatic ACC treated with a standard therapy is achieved. Long-term survivors were selected to allow evaluation of delayed tumor response to mitotane. Records from patients with metastatic ACC that survived for > 24 months were retrieved. Tumor response was analyzed according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Time until a tumor response, after treatment initiation or therapeutic plasma mitotane level, was analyzed. Sixty-eight patients were analyzed. The first-line systemic therapy was mitotane as a monotherapy (M) (n = 57) or cytotoxic polychemotherapy plus/minus mitotane (PC ± M) (n = 11). The second-line therapy was M (n = 2) or PC ± M (n = 41). Thirty-two PRs occurred in 30/68 patients (44.1%): this was obtained for 13 (40.6%) during M and during PC ± M for 19/32 responders (59.4%). PRs were observed within 6 months of starting M or PC ± M in 76.9 and 94.7% of responses, respectively, within 6 months of therapeutic plasma mitotane being first observed in 88.9% of responses with M and in 53.3% of responses with PC ± M. All PRs (but one) occurred within 1 year after initiating treatment. To conclude, Most patients with metastatic ACC and long survival times had PRs within the first 6 months of standard systemic therapy, and almost all within the first year. The absence of response after that period could be considered as a treatment failure. Maintenance of mitotane therapy in non-responders after 1 year should be questioned in future randomized trials

Treatment of refractory thyroid cancer

Distant metastases from thyroid cancer of follicular origin are uncommon. Treatment includes levothyroxine administration, focal treatment modalities with surgery, external radiation therapy and thermal ablation, and radioiodine in patients with uptake of 131I in their metastases. Two-thirds of distant metastases become refractory to radioiodine at some point, and when there is a significant tumor burden and documented progression on imaging, a treatment with a kinase inhibitor may provide benefits

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