No abstract

It has already been shown that remnant ablation in patients with thyroid cancer and lymph node (LN) metastases has similar results when patients are prepared after recombinant human thyroid-stimulating hormone (rhTSH) therapy or thyroid hormone withdrawal (THW). Due to the current changes in the risk-of-recurrence classifications, we decided to evaluate the initial response to treatment and the outcome at medium-term follow-up in 40 consecutive patients with clinically relevant lymph nodes who received radioiodine remnant ablation after rhTSH therapy (n = 20) or THW (n = 20). Each patient received either 100 or 150 mCi 131-I for ablation based on TNM status, and the mean amounts of 131-I used in the 2 groups were not significantly different. An excellent response to treatment was observed in 45% of the patients prepared after rhTSH therapy compared to 20% of those prepared after THW (p = 0.08). Three patients (2 in the THW group and 1 in the rhTSH group) who had N1a in the initial surgery presented with structural persistence as an initial response to treatment. One patient in the THW group had a follow-up of the persistent disease with no surgical treatment, and 2 others received a lateral LN dissection. When the status at final follow-up was considered (median follow-up 3.3 years, range 3-4.2), 60% of the patients ablated after rhTSH therapy were considered with no evidence of disease, compared to 30% of those who underwent THW. The frequency of structural persistence (metastatic LN) was similar in the 2 groups (15 vs. 25%), and the distribution of the responses at final follow-up was not statistically significantly different (p = 0.12). We conclude that preparation after rhTSH therapy seems to be as effective as after THW for patients with clinically relevant LN metastases.

The cumulative evidence over the past decades has shown that the incidence of differentiated thyroid carcinoma (DTC) has exponentially increased. Approximately 10% of patients with DTC exhibit recurrent or metastatic disease, and about two-thirds of the latter will be defined as refractory to radioactive iodine (RAIR) treatment. Since this condition implies 10-year survival rates less than 10% after detection, using available treatments, such as systemic and targeted therapies, have become increasingly relevant. The initiation of these treatments aims to reach stabilization, tumor volume reduction, and/or symptom improvement and it should be decided by highly specialized endocrinologists/oncologists on the basis of patient’s features. Considering that despite enlarged progression-free survival was proven, multikinase inhibitors remain non-curative, their benefits last for a limited time and the side effects potentially cause harm and quality of life reduction. In this context, molecular testing of cancer cells provides a promising spectrum of targeted therapies that offer increased compatibility with individual patient needs by improving efficacy, progression free survival, overall survival and adverse events profile. This review article aims to provide a summary of the current therapeutic strategies in advanced RAIR-DTC, including approved target therapies as well as those for off-label use, RAI resensitization agents, and immunotherapy.

Background: Sorafenib and lenvatinib are multi-kinase inhibitors (MKI) approved to treatfor patients with radioactive iodine-refractory (RAI-R) differentiated thyroid cancer (DTC). There is no consensus on when to initiate MKI treatment. The objective of this study was to evaluate time to symptomatic progression (TTSP) in patients with RAI-R DTC for whom the decision to treat with an MKI was made at study entry.Methods: International, prospective, open-label, non-interventional cohort study (NCT02303444). Eligible patients had asymptomatic, progressive RAI-R DTC, with ≥1 lesion ≥1 cm in diameter and life expectancy ≥6 months. The decision to treat with an MKI was at the treating physician's discretion. The pPrimary endpoint was TTSP from study entry. Two cohorts were evaluated: patients for whom a decision to initiate treatment with an MKI was made at study entry (Cohort 1) and patients for whom there was a decision not to initiate an MKI at study entry patients without a decision to initiate treatment with an MKI (Cohort 2). Based on interim analysis, it was decided to compare the cohorts Cohorts were compared descriptively. Results: The full analysis set (FAS) comprised 647 patients from 19 countries. The median duration of observation was 35.5 months (range <1-59.4). Of 344 MKI-treated patients, 209 received sorafenib, 191 received lenvatinib, and 19 received another MKI at some point. Median TTSP was 55.4 months (interquartile range [IQR] 18.6-NE) overall (N=647), 55.4 months (IQR 15.2-NE) in Cohort 1 (n=169), and 51.4 months (IQR 20.0-NE) in Cohort 2 (n=478). TTSP ≥36 months was achieved in 64.5% of patients overall, 59.5% of patients in Cohort 1, and 66.4% of patients in Cohort 2. Median post-progression survival in the FAS was 28.4 months and median Median overall survival (OS) from classification as RAI-R was 167 months and. Median median PFS from start of MKI therapy was 19.2 months and from start of sorafenib therapy 16.7 months.