Background: Sorafenib and lenvatinib are multikinase inhibitors (MKIs) approved for 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, noninterventional 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. Primary endpoint was TTSP from study entry. Two cohorts were evaluated: patients for whom a decision to initiate 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 (Cohort 2). Cohorts were compared descriptively. Results: The full analysis set (FAS) comprised 647 patients. 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–not estimable [NE]) overall, 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 overall survival from classification as RAI-R was 167 months and median progression-free survival from start of MKI therapy was 19.2 months and from start of sorafenib therapy 16.7 months. Among sorafenib-treated patients, 70% had dose modifications, 35% had a dose reduction, 89% experienced ≥1 treatment-emergent adverse event (TEAE), and 82% experienced ≥1 drug-related TEAE. Conclusions: This real-world study provides valuable insight into outcomes in patients with asymptomatic, progressive RAI-R DTC under observation or receiving MKI treatment. TTSP in the FAS provides insight into the current prognosis for patients with RAI-R DTC in the era of MKIs. Registration: NCT02303444.

The advent of tyrosine kinase inhibitors (TKIs) has changed the treatment of RAI refractory, unresectable recurrent differentiated thyroid cancer (DTC), which was formerly treated with multidisciplinary remedies. Here we describe the case of a 64-year-old woman who underwent total thyroidectomy with tracheal resection and suffered from a recurrent tumor in the neck and multiple lung and bone metastases 3 and 11 months, respectively, after the operation. Multimodal therapies, RI (I-131), EBRT, and taxane-based chemotherapy were ineffective, and sorafenib was started as a TKI. However, because of disease progression, sorafenib was replaced by lenvatinib after 9 months. The effect of lenvatinib has continued for more than 1 year and 9 months, and the patient has well survived. During the treatment period, a tracheal pin-hole fistula suddenly emerged, which was naturally cured by the temporary cessation of lenvatinib. Adverse events such as hypertension, proteinuria, and diabetes as innate complications have been successfully managed until the present according to our institute regulations. Even where multimodal treatment was ineffective, lenvatinib was suggested to be an alternative treatment option for RAI refractory recurrent DTC and patient could have a chance to be controlled successfully.

Endoscopic thyroidectomy (ET) or robotic thyroidectomy is yet to be applied to thyroid carcinoma invasive to the trachea and to wide lymph node node metastasis. On the other hand, small-incision thyroidectomy lacks sufficient working space and clear vision. The author has newly developed hybrid-type endoscopic thyroidectomy (HET) to overcome these problems.

Some poorly differentiated thyroid carcinomas (PDTC) arise from pre-existing, well-differentiated carcinomas of follicular cell origin; however, others most likely arise de novo. The case of a PDTC adjacent to a pre-existing nodular goiter is very rare. A patient had a PDTC, a widely invasive, cellular tumor with cells that lacked the nuclear features of a papillary thyroid carcinoma. Carcinoma cells were arranged in trabecular, solid, and microfollicular histological patterns and displayed high mitotic activity. A nodule partially encapsulated in a thick fibrous capsule was found adjacent to the PDTC. The nodule was composed of small or dilated follicles, without papillary carcinoma-like nuclear features, that were consistent with a nodular goiter. The PDTC showed a high Ki-67 labeling index and an NRAS gene mutation (codon 61, Q61K). These results support our diagnosis of a PDTC, probably arising from a nodular goiter.