We sought to assess whether extensive surgical treatment, postsurgical radioiodine therapy, or both decrease the risk of locoregional recurrence (LR) after curative primary treatment in children and adolescents diagnosed with differentiated thyroid cancer (DTC) at age #18 y. Methods: To determine the incidence of and identify predictive factors for thyroid bed recurrence (TBR) or lymph node recurrence (NR), we performed a chart review and retrospective multivariate Cox regression analysis on 235 patients with DTC diagnosed at age #18 y and managed with curative intent at our tertiary referral center from 1973 to 2002; 40 of these patients had distant metastases at diagnosis. We also determined overall and recurrence-free survival and generated curves for these variables using Kaplan-Meier and Cox univariate analysis. Results: During a median follow-up of 82 mo (range, 5-402 mo), no DTC-related deaths occurred, 203 (86%) children remained recurrence-free, and 32 (14%) children had LR, including TBR in 9 (28% of LR), NR in 20 (63% of LR), and both in 3 (9% of LR). Among patients treated with radical intent and showing no distant metastases, the most recent thyroglobulin level was ,1 ng/mL in all but 4% of cases. The median time from the first surgery to LR was 37 mo (range, 9-280 mo). In multivariate analysis, significant risk factors for TBR were less than total thyroidectomy and lack of postsurgical radioiodine treatment (respective risk increases of 9.5 [P 5 0.04] and 11 times [P 5 0.03]). For NR, classic papillary histology, incomplete primary lymph node management (i.e., lack of modified lymphadenectomy of affected lymph nodes or lack of confirmation of disease-free nodes by intraoperative staging), and absence of adjuvant radioiodine therapy were independent significant predictive factors that increased the recurrence risk by 1.9 (P 5 0.02), 3.3 (P 5 0.02), and 3.2 (P 5 0.02) times, respectively. Age or sex did not correlate with LR risk. Conclusion: In DTC patients #18 y of age, extensive initial therapy-consisting of total thyroidectomy combined with modified lymphadenectomy performed in case of lymph node metastases and followed by radioiodine therapy-is associated with a substantial decrease of DTC LR risk.

BackgroundPrimary analysis of the double-blind, phase III Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer (EXAM) trial demonstrated significant improvement in progression-free survival with cabozantinib versus placebo in patients with progressive medullary thyroid cancer (MTC). Final analysis of overall survival (OS), a key secondary endpoint, was carried out after long-term follow-up.Patients and methodsEXAM compared cabozantinib with placebo in 330 patients with documented radiographic progression of metastatic MTC. Patients were randomized (2:1) to cabozantinib (140 mg/day) or placebo. Final OS and updated safety data are reported.ResultsMinimum follow-up was 42 months. Kaplan–Meier analysis showed a 5.5-month increase in median OS with cabozantinib versus placebo (26.6 versus 21.1 months) although the difference did not reach statistical significance [stratified hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.64–1.12; P = 0.24]. In an exploratory assessment of OS, progression-free survival, and objective response rate, cabozantinib appeared to have a larger treatment effect in patients with RET M918T mutation–positive tumors compared with patients not harboring this mutation. For patients with RET M918T-positive disease, median OS was 44.3 months for cabozantinib versus 18.9 months for placebo [HR, 0.60; 95% CI, 0.38–0.94; P = 0.03 (not adjusted for multiple subgroup analyses)], with corresponding values of 20.2 versus 21.5 months (HR, 1.12; 95% CI, 0.70–1.82; P = 0.63) in the RET M918T–negative subgroup. Median treatment duration was 10.8 months with cabozantinib and 3.4 months with placebo. The safety profile for cabozantinib remained consistent with that of the primary analysis.ConclusionThe secondary end point was not met in this final OS analysis from the trial of cabozantinib in patients with metastatic, radiographically progressive MTC. A statistically nonsignificant increase in OS was observed for cabozantinib compared with placebo. Exploratory analyses suggest that patients with RET M918T–positive tumors may experience a greater treatment benefit with cabozantinib.Trial Registration NumberNCT00704730

No abstract

There are 5 main histological types of thyroid cancers (TCs): papillary, follicular (also known as differentiated), poorly differentiated, anaplastic (the most aggressive form), and medullary TC, and only the latter arises from thyroid C cells. These different forms of TCs show significant variability, both among and within tumours. This great variation is particularly notable among the first 4 types, which all originate from thyroid follicular cells. Importantly, this heterogeneity is not limited to histopathological diversity only but is also manifested as variation in several genetic and/or epigenetic alterations, the numbers of interactions between the tumour and surrounding microenvironment, and interpatient differences, for example. All these factors contribute to the great complexity in the development of a tumour from cancer cells. In the present review, we summarise the knowledge accumulated about the heterogeneity of TCs. Further research in this direction should help to gain a better understanding of the underlying mechanisms contributing to the development and diversity of TCs, paving the way toward more effective treatment strategies.

No abstract