After the accident at the Fukushima Daiichi Nuclear Power Plant, the thyroid ultrasound screening program for children aged 0–18 at the time of the accident was started from October 2011. The prevalence of thyroid carcinomas in that population has appeared to be very high (84 cases per 296,253). To clarify the pathogenesis, we investigated the presence of driver mutations in these tumours. 61 classic papillary thyroid carcinomas (PTCs), two follicular variant PTCs, four cribriform-morular variant PTCs and one poorly-differentiated thyroid carcinoma were analysed. We detected BRAF^V600E in 43 cases (63.2%), RET/PTC1 in six (8.8%), RET/PTC3 in one (1.5%) and ETV6/NTRK3 in four (5.9%). Among classic and follicular variant PTCs, BRAF^V600E was significantly associated with the smaller size. The genetic pattern was completely different from post-Chernobyl PTCs, suggesting non-radiogenic etiology of these cancers. This is the first study demonstrating the oncogene profile in the thyroid cancers discovered by large mass screening, which probably reflects genetic status of all sporadic and latent tumours in the young Japanese population. It is assumed that BRAF^V600E may not confer growth advantage on paediatric PTCs, and many of these cases grow slowly, suggesting that additional factors may be important for tumour progression in paediatric PTCs.

The accident at the Fukushima Daiichi Nuclear Power Plant occurred after the Great East Japan Earthquake on 11 March 2011, releasing a large amount of radioactive materials into the atmosphere. Questions were raised regarding the health effects of radiation exposure, which led to increased anxiety among the Fukushima residents about the possible development of thyroid cancer. Thus, thyroid ultrasound examinations began for those who were from the areas where the radiation doses were highest, and will continue for the long term. In total, 300 476 subjects aged 18 years or younger at the time of the disaster were screened from 9 October 2011 to 31 March 2014. The participation rate was 81.7% of the total population of this age and in the affected area. Among them, the proportions of those who fell into the categories A1 (no nodules or cysts present), A2 (nodule ≤ 5 mm or cyst ≤ 20 mm diameter), B (nodule > 5 mm or cyst > 20 mm diameter) and C (immediate need for further investigation) were 51.5, 47.8, 0.8 and 0%, respectively; 2294 subjects in categories B and C were recommended to undergo a confirmatory examination; 113 were subsequently diagnosed with malignancy or suspected malignancy by fine needle aspiration cytology. The full-scale survey (second round survey) began in April 2014, and was completed by 30 June 2015, and comprised 169 455 subjects (participation rate; 44.7%). The proportions of those who fell into the categories A1, A2, B and C were 41.6, 57.6, 0.8 and 0% (no case), respectively; 1223 subjects in category B were recommended to undergo a confirmatory examination, 25 of these were subsequently diagnosed with malignancy or suspected malignancy by fine needle aspiration cytology. The thyroid cancers identified in this survey so far are unlikely to be due to radiation exposure, and are more likely to be the result of screening using highly sophisticated ultrasound techniques. However, it would be advisable to continue long-term screening to determine whether the risk of childhood and adolescent thyroid cancer due to radiation exposure increases or not.

Background: Anaplastic thyroid cancer (ATC) is a rare and extremely aggressive malignancy, with a median survival of less than 6 months due to rapid progression and resistance to multimodal therapies. Effective treatment strategies have not been identified. A prospective clinical study was performed to objectively evaluate outcomes of treatment with paclitaxel. Methods: An investigator-initiated, multicenter, nonrandomized, open-label, single-arm study to evaluate the feasibility and efficacy of weekly paclitaxel (80 mg/m ² ) administration for patients with pathologically confirmed ATC was conducted in a nationwide organization. Results: Feasibility was analyzed in 56 patients. More than one course of treatment was performed in 52 (93%) patients retaining sufficient dose intensity (>84%). No patient had to terminate the treatment because of an adverse event. The median overall survival was 6.7 months [confidence interval 4.4–9.0]. The 6-month survival was 54%. Among the 42 patients with an evaluable lesion, none demonstrated complete remission, 9 (21%) showed partial remission, 22 (52%) achieved stable disease, and 8 (19%) exhibited progressive disease; 3 did not complete the initial treatment course. The objective response rate was 21%, and the clinical benefit rate was 73%. The median time to progression was 1.6 months. Statistically, no additional effect of concomitant radiation was demonstrated in 6 patients receiving combined therapy. Eight patients, in whom a complete post-treatment surgical removal of the tumor was feasible, survived significantly longer (median 7.6 months [CI 8.1–23.0]) than the other 34 patients in whom the tumor could not be completely removed after chemotherapy (5.4 months [CI 3.0–7.8], p = 0.018). Summary: The study demonstrates objective and accurate information concerning the feasibility and efficacy of a standardized treatment with weekly paclitaxel administration for ATC patients. Conclusions: Weekly paclitaxel administration for ATC patients can be of clinical benefit in a neo-adjuvant setting.

Background: The tumor–node–metastasis (TNM) classification system to categorized anaplastic thyroid cancer (ATC) was revised. Methods: The revised system was evaluated using a large database of ATC patients. Results: A total of 757 patients were analyzed. The proportion and median overall survival values (OS: months) for each T category were T1 (n = 8, 1.1%, 12.5), T2 (n = 43, 5.7%, 10.9), T3a (n = 117, 15.5%, 5.7), T3b (n = 438, 57.9%, 3.9), and T4 (n = 151, 19.9%, 5.0). The OS of the N0 and N1 patients were 5.9 and 4.3, respectively (log-rank p < 0.01). Sixty-three (58.3%) patients migrated from stage IV A to IV B by revision based on the existence of nodal involvement and 422 patients (55.7%) were stratified into stage IV B, without a worsening of their OS (6.1), leaving 45 patients (5.9%) in stage IV A with fair OS (15.8). The hazard ratios for the survival of the patients of stage IV B compared to stage IV A increased from 1.1 to 2.1 by the revision. No change was made for stage IV C (n = 290, 38.8%, 2.8). Conclusion: The revised TNM system clearly indicated the prognoses of ATC patients by extracting rare patients with fair prognoses as having stage IV A disease and categorized many heterogeneous patients in stage IV B.

Background: The BRAF^V600E mutation is the most frequent genetic abnormality in adult papillary thyroid carcinomas (PTCs). On the other hand, various chromosomal rearrangements are more prevalent in childhood and adolescent PTCs. The aim of the present study was to identify novel rearrangements in PTCs from young patients. Methods: Among 63 postoperative specimens of childhood and adolescent PTCs, which had been discovered by the thyroid ultrasound screening program in Fukushima, nine samples without prevalent known oncogenes, BRAF^V600E, RAS, RET/PTC1, RET/PTC3, and ETV6/NTRK3, were analyzed in the current study by quantitative real-time reverse transcription polymerase chain reaction to screen for novel fusion genes by comparing transcript expression between extracellular and kinase domains of ALK, NTRK1, NTRK3, and RET. Results: Of the above nine samples, five samples were suspected to harbor a fusion, and using subsequent 5′ rapid amplification of cDNA end (RACE), two already reported fusion oncogenes, STRN/ALK and TPR/NTRK1, and three novel fusions, SQSTM1/NTRK3, AFAP1L2/RET, and PPFIBP2/RET, were identified. Functional analyses of these three chimeric genes were performed, and their transforming abilities were confirmed through the activation of mitogen-activated protein kinase (MAPK). Conclusions: Three novel fusion oncogenes have been identified in young PTC patients in Fukushima, suggesting that rare fusions may be present among the cases negative for known oncogenes in this age group and that such rearrangements can play a significant role in thyroid carcinogenesis.