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Background Nonmedullary thyroid cancer (NMTC) comprises approximately 90% of all thyroid cancers, and about 3% to 9% of NMTC cases have a familial origin. Familial NMTC (FNMTC) in the absence of a documented familial cancer syndrome such as Cowden syndrome is characterized by the occurrence of thyroid cancer of follicular cell origin in 2 or more first-degree relatives. Methods Whole-exome sequencing (WES) was used to identify pathogenic genetic variants in 2 Persian families with FNMTC. The purpose of this work is to assess the pathogenic status of these variants as well as the cosegregation status of the variants observed in the examined families. Results By analyzing WES data in the first family, SRGAP1 : NM_020762: exon16: c.C1849T was identified as a pathogenic variant. This variant was confirmed by Sanger sequencing. In the second family, the variant FOXE1 : NM_004473: exon1: c.531_532insCGCGA was identified but was not confirmed by Sanger sequencing. Conclusion Based on the data, SRGAP1 can be a potential candidate gene for susceptibility to FNMTC in the first family. However, additional analyses like whole genome sequencing and copy number variations are required to ascertain the disease status in second family. [ABSTRACT FROM AUTHOR]

Purpose: Proton therapy is an emerging therapy for several malignancies owing to its favorable therapeutic ratio. There are very limited data on the use of proton therapy in the management of thyroid carcinoma. Our objective was to review the safety, feasibility, and outcomes of proton therapy for patients with thyroid cancer treated to the head and neck. Methods: From our institution's proton database from 2012 to 2021, we identified 22 patients with thyroid cancer treated with proton beam therapy. We evaluated outcomes and toxicities. Results: Median follow-up was 26 months. Of the 22 patients, 50% were female. The mean age was 65 years. Three patients had anaplastic cancer; 13, papillary carcinoma; 2, follicular carcinoma; and 2, poorly differentiated carcinoma. Forty-six percent had T4 disease. Primary targets were the central neck compartment, level VI, and upper mediastinum. Radiation dose was 60 GyRBE adjuvantly, and 70 GyRBE for gross disease (range, 6000-7600 GyRBE). Eight patients underwent upfront adjuvant radiation, and 3 received definitive radiation for unresectable disease upfront. Eleven patients received either salvage or palliative radiation. Fifty-nine percent of patients had extrathyroidal extension, and 64% of patients had gross disease in the neck before treatment. Fifty percent of patients had metastatic disease before treatment. Sixteen patients received concurrent chemotherapy, 63% of these patients received doxorubicin. For all patients, 1-year local regional recurrence (LRR) was 0%, and overall survival (OS) was 90%. Acute grade 3+ toxicities occurred in 27% of patients, the most frequent being dermatitis (27%). Three patients required a percutaneous endoscopic gastrostomy tube after radiation therapy (RT), 2 owing to progression. There were no grade 4+ toxicities. Conclusions: Proton therapy for thyroid cancer appears feasible and effective with minimal toxicities. Prospective studies comparing proton therapy with intensity-modulated RT, to evaluate the clinical efficacy of using proton therapy to reduce toxicities in patients undergoing radiation for thyroid cancer, are warranted.

Background: Nonmedullary thyroid cancer (NMTC) comprises approximately 90% of all thyroid cancers, and about 3% to 9% of NMTC cases have a familial origin. Familial NMTC (FNMTC) in the absence of a documented familial cancer syndrome such as Cowden syndrome is characterized by the occurrence of thyroid cancer of follicular cell origin in 2 or more first-degree relatives., Methods: Whole-exome sequencing (WES) was used to identify pathogenic genetic variants in 2 Persian families with FNMTC. The purpose of this work is to assess the pathogenic status of these variants as well as the cosegregation status of the variants observed in the examined families., Results: By analyzing WES data in the first family, SRGAP1: NM_020762: exon16: c.C1849T was identified as a pathogenic variant. This variant was confirmed by Sanger sequencing. In the second family, the variant FOXE1: NM_004473: exon1: c.531_532insCGCGA was identified but was not confirmed by Sanger sequencing., Conclusion: Based on the data, SRGAP1 can be a potential candidate gene for susceptibility to FNMTC in the first family. However, additional analyses like whole genome sequencing and copy number variations are required to ascertain the disease status in second family., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The first and most important step in characterizing familial nonmedullary thyroid carcinoma (NMTC) is to distinguish the true familial patients, which is the prerequisite for all accurate analyses. This study aimed to investigate whether patients from families with ≥3 first-degree relatives affected with NMTC have different characteristics than patients from families with only two affected members, and to compare these patients with those with sporadic disease. Methods: We analyzed the clinicopathological features and prognosis of 209 familial and 1120 sporadic cases of NMTC. Familial patients were further divided into two subgroups: families with two affected members and families with ≥3 affected members. Results: The familial group had a significantly higher risk of bilateral growth, multifocality, extrathyroidal extension, and lateral lymph node metastasis than the sporadic group (P < 0.05). These main features were also different between the group with ≥3 affected members and the sporadic group. The only difference between the two affected members' group and the sporadic group was incidence of multifocality (P < 0.05). The probability of disease recurrence in patients from families with ≥3 affected members was significantly higher than that in sporadic cases (14.46% vs. 5.27%; P = 0.001), while the probability in patients from families with two affected members was similar to that in sporadic patients (6.35% vs. 5.27%; P = 0.610). The Kaplan–Meier survival analysis showed a statistically significant difference in disease-free survival between the two subgroups (85.54% vs. 93.65%; P = 0.045). Conclusions: Patients from families with ≥3 members affected by NMTC have more aggressive features and a worse prognosis than those from families with only two affected members. Patients from families with ≥3 affected first-degree relatives may be considered to have true familial NMTC.

Background: Familial nonmedullary thyroid carcinoma (FNMTC) is a variant of nonmedullary thyroid carcinoma(NMTC) with particular clinicopathologic features. In recent years, a number of studies have shown that FNMTC is more invasive than sporadic NMTC(SNMTC). The purpose of this study was to explore the differences in clinicopathologic features of FNMTC between different types of families and to determine in which of these families more invasive FNMTC occurred. Methods: We retrospectively reviewed all patients with thyroid carcinoma admitted to Peking Union Medical College Hospital from January 2009 to July 2013 in the database. Of all 2000 cases, 55 met the inclusive criteria for FNMTC and were studied. There are two different grouping methods. The first is that all samples were allocated to families with three or more first-degree relatives affected (FNMTC-3 group) and families with only two affected first-degree relatives (FNMTC-2 group). The second is that all patients were divided into families with three or more affected first-degree relatives over two generations (FNMTC-3-2 group) and the other families. We compared the clinicopathologic features such as sex, age, tumor size, multifocality, location, complications by thyroiditis, complications by benign thyroid nodules, surgical procedure, capsule invasion, histological type, lymph node metastases, tumor node metastasis stage, and BRAF mutation between FNMTC-2 group and FNMTC-3 group. We also made the same comparison between FNMTC-3-2 group and other families. Results: No pronounced differences in clinicopathological features were present between FNMTC-2 group and FNMTC-3 group. The proportion of FNMTC-3-2 group aged

Purpose: Proton therapy is an emerging therapy for several malignancies owing to its favorable therapeutic ratio. There are very limited data on the use of proton therapy in the management of thyroid carcinoma. Our objective was to review the safety, feasibility, and outcomes of proton therapy for patients with thyroid cancer treated to the head and neck., Methods: From our institution's proton database from 2012 to 2021, we identified 22 patients with thyroid cancer treated with proton beam therapy. We evaluated outcomes and toxicities., Results: Median follow-up was 26 months. Of the 22 patients, 50% were female. The mean age was 65 years. Three patients had anaplastic cancer; 13, papillary carcinoma; 2, follicular carcinoma; and 2, poorly differentiated carcinoma. Forty-six percent had T4 disease. Primary targets were the central neck compartment, level VI, and upper mediastinum. Radiation dose was 60 GyRBE adjuvantly, and 70 GyRBE for gross disease (range, 6000-7600 GyRBE). Eight patients underwent upfront adjuvant radiation, and 3 received definitive radiation for unresectable disease upfront. Eleven patients received either salvage or palliative radiation. Fifty-nine percent of patients had extrathyroidal extension, and 64% of patients had gross disease in the neck before treatment. Fifty percent of patients had metastatic disease before treatment. Sixteen patients received concurrent chemotherapy, 63% of these patients received doxorubicin. For all patients, 1-year local regional recurrence (LRR) was 0%, and overall survival (OS) was 90%. Acute grade 3+ toxicities occurred in 27% of patients, the most frequent being dermatitis (27%). Three patients required a percutaneous endoscopic gastrostomy tube after radiation therapy (RT), 2 owing to progression. There were no grade 4+ toxicities., Conclusions: Proton therapy for thyroid cancer appears feasible and effective with minimal toxicities. Prospective studies comparing proton therapy with intensity-modulated RT, to evaluate the clinical efficacy of using proton therapy to reduce toxicities in patients undergoing radiation for thyroid cancer, are warranted., Competing Interests: Conflicts of Interest: The authors have no relevant conflicts of interest to disclose., (©Copyright 2022 The Author(s).)

Background: The first and most important step in characterizing familial nonmedullary thyroid carcinoma (NMTC) is to distinguish the true familial patients, which is the prerequisite for all accurate analyses. This study aimed to investigate whether patients from families with ≥3 first-degree relatives affected with NMTC have different characteristics than patients from families with only two affected members, and to compare these patients with those with sporadic disease., Methods:: We analyzed the clinicopathological features and prognosis of 209 familial and 1120 sporadic cases of NMTC. Familial patients were further divided into two subgroups: families with two affected members and families with ≥3 affected members., Results:: The familial group had a significantly higher risk of bilateral growth, multifocality, extrathyroidal extension, and lateral lymph node metastasis than the sporadic group (P < 0.05). These main features were also different between the group with ≥3 affected members and the sporadic group. The only difference between the two affected members' group and the sporadic group was incidence of multifocality (P < 0.05). The probability of disease recurrence in patients from families with ≥3 affected members was significantly higher than that in sporadic cases (14.46% vs. 5.27%; P = 0.001), while the probability in patients from families with two affected members was similar to that in sporadic patients (6.35% vs. 5.27%; P = 0.610). The Kaplan-Meier survival analysis showed a statistically significant difference in disease-free survival between the two subgroups (85.54% vs. 93.65%; P = 0.045)., Conclusions:: Patients from families with ≥3 members affected by NMTC have more aggressive features and a worse prognosis than those from families with only two affected members. Patients from families with ≥3 affected first-degree relatives may be considered to have true familial NMTC., Competing Interests: There are no conflicts of interest.