Association between papillary thyroid cancer and primary aldosteronism in individuals with hypertension.

BACKGROUND: Aldosterone excess chronically induces oxidative stress and cell proliferation. Previously, a single study investigated primary aldosteronism (PA) in patients with papillary thyroid cancer (PTC), albeit without a matched control group. METHODS: We conducted a propensity score matched case-control study to investigate the association between PA and PTC in individuals with arterial hypertension (HT). PA was investigated in 137 patients with PTC and HT. The control group included 137 (1:1) age, sex-, and body mass index (BMI)-matched individuals with HT. We conducted a secondary analysis in which the controls were also matched according to HT stage. RESULTS: The prevalence of PA was 29.20% (95% confidence interval [CI], 21.91%-37.68%) in the PTC group and 20.44% (95% CI, 14.22%-28.35%) in the controls not matched for HT stage (p = 0.093). Although the PA prevalence was similar in both groups, the frequency of severe HT (stage III or resistant) was significantly lower in the PTC group (23%) compared to the hypertensive controls (73%, p < 0.001). After matching the controls by HT stage, the prevalence of PA in the PTC group was significantly higher compared to the hypertensive controls (9.56%; 95% CI, 5.39%-16.1%, p < 0.0001). In the multivariable analysis, PTC was independently associated with PA in both unmatched hypertensive individuals (odds ratio [OR] 4.74; 95% CI, 2.26-10.55; p< 0.001) and in those matched for HT stage (OR 5.88, 95% CI, 2.79-13.37; p< 0.001). CONCLUSION: PTC was an independent variable associated with a diagnosis of PA in hypertensive individuals. Therefore, we propose the association between PTC and HT as a new recommendation for PA screening regardless of HT severity.

Neoadjuvant Treatment of Locally Advanced Thyroid Cancer: A Preliminary Latin American Experience.

Background: Surgical resection is not always achievable in thyroid cancer patients. Neoadjuvant therapy is rarely used, but recent trends favor multikinase inhibitors or selective tyrosine kinase inhibitors. These aim to reduce tumor volume, enabling previously unfeasible surgeries. Patients and Methods: Consecutive patients with locally advanced malignant thyroid tumors who received systemic therapies with a neoadjuvant intention were included in this retrospective multicenter case series conducted in five Latin American referral centers. Primary outcomes were pre- versus postneoadjuvant response evaluations using the Response Evaluation Criteria in Solid Tumors, feasibility of surgery, and completeness of resection. Secondary outcomes were mortality and status at the last visit. Results: Twenty-seven patients were included in this analysis. Patients with unresectable differentiated thyroid cancer (DTC) or poorly differentiated thyroid cancer (PDTC) received sorafenib (n = 6) or lenvatinib (n = 12), those with medullary thyroid cancer (MTC) were treated with vandetanib (n = 5) or selpercatinib (n = 1), and those with anaplastic thyroid cancer (ATC) harboring a BRAFV600E mutation (n = 3) received dabrafenib and trametinib. The median patient age was 66 years (range 12-82), and 52% of the patients were female. In patients with PTC and PDTC, the median reduction in the diameter of the primary tumor was 25% (range 0-100%) after a median of 6 months of treatment. Surgical intervention was performed in 10 (55%) of the patients. Among these, six patients (60%) achieved R0/R1 resection status. Six patients with MTC had a median reduction in tumor diameter of 24.5% (range 1-49) after a median treatment time of 9.5 months. Only one patient receiving selpercatinib, with a tumoral reduction of 25% could undergo surgery, resulting in an R2 resection due to extensive mediastinal extension. Three patients with ATC showed a median tumor diameter reduction of 42% (range 6.7-50) after a median treatment time of 2 months. Two patients underwent surgical intervention and achieved R1 and R2 resection, respectively. Conclusions: While neoadjuvant therapy achieved tumoral responses, surgical resection was feasible in 55% of DTC, 33% of ATC, and 16% of MTC patients, with R0/R1 resection in 26% of the cohort, underscoring the need for patient selection and further research in this area.

Identification of Predictors of Metastatic Potential in Paragangliomas to Develop a Prognostic Score (PSPGL).

Context: Paragangliomas (PGLs) are rare tumors in adrenal and extra-adrenal locations. Metastasis are found in approximately 5% to 35% of PGLs, and there are no reliable predictors of metastatic disease. Objective: This work aimed to develop a prognostic score of metastatic potential in PGLs. Methods: A retrospective analysis was conducted of clinical data from a cohort with PGLs and tumor histological assessment. Patients were divided into metastatic PGL (presence of metastasis) and nonmetastatic PGL (absence of metastasis ≥96 months of follow-up) groups. Univariate and multivariable analysis were performed to identify predictors of metastatic potential. A prognostic score was developed based on coefficients of multivariable analysis. Kaplan-Meier curves were generated to estimate disease-specific survival (DSS). Results: Out of 263 patients, 35 patients had metastatic PGL and 110 patients had nonmetastatic PGL. In multivariable analysis, 4 features were independently related to metastatic disease and composed the Prognostic Score of Paragangliomas (PSPGL): presence of central or confluent necrosis (33 points), more than 3 mitosis/10 high-power field (HPF) (28 points), extension into adipose tissue (20 points), and extra-adrenal location (19 points). A PSPGL of 24 or greater showed similar sensitivity with higher specificity than the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP). PSPGL less than or equal to 20 was associated with a risk of metastasis of approximately 10%, whereas a PSPGL of 40 or greater was associated with approximately 80%. The presence of metastasis and Ki-67 of 3% or greater were related to lower DSS. Conclusion: The PSPGL, composed of 4 easy-to-assess parameters, demonstrated good performance in predicting metastatic potential and good ability in estimating metastasis risk.

Not Only RET but NF1 and Chromosomal Instability Are Seen in Young Patients with Sporadic Medullary Thyroid Carcinoma.

Context: Genetic analysis of sporadic medullary thyroid carcinoma (MTC) has revealed somatic variants in RET, RAS, and occasionally other genes. However, around 20% of patients with sporadic MTC lack a known genetic driver. Objective: To uncover potential new somatic or germline drivers, we analyze a distinct cohort of patients with sporadic, very early-onset, and aggressive MTC. Methods: Germline and somatic DNA exome sequencing was performed in 19 patients, previously tested negative for germline RET variants. Results: Exome sequencing of 19 germline samples confirmed the absence of RET and identified an NF1 pathogenic variant in 1 patient. Somatic sequencing was successful in 15 tumors revealing RET variants in 80%, predominantly p.Met918Thr, which was associated with disease aggressiveness. In RET-negative tumors, pathogenic variants were found in HRAS and NF1. The NF1 germline and somatic variants were observed in a patient without a prior clinical diagnosis of neurofibromatosis type 1, demonstrating that the loss of heterozygosity of NF1 functions as a potential MTC driver. Somatic copy number alterations analysis revealed chromosomal alterations in 53.3% of tumors, predominantly in RET-positive cases, with losses in chromosomes 9 and 22 being the most prevalent. Conclusion: This study reveals that within a cohort of early-onset nonhereditary MTC, RET remains the major driver gene. In RET-negative tumors, NF1 and RAS are drivers of sporadic MTC. In addition, in young patients without a RET germline mutation, a careful clinical evaluation with a consideration of germline NF1 gene analysis is ideal to exclude Neurofibromatosis type 1 (NF1).

Intraoperative radiofrequency ablation for unresectable abdominal paraganglioma: a case report.

For pheochromocytoma and paraganglioma (PPGL), the efficacy of percutaneous ablative therapies in achieving control of metastatic tumors measuring <3 cm had been demonstrated in only few reports, and intraoperative radiofrequency ablation (RFA) of locally invasive primary PPGLs has not been reported. We presented the case of a 31-year-old man who had a 9-cm functioning unresectable PPGL. He was treated with 13 cycles of cytotoxic chemotherapy without objective tumor response, according to the Response Evaluation Criteria in Solid Tumors (RECIST). Subsequently, magnetic resonance imaging revealed a 9.0 × 8.6 × 6.0-cm retroperitoneal mass that extended to the inferior portion of the inferior vena cava, the inferior mesenteric artery, and the infrarenal aorta. Biochemical evaluation demonstrated high level of plasma normetanephrine (20.2 nmol/L, normal range <0.9 nmol/L). Genetic investigation showed the germline pathogenic variant c.1591delC (p. Ser198Alafs*22) in the SDHB gene. I131-metaiodobenzylguanidine scintigraphy was negative and Ga68-dotatate PET-CT scan showed high tumor uptake without distant metastases. On open laparotomy, tumor debulking was not possible. Therefore, intraoperative RFA was performed by a highly experienced team of interventional radiologists. At 12 months after the RFA, the tumor volume decreased from 208 to 45 mL (78%), plasma normetanephrine decreased from 20.2 to 2.6 nmol/L (87%), and the doxazosin dose was reduced from 16 to 8 mg/day. To our best knowledge, this was the first report on intraoperative RFA that markedly reduced the size of a large primary unresectable PPGL, along with clinical and biochemical responses.

Differentiated thyroid carcinoma: what the nonspecialists needs to know.

Differentiated thyroid carcinoma (DTC) accounts for most cases of thyroid cancer, and the heterogeneity of DTC requires that management decisions be taken by a multidisciplinary team involving endocrinologists, head and neck surgeons, nuclear medicine physicians, pathologists, radiologists, radiation oncologists, and medical oncologists. It is important for nonspecialists to recognize and refer patients with DTC who will benefit from a specialized approach. Recent advances in knowledge and changes in management of DTC call for the need to raise awareness on the part of these nonspecialist physicians, including general endocrinologists and medical oncologists at large. We provide an overview of diagnostic and therapeutic principles in DTC, especially those that bear direct implication on day-to-day management of these patients by generalists. Patients with DTC may be broadly categorized as having localized, locally persistent/recurrent, or metastatic disease. Current recommendations for DTC include a three-tiered system that classifies patients with localized disease into low, intermediate, or high risk of persistent or recurrent disease. Risk stratification should be performed at baseline and repeated on an ongoing basis, depending on clinical evolution. One of the overarching goals in the management of DTC is the need to personalize treatment by tailoring its modality and intensity according to ongoing prognostic stratification, evolving knowledge about the disease, and patient characteristics and preference. In metastatic disease that is refractory to radioactive iodine, thyroid tumors are being reclassified into molecular subtypes that better reflect their biological properties and for which molecular alterations can be targeted with specific agents.

Increased Progression-Free Survival with Cabozantinib Versus Placebo in Patients with Radioiodine-Refractory Differentiated Thyroid Cancer Irrespective of Prior Vascular Endothelial Growth Factor Receptor-Targeted Therapy and Tumor Histology: A Subgroup Analysis of the COSMIC-311 Study.

Background: Lenvatinib and sorafenib are standard of care first-line treatments for advanced, radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC). However, most patients eventually become treatment-resistant and require additional therapies. The phase 3 COSMIC-311 study investigated cabozantinib in patients with RAIR DTC who progressed on lenvatinib, sorafenib, or both and showed that cabozantinib provided substantial clinical benefit. Presented in this study is an analysis of COSMIC-311 based on prior therapy and histology. Methods: Patients were randomized 2:1 (stratification: prior lenvatinib [yes/no]; age [≤65, >65 years]) to oral cabozantinib (60 mg tablet/day) or matched placebo. Eligible patients received 1-2 prior vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitors for DTC (lenvatinib or sorafenib required), had a confirmed DTC diagnosis, and were refractory to or ineligible for radioiodine therapy. For this analysis, progression-free survival (PFS) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 by a blinded independent radiology committee were evaluated by prior therapy (lenvatinib only, sorafenib only, both) and histology (papillary, follicular, oncocytic, poorly differentiated). Results: Two hundred fifty-eight patients were randomized (170 cabozantinib/88 placebo) who previously received sorafenib only (n = 96), lenvatinib only (n = 102), or both (n = 60). The median follow-up was 10.1 months. The median PFS (months) with cabozantinib/placebo was 16.6/3.2 (sorafenib only: hazard ratio [HR] 0.13 [95% confidence interval, CI, 0.06-0.26]), 5.8/1.9 (lenvatinib only: HR 0.28 [95% CI 0.16-0.48]), and 7.6/1.9 (both: HR 0.27 [95% CI 0.13-0.54]). The ORR with cabozantinib/placebo was 21%/0% (sorafenib only), 4%/0% (lenvatinib only), and 8%/0% (both). Disease histology consisted of 150 papillary and 113 follicular, including 43 oncocytic and 36 poorly differentiated. The median PFS (months) with cabozantinib/placebo was 9.2/1.9 (papillary: HR 0.27 [95% CI 0.17-0.43]), 11.2/2.5 (follicular: HR 0.18 [95% CI 0.10-0.31]), 11.2/2.5 (oncocytic: HR 0.06 [95% CI 0.02-0.21]), and 7.4/1.8 (poorly differentiated: HR 0.18 [95% CI 0.08-0.43]). The ORR with cabozantinib/placebo was 15%/0% (papillary), 8%/0% (follicular), 11%/0% (oncocytic), and 9%/0% (poorly differentiated). Safety outcomes evaluated were consistent with those previously observed for the overall population. Conclusions: Results indicate that cabozantinib benefits patients with RAIR DTC, regardless of prior lenvatinib or sorafenib treatments or histology. Clinical Trial Registration Number: NCT03690388.

Management of radioiodine refractory differentiated thyroid cancer: the Latin American perspective.

Radioiodine (RAI) refractory differentiated thyroid cancer is an uncommon and challenging situation that requires a multidisciplinary approach to therapeutic strategies. The definition of RAI-refractoriness is usually a clear situation in specialized centers. However, the right moment for initiation of multikinase inhibitors (MKI), the time and availability for genomic testing, and the possibility of prescribing MKI and selective kinase inhibitors differ worldwide.Latin America (LA) refers to the territories of the world that stretch across two regions: North America (including Central America and the Caribbean) and South America, containing 8.5% of the world's population. In this manuscript, we critically review the current standard approach recommended for patients with RAI refractory differentiated thyroid cancer, emphasizing the challenges faced in LA. To achieve this objective, the Latin American Thyroid Society (LATS) convened a panel of experts from Brazil, Argentina, Chile, and Colombia. Access to MKI compounds continues to be a challenge in all LA countries. This is true not only for MKI but also for the new selective tyrosine kinase inhibitor, which will also require genomic testing, that is not widely available. Thus, as precision medicine advances, significant disparities will be made more evident, and despite efforts to improve coverage and reimbursement, molecular-based precision medicine remains inaccessible to most of the LA population. Efforts should be undertaken to alleviate the discrepancies between the current state-of-the-art care for RAI-refractory differentiated thyroid cancer and the present situation in Latin America.

Differentiated thyroid carcinoma: what the nonspecialists needs to know

ABSTRACT Differentiated thyroid carcinoma (DTC) accounts for most cases of thyroid cancer, and the heterogeneity of DTC requires that management decisions be taken by a multidisciplinary team involving endocrinologists, head and neck surgeons, nuclear medicine physicians, pathologists, radiologists, radiation oncologists, and medical oncologists. It is important for nonspecialists to recognize and refer patients with DTC who will benefit from a specialized approach. Recent advances in knowledge and changes in management of DTC call for the need to raise awareness on the part of these nonspecialist physicians, including general endocrinologists and medical oncologists at large. We provide an overview of diagnostic and therapeutic principles in DTC, especially those that bear direct implication on day-to-day management of these patients by generalists. Patients with DTC may be broadly categorized as having localized, locally persistent/recurrent, or metastatic disease. Current recommendations for DTC include a three-tiered system that classifies patients with localized disease into low, intermediate, or high risk of persistent or recurrent disease. Risk stratification should be performed at baseline and repeated on an ongoing basis, depending on clinical evolution. One of the overarching goals in the management of DTC is the need to personalize treatment by tailoring its modality and intensity according to ongoing prognostic stratification, evolving knowledge about the disease, and patient characteristics and preference. In metastatic disease that is refractory to radioactive iodine, thyroid tumors are being reclassified into molecular subtypes that better reflect their biological properties and for which molecular alterations can be targeted with specific agents.

Physicians' preferences for radioiodine treatment of differentiated thyroid cancer in Brazil: an observational study

ABSTRACT Objective The aim of this observational, cross-sectional study was to investigate physicians' preferences for radioiodine (RAI) treatment in patients with differentiated thyroid cancer (DTC) in Brazil and the factors influencing RAI indications. Materials and methods A survey was distributed to physicians potentially involved in DTC care in Brazil to understand the factors influencing RAI indications. The survey collected information on the profiles of the physicians, along with the characteristics of their workplaces and their preferences regarding RAI indications in three hypothetical clinical cases. Cases 1, 2, and 3 described the cases of patients with DTC and variations to the case that included different scenarios to assess how the respondents would change their RAI recommendations. The analysis included the RAI indications across different medical specialties. Results A total of 175 physicians answered the survey. There was considerable variability in RAI recommendations in all three cases. The training background influenced the respondents' preferences for RAI indications and their approaches to preparing patients for RAI treatment. Conclusion The findings of this study reaffirm the need for a Brazilian consensus among physicians across multiple specialties to help guide health care professionals treating patients with DTC in Brazil.

Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer.

BACKGROUND: Selpercatinib, a highly selective, potent RET inhibitor, has shown efficacy in advanced RET-mutant medullary thyroid cancer in a phase 1-2 trial, but its efficacy as compared with approved multikinase inhibitors is unclear. METHODS: We conducted a phase 3, randomized trial comparing selpercatinib as first-line therapy with the physician's choice of cabozantinib or vandetanib (control group). Eligible patients had progressive disease documented within 14 months before enrollment. The primary end point in the protocol-specified interim efficacy analysis was progression-free survival, assessed by blinded independent central review. Crossover to selpercatinib was permitted among patients in the control group after disease progression. Treatment failure-free survival, assessed by blinded independent central review, was a secondary, alpha-controlled end point that was to be tested only if progression-free survival was significant. Among the other secondary end points were overall response and safety. RESULTS: A total of 291 patients underwent randomization. At a median follow-up of 12 months, median progression-free survival as assessed by blinded independent central review was not reached in the selpercatinib group and was 16.8 months (95% confidence interval [CI], 12.2 to 25.1) in the control group (hazard ratio for disease progression or death, 0.28; 95% CI, 0.16 to 0.48; P<0.001). Progression-free survival at 12 months was 86.8% (95% CI, 79.8 to 91.6) in the selpercatinib group and 65.7% (95% CI, 51.9 to 76.4) in the control group. Median treatment failure-free survival as assessed by blinded independent central review was not reached in the selpercatinib group and was 13.9 months in the control group (hazard ratio for disease progression, discontinuation due to treatment-related adverse events, or death, 0.25; 95% CI, 0.15 to 0.42; P<0.001). Treatment failure-free survival at 12 months was 86.2% (95% CI, 79.1 to 91.0) in the selpercatinib group and 62.1% (95% CI, 48.9 to 72.8) in the control group. The overall response was 69.4% (95% CI, 62.4 to 75.8) in the selpercatinib group and 38.8% (95% CI, 29.1 to 49.2) in the control group. Adverse events led to a dose reduction in 38.9% of the patients in the selpercatinib group, as compared with 77.3% in the control group, and to treatment discontinuation in 4.7% and 26.8%, respectively. CONCLUSIONS: Selpercatinib treatment resulted in superior progression-free survival and treatment failure-free survival as compared with cabozantinib or vandetanib in patients with RET-mutant medullary thyroid cancer. (Funded by Loxo Oncology, a subsidiary of Eli Lilly; LIBRETTO-531 ClinicalTrials.gov number, NCT04211337.).

Diagnosis and Management of Tropomyosin Receptor Kinase Fusion-Positive Thyroid Carcinomas: A Review.

Importance: Thyroid epithelial malignant neoplasms include differentiated thyroid carcinomas (papillary, follicular, and oncocytic), follicular-derived high-grade thyroid carcinomas, and anaplastic and medullary thyroid carcinomas, with additional rarer subtypes. The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions has fostered developments in precision oncology, with the approval of tropomyosin receptor kinase inhibitors (larotrectinib and entrectinib) for patients with solid tumors, including advanced thyroid carcinomas, harboring NTRK gene fusions. Observations: The relative rarity and diagnostic complexity of NTRK gene fusion events in thyroid carcinoma present several challenges for clinicians, including variable access to robust methodologies for comprehensive NTRK fusion testing and poorly defined algorithms of when to test for such molecular alterations. To address these issues in thyroid carcinoma, 3 consensus meetings of expert oncologists and pathologists were convened to discuss diagnostic challenges and propose a rational diagnostic algorithm. Per the proposed diagnostic algorithm, NTRK gene fusion testing should be considered as part of the initial workup for patients with unresectable, advanced, or high-risk disease as well as following the development of radioiodine-refractory or metastatic disease; testing by DNA or RNA next-generation sequencing is recommended. Detecting the presence of NTRK gene fusions is important to identify patients eligible to receive tropomyosin receptor kinase inhibitor therapy. Conclusions and Relevance: This review provides practical guidance for optimal integration of gene fusion testing, including NTRK gene fusion testing, to inform the clinical management in patients with thyroid carcinoma.

Fructosamine and glycated hemoglobin as biomarkers of glycemic control in people with type 2 diabetes mellitus and cancer (GlicoOnco study).

INTRODUCTION: Glycemic control is important to avoid diabetes complications in individuals with cancer. There is no evidence for HbA1c and fructosamine as reliable biomarkers in these conditions. There are particularities in caring for patients with diabetes and cancer that can alter these biomarkers. OBJECTIVE: The aim of this study was to evaluate HbA1c and fructosamine as glycemic biomarkers in people with type 2 diabetes and cancer, undergoing clinical or surgical oncological treatment. METHODS: The authors conducted a single-center, retrospective analysis with people who have cancer and diabetes. Comparison of glycemic biomarkers (HbA1c, fructosamine, and Self-Monitoring of Blood Glucose [SMBG]) was performed including evaluation in individuals undergoing chemotherapy, using glucocorticoids, with anemia, hypoproteinemia or with reduced estimated Glomerular Filtration Rate (eGFR). RESULTS: There was a strong positive correlation between fructosamine and HbA1c (n = 318, r = 0.66, p < 0.001) in people with diabetes and cancer even in those under chemotherapy (n = 101, r = 0.61, p < 0.001) or using glucocorticoids (n = 96, r = 0.67, p<0.001). There was a strong correlation between HbA1c and fructosamine in subjects with anemia (n = 111, r = 0.66, p < 0.001), hypoproteinemia (n = 54, r = 0.67, p < 0.001), or with eGFR ≥ 60 mL/min/1.73 m2 (n = 189, r = 0.70, p < 0.001), and moderate correlation with hypoalbuminemia (n = 21, r = 0.54, p = 0.001) and with reduced eGFR (n = 67, r = 0.57, p < 0.001). The correlations between fructosamine and HbA1c with SMBG were moderate (n = 164, r = 0.49, p < 0.001; n = 111, r = 0.55, p < 0.001, respectively), strong in subjects undergoing chemotherapy, with hypoalbuminemia or hypoproteinemia, and at least moderate, if eGFR < 60 mL/min/1.73 m2 or with anemia. CONCLUSIONS: Fructosamine and HbA1c can be used as glycemic biomarkers in people with diabetes and cancer, even in those with anemia, hypoproteinemia, or undergoing chemotherapy.

Ultrasound in cervical traumatic neuromas after neck dissection in thyroid carcinoma patients: descriptive analysis and diagnostic accuracy.

Objective: Cervical traumatic neuromas (CTNs) may appear after lateral neck dissection for metastatic thyroid carcinoma. If they are misdiagnosed as metastatic lymph nodes (LNs) in follow-up neck ultrasound (US), unnecessary and uncomfortable fine-needle aspiration biopsy are indicated. The present study aimed to describe US features of CTNs and to assess the US performance in distinguishing CTNs from abnormal LNs. Subjects and methods: Retrospective evaluation of neck US images of 206 consecutive patients who had lateral neck dissection as a part of thyroid cancer treatment to assess CTN´s US features. Diagnostic accuracy study to evaluate US performance in distinguishing CTNs from abnormal LNs was performed. Results: Eight-six lateral neck nodules were selected for analysis: 38 CTNs and 48 abnormal LNs. CTNs with diagnostic cytology were predominantly hypoechogenic (100% vs. 45%; P = 0.008) and had shorter diameters than inconclusive cytology CTNs: short axis (0.39 cm vs. 0.50 cm; P = 0.03) and long axis (1.64 cm vs. 2.35 cm; P = 0.021). The US features with the best accuracy to distinguish CTNs from abnormal LNs were continuity with a nervous structure, hypoechogenic internal lines, short/long axis ratio ≤ 0.42, absent Doppler vascularization, fusiform morphology, and short axis ≤ 0.48 cm. Conclusion: US is a very useful method for assessing CTNs, with good performance in distinguishing CTNs from abnormal LNs.

Evidence for a Founder Effect of SDHB Exon 1 Deletion in Brazilian Patients With Paraganglioma.

CONTEXT: Limited information is available concerning the genetic spectrum of pheochromocytoma and paraganglioma (PPGL) patients in South America. Germline SDHB large deletions are very rare worldwide, but most of the individuals harboring the SDHB exon 1 deletion originated from the Iberian Peninsula. OBJECTIVE: Our aim was to investigate the spectrum of SDHB genetic defects in a large cohort of Brazilian patients with PPGLs. METHODS: Genetic investigation of 155 index PPGL patients was performed by Sanger DNA sequencing, multiplex ligation-dependent probe amplification, and/or target next-generation sequencing panel. Common ancestrality was investigated by microsatellite genotyping with haplotype reconstruction, and analysis of deletion breakpoint. RESULTS: Among 155 index patients, heterozygous germline SDHB pathogenic or likely pathogenic variants were identified in 22 cases (14.2%). The heterozygous SDHB exon 1 complete deletion was the most frequent genetic defect in SDHB, identified in 8 out of 22 (36%) of patients. Haplotype analysis of 5 SDHB flanking microsatellite markers demonstrated a significant difference in haplotype frequencies in a case-control permutation test (P = 0.03). More precisely, 3 closer/informative microsatellites were shared by 6 out of 8 apparently unrelated cases (75%) (SDHB-GATA29A05-D1S2826-D1S2644 | SDHB-186-130-213), which was observed in only 1 chromosome (1/42) without SDHB exon 1 deletion (X2 = 29.43; P < 0.001). Moreover, all cases with SDHB exon 1 deletion had the same gene breakpoint pattern of a 15 678 bp deletion previously described in the Iberian Peninsula, indicating a common origin. CONCLUSION: The germline heterozygous SDHB exon 1 deletion was the most frequent genetic defect in the Brazilian PPGL cohort. Our findings demonstrated a founder effect for the SDHB exon 1 deletion in Brazilian patients with paragangliomas.

Ultrasound in cervical traumatic neuromas after neck dissection in thyroid carcinoma patients: descriptive analysis and diagnostic accuracy

ABSTRACT Objective: Cervical traumatic neuromas (CTNs) may appear after lateral neck dissection for metastatic thyroid carcinoma. If they are misdiagnosed as metastatic lymph nodes (LNs) in follow-up neck ultrasound (US), unnecessary and uncomfortable fine-needle aspiration biopsy are indicated. The present study aimed to describe US features of CTNs and to assess the US performance in distinguishing CTNs from abnormal LNs. Subjects and methods: Retrospective evaluation of neck US images of 206 consecutive patients who had lateral neck dissection as a part of thyroid cancer treatment to assess CTN's US features. Diagnostic accuracy study to evaluate US performance in distinguishing CTNs from abnormal LNs was performed. Results: Eight-six lateral neck nodules were selected for analysis: 38 CTNs and 48 abnormal LNs. CTNs with diagnostic cytology were predominantly hypoechogenic (100% vs. 45%; P = 0.008) and had shorter diameters than inconclusive cytology CTNs: short axis (0.39 cm vs. 0.50 cm; P = 0.03) and long axis (1.64 cm vs. 2.35 cm; P = 0.021). The US features with the best accuracy to distinguish CTNs from abnormal LNs were continuity with a nervous structure, hypoechogenic internal lines, short/long axis ratio ≤ 0.42, absent Doppler vascularization, fusiform morphology, and short axis ≤ 0.48 cm. Conclusion: US is a very useful method for assessing CTNs, with good performance in distinguishing CTNs from abnormal LNs.

Fructosamine and glycated hemoglobin as biomarkers of glycemic control in people with type 2 diabetes mellitus and cancer (GlicoOnco study)

Abstract Introduction Glycemic control is important to avoid diabetes complications in individuals with cancer. There is no evidence for HbA1c and fructosamine as reliable biomarkers in these conditions. There are particularities in caring for patients with diabetes and cancer that can alter these biomarkers. Objective The aim of this study was to evaluate HbA1c and fructosamine as glycemic biomarkers in people with type 2 diabetes and cancer, undergoing clinical or surgical oncological treatment. Methods The authors conducted a single-center, retrospective analysis with people who have cancer and diabetes. Comparison of glycemic biomarkers (HbA1c, fructosamine, and Self-Monitoring of Blood Glucose [SMBG]) was performed including evaluation in individuals undergoing chemotherapy, using glucocorticoids, with anemia, hypoproteinemia or with reduced estimated Glomerular Filtration Rate (eGFR). Results There was a strong positive correlation between fructosamine and HbA1c (n = 318, r= 0.66, p < 0.001) in people with diabetes and cancer even in those under chemotherapy (n = 101, r= 0.61, p < 0.001) or using glucocorticoids (n = 96, r= 0.67, p<0.001). There was a strong correlation between HbA1c and fructosamine in subjects with anemia (n = 111, r= 0.66, p < 0.001), hypoproteinemia (n = 54, r= 0.67, p < 0.001), or with eGFR ≥ 60 mL/min/1.73 m2 (n = 189, r= 0.70, p < 0.001), and moderate correlation with hypoalbuminemia (n = 21, r= 0.54, p = 0.001) and with reduced eGFR (n = 67, r= 0.57, p < 0.001). The correlations between fructosamine and HbA1c with SMBG were moderate (n = 164, r= 0.49, p < 0.001; n = 111, r= 0.55, p < 0.001, respectively), strong in subjects undergoing chemotherapy, with hypoalbuminemia or hypoproteinemia, and at least moderate, if eGFR < 60 mL/min/1.73 m2 or with anemia. Conclusions Fructosamine and HbA1c can be used as glycemic biomarkers in people with diabetes and cancer, even in those with anemia, hypoproteinemia, or undergoing chemotherapy.

Cabozantinib for previously treated radioiodine-refractory differentiated thyroid cancer: Updated results from the phase 3 COSMIC-311 trial.

BACKGROUND: At an interim analysis (median follow-up, 6.2 months; n = 187), the phase 3 COSMIC-311 trial met the primary end point of progression-free survival (PFS): cabozantinib improved PFS versus a placebo (median, not reached vs. 1.9 months; p < .0001) in patients with previously treated radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). The results from an exploratory analysis using an extended datacut are presented. METHODS: Patients 16 years old or older with RAIR-DTC who progressed on prior lenvatinib and/or sorafenib were randomized 2:1 to oral cabozantinib tablets (60 mg/day) or a placebo. Placebo patients could cross over to open-label cabozantinib upon radiographic disease progression. The objective response rate (ORR) in the first 100 randomized patients and the PFS in the intent-to-treat population, both according to Response Evaluation Criteria in Solid Tumors version 1.1 by blinded, independent review, were the primary end points. RESULTS: At the data cutoff (February 8, 2021), 258 patients had been randomized (cabozantinib, n = 170; placebo, n = 88); the median follow-up was 10.1 months. The median PFS was 11.0 months (96% confidence interval [CI], 7.4-13.8 months) for cabozantinib and 1.9 months (96% CI, 1.9-3.7 months) for the placebo (hazard ratio, 0.22; 96% CI, 0.15-0.32; p < .0001). The ORR was 11.0% (95% CI, 6.9%-16.9%) versus 0% (95% CI, 0.0%-4.1%) (p = .0003) with one complete response with cabozantinib. Forty placebo patients crossed over to open-label cabozantinib. Grade 3/4 treatment-emergent adverse events occurred in 62% and 28% of the cabozantinib- and placebo-treated patients, respectively; the most common were hypertension (12% vs. 2%), palmar-plantar erythrodysesthesia (10% vs. 0%), and fatigue (9% vs. 0%). There were no grade 5 treatment-related events. CONCLUSIONS: At extended follow-up, cabozantinib maintained superior efficacy over a placebo in patients with previously treated RAIR-DTC with no new safety signals.

Treatment strategies for low-risk papillary thyroid carcinoma: a position statement from the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism (SBEM).

Increasingly sensitive diagnostic methods, better understanding of molecular pathophysiology, and well-conducted prospective studies have changed the current approach to patients with thyroid cancer, requiring the implementation of individualized management. Most patients with papillary thyroid carcinoma (PTC) are currently considered to have a low risk of mortality and disease persistence/recurrence. Consequently, current treatment recommendations for these patients include less invasive or intensive therapies. We used the most recent evidence to prepare a position statement providing guidance for decisions regarding the management of patients with low-risk PTC (LRPTC). This document summarizes the criteria defining LRPTC (including considerations regarding changes in the TNM staging system), indications and contraindications for active surveillance, and recommendations for follow-up and surgery. Active surveillance may be an appropriate initial choice in selected patients, and the criteria to recommend this approach are detailed. A section is dedicated to the current evidence regarding lobectomy versus total thyroidectomy and the potential pitfalls of each approach, considering the challenges during long-term follow-up. Indications for radioiodine (RAI) therapy are also addressed, along with the benefits and risks associated with this treatment, patient preparation, and dosage. Finally, this statement presents the best follow-up strategies for LRPTC after lobectomy and total thyroidectomy with or without RAI.