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 post-neoadjuvant response evaluations using the Response Evaluation Criteria in Solid Tumors, feasibility of surgery and completeness of resection. Secundary outcomes were mortality and status at 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 BRAF V600E 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 ten (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 50% 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.

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).

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.

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.

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.

Effects of glucocorticoids on interstitial glucose concentrations in individuals with hematologic cancer and without known diagnosis of diabetes: a pilot study.

OBJECTIVE: To analyze interstitial glucose behavior during glucocorticoid use in non-diabetic patients receiving chemotherapy for hematologic malignancies. METHODS: Prospective pilot study carried out to assess interstitial glucose levels in 15 non-diabetic individuals with hematologic malignancies who received glucocorticoids in combination with chemotherapy. The FreeStyle Libre flash monitoring system (Abbott Diabetes Care) was used for up to 14 days to measure interstitial glucose. RESULTS: Median age and body mass index were 53 (42-61) years and 25 (23-28) kg/m2 respectively. Interstitial glucose levels >180mg/dL lasting at least one hour were detected in 60% of participants. Interstitial glucose profile parameters (median and peak interstitial glucose levels and percentage of time during which interstitial glucose levels were >180mg/dL) were significantly (p<0.01) higher during glucocorticoid use (115mg/dL, 218mg/dL and 10% respectively) than after glucocorticoid discontinuation (97mg/dL, 137mg/dL and 0% respectively). Mean interstitial glucose levels increased in the afternoon and at night during glucocorticoid use. CONCLUSION: This pilot study was the first to evaluate interstitial glucose levels in non-diabetic individuals using glucocorticoids in treatment of hematologic cancer. Glucocorticoid use during chemotherapy significantly increases interstitial glucose levels in these patients.

How to Identify Cervical Traumatic Neuromas in the Post-operative Neck Dissection: Brief Review of the Cervical Plexus Ultrasound.

Cervical traumatic neuromas (CTNs) are a non-neoplastic hyperplasia of damaged nerves and may be misinterpreted as metastatic lymph nodes during cervical ultrasound of patients with thyroid cancer after lateral neck dissection, resulting in unnecessary and painful fin-needle aspiration biopsy. The anatomy of the cervical plexus is challenging, and the correct identification and recognition of its neural roots and branches on ultrasound are key to the correct CTN diagnosis. This review outlines the US technique used to characterize CTNs in 10 standardized steps and describes the sonographic features of the cervical plexus, to assist the radiologist in the recognition of CTNs and their differentiation from lymph node metastases.

Risk factors associated with disease-specific mortality in papillary thyroid cancer patients with distant metastases.

PURPOSE: Papillary thyroid carcinoma (PTC) is among the most curable cancer types. Even though uncommon, some patients present distant metastatic disease at diagnosis or during the follow-up and most of them have long-term survival. However, there continues to be controversies regarding what clinicopathological features are associated with mortality in these patients. This paper evaluates the factors related to poor disease-specific survival (DSS) in patients with metastatic PTC. METHODS: A retrospective cohort study included PTC patients with distant metastasis from a tertiary public oncological center. Clinicopathological features, treatment modalities, and outcome were reviewed. RESULTS: Between 1986 and 2014, 108 patients were diagnosed with metastatic PTC. In the multivariate analysis male sex (HR = 2.65; 95%CI: 1.08-6.53; P = 0.033), radioiodine refractory disease (HR = 9.50; 95%CI: 1.23-73.38; P = 0.031) and metastasis at multiple sites (HR = 5.91; 95%CI: 1.80-19.32; P = 0.003) were independent risk factors for death in patients with metastatic PTC. CONCLUSION: Male patients with metastatic PTC, with radioiodine refractory disease and metastasis at multiple sites have a high risk of death.

Effects of glucocorticoids on interstitial glucose concentrations in individuals with hematologic cancer and without known diagnosis of diabetes: a pilot study

ABSTRACT Objective To analyze interstitial glucose behavior during glucocorticoid use in non-diabetic patients receiving chemotherapy for hematologic malignancies. Methods Prospective pilot study carried out to assess interstitial glucose levels in 15 non-diabetic individuals with hematologic malignancies who received glucocorticoids in combination with chemotherapy. The FreeStyle Libre flash monitoring system (Abbott Diabetes Care) was used for up to 14 days to measure interstitial glucose. Results Median age and body mass index were 53 (42-61) years and 25 (23-28) kg/m2 respectively. Interstitial glucose levels >180mg/dL lasting at least one hour were detected in 60% of participants. Interstitial glucose profile parameters (median and peak interstitial glucose levels and percentage of time during which interstitial glucose levels were >180mg/dL) were significantly (p<0.01) higher during glucocorticoid use (115mg/dL, 218mg/dL and 10% respectively) than after glucocorticoid discontinuation (97mg/dL, 137mg/dL and 0% respectively). Mean interstitial glucose levels increased in the afternoon and at night during glucocorticoid use. Conclusion This pilot study was the first to evaluate interstitial glucose levels in non-diabetic individuals using glucocorticoids in treatment of hematologic cancer. Glucocorticoid use during chemotherapy significantly increases interstitial glucose levels in these patients.

Thyroid collision tumor containing oncocytic carcinoma, classical and hobnail variants of papillary carcinoma and areas of poorly differentiated carcinoma

SUMMARY Collision tumors are rare and may comprise components with different behavior, treatments, and prognosis. We report an unprecedented case of aggressive thyroid collision tumor containing widely invasive oncocytic carcinoma (OC), classical and hobnail (HPTC) variants of papillary carcinoma, and poorly differentiated carcinoma (PDTC). The patient underwent total thyroidectomy, radioactive iodine therapy, and within months progressed with local recurrence, and pulmonary metastases requiring neck dissection, external radiotherapy and systemic treatment with sorafenib. The rapid progression, dedifferentiated metastatic lesions, and failure to treatments resulted in the patient´s death. The great variety of histological types and the evolution of this case were a challenge for the management of metastatic disease. Widely invasive OC, HPTC and PDTC are considered to have a worse prognosis. HPTC has never been reported as a component of a collision tumor. HPTC and PDTC should call attention to a possible higher-grade transformation.

Thyroid collision tumor containing oncocytic carcinoma, classical and hobnail variants of papillary carcinoma and areas of poorly differentiated carcinoma.

Collision tumors are rare and may comprise components with different behavior, treatments, and prognosis. We report an unprecedented case of aggressive thyroid collision tumor containing widely invasive oncocytic carcinoma (OC), classical and hobnail (HPTC) variants of papillary carcinoma, and poorly differentiated carcinoma (PDTC). The patient underwent total thyroidectomy, radioactive iodine therapy, and within months progressed with local recurrence, and pulmonary metastases requiring neck dissection, external radiotherapy and systemic treatment with sorafenib. The rapid progression, dedifferentiated metastatic lesions, and failure to treatments resulted in the patient's death. The great variety of histological types and the evolution of this case were a challenge for the management of metastatic disease. Widely invasive OC, HPTC and PDTC are considered to have a worse prognosis. HPTC has never been reported as a component of a collision tumor. HPTC and PDTC should call attention to a possible higher-grade transformation.

Comparison of 18F-NaF PET/CT with Other Imaging Methods in the Detection of Bone Metastases in Patients with Medullary Thyroid Cancer: a Report of a Series of 31 Cases.

PURPOSE: To compare the 18F-NaF PET/CT studies (18F-NaF) with other imaging methods in the detection of skeletal metastases (SM) in patients with medullary thyroid cancer (MTC). METHODS: We retrospectively analyzed 31 patients with MTC who performed 18F-NaF to assess SM. The results of the 18F-NaF were compared with other imaging methods performed for metastasis detection: 99Tc-MDP bone scan (BS), magnetic resonance imaging (MRI), contrast-enhanced CT (CT), and 68Ga-Dotatate and 18F-FDG PET/CT studies. A qualitative analysis comparing the 18F-NaF findings with the ones of the other methods was performed, and the results were classified as superior (>), equal (=), and inferior (<). RESULTS: Eleven patients had no bone metastases detected on any of the imaging methods used. Twenty patients presented SM depicted on 18F-NaF. Of these 20 patients, 12 performed bone scan (in 9 18F-NaF > BS and in 3 18F-NaF = BS), 1 performed 18F-FDG (18F-NaF > 18F-FDG), 4 performed 68Ga-Dotatate (in 2 18F-NaF > 68Ga-Dotatate and in 2 18F-NaF = 68Ga-Dotatate), 20 performed CT of at least one body segment (in 15 18F-NaF = CT and in 5 18F-NaF > CT), and 16 performed MRI of at least one body segment, and in all of them, the 18F-NaF was equal to the MRI. Beside this, the 18F-NaF detected SM in body segments not routinely scanned in MRI and CT. CONCLUSION: In patients with MTC, the 18F-NaF seems to be equal or superior to other imaging modalities in the detection of SM and allows the analysis of the whole skeletal in a single study.

Diagnostic performance of thyroid ultrasound in Hürthle cell carcinomas

ABSTRACT Objective Hürthle cell carcinomas (HCCs) of the thyroid have been recently reclassified as a separate entity due to their distinct clinical and molecular profiles. Few studies have assessed the ability of preoperative characteristics in differentiating HCCs from Hürthle cell adenomas (HCAs) due to the low prevalence of both lesions. This study aimed to compare the preoperative features of HCCs and HCAs and evaluate the diagnostic performance of ultrasound in distinguishing between both. Subjetcs and methods Retrospective study including 101 patients (52 HCCs and 49 HCAs) who underwent thyroid surgery from 2000 to 2016. Clinical, ultrasonographic, and histological data were reviewed. Diagnostic performance of suspicious sonographic features was analyzed in 51 cases (24 HCCs and 27 HCAs). Results Hürthle cell neoplasms were predominant in females. Subjects ≥ 55 years represented 58% of the cases of HCCs and 53% of those of HCAs. Carcinomas were significantly larger (p < 0.001), and a tumor size ≥ 4 cm significantly increased the risk of malignancy (odds ratio 3.67). Other clinical, cytologic, and sonographic data were similar between HCCs and HCAs. Among the HCCs, the lesions were purely solid in 54.2%, hypoechoic in 37.5%, and had coarse calcifications in 12.5%, microcalcifications in 8.3%, irregular contours in 4.2%, and a taller-than-wide shape in 16.7%. Predominantly/exclusive intranodular vascularization was observed in 52.6%. Overall, 58% of the HCCs were classified as TI-RADS 4 or 5 compared with 48% of the HCAs. TI-RADS 4 or 5 had a specificity of only 51.8% and a positive likelihood ratio of 1.21. Conclusions Apart from the lesion size, no other preoperative feature adequately distinguished HCCs from HCAs. Sonographic characteristics raising suspicion for malignancy, which are mostly present in papillary carcinomas, were infrequent in HCCs. New tools must be developed to improve preoperative diagnosis and deferral of surgery in cases of adenomas.