Imaging Medullary Thyroid Carcinoma with Persistent Elevated Calcitonin Levels

Giraudet, Anne Laure; Vanel, D.; Leboulleux, Sophie; Aupérin, Anne; Dromain, Clarisse; Chami, L.; Tovo, Noël Ny; Lumbroso, J.; Lassau, Nathalie; Bonniaud, G.; Hartl, Dana M.; Travagli, J. P.; Baudin, Éric; Schlumberger, Martin

doi:10.1210/jc.2007-1211

Cited by 233 publications

(180 citation statements)

References 34 publications

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“…For local or regional recurrence in the neck and mediastinum, reoperation is the main treatment. However, cure is achieved only in 5-35% of the reoperated patients, and the remainder of patients are at high risk of developing distant metastasis (Wells et al 1982, Giraudet et al 2007. Distant metastases that are observed at presentation in 7-23% of unselected patients with MTC are the main cause of MTC-related death with survival rates of 25% at 5 years after their detection (Bergholm et al 1997, Modigliani et al 1998.…”

Section: Introductionmentioning

confidence: 99%

Overexpression and activation of EGFR and VEGFR2 in medullary thyroid carcinomas is related to metastasis

Rodríguez‐Antona

Pallarés²,

Montero‐Conde³

et al. 2010

Endocrine-Related Cancer

118

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Therapeutic options for patients with metastatic medullary thyroid carcinoma (MTC) are limited due to lack of effective treatments. Thus, there is a need to thoroughly characterize the pathways of molecular pathogenesis and to identify potential targets for therapy in MTC. Since epidermal growth factor receptor (EGFR) seems to play a crucial role for RET activation, a key feature of MTCs, and several promising EGFR/vascular endothelial growth factor receptor 2 (VEGFR2)-targeted drugs have been developed, the present study was designed to investigate whether these proteins are altered in MTCs. We used a well-characterized series of 153 MTCs to evaluate EGFR activation by sequencing and FISH analysis, and to perform EGFR and VEGFR2 immunohistochemistry. EGFR tyrosine kinase domain mutations were not a feature of MTCs; however, EGFR polysomy and a strong EGFR expression were detected in 15 and 13% of the tumors respectively. Interestingly, EGFR was significantly overexpressed in metastases compared with primary tumors (35 vs 9%, PZ0.002). We also studied whether specific RET mutations were associated with EGFR status, and found a decrease in EGFR polysomies (PZ0.006) and a tendency towards lower EGFR expression for the most aggressive RET mutations (918, 883). Concerning VEGFR2, metastasis showed a higher expression than primary tumors (PZ2.8!10 K8 ). In this first study investigating the relationship between EGFR, RET, and VEGFR2 in a large MTC series, we found an activation of EGFR and VEGFR2 in metastasis, using both independent and matched primary/metastasis samples. This suggests that some MTC patients may benefit from existing anti-EGFR/VEFGR2 therapies, although additional preclinical and clinical evidence is needed.

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Section: Introductionmentioning

confidence: 99%

Overexpression and activation of EGFR and VEGFR2 in medullary thyroid carcinomas is related to metastasis

Rodríguez‐Antona

Pallarés²,

Montero‐Conde³

et al. 2010

Endocrine-Related Cancer

118

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“…Diagnosis of the sporadic form is usually established late in life (approximately the fifth or sixth decade). Neck lymph node metastases are detected in approximately 50% of cases at the time of diagnosis, while distant metastases occur in 20% of cases (8)(9)(10)(11) (B). Early surgical intervention is the only curative therapeutic approach (11) (B).…”

Section: (A/b)mentioning

confidence: 99%

“…Neck metastases appear early during the course of MTC (9,65) (B). Distant metastases are detected in 7-17% of all cases at the time of diagnosis and frequently appear in multiple sites (lungs, liver, bones, and less often in the brain and skin) (10,11,66,67) Individuals with hereditary MTC should be screened for pheochromocytoma, given their high risk of that disease (72) (B). As up to 10% of apparently sporadic MTC have a RET germline mutation, the presence of pheochromocytoma should be excluded in any patient with suspected MTC before the thyroidectomy, due to the high risk of anesthesia and the surgical procedure (73,74)(D/B).…”

Section: Recommendationmentioning

confidence: 99%

Diagnóstico, tratamento e seguimento do carcinoma medular de tireoide: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia

Maia

Siqueira

Kulcsar

et al. 2014

Arq Bras Endocrinol Metab

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Introduction: Medullary thyroid carcinoma (MTC) originates in the thyroid parafollicular cells and represents 3-4% of the malignant neoplasms that affect this gland. Approximately 25% of these cases are hereditary due to activating mutations in the REarranged during Transfection (RET) proto-oncogene. The course of MTC is indolent, and survival rates depend on the tumor stage at diagnosis. The present article describes clinical evidence-based guidelines for the diagnosis, treatment, and follow-up of MTC. Objective: The aim of the consensus described herein, which was elaborated by Brazilian experts and sponsored by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism, was to discuss the diagnosis, treatment, and follow-up of individuals with MTC in accordance with the latest evidence reported in the literature. Materials and methods: After clinical questions were elaborated, the available literature was initially surveyed for evidence in the MedLine-PubMed database, followed by the Embase and Scientific Electronic Library Online/Latin American and Caribbean Health Science Literature (SciELO/Lilacs) databases. The strength of evidence was assessed according to the Oxford classification of evidence levels, which is based on study design, and the best evidence available for each question was selected. Results: Eleven questions corresponded to MTC diagnosis, 8 corresponded to its surgical treatment, and 13 corresponded to follow-up, for a total of 32 recommendations. The present article discusses the clinical and molecular diagnosis, initial surgical treatment, and postoperative management of MTC, as well as the therapeutic options for metastatic disease. Conclusions: MTC should be suspected in individuals who present with thyroid nodules and family histories of MTC, associations with pheochromocytoma and hyperparathyroidism, and/or typical phenotypic characteristics such as ganglioneuromatosis and Marfanoid habitus. Fine-needle nodule aspiration, serum calcitonin measurements, and anatomical-pathological examinations are useful for diagnostic confirmation. Surgery represents the only curative therapeutic strategy. The therapeutic options for metastatic disease remain limited and are restricted to disease control. Judicious postoperative assessments that focus on the identification of residual or recurrent disease are of paramount importance when defining the follow-up and later therapeutic management strategies. Arq Bras Endocrinol Metab. 2014;58(7):667-700

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“…Two studies showed that FDG PET/CT outperforms CT and MRI for the detection of neck and mediastinal disease, but is inferior to CT for the detection of lung and liver metastases, and to MRI for the identification of metastases to bone [17,18]. Three studies have examined serum Ct levels and the likelihood of a positive FDG PET scan.…”

mentioning

confidence: 99%

Evolving paradigms for successful molecular imaging of medullary thyroid carcinoma

Rubello

Wong

Marzola

et al. 2012

Eur J Nucl Med Mol Imaging

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Imaging Medullary Thyroid Carcinoma with Persistent Elevated Calcitonin Levels

Abstract: The most efficient imaging work-up for depicting MTC tumor sites would consist of a neck US, chest CT, liver MRI, bone scintigraphy, and axial skeleton MRI. FDG PET scan appeared to be less sensitive and of low prognostic value.

Cited by 233 publications

References 34 publications

Overexpression and activation of EGFR and VEGFR2 in medullary thyroid carcinomas is related to metastasis

Overexpression and activation of EGFR and VEGFR2 in medullary thyroid carcinomas is related to metastasis

Diagnóstico, tratamento e seguimento do carcinoma medular de tireoide: recomendações do Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia

Evolving paradigms for successful molecular imaging of medullary thyroid carcinoma

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