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Endocrine-related Cancer May 2022Medullary thyroid carcinoma (MTC) is a rare malignancy comprising 1-2% of all thyroid cancers in the United States. Approximately 20% of cases are familial, secondary to... (Review)
Review
Medullary thyroid carcinoma (MTC) is a rare malignancy comprising 1-2% of all thyroid cancers in the United States. Approximately 20% of cases are familial, secondary to a germline RET mutation, while the remaining 80% are sporadic and also harbour a somatic RET mutation in more than half of all cases. Up to 15-20% of patients will present with distant metastatic disease, and retrospective series report a 10-year survival of 10-40% from time of first metastasis. Historically, systemic therapies for metastatic MTC have been limited, and cytotoxic chemotherapy has demonstrated poor objective response rates. However, in the last decade, targeted therapies, particularly multitargeted tyrosine kinase inhibitors (TKIs), have demonstrated prolonged progression-free survival in advanced and progressive MTC. Both cabozantinib and vandetanib have been approved as first-line treatment options in many countries; nevertheless, their use is limited by high toxicity rates and dose reductions are often necessary. New generation TKIs, such as selpercatinib or pralsetinib, that exhibit selective activity against RET, have recently been approved as a second-line treatment option, and they exhibit a more favourable side-effect profile. Peptide receptor radionuclide therapy or immune checkpoint inhibitors may also constitute potential therapeutic options in specific clinical settings. In this review, we aim to present all current therapeutic options available for patients with progressive MTC, as well as new or as yet experimental treatments.
Topics: Carcinoma, Neuroendocrine; Humans; Progression-Free Survival; Retrospective Studies; Thyroid Neoplasms
PubMed: 35521769
DOI: 10.1530/ERC-21-0368 -
Der Chirurg; Zeitschrift Fur Alle... Nov 2021Endocrine tumors and here in particular gastrointestinal neuroendocrine neoplasms (GEP-NET), pheochromocytomas (PC), paragangliomas (PGL) and thyroid tumors are prime... (Review)
Review
Endocrine tumors and here in particular gastrointestinal neuroendocrine neoplasms (GEP-NET), pheochromocytomas (PC), paragangliomas (PGL) and thyroid tumors are prime examples of the importance of molecular pathology and molecular biology for the diagnostics, classification and ultimately also the (surgical) treatment of these diseases. The GEP-NETs are graded using the Ki-67 index. This determines the type of molecular imaging (DOTA/DOPA/FDG-PET/CT), the possible treatment (surgical and/or radiopeptide therapy), antiproliferative and symptom-controlling treatment with somatostatin analogues and ultimately also the prognosis. The PC/PGLs can be hereditary (MEN2A, VHL, NF1, SDH mutations), which significantly influences the surgical treatment and preoperative medication. Molecular imaging is very important and can lead the way in cases of borderline biochemistry. Adrenal carcinomas can also be genetically determined. In the case of thyroid tumors, the pathology of the C‑cell (C-cell hyperplasia, medullary thyroid carcinoma) should be emphasized. In the case of hereditary diseases (FMTC, MEN2), early prophylactic surgery is often necessary and prevents the occurrence of advanced carcinomas; however, the determination of the extent of resection in follicular lesions or the distinction between noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and follicular variants of papillary thyroid carcinoma can also be determined with the help of specific markers. Overall, molecular pathology has an increasingly more important role in these entities and is also the topic of ongoing research projects.
Topics: Adrenal Gland Neoplasms; Carcinoma, Neuroendocrine; Humans; Positron Emission Tomography Computed Tomography; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 34618164
DOI: 10.1007/s00104-021-01512-8 -
Minerva Endocrinology Mar 2021Familial non-medullary thyroid cancer (FNMTC) constitutes 3-9% of all thyroid cancers and occurs in two or more first-degree relatives in the absence of predisposing... (Review)
Review
Familial non-medullary thyroid cancer (FNMTC) constitutes 3-9% of all thyroid cancers and occurs in two or more first-degree relatives in the absence of predisposing environmental factors. Out of all FNMTC cases, only 5% are represented by syndromic forms (Gardner's Syndrome, familial adenomatous polyposis, Cowden's Syndrome, Carney complex 1, Werner's Syndrome and DICER1 syndrome), in which thyroid cancer occurs as a minor component and the genetic alterations are well-known. The non-syndromic forms represent the majority of all FNMTCs (95%), and the thyroid cancer is the predominant feature. Several low penetration susceptibility risk loci or genes (i.e. TTF1, FOXE1, SRGAP1, SRRM2, HABP2, MAP2K5, and DUOX2), here fully reviewed, have been proposed in recent years with a possible causative role, though the results are still not conclusive or reliable. FNMTC is indistinguishable from sporadic non-medullary thyroid cancer (sNMTC), which means that FNMTC cannot be diagnosed until at least one of the patient's first-degree relatives is affected by tumor. Some studies reported that the non-syndromic FNMTC is more aggressive than the sNMTC, being characterized by a younger age of onset and a higher rate of multifocal and bilateral tumors, extrathyroidal extension, lymph node metastasis, and recurrence. On the contrary, other studies did not find clinical differences between non-syndromic FNMTCs and sporadic cases. Here, I reported an extensive review on genetic and clinico-pathological features of the FNMTC, with particular attention on novel genetic risk factors for non-syndromic forms.
Topics: Humans; Neoplasm Recurrence, Local; Risk Factors; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 33045820
DOI: 10.23736/S2724-6507.20.03338-6 -
Turk Patoloji Dergisi 2022< strong > Objective: < /strong > Medullary thyroid carcinoma (MTC) is a rare tumor originating from parafollicular C cells. It has more aggressive biologic behavior...
< strong > Objective: < /strong > Medullary thyroid carcinoma (MTC) is a rare tumor originating from parafollicular C cells. It has more aggressive biologic behavior than differentiated thyroid carcinomas, and it is insensitive to treatment with radioactive iodine. Vandetanib and cabozantinib are the newly approved tyrosine kinase inhibitors in advanced stages, but novel effective systemic therapeutics could be crucial and needed for the clinical management of these patients. We aimed to evaluate the Programmed death-ligand 1 (PD-L1) expression, which is a novel immunotherapy target, in our MTC cohort, and determine whether it has an association with clinical and pathological features. < strong > Material and Method: < /strong > This retrospective study involved 41 cases of MTC with a median follow-up of 54 months. PD-L1 monoclonal antibody (SP263 clone) was investigated immunohistochemically. Complete and/or partial membranous staining pattern in more than 1% of tumor cells was considered positive. The correlations of PD-L1 expression with clinicopathologic and prognostic features were analyzed. < strong > Results: < /strong > PD-L1 positivity was detected in 5 (12.2%) of 41 tumors. The extent of PD-L1 staining was low ( < 5%) for all tumors. There was no clinicopathologic and prognostic relevance regarding PD-L1 expression in our MTC patients. < strong > Conclusion: < /strong > Although PD-L1 expression could be a potential biomarker to predict the prognosis of various cancers and response to checkpoint inhibitors, we did not find any significant correlation between PD-L1 expression and clinicopathologic features in our cases. Studies with larger patient numbers are still required to perform a more comprehensive analysis.
Topics: B7-H1 Antigen; Biomarkers, Tumor; Carcinoma, Neuroendocrine; Humans; Iodine Radioisotopes; Prognosis; Retrospective Studies; Thyroid Neoplasms
PubMed: 34580845
DOI: 10.5146/tjpath.2021.01558 -
Endocrinology, Diabetes & Metabolism Jul 2021PD-L1 expression in MTC is hot topic since, if it is demonstrated that PD-L1 is highly expressed in this cancer, thus immunotherapy against checkpoint inhibitors could...
PD-L1 expression in MTC is hot topic since, if it is demonstrated that PD-L1 is highly expressed in this cancer, thus immunotherapy against checkpoint inhibitors could become an important therapeutic tool in MTC treatment. To answer this question, we evaluated PD-L1 expression in MCT tumour tissues, using an anti-PD-L1 22C3 antibody and found a high expression in 6 of the 8 patients (75%). Similarly, two other recent studies reported a higher PD-L1 expression. According to our results, MTC cells present a significative PD-L1 expression, raising the hypothesis that immunotherapy, such as pembrolizumab, could have a role on MCT treatment. The authors believe this is a fundamental question and may impact the future of MTC treatment.
Topics: B7-H1 Antigen; Carcinoma, Neuroendocrine; Humans; Immunologic Factors; Immunotherapy; Thyroid Neoplasms
PubMed: 34277966
DOI: 10.1002/edm2.241 -
Seminars in Nuclear Medicine Jul 2023Currently, there is a discrepancy among the available guidelines on the usefulness of nuclear medicine techniques in medullary thyroid cancer (MTC) diagnosis and... (Review)
Review
Currently, there is a discrepancy among the available guidelines on the usefulness of nuclear medicine techniques in medullary thyroid cancer (MTC) diagnosis and treatment. Aim of this review is to provide an update on diagnostic and therapeutic nuclear medicine techniques in this setting. Evidence-based data clearly demonstrates the usefulness of PET/CT with different radiopharmaceuticals in recurrent MTC (in particular when serum calcitonin is higher than 150 pg/mL or calcitonin doubling time is shortened) and F-FDOPA should be the preferred PET radiopharmaceutical. If F-FDOPA PET/CT is negative or unavailable, F-FDG PET/CT or Ga-DOTA-peptides PET/CT could be performed for MTC restaging. There is currently insufficient evidence to recommend PET/CT with several radiopharmaceuticals for MTC staging. Clinical experience on PET/MRI with different radiopharmaceuticals in MTC is still limited. Several investigational nuclear medicine therapeutic options are currently under evaluation in metastatic MTC. More data are needed to evaluate the efficacy, toxicity, and role of these therapeutic options in the management of MTC patients.
Topics: Humans; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Calcitonin; Fluorodeoxyglucose F18; Nuclear Medicine; Neoplasm Recurrence, Local; Carcinoma, Neuroendocrine; Thyroid Neoplasms
PubMed: 36702731
DOI: 10.1053/j.semnuclmed.2023.01.003 -
Endocrinology and Metabolism Clinics of... Jun 2022Medullary thyroid cancer is a rare thyroid malignancy with unique management considerations. In general, small intrathyroidal tumors are cured by total thyroidectomy... (Review)
Review
Medullary thyroid cancer is a rare thyroid malignancy with unique management considerations. In general, small intrathyroidal tumors are cured by total thyroidectomy with central compartment dissection, while large tumors and those with disease spread to regional lymph nodes and distant organs (most commonly lung, liver, and bone) are more difficult to cure. The last decade has seen significant progress in the treatment of advanced MTC, largely due to the discovery and availability of novel targeted therapies, including new drugs specifically targeting the RET protooncogone.
Topics: Carcinoma, Neuroendocrine; Humans; Proto-Oncogene Proteins c-ret; Thyroid Neoplasms; Thyroidectomy
PubMed: 35662447
DOI: 10.1016/j.ecl.2022.02.001 -
Current Medicinal Chemistry 2020Thyroid cancer is the most common endocrine malignancy and it accounts for 1% of all newly diagnosed tumors. Approximately 10% of patients with differentiated thyroid... (Review)
Review
Thyroid cancer is the most common endocrine malignancy and it accounts for 1% of all newly diagnosed tumors. Approximately 10% of patients with differentiated thyroid carcinomas (DTC) and 30% with medullary thyroid carcinoma (MTC) could not be cured with locoregional treatment and could develop metastatic disease. In addition, one of the most aggressive solid tumors can arise from the thyroid gland, the anaplastic thyroid carcinoma, with a median overall survival of less than 6 months. Currently, only four drugs are approved for the treatment of DTC and MTC and several unmet needs are focusing the scientific discussions, including the resistant setting, the off-target side effects that may reduce the efficacy and the molecular knowledge-based combinations. In this review, we aimed to discuss the current molecular landscape and treatment of thyroid cancers, and the ongoing clinical and translational research lines focusing on new drugs and drug combinations to improve the inhibition of driver mutations, such as BRAF and RET, and how systemic therapies that improved outcomes of other cancer types, like immunotherapy and peptide receptor radionuclide therapy, may play a role in the future management of advanced thyroid cancers.
Topics: Humans; Immunotherapy; Mutation; Thyroid Neoplasms
PubMed: 32056516
DOI: 10.2174/0929867327666200214125712 -
Endocrinologia, Diabetes Y Nutricion Apr 2021Familial non-medullary thyroid cancer is defined as the presence of non-medullary thyroid cancer in two or more first-degree relatives, in the absence of other... (Review)
Review
Familial non-medullary thyroid cancer is defined as the presence of non-medullary thyroid cancer in two or more first-degree relatives, in the absence of other predisposing factors. It represents up to 9% of differentiated thyroid cancers, and only a minority appears in well-known hereditary syndromes that associate thyroid cancer among many other clinical manifestations. However, in more than 95% of cases, thyroid cancer appears isolated, and its genetic causes have yet to be elucidated. We review here the current knowledge of the genetic basis of this pathology, as well as its clinical characteristics. Understanding the genetic mechanisms implied would help to comprehend the metabolic pathways involved, with the consequent potential therapeutic application. In addition, it would allow genetic counseling and to focus our efforts on patients at risk of developing this disorder.
Topics: Humans; Neoplastic Syndromes, Hereditary; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 34266638
DOI: 10.1016/j.endien.2020.08.013 -
Clinical Endocrinology Nov 2022The eighth edition of the American Joint Committee on Cancer tumour, node, and metastasis staging system did not take T stage into consideration when evaluating Stage...
BACKGROUND
The eighth edition of the American Joint Committee on Cancer tumour, node, and metastasis staging system did not take T stage into consideration when evaluating Stage IV C medullary thyroid carcinoma (MTC) patients. The aim of this study is to investigate the clinical outcomes and implications of T stage in this population.
METHODS
Eligible patients from the Surveillance, Epidemiology, and End Results database and the Department of Thyroid Surgery in West China Hospital of Sichuan University and who were diagnosed with Stage IV C MTC were included in this study. The overall survival (OS), the cancer-specific survival (CSS), and the precise cause of MTC-induced death were analysed. The potential risk factors, including the T stage, in the OS and CSS were evaluated by univariate and multivariate Cox regression models.
RESULTS
This retrospective study enroled 204 Stage IV C MTC patients. The 5- and 10-year OS rates were 31.8% and 17.1%, respectively, and the 5- and 10-year CSS rates were 40.4% and 22.5%, respectively. More importantly, the rates of MTC-induced death between primary or distant metastatic lesions in Stage IV C MTC patients were comparable in our institution. Additionally, the univariate and multivariate analyses demonstrated that the presence of an advanced T stage was an independent prognostic factor for both the OS (T4 vs. T1-T3, hazard ratio [HR]: 1.714, 95% confidence interval [CI]: 1.175-2.500, p = .005) and the CSS (T4 vs. T1-T3, HR: 1.848, 95% CI: 1.229-2.780, p = .003).
CONCLUSION
To achieve a better risk stratification, further classification of Stage IV C MTC patients by the T stage may be preferable.
Topics: Carcinoma, Neuroendocrine; Humans; Neoplasm Staging; Prognosis; Retrospective Studies; Thyroid Neoplasms
PubMed: 35261045
DOI: 10.1111/cen.14717