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Endocrine Aug 2023To summarize the more robust evidence about the performance of tools useful for diagnosis of medullary thyroid carcinoma (MTC) such as calcitonin (Ctn) and other... (Review)
Review
PURPOSE
To summarize the more robust evidence about the performance of tools useful for diagnosis of medullary thyroid carcinoma (MTC) such as calcitonin (Ctn) and other circulating markers, ultrasound (US), fine-needle aspiration (FNA), and other imaging procedures.
METHODS
This systematic review of systematic reviews was carried out according to a predefined protocol. A search string was created. An electronical comprehensive search of literature was performed on December 2022. Quality assessment of eligible systematic reviews was performed and main findings were described.
RESULTS
Twenty-three systematic reviews were included and several findings were achieved. Ctn is the most reliable diagnostic marker of MTC with no evidence of improvement with stimulation test. CEA doubling time is more reliable than Ctn in identifying MTC with poorer prognosis. US sensitivity is suboptimal in MTC and only just over half of cases are at high risk according to Thyroid Imaging And Reporting Data Systems. Cytology can correctly detect MTC in just over half of cases and measuring Ctn in washout fluid from FNA is necessary. PET/CT is useful for detecting recurrent MTC.
CONCLUSIONS
Future guidelines of both thyroid nodule management and MTC diagnosis should consider these evidence-based data.
Topics: Thyroid Neoplasms; Thyroid Nodule; Positron Emission Tomography Computed Tomography; Diagnostic Tests, Routine; Calcitonin; Systematic Reviews as Topic; Biopsy, Fine-Needle
PubMed: 36877452
DOI: 10.1007/s12020-023-03326-6 -
Therapeutic Advances in Medical Oncology 2022Cabozantinib is approved, in various settings, for the treatment of renal cell carcinoma, medullary thyroid cancer, and hepatocellular carcinoma, and it has been... (Review)
Review
BACKGROUND
Cabozantinib is approved, in various settings, for the treatment of renal cell carcinoma, medullary thyroid cancer, and hepatocellular carcinoma, and it has been investigated for the treatment of other cancers. With the available evidence and the real-world performance of cabozantinib compared with clinical trial data, we performed a systematic review of cabozantinib monotherapy as treatment for solid tumors in adults.
METHODS
This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and registered with PROSPERO (CRD42020144680). We searched for clinical and observational studies of cabozantinib monotherapy for solid tumors using Embase, MEDLINE, and Cochrane databases (October 2020), and screened relevant congress abstracts. Eligible studies reported clinical or safety outcomes, or biomarker data. Small studies ( < 25) and studies of cabozantinib combination therapies were excluded. Quality was assessed using National Institute for Health and Care Excellence methodology, and study characteristics were described qualitatively.
RESULTS
Of 2888 citations, 114 were included (52 randomized studies, 29 observational studies, 32 nonrandomized phase I or II studies or pilot trials, and 1 analysis of data from a randomized study and a nonrandomized study). Beyond approved indications, other tumors studied were castration-resistant prostate cancer, urothelial carcinoma, Ewing sarcoma, osteosarcoma, uveal melanoma, non-small-cell lung cancer, Merkel cell carcinoma, glioblastoma, pheochromocytomas and paragangliomas, cholangiocarcinoma, gastrointestinal stromal tumor, colorectal cancer, salivary gland cancer, carcinoid and pancreatic neuroendocrine tumors, and breast, endometrial and ovarian cancers. The most common adverse events were hypertension, diarrhea, and fatigue.
CONCLUSION
The identified evidence demonstrates the positive efficacy/effectiveness of cabozantinib monotherapy in various solid tumor types, with safety findings being consistent with those observed with other VEGFR-targeting tyrosine kinase inhibitors. When available, real-world findings were consistent with the data reported from clinical trials. A limitation of this review is the high proportion of abstracts; however, this allowed us to capture the most up-to-date findings.
PubMed: 35847482
DOI: 10.1177/17588359221107112 -
Reviews in Endocrine & Metabolic... Aug 2023Although calcitonin (Ctn) measurement is recognized as the most accurate diagnostic test for medullary thyroid carcinoma (MTC), its routine execution is not universally... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although calcitonin (Ctn) measurement is recognized as the most accurate diagnostic test for medullary thyroid carcinoma (MTC), its routine execution is not universally accepted for several reasons, including the lack of recommendations for managing indeterminate Ctn values (ICV); such as 10-to-100 pg/mL. This study aimed to gather data on 1) the frequency of ICV among patients undergoing Ctn test and 2) the MTC rate among patients with ICV.
METHODS
This review was conducted according to the Meta-analyses Of Observational Studies in Epidemiology guidelines. PubMed and Cochrane databases were searched, with no language restrictions. The final search was completed on January 2023. Then, quality assessment and proportion meta-analyses were performed.
RESULTS
The online search retrieved 233 articles and 15 were included for quantitative analysis. The risk of bias was low. The number of patients undergone Ctn testing was 29,533. The pooled percentage of those with ICV was 1.7% (95% confidence interval [CI]:1.2-2.3). The pooled proportion of MTC incidence among patients with ICV was 9.6% (95% CI:5-14.1). Heterogeneity was explained by the covariates of Ctn assay sensitivity and the resection rate. The subgroup with Ctn 10-20 pg/mL showed a significantly lower MTC rate than the subgroup with Ctn 20-100 pg/mL.
CONCLUSIONS
The percentage of ICV among patients with thyroid nodules who underwent Ctn testing is negligible. The rate of MTC in patients with ICV cannot be overlooked. Among the ICV intervals, the risk of MTC increases significantly when Ctn is above 20 pg/mL.
Topics: Humans; Thyroid Nodule; Calcitonin; Prevalence; Thyroid Neoplasms
PubMed: 37254023
DOI: 10.1007/s11154-023-09811-7 -
Frontiers in Oncology 2022Medullary thyroid carcinoma (MTC) is one of the common malignant endocrine tumors, which seriously affects human health. Although surgical resection offers a potentially...
Medullary thyroid carcinoma (MTC) is one of the common malignant endocrine tumors, which seriously affects human health. Although surgical resection offers a potentially curative therapeutic option to some MTC patients, most patients do not benefit from it due to the difficulty to access the tumors and tumor metastasis. The survival rate of MTC patients has improved with the recent advances in the research, which has improved our understanding of the molecular mechanism underlying MTC and enabled the development and approval of novel targeted drugs. In this article, we reviewed the molecular mechanisms related to MTC progression and the principle for the design of molecular targeted drugs, and proposed some future directions for prospective studies exploring targeted drugs for MTC.
PubMed: 36544713
DOI: 10.3389/fonc.2022.993725 -
Nuclear Medicine Communications Dec 2023Detecting medullary thyroid carcinoma (MTC) metastatic lesions accurately is still a challenge for clinicians. PET/computed tomography (PET/CT) seems to be the most... (Meta-Analysis)
Meta-Analysis
Sensitivities evaluation of five radiopharmaceuticals in four common medullary thyroid carcinoma metastatic sites on PET/CT: a network meta-analysis and systematic review.
OBJECTIVES
Detecting medullary thyroid carcinoma (MTC) metastatic lesions accurately is still a challenge for clinicians. PET/computed tomography (PET/CT) seems to be the most effective method in recent years. However, the sensitivity of each radiopharmaceutical varies greatly in different metastatic sites. We aim to investigate and compare five novel and common PET or PET/CT radiopharmaceutical sensitivities at the four most frequent metastatic sites by network meta-analysis.
METHODS
We searched for studies evaluating PET/CT radiopharmaceutical sensitivities at different metastatic sites in PubMed, Web of Science, Embase, and Cochrane Library. The risk bias was analyzed, and publication bias was accessed by funnel plot asymmetry tests. We performed both global inconsistency and local inconsistency tests by evaluating the agreement between direct and indirect comparisons. Then, we made pairwise meta-analyses and network meta-analyses for each metastatic site. Finally, we performed the surface under the cumulative ranking curves (SUCRA) and calculated the SUCRA values to rank the probability of each radiopharmaceutical being the most sensitive method.
RESULTS
In our results, 243 patients from 9 clinical studies which accessed sensitivities of different radiopharmaceuticals in MTC metastatic sites were included. For lymph nodes and liver, TF2/ 68 Ga-SSM288 showed the highest SUCRA values (0.974 in lymph nodes, 0.979 in liver). The SUCRA values for 18 F-DOPA and 68 Ga-SSA for bone metastatic lesions were nearly identical (0.301 and 0.319, respectively) and were higher than the other three radiopharmaceuticals. For lung lesions, 11 C-methionine had the highest SUCRA value (0.412).
CONCLUSION
TF2/ 68 Ga-SSM288 had the best sensitivity in lymph nodes and liver lesions. 11 C-methionine was most sensitive in lung lesions. While 18 F-DOPA and 68 Ga-SSA had familiar sensitivities to be the best two radiopharmaceuticals.
Topics: Humans; Radiopharmaceuticals; Positron Emission Tomography Computed Tomography; Network Meta-Analysis; Thyroid Neoplasms; Dihydroxyphenylalanine; Methionine
PubMed: 37769014
DOI: 10.1097/MNM.0000000000001773 -
Biomedicines Mar 2023We have performed a systematic review to evaluate the efficacy and safety of [Lu]Lu-DOTA-TATE, a radioligand therapy, in advanced somatostatin receptor-positive... (Review)
Review
Efficacy and Safety of [Lu]Lu-DOTA-TATE in Adults with Inoperable or Metastatic Somatostatin Receptor-Positive Pheochromocytomas/Paragangliomas, Bronchial and Unknown Origin Neuroendocrine Tumors, and Medullary Thyroid Carcinoma: A Systematic Literature Review.
BACKGROUND
We have performed a systematic review to evaluate the efficacy and safety of [Lu]Lu-DOTA-TATE, a radioligand therapy, in advanced somatostatin receptor-positive pheochromocytoma/paraganglioma (PPGL), thymic neuroendocrine tumor (NET), bronchial NET, unknown primary NET, or medullary thyroid carcinoma (MTC).
METHODS
Studies identified in PubMed from inception to 13 May 2021 must have assessed [Lu]Lu-DOTA-TATE as a single agent and reported outcome data for the specific NET types of interest.
RESULTS
Two independent reviewers performed the screening and data extraction, resulting in 16 publications: PPGL ( = 7), bronchial NETs ( = 6; one also included NETs of unknown origin), and MTC ( = 3). Overall, [Lu]Lu-DOTA-TATE offers encouraging antitumor activity (overall tumor response rates and disease control rates) across NET types. Safety was favorable with most adverse events mild to moderate in severity, transient, and consistent with those seen in patients with gastroenteropancreatic (GEP)-NETs.
CONCLUSIONS
[Lu]Lu-DOTA-TATE has been used effectively in clinical practice to treat NETs of non-GEP origin.
PubMed: 37189646
DOI: 10.3390/biomedicines11041024 -
European Archives of... Feb 2024Compared with other types of thyroid carcinoma, patients with medullary thyroid carcinoma (MTC) are more likely to develop cervical lymph node metastasis. This study was... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Compared with other types of thyroid carcinoma, patients with medullary thyroid carcinoma (MTC) are more likely to develop cervical lymph node metastasis. This study was conducted to clarify the risk factors for cervical lymph node metastasis (central lymph node metastasis or lateral cervical lymph node metastasis) in MTC by meta-analysis, and to provide evidence-based basis for the treatment and prognosis of MTC.
METHODS
The literatures related to cervical lymph node metastasis in medullary thyroid carcinoma were searched in PubMed, Embase, Web of Science, Cochrane, CNKI and Wanfang databases, and statistical analysis was performed using Revman 5.3 and Stata 14.0 software.
RESULTS
A total of 28 papers were included in this paper, and meta-analysis showed that the occurrence of central lymph node metastasis (CLNM) in MTC patients was significantly associated with tumor size (OR = 3.07, 95%CI: 2.04-4.63, P < 0.00001), multifocality (OR = 0.29, 95%CI: 0.19-0.44, P < 0.00001), bilaterality (OR = 3.75, 95% CI: 1.95-7.14, P < 0.0001), capsular invasion (OR = 9.88, 95% CI: 5.93-16.45, P < 0.00001) and extrathyroidal extension (OR = 5.48, 95% CI: 2.61-11.51, P < 0.00001). While the occurrence of lateral cervical lymph node metastasis (LLNM) in MTC patients was strongly correlated with gender (OR = 2.97, 95%CI: 2.46-3.58, P < 0.00001), tumor size (OR = 3.88, 95%CI: 1.90-7.92, P = 0.0002 < 0.05), multifocality (OR = 0.43, 95%CI: 0.35-0.51, P < 0.00001), bilaterality (OR = 2.93, 95% CI: 1.72-4.98, P < 0.0001), capsular invasion (OR = 8.44, 95% CI: 6.11-11.64, P < 0.00001), extrathyroidal extension (OR = 7.04, 95% CI: 5.54-8.94, P < 0.00001), margin of the tumor (OR = 4.47, 95% CI: 2.37-8.44, P < 0.00001), shape of the tumor (OR = 6.81, 95% CI: 3.64-12.73, P < 0.00001), preoperative calcitonin level (SMD = 1.39, 95% CI: 0.98-1.80, P < 0.00001), preoperative carcinoembryonic antigen level (SMD = 0.97, 95% CI: 0.74-1.20, P < 0.00001) and CLNM (OR = 19.70, 95% CI: 14.16-27.43, P < 0.00001).
CONCLUSION
Tumor size, multifocality, bilaterality, capsular invasion and extrathyroidal extension are the main risk factors for developing CLNM in MTC patients; And risk factors for developing LLNM in MTC patients include: gender, tumor size, multifocality, bilaterality, capsular invasion, extrathyroidal extension, margin of the tumor, shape of the tumor, preoperative calcitonin level, preoperative carcinoembryonic antigen level and central lymph node metastasis. These risk factors can guide the individualized treatment plan and improve the prognosis of MTC patients.
Topics: Humans; Calcitonin; Lymphatic Metastasis; Carcinoembryonic Antigen; Thyroid Neoplasms; Lymph Nodes; Risk Factors; Retrospective Studies; Carcinoma, Neuroendocrine
PubMed: 37801162
DOI: 10.1007/s00405-023-08249-6 -
European Thyroid Journal Apr 2021Tyrosine kinase inhibitors (TKIs) have been used in patients with advanced medullary thyroid carcinoma (MTC); however, data on their effectiveness and safety are...
INTRODUCTION
Tyrosine kinase inhibitors (TKIs) have been used in patients with advanced medullary thyroid carcinoma (MTC); however, data on their effectiveness and safety are limited. The aim of this systematic review and meta-analysis was to document clinical response and toxicities of TKIs in advanced MTC.
METHODS
We systematically searched major databases for articles or abstracts on TKI use in MTC patients until May 2018. Objective response (OR), defined as the sum of complete + partial response, expressed as percentage, was our primary endpoint, while disease stability, disease progression (DP), median progression-free survival (PFS), and drug discontinuation rate due to adverse events (AEs) were secondary endpoints. Pooled percentages, PFS time, and 95% CIs were reported.
RESULTS
Thirty-three publications were finally included in the analysis: 1 phase IV, 2 phase III trials evaluating vandetanib and cabozantinib, respectively, 20 phase I or II studies, and the remaining 10 studies of retrospective-observational nature. OR was documented in 28.6% (95% CI 25.9-31.9) of patients. Stable disease was recorded in 46.2% (95% CI 43.3-49.1). Overall, DP was observed in 22.9% (95% CI 20.4-27.6). Grade 3 or more AEs occurred in 48.5% (95% CI 45.5-51.5) of patients, and drug discontinuation was reported in 44.7% (95% CI 41.7-47.6). In general, use of TKIs conferred a PFS of 23.3 months (95% CI 21.07-25.5). In particular, vandetanib induced an OR in 33.8% (95% CI 29.6-38.0) of patients and cabozantinib in 27.7% (95% CI 22.05-33.4). DP occurred in 23.7% (95% CI 19.9-27.6) with vandetanib use and in 22.6% (95% CI 17.4-27.9) in cabozantinib-treated patients. Sorafenib, the third most frequently studied drug, showed intermediate efficacy, but higher discontinuation rates.
CONCLUSION
Treatment with TKIs in MTC patients with progressive disease is associated with a moderate therapeutic benefit, with achievement of either disease stability or partial response in 73%. The toxicity of these drugs is not negligible, but it is, nonetheless, manageable.
PubMed: 33981617
DOI: 10.1159/000509457 -
Thyroid Research Dec 2022The debate on whether or not there is a difference in the incidence of thyroid cancer between the patients with Solitary thyroid Nodule (STN) and Multinodular Goiter... (Review)
Review
BACKGROUND
The debate on whether or not there is a difference in the incidence of thyroid cancer between the patients with Solitary thyroid Nodule (STN) and Multinodular Goiter (MNG) has been constantly present for the last few decades. With newer studies yielding mixed results, it was imperative to systematically compile all available literature on the topic.
METHODS
PubMed/MEDLINE, Cochrane Central, ScienceDirect, GoogleScholar, International Clinical Trials registry, and reference lists of the included articles were systematically searched for article retrieval. No filter was applied in terms of time, study design, language or country of publication. Rigorous screening as per PRISMA guidelines was undertaken by 2 independent reviewers in order to identify the articles that were most relevant to the topic.
RESULTS
Twenty-two studies spanning from 1992 to 2018 were included in this analysis and encompassed 50,321 patients, 44.2% of which belonged to the STN subgroup and 55.37% to the MNG subgroup. MNG was found to be associated with a significantly lower risk of thyroid cancer (OR = 0.76; 95% CI 0.61-0.96) when compared with STN. Papillary carcinoma was the most frequently occurring carcinoma across both groups, followed by follicular and medullary carcinomas. A subgroup analysis was performed to assess the efficacy of the two most commonly employed diagnostic tools i.e. surgery and fine needle aspiration cytology (FNAC), however it yielded nonsignificant results, indicating a comparable usefulness of the two. Another subgroup analysis run on the basis of the presumed iodine status of the participants also yielded nonsignificant results.
CONCLUSION
There is a higher incidence of thyroid cancer among patients of STN, however, given the low quality of existing evidence on the topic, it is crucial to conduct larger studies that can establish association with a greater precision.
PubMed: 36464691
DOI: 10.1186/s13044-022-00140-6 -
Endocrine Connections Apr 2021Calcitonin-secreting neuroendocrine neoplasms of the lung are rare, with few cases reported in the literature. Differentiating between medullary thyroid carcinoma and an...
Calcitonin-secreting neuroendocrine neoplasms of the lung are rare, with few cases reported in the literature. Differentiating between medullary thyroid carcinoma and an ectopic source of calcitonin secretion can represent a complex diagnostic conundrum for managing physicians, with cases of unnecessary thyroidectomy reported in the literature. This manuscript reports a case of ectopic hypercalcitonaemia from a metastatic neuroendocrine neoplasm of the lung with concurrent thyroid pathology and summarises the results of a systematic review of the literature. Medical Literature Analysis and Retrieval System Online, Excerpta Medica, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and SCOPUS databases were systematically and critically appraised for all peer reviewed manuscripts that suitably fulfilled the inclusion criteria established a priori. The protocol for this systematic review was developed according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols, and followed methods outlined in The Cochrane Handbook for Systematic Reviews of Interventions. This systematic review is registered with PROSPERO. It is vital to consider diagnoses other than medullary thyroid carcinoma when presented with a patient with raised calcitonin, as it is not pathognomonic of medullary thyroid carcinoma. Lung neuroendocrine neoplasms can appear similar to medullary thyroid carcinoma histologically, they can secrete calcitonin and metastasize to the thyroid. Patients with medullary thyroid carcinoma may show stimulated calcitonin values over two or more times above the basal values, whereas calcitonin-secreting neuroendocrine neoplasms may or may not show response to stimulation tests. The present review summarises existing evidence from cases of ectopic hypercalcitonaemia to lung neuroendocrine neoplasms.
PubMed: 33764887
DOI: 10.1530/EC-21-0071