RESUMO
BACKGROUND: Neuroendocrine Carcinomas (NECs) prognosis is poor.No standard second-line therapy is currently recognized after failure of platinum-based first-line treatment. FOLFIRI and CAPTEM regimens have shown promising activity in preliminary studies. We aimed to evaluate these regimens in metastatic NEC patients. METHODS: This is an open-label, multicenter, randomized non-comparative phase II trial to evaluate the activity and safety of FOLFIRI or CAPTEM in metastatic NEC patients. Primary endpoints were the 12 weeks-Disease Control Rate (12w-DCR) by investigator assessment per RECIST v1.1 and safety per CTCAE v5.0. Additional endpoints included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Patients' serum samples were subject to NGS miRNome profiling in comparison with healthy donors to reveal differentially expressed miRNAs as candidate circulating biomarkers. RESULTS: The study was halted for futility at interim analysis, as the minimum 12w-DCR threshold of 10 out of 25 patients required for the first step was not reached. From 06/03/2017 to 18/01/2021, 53 out of 112 patients were enrolled. Median follow-up was 22.6 months (range: 1.4-60.4). The 12w-DCR was 39.1 % in the FOLFIRI arm and 28.0 % in the CAPTEM arm. In the FOLFIRI subgroup the 12-months OS rate was 28.4 % (95 % CI: 12.7-46.5) while in the CAPTEM subgroup it was 32.4 % (95 % CI: 14.9-51.3). The most common G3-G4 side effects were neutropenia (n = 5, 18.5 %) and anemia (n = 2, 7.4 %) for FOLFIRI and G3-G4 thrombocytopenia (n = 2, 8.0 %), G4 nausea/vomiting (n = 1, 4.0 %) for CAPTEM. Three microRNAs emerged as NEC independent predictors. High expression values were found to be significantly associated with decreased PFS and OS. CONCLUSION: The safety profile of FOLFIRI and CAPTEM was manageable. FOLFIRI and CAPTEM chemotherapy showed comparable activity in the second-line setting after progression on etoposide/platinum. GOV IDENTIFIER: NCT03387592.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Camptotecina , Carcinoma Neuroendócrino , Fluoruracila , Leucovorina , Humanos , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Pessoa de Meia-Idade , Leucovorina/uso terapêutico , Leucovorina/efeitos adversos , Fluoruracila/uso terapêutico , Fluoruracila/efeitos adversos , Idoso , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/mortalidade , Adulto , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Camptotecina/efeitos adversos , Etoposídeo/uso terapêutico , Etoposídeo/efeitos adversos , Etoposídeo/administração & dosagem , Temozolomida/uso terapêutico , Temozolomida/efeitos adversos , Intervalo Livre de ProgressãoRESUMO
PURPOSE: There is still controversy in different guidelines regarding the necessity of routine preoperative calcitonin (Ctn) testing in medullary thyroid cancer (MTC). The level of preoperative Ctn may influence the extent of surgery. METHODS: This retrospective multicenter cohort study involved 149 MTC patients from 6 centers between 2013 to 2023. Clinical characteristics, surgical procedure and clinical outcomes were compared between Ctn-screened and Non-screened group. Kaplan-Meier method was used to estimate recurrence-free survival (RFS) and overall survival (OS). RESULTS: In total, 127 MTC patients with preoperative Ctn screening and 22 MTC patients without screening were analyzed. MTC patients with preoperative Ctn screening underwent more radical surgical procedures including total thyroidectomy and lymph node dissection, compared to those without screening (84.3% vs. 68.2% and 91.3% vs. 72.7%, respectively). The rate of recurrence and death were lower in the Ctn-screened group (16.1% vs. 36.4%, 0.8% vs. 18.2%, respectively). The survival curve showed a significantly better overall survival in Ctn-screened group than Non-screened group (HR:17.932, 95% CI 1.888-170.294, p-value = 0.001), while no significant difference was observed of RFS between two groups (HR:1.6, 95% CI 0.645-3.966, p-value = 0.307). CONCLUSION: Preoperative Ctn screening can prompt surgeons choosing more radical initial surgical treatment for MTC patients, potentially leading to better long-term outcomes. Further evaluation of the cost-effectiveness of routine Ctn screening in thyroid nodule patients is warranted.
Assuntos
Calcitonina , Carcinoma Neuroendócrino , Neoplasias da Glândula Tireoide , Tireoidectomia , Humanos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/mortalidade , Estudos Retrospectivos , Feminino , Masculino , Calcitonina/sangue , Pessoa de Meia-Idade , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/cirurgia , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/diagnóstico , Adulto , Prognóstico , Idoso , Cuidados Pré-Operatórios/métodosRESUMO
Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor originating from the parafollicular cells (C cells) of the thyroid gland, classified as sporadic and hereditary. Calcitonin (Ctn) secreted by the C cells is a specific serological marker for MTC, which is of great value in diagnosis, treatment and postoperative management of MTC. The effect of chemoradiotherapy and 131I therapy on MTC is limited, with surgery being the primary therapy. Given the aggressive nature and relatively poor prognosis of MTC, the reasonable surgical extent is crucial for improving cure rate and prognosis of patients. However, there are still some controversies regarding the extent of surgery for MTC. This article elaborates on the research progress and controversies of serum Ctn levels in assisting the evaluation of the extent of surgery for MTC.
Assuntos
Calcitonina , Carcinoma Neuroendócrino , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/cirurgia , Calcitonina/sangue , Carcinoma Neuroendócrino/sangue , Prognóstico , Carcinoma Medular/cirurgia , Carcinoma Medular/sangueRESUMO
PURPOSE: Medullary thyroid carcinoma (MTC) in MEN2B syndrome is associated with germline RET mutation. Patients harboring de novo mutations are usually diagnosed at more advanced disease stages. We present a young woman with Met918Th mutation diagnosed with stage IV MTC at age 10 years. METHODS: The disease progressed despite total thyroidectomy and multiple surgical interventions for cervical lymph node recurrences, leading to distant metastases in the fifth year after the initial diagnosis. Subsequently, she underwent five different types of tyrosine kinase inhibitor (TKI) treatments. The 17-year disease course was divided into periods defined by four surgical interventions and sequential treatment intervals with four multikinase (sunitinib, vandetanib, cabozantinib, and lenvatinib) and one RET-selective TKI (selpercatinib). Tumor growth for different phases of spontaneous development and drug treatment intervals was characterized by changes in serial log-transformed calcitonin measurements (n = 114). RESULTS: Three operations (one for calcitonin-producing adrenal pheochromocytoma) were associated with drops in calcitonin levels. All of the nonselective TKIs were stopped due to adverse effects. As reflected by the negative calcitonin doubling rate, the best treatment response was observed with selpercatinib, which was associated with an initial large drop followed by a decreasing calcitonin trajectory over 514 days without any major side effects. CONCLUSION: This case of MEN2B medullary thyroid cancer with long-term survival presents how the effectiveness of different treatment modalities can be estimated using log-transformed calcitonin levels. Furthermore, our experience supports the view that serial calcitonin measurements may be more sensitive than radiological follow-up in advanced MTC. Our patient also represents a new case of rarely reported calcitonin-producing pheochromocytomas.
Assuntos
Calcitonina , Carcinoma Neuroendócrino , Neoplasia Endócrina Múltipla Tipo 2b , Neoplasias da Glândula Tireoide , Humanos , Calcitonina/sangue , Calcitonina/uso terapêutico , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Feminino , Neoplasia Endócrina Múltipla Tipo 2b/genética , Neoplasia Endócrina Múltipla Tipo 2b/sangue , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/genética , Proteínas Proto-Oncogênicas c-ret/genética , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
Background: Early cervical lymph node (LN) metastasis is an important cause of poor survival in patients with medullary thyroid cancer (MTC). This study evaluated whether the preoperative serum calcitonin level in combination with ultrasonographic features of MTC can be used to assess the LN status as well as predict the risk of metastasis in patients with MTC. Methods: We retrospectively analyzed the clinical data of 95 patients with MTC, and a nomogram model was constructed and validated. Using integrated database analysis of The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx), we mined pathways wherein CALCA is involved, identified calcitonin-related genes, and analyzed their functions. Results: Correlation analysis revealed a significant association between the infiltrating range, diameter, calcification, blood flow, the preoperative serum calcitonin level, and metastasis. The metastasis risk-prediction model showed great accuracy in determining the risk of metastasis in MTC (area under the curve of the receiver operating characteristic [ROC] curve: 0.979 [95% confidence interval 0.946-1.000]). Decision curve analysis (DCA) showed that the model has excellent clinical utilization potential. Significantly, CALCA, the mRNA for calcitonin, was highly expressed in thyroid cancer tissues and associated with the cytokine-cytokine receptor and neuroactive ligand-receptor interaction pathways as well as the cell-adhesion molecules. ROC curve indicated that the CNTFR, CD27, GDF6, and TSLP genes, which are related to the cytokine-cytokine receptor interaction pathway, could indicate the risk of metastasis in MTC. Conclusions: The preoperative serum calcitonin level, in combination with ultrasonographic features, can be used to predict the risk of metastasis in patients with MTC and constitute a noninvasive accurate method for preoperative diagnosis of MTC.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina/sangue , Peptídeo Relacionado com Gene de Calcitonina/genética , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/diagnóstico por imagem , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Idoso , Carcinoma Neuroendócrino/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Período Pré-Operatório , Estudos Retrospectivos , Medição de Risco , Neoplasias da Glândula Tireoide/genética , UltrassonografiaRESUMO
AIM: Calcitonin (Ctn) measurement in patients with thyroid disease could potentially increase the detection rates of medullary thyroid carcinoma (MTC) but remains a controversial issue. The aim of this study was to evaluate routine preoperative Ctn measurements. METHODS: All patients with thyroid surgery documented in the prospective StuDoQ|Thyroid registry between March 2017 and September 2020 were included. Cutoff levels for Ctn were determined with receiver-operating characteristic analyses to assess the preoperative diagnosis of MTC in subgroups for females and males. FINDINGS: In 29 590 of 39 679 patients (75%) participating in the registry, routine preoperative Ctn testing was performed. In 357 patients (227 females and 130 males), histopathology confirmed MTC with a mean tumor size of 14.7 mm (±12.43). Biochemical cure was achieved in 71.4% of the patients. Ctn levels between 11 and 20 pg/mL were seen in 2.6% of the patients, and only 0.7% of the patients had Ctn levels above 21 pg/mL. Cutoff levels for the diagnosis of MTC were 7.9 pg/mL for females and 15 pg/mL for males (P < 0.001). The sensitivity and specificity for females were 95 and 98%, and 96 and 97% for males, respectively. CONCLUSION: Routine Ctn testing is a reliable predictor for MTC and provides the opportunity for earlier thyroidectomy before lymph node metastases occur, resulting in a better prognosis. Females with Ctn levels >7.9 pg/mL and males >15 pg/mL without any other extrathyroidal sources for an elevated Ctn should be monitored. Thyroid surgery should be considered if Ctn levels are increasing or ultrasound detects suspicious thyroid lesions.
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Biomarcadores Tumorais/sangue , Calcitonina/sangue , Carcinoma Neuroendócrino/sangue , Período Pré-Operatório , Doenças da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Áustria/epidemiologia , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/cirurgia , Feminino , Alemanha/epidemiologia , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 2a/epidemiologia , Prognóstico , Valores de Referência , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , UltrassonografiaRESUMO
Medullary thyroid cancer (MTC) is the third frequent subtype of thyroid cancer-driving from thyroid C-cells. The first-line strategy to treat MTC is surgery, but tumor recurrence and patients' mortality rate have still been demonstrated in approximately 4-10% of MTC cases. Therefore, to treat and prevent the progressive form of the disease, the early diagnosis of MTC is assumed to play a critical role. In this regard, recently, circulating biomarkers have drawn researchers' attention for their nonaggressive manners in the sample collection. In this systematic review, we aimed to focus on circulating biomarkers and their applications in MTC diagnosis, prognosis and follow-up, and we discussed their clinical application and how they can affect clinical decision making in the future. A literature search (from 2000 to 2021) was accomplished on MTC circulating biomarkers in different databases, and only English articles were evaluated. We found that calcitonin (CT) and carcinoembryonic antigen (CEA) are the most important circulating biomarkers in the MTC diagnosis. Other circulating biomarkers included pro-calcitonin (Pro-CT), pro-Gastrin releasing peptide (Pro-GRP), carbohydrate antigen 19-9 (CA 19-9) and chromogranin A (CgA). Some novel circulating biomarkers comprised vaspin and retinol-binding protein-4 (RBP4), myostatin, tumor cells (CTCs), RET M918T mutated cfDNA, circulating tumor DNA (ctDNA), miR-375 and Alu83 and Alu244 cfDNAs. Several circulating biomarkers have been identified to optimize the accuracy of diagnosis and offer new prognostic criteria, which should be verified before any clinical application. Although different circulating biomarkers contributed to MTC have been discovered, a few of them could be used in clinical diagnosis. In many cases, the application of each marker may not be useful lonely; therefore, a combination of two or more biomarkers could open a new avenue in the diagnosis, prognosis and prediction of MTC.
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Biomarcadores Tumorais/sangue , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/terapia , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/terapia , Humanos , PrognósticoRESUMO
Medullary thyroid carcinoma (MTC) is relatively rare, and has the main feature of calcitonin (Ct) secretion. However, a few cases of MTC with negative serum calcitonin have been reported in the literature, so the diagnosis and follow up of Ct-negative MTCs are still a challenge. Here we present three cases of Ct-negative MTCs, illustrating the rarity of the disease and challenges in managing it, together with a review of the literature of 39 MTCs with negative serum Ct.
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Calcitonina/sangue , Carcinoma Neuroendócrino , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Adulto , Idoso , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/química , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/química , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/sangue , Nódulo da Glândula Tireoide/química , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/patologia , Adulto JovemRESUMO
Pancreatic neuroendocrine neoplasms (pNEN) are highly variable in their postresection survival. Determination of preoperative risk factors is essential for treatment strategies. C-reactive protein (CRP) has been implicated in the pathogenesis of pNEN and shown to be associated with survival in different tumour entities. Patients undergoing surgery for pNEN were retrospectively analysed. Patients were divided into three subgroups according to preoperative CRP serum levels. Clinicopathological features, overall and disease-free survival were assessed. Uni- and multivariable survival analyses were performed. 517 surgically resected pNEN patients were analysed. CRP levels were significantly associated with relevant clinicopathological parameters and prognosis and were able to stratify subgroups with significant and clinically relevant differences in overall and disease-free survival. In univariable sensitivity analyses CRP was confirmed as a prognostic factor for overall survival in subgroups with G2 differentiation, T1/T2 and T3/T4 tumour stages, patients with node positive disease and with and without distant metastases. By multivariable analysis, preoperative CRP was confirmed as an independent predictor of postresection survival together with patient age and the established postoperative pathological predictors grading, T-stage and metastases. Preoperative serum CRP is a strong predictive biomarker for both overall and disease free survival of surgically resected pNEN. CRP is associated with prognosis independently of grading and tumour stage and may be of additional use for treatment decisions.
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Biomarcadores Tumorais , Proteína C-Reativa , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/mortalidade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/mortalidade , Idoso , Carcinoma Neuroendócrino/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Pancreáticas/diagnóstico , Prognóstico , Modelos de Riscos Proporcionais , Curva ROCRESUMO
Introduction: Medullary thyroid carcinoma (MTC) is a rare cancer that accounts for 5% of thyroid cancers. Serum calcitonin is a good biomarker for MTC, which is used for diagnosis, prognosis, and monitoring of recurrence. Calcitonin-negative MTC (CNMTC) is rare but confounds diagnostic and prognostic directions. This study introduces 19 cases of CNMTC in a single center. Method: From 2002 March to 2020 July, more than 76,500 patients had undergone thyroid surgery due to thyroid cancer at the Severance Hospital, and a total of 320 patients were diagnosed with MTC (0.4%). Serum calcitonin levels were obtained from every patient who was suspected with MTC. These patients had undergone either bilateral total thyroidectomy or unilateral thyroidectomy with central compartment lymph node dissection, and additional modified radical lymph node dissection if lateral lymph node metastasis was positive. Postoperative monitoring and out-patient clinic follow-up were performed with obtaining the serum calcitonin levels. Result: Nineteen patients tested negative for calcitonin preoperatively (6%). The mean preoperative calcitonin level was 5.1pg/mL if undetectable level is regarded as 0pg/mL. Only two patients were males, and the female bias was significant (p = 0.017). No one except two patients with modified radical neck dissection showed central compartment lymph node metastasis. Every patient's postoperative calcitonin level remained low. The median follow-up period was 71 months. There was no recurrence and only one fatality, and the overall survival rate was 95%. Conclusion: Since incidence of CNMTC is not negligible, MTC should not be ruled out in the diagnostic phase even if serum calcitonin is negative in preoperative examination. We presented 19 cases of CNMTC whose prognosis in general were favorable. Markers of serum and immunohistochemical samples other than calcitonin should be actively examined.
Assuntos
Calcitonina/sangue , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/epidemiologia , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Calcitonina/metabolismo , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/cirurgia , Criança , Estudos de Coortes , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Mortalidade , Estadiamento de Neoplasias , Prognóstico , República da Coreia/epidemiologia , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adulto JovemRESUMO
Background: Procalcitonin (proCt) was recently proposed as an alternative or in addition to calcitonin (Ct) in medullary thyroid cancer (MTC) diagnostics. Methods: Serum basal Ct (bCt) and proCt (bproCt) levels were measured before surgery from a consecutive series of patients with (n=43) and without (n=75) MTC, retrospectively collected in Padua. Serum bproCt, bCt and stimulated proCt and Ct (sproCt and sCt) were measured in another consecutive series of 33 patients seen at three tertiary-level institutions undergoing a calcium stimulation test prior to surgery, 20 of them with a final diagnosis of MTC, and 13 with non-MTC nodular disease. Results: Median bproCt levels were higher in MTC than in non-MTC. A positive correlation was found for bproCt with bCt (P<0.01, R2 = 0.75), and with tumor size (P<0.01, R2 = 0.39). The cut-off for bproCt differentiating between MTC and non-MTC patients was >0.07 ng/ml (sensitivity: 85.7%, specificity: 98.9%, positive predictive value [PPV]: 98.2%, negative predictive value [NPV]: 90.6%, P<0.01). While bproCt was >0.07 ng/ml in 38/39 (97.4%) patients with MTC >10 mm, it was above said cut-off only in 15/23 (65.2%) patients with tumors ≤10 mm. A sproCt >0.19 ng/ml was able to identify MTC [sensitivity: 90.0%, specificity:100.0%, PPV: 100.0%, NPV: 86.7% (P<0.01)]. Conclusions: Our data suggest that bproCt can be a good adjunct to Ct for MTC diagnostic purposes. In consideration of its high specificity, it can be used in combination with Ct in MTC diagnostics, particularly in the case of mildly elevated basal Ct levels.
Assuntos
Carcinoma Neuroendócrino/diagnóstico , Pró-Calcitonina/sangue , Neoplasias da Glândula Tireoide/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Cálcio , Carcinoma Neuroendócrino/sangue , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/sangueRESUMO
Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that has caused a worldwide pandemic. The majority of medullary thyroid cancers present as a thyroid nodule. At the time of diagnosis, cervical lymph nodes and distant metastases are frequently detected. Case Report: Here, we present a case of a 46-year-old man with coronavirus disease (COVID) pneumonia, who had persistently high serum procalcitonin levels despite normal C-reactive protein levels. The attending infectologist happened to be a colleague who spent some time, as part of her internal medicine rotation, in the Endocrine Ward and recalled that medullary thyroid cancer might be the cause. This led to the timely workup and treatment of the medullary cancer.
Assuntos
COVID-19/complicações , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/diagnóstico , Endocrinologia/métodos , Pró-Calcitonina/sangue , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/diagnóstico , Biomarcadores Tumorais/sangue , Proteína C-Reativa/biossíntese , Carcinoma Neuroendócrino/complicações , Humanos , Achados Incidentais , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Neoplasias da Glândula Tireoide/complicações , Nódulo da Glândula TireoideRESUMO
Background: Serum calcitonin level is a useful biomarker for predicting primary tumor size, the extent of lymph node, and distant metastasis in patients with medullary thyroid carcinoma (MTC). However, the association between preoperative serum calcitonin levels and long-term oncologic outcomes has not yet been established. The aims of this study were to determine the preoperative serum calcitonin cut-off value for predicting disease recurrence and to evaluate its prognostic value. Methods: Patients with MTC (n = 169) who were treated at a tertiary referral hospital in Korea between 1995 and 2019 were enrolled. To determine the preoperative serum calcitonin cut-off value for predicting structural recurrence, the maximum of the standardized log-rank statistics of all possible cut-off values was used. Multivariable Cox regression analysis was used to determine prognostic factors for disease-free survival. Results: The overall disease-free survival rate was 75.7%. The preoperative serum calcitonin cut-off value that predicted structural recurrence was 309 pg/mL. Preoperative serum calcitonin levels of > 309 pg/mL were the strongest independent predictor of disease recurrence (hazard ratio (HR) 5.33, 95% confidence interval (85% CI) 1.67-16.96; P = 0.005). Lateral lymph node metastasis (HR 3.70, 95% CI 1.61-8.51; P = 0.002) and positive resection margins (HR 3.57, 95% CI 1.44-8.88; P = 0.006) were also significant predictors of disease recurrence. Conclusions: The preoperative serum calcitonin cut-off value is useful in clinical practice. It is also the best predictive factor for disease-free survival. Preoperative serum calcitonin levels may help determine the optimal postoperative follow-up strategy for patients with MTC.
Assuntos
Calcitonina/sangue , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/cirurgia , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/cirurgia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Valores de Referência , Estudos RetrospectivosRESUMO
Since medullary thyroid carcinoma is an aggressive cancer, it is important to have an early detection based on stimulated calcitonin (CT), especially when basal-CT is slightly elevated. The objective of this work was to set specific thresholds for basal-CT- and calcium-stimulated calcitonin for prediction of thyroid malignancy in female population. The study included 2 groups: group A-women with elevated basal-CT (>9.82 pg/ml) and group B-women with normal basal-CT (control group). After calcium stimulation test precise protocol, histopathological reports of those that required surgery were correlated with both basal and stimulated calcitonin. The best basal and stimulated calcitonin cut-offs for distinguishing female patients with medullary thyroid carcinoma or C-Cell-hyperplasia from other pathologies or normal cases were: 12.9 pg/ml, respectively 285.25 pg/ml. For basal-CT above 30 pg/ml, malignancy was diagnosed in 9/9 patients (100%): 9 MTC. For stimulated calcitonin above 300 pg/ml, malignancy was diagnosed in 17/21 patients (80.95%): 12 MTC and 5 papillary thyroid carcinomas. The smallest nodule that proved to be medullary thyroid carcinoma had only 0.56/0.34/0.44 cm on ultrasound, with no other sonographic suspicious criteria. In conclusion, we have identified in Romanian female population basal and stimulated calcitonin thresholds to discriminate medullary thyroid carcinoma or C-Cell-hyperplasia from other cases. We recommend thyroid surgery in all women with stimulated calcitonin above 285 pg/ml. Further studies on larger groups are necessary to establish and confirm male and female cut-offs for early diagnosis of medullary thyroid carcinoma, and interestingly, maybe for macro-papillary thyroid carcinomas alike. The calcium administration has minimum side-effects, but continuous cardiac monitoring is required.
Assuntos
Biomarcadores Tumorais/sangue , Calcitonina/sangue , Cálcio/administração & dosagem , Carcinoma Neuroendócrino/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Adulto , Idoso , Cálcio/sangue , Carcinoma Neuroendócrino/sangue , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias da Glândula Tireoide/sangue , Adulto JovemRESUMO
BACKGROUND: Studies have shown that elevated serum lactate dehydrogenase (LDH) concentration can lead to poor prognosis in patients with small cell lung cancer and lung adenocarcinoma, but its relationship with the prognosis of patients with lung large-cell neuroendocrine carcinoma (L-LCNEC) is not clear. This study aims to explore the influence of L-LCNEC preoperative serum LDH concentration and postoperative LDH concentration change trend on the disease-free survival (DFS) of patients after surgery, so as to judge the clinical prognosis of L-LCNEC provides new ideas. METHODS: Collected the clinical data. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value, while the Kaplan-Meier and Cox proportional hazard model were used to analyze data. RESULTS: DFS was shortened in patients with high serum LDH concentration before operation and increased LDH concentration after operation (P<0.001, P<0.001). The preoperative LDH concentration and postoperative LDH concentration change trend were independent prognostic factors for patients (P<0.001, P=0.037). CONCLUSIONS: Preoperative LDH concentration and its postoperative concentration change trend in patients with L-LCNEC are independent prognostic factors for DFS of patients.
Assuntos
Carcinoma de Células Grandes/enzimologia , Carcinoma Neuroendócrino/enzimologia , L-Lactato Desidrogenase/sangue , Neoplasias Pulmonares/enzimologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Grandes/sangue , Carcinoma de Células Grandes/mortalidade , Carcinoma de Células Grandes/cirurgia , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos RetrospectivosRESUMO
BACKGROUND: Calcitonin (Ct) is a sensitive diagnostic biomarker and one of the most important prognostic factors in medullary thyroid cancer (MTC). This study aimed to evaluate progression-free survival and recurrence rates of MTC associated with undetectable compared with normalized serum Ct levels after surgery. METHODS: This retrospective observational study included patients operated for MTC at the Digestive and Endocrine Surgery Department of Lyon Sud Hospital Centre between 2000 and 2019. Clinical and pathological factors were correlated with postoperative Ct concentrations. Undetectable and normalized Ct concentrations were defined as below 2 pg/ml and 2-10 pg/ml respectively. RESULTS: Overall, 176 patients were treated for MTC, and 127 were considered biochemically cured after surgery. Of these, 24 and 103 had normalized and undetectable Ct concentrations respectively. Patients with Ct level normalization had a 25 per cent risk of disease recurrence, compared with 3 per cent in patients with undetectable Ct levels after surgery. The presence of metastasis in two or more compartments was predictive of failure to achieve undetectable Ct concentrations after surgery and an increased risk of recurrence. CONCLUSION: Among patients with biochemically cured MTC, those with undetectable or normalized Ct concentrations after surgery had different risks of recurrence. Simply assessing postoperative Ct normalization can be falsely reassuring, and long-term follow-up is needed. LAY SUMMARY: Calcitonin (Ct) is a sensitive diagnostic biomarker and one of the most important prognostic factors for medullary thyroid cancer outcomes; however, the significance of postoperative Ct levels remains controversial. This study evaluated the differences between normal and undetectable postoperative Ct levels in patients who had undergone surgical treatment for medullary thyroid cancer. Patients who experienced postoperative Ct level normalization had a higher risk of disease recurrence than those with undetectable Ct levels after surgery.
Calcitonin (Ct) is a sensitive diagnostic biomarker and one of the most important prognostic factors for medullary thyroid cancer outcomes; however, the significance of postoperative Ct levels remains controversial. This study evaluated the differences between normal and undetectable postoperative Ct levels in patients who had undergone surgical treatment for medullary thyroid cancer. Patients who experienced postoperative Ct level normalization had a higher risk of disease recurrence than those with undetectable Ct levels after surgery.
Assuntos
Calcitonina/sangue , Carcinoma Neuroendócrino/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Pós-Operatório , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/diagnóstico , Fatores de TempoRESUMO
Purpose: Having previously demonstrated that tissue miR-375 expression in medullary thyroid carcinoma (MTC) tissues is linked to prognosis, the aim of this study was to assess the diagnostic and prognostic value of circulating miR-375 levels in MTC patients. Methods: A series of 68 patients with MTC was retrospectively retrieved and assessed in terms of their clinicopathological characteristics. MiR-375 levels were measured in all patients' presurgical blood samples. Both serum and tissue levels were tested prior to surgery in a subgroup of 57 patients. Serum miR-375 levels were also measured in serum from 49 patients with non-C-cell thyroid nodular diseases (non-CTN), 14 patients with pheochromocytoma, and 19 healthy controls. Results: Circulating miR-375 levels were 101 times higher in the serum of patients with MTC than in all other patients and controls, with no overlap (P < 0.01). No correlation emerged between serum and tissue miR-375 levels. Serum miR-375 levels were higher in MTC patients with N0 than in those with N1 disease (P = 0.01), and also in patients who were biochemically cured than in those who were not (P = 0.02). In the whole series of patients and controls, calcitonin (CT) and serum miR-375 levels were correlated at diagnosis (R2 = 0.40, P < 0.01), but in a U-shaped manner: a positive correlation was found with low CT levels, then the correlation turns negative as CT rises (in MTC patients). A negative correlation was indeed found in MTC patients between serum miR-375 and CT (R2 = -0.10, P = 0.01). On ROC curve analysis, a cut-off of 2.1 for serum miR-375 proved capable of distinguishing between MTC patients and the other patients and controls with a 92.6% sensitivity and a 97.6% specificity (AUC: 0.978, P < 0.01). Conclusions: Serum miR-375 levels can serve as a marker in the diagnosis of MTC, with a remarkable specificity. Serum miR-375 also proved a novel marker of prognosis in this disease. Further in vitro experiments to corroborate our results are currently underway.
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Carcinoma Medular/sangue , Carcinoma Neuroendócrino/sangue , Regulação Neoplásica da Expressão Gênica , MicroRNAs/sangue , Feocromocitoma/sangue , Neoplasias da Glândula Tireoide/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Carcinoma Medular/cirurgia , Carcinoma Neuroendócrino/cirurgia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Feocromocitoma/cirurgia , Prognóstico , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/cirurgia , Adulto JovemRESUMO
BACKGROUND: Medullary thyroid carcinoma (MTC) comprises 1-2% of all thyroid cancers, yet 15% of all thyroid cancer-related deaths. While up to 20% of cases may be predicted due to autosomal dominant germline mutations, 80% of cases are sporadic. However, due to non-specific presenting symptoms and diagnostic imaging, prompt diagnosis and treatment has remained elusive. This article will further investigate the limitations of MTC diagnosis and look into future areas for diagnostic improvement. METHODS: Relevant articles were identified using a systematic PubMed and Google Scholar search. RESULTS: Prophylactic total thyroidectomy for the 20% of MTC cases that are present in autosomal dominant disorder provides definitive treatment. Serum calcitonin (Ctn) screening has several technical limitations due to population variability and laboratory assay interference, but advances in laboratory technology and combined use with fine needle aspiration increase its sensitivity. Other serum assays such as carcinoembryonic antigen and procalcitonin have limited applicability. Thyroid ultrasound remains the gold standard for the initial diagnostic planning, with limited application for CT, MRI, and PET imaging. CONCLUSION: With complete surgical resection the only definitive treatment, early MTC diagnosis has presented an elusive challenge, mainly due to its relative rarity and difficulty in finding an economic screening strategy. Careful family history combined with fine needle aspiration with serum Ctn analysis can improve diagnostic sensitivity and specificity to greater than 95%.
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Calcitonina/sangue , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/diagnóstico por imagem , Testes Genéticos/métodos , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Biomarcadores Tumorais/sangue , Biópsia por Agulha Fina , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/cirurgia , Feminino , Humanos , Masculino , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Ultrassonografia/métodosRESUMO
Pancreatic cancer (PC) has been the fourth cancer-related death worldwide, diagnosed at an unresectable stage due to its rapid progression and few symptoms of this disease at early stages. The aim of this study was to determine the association between the diversity of T-cell receptor (TCR) repertoire and clinicopathological characteristics of patients with PC and other benign pancreatic diseases. In order to make a comprehensive analysis the TCR repertoire, high-throughput sequencing was used to differentiate complementarity determining region 3 (CDR3) of the TCR ß chain in peripheral blood samples from 3 PC, 3 chronic pancreatitis, 3 pancreatic cystic lesions and 3 pancreatic neuroendocrine tumour patients. We found that there were significant differences related to TCR repertoire between PC and other pancreatic diseases, and PC is a relatively immunosuppressive tumour. Changes of peripheral TCR repertoire may be used to predict the progression of PC and the response to immunotherapy. And there may exist novel-specific antigens in PC patients which could be used to design targeting immunotherapy in the nearly future.
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Biomarcadores/metabolismo , Carcinoma Neuroendócrino/patologia , Regulação da Expressão Gênica , Cisto Pancreático/patologia , Neoplasias Pancreáticas/patologia , Pancreatite Crônica/patologia , Receptores de Antígenos de Linfócitos T/metabolismo , Adulto , Idoso , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/metabolismo , Regiões Determinantes de Complementaridade/genética , Regiões Determinantes de Complementaridade/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cisto Pancreático/sangue , Cisto Pancreático/genética , Cisto Pancreático/metabolismo , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Pancreatite Crônica/sangue , Pancreatite Crônica/genética , Pancreatite Crônica/metabolismo , Prognóstico , Receptores de Antígenos de Linfócitos T/genética , Estudos RetrospectivosRESUMO
Background/aim: Medullary thyroid cancer (MTC) originates from parafollicular cells (C cell) and produces calcitonin (CT). Basal serum CT was used in the diagnosis and treatment of MTC. If basal CT level is 100 pg/mL or higher, it is likely to have MTC, but if basal CT level is below 10 pg/mL, the probability of developing thyroid disease is low. In cases with basal CT level between 10100 pg/mL, pentagastrin-stimulated (PS) CT level is studied to evaluate MTC and C cell hyperplasia (CHH). This study aimed to determine cut-off value for basal and PS peak CT level for diagnosis of MTC. Materials and methods: We retrospectively reviewed files of patients presented to endocrine outpatient clinic of Ege University, Medicine School, between 2010 and 2019; 176 patients with basal CT level of 10100 pg/mL and patients with PS test were included to the study. Results: The receiver operating characteristic curve (ROC) analysis was used to determine cut-off value for basal CT that can discriminate cases with MTC and those with nodular goiter. Cut-off value for basal CT was calculated as 46.5 pg/mL (specificity; 100 %, sensitivity; 74 %). In the ROC analysis for peak PS CT, cut-off value was calculated as 285 pg/mL (specificity:100 %; sensitivity:82 %). When peak CT level was > 290 pg/mL in PS test, both specificity and sensitivity for MTC were determined as 100 %. The PS peak CT level > 285 pg/ mL was significant for MTC diagnosis while range of 117274 pg/mL was significant for CHH. Conclusion: In this study, cut-off value was calculated as 46.5 pg/mL for basal CT, whereas 285 pg/mL for PS peak CT in the diagnosis of preoperative MTC.