Preoperative Calcitonin Levels Research Articles

Does the extent of neck surgery based on preoperative calcitonin level influence survival in medullary thyroid carcinoma: a retrospective tertiary centre experience.

Medullary thyroid carcinoma (MTC) is a rare thyroid cancer arising from the calcitonin-secreting parafollicular cells. Previous studies suggested a preoperative calcitonin level >200ng/l is an indication for prophylactic lateral neck dissection (LND) to remove micrometastases and improve survival outcomes. This retrospective single-centre study assessed the efficacy of preoperative calcitonin levels as a marker for determining need for prophylactic LND in MTC. Data were obtained on demographics, preoperative calcitonin levels, size and laterality of index tumour, type of neck dissection (central neck dissection (CND), LND), nodes removed, levels with involved nodes, number of nodes histologically involved, mortality, adjuvant therapy and locoregional recurrence. A total of 33 patients were identified from St George's University Hospitals NHS Foundation Trust between 1 January 2001 and 19 August 2021; 8 were excluded for data quality issues. Of the 18 classified with a high preoperative calcitonin level (>200ng/l), 10 (56%) had a LND and 8 (44%) had a CND. In the low-calcitonin group, three (43%) patients had a CND only and four (57%) had a LND. There was no difference in absolute or disease-free survival between the low and high groups (p=0.960, p=0.817), or between those who had a CND and LND in the high-calcitonin group (p=0.607, hazard ratio (HR) 0.55; p=0.129, HR 8.78). There was no statistically significant difference in outcomes between high and low calcitonin groups. A selective approach to performing LND in MTC patients based on clinical and imaging findings suggesting disease presence in the lateral neck should be explored further.

Precision medicine in endocrinology exemplified by medullary thyroid cancer

Medullary thyroid cancer (MTC) is a prime example for precision medicine in endocrinology and underlines the immediate benefits of basic, translational and healthcare research for patients with a rare disease in clinical . A mutation in the rearranged during transfection (RET) proto-oncogene that codes for a transmembrane receptor protein tyrosine kinase, leads to constitutive activation of the kinase, which is the decisive pathomechanism for the disease. The MTC occurs in a sporadic (somatic RET mutation) or hereditary form (RET germline mutation, multiple endocrine neoplasia types 2 and 3). For germline mutation carriers the timing of preventive thyroidectomy depends on the RET genotype. For advanced metastasized RET-mutant MTC, selective RET kinase inhibitors are available, which are currently considered to be game changers in the treatment. Based on the specific tumor marker calcitonin, MTC can be identified at an early stage during the differential diagnosis of thyroid nodules. The preoperative calcitonin level even enables statements on the degree of dissemination of the disease and on the probability of a cure through surgery. A new development is the consideration of desmoplasia as a histopathological biomarker for the metastatic potential of a MTC, which could possibly modify the operative approach as well as the future MTC nomenclature. Furthermore, the postoperative calcitonin level and the calcitonin doubling time are highly valid prognostic markers for tumor burden and biological aggressiveness of MTC and therefore decisive for patient follow-up. Biochemical, molecular and histological markers enable a risk-adapted surgical treatment and together with new targeted systemic treatments have contributed to a paradigm shift in the diagnostics, prognosis and treatment of MTC in recent years. Endocrine precision medicine for MTC therefore enabled a change from the previous purely symptom-oriented to a modern preventive and individualized treatment.

Risk factors for cervical lymph node metastasis in the central or lateral cervical region in medullary thyroid carcinoma: a systematic review and meta-analysis.

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. 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. 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). 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.

Preoperative identification of low-risk medullary thyroid carcinoma: potential application to reduce total thyroidectomy

Current guidelines recommend total thyroidectomy with central lymph node dissection (CND) for patients with medullary thyroid carcinoma (MTC). This study aimed to identify low-risk MTC patients who may be candidates for lobectomy. We retrospectively reviewed MTC patients who underwent primary surgery at a tertiary referral center from 1998 to 2019. Eighty-five MTC patients were enrolled, excluding patients with primary tumor size > 2.0 cm. Among them, one (1.2%) patient had bilateral tumors. During a median follow-up of 84 months, 12 of the 85 patients experienced structural recurrence. 13 patients had occult lymph node metastasis, and structural recurrence occurred in 2 patients. Factors that significantly affected disease-free survival were clinical N stage (cN0 vs. cN1, log-rank P < 0.001), pathological N stage (pN0 vs. pN1, P < 0.001), and preoperative calcitonin levels (≤ 250 vs. > 250 pg/mL, P = 0.017). After categorizing patients into four groups, patients with preoperative calcitonin levels > 250 pg/mL and cN1 or pN1 had a significantly worse prognosis. Patients with a primary tumor size of 2 cm or less, cN0, and preoperative calcitonin of 250 pg/mL or less can be classified as low-risk MTC patients. We used preoperative clinical information to identify low-risk MTC patients. Lobectomy with prophylactic CND may be a potential therapeutic approach.

Value of lymph node ratio as a prognostic factor of recurrence in medullary thyroid cancer.

The purpose of this study is to evaluate the relationship between lymph node status (the number of resected lymph nodes; the number of metastatic lymph nodes, LNM, and lymph node ratio, LNR) and biochemical recurrence, disease-free survival (DFS), as well as overall survival (OS) in medullary thyroid carcinoma (MTC). This study enrolled MTC patients at Tianjin Medical University Cancer Institute and Hospital between 2011 and 2019. We used Logistic regression analysis, Cox regression models and Kaplan-Meier test to identify risk factors influencing biochemical recurrence, DFS, and OS. We identified 160 patients who satisfied the inclusion criteria from 2011 to 2019. We used ROC analysis to define the cut-off value of LNR with 0.24. Multifocality, preoperative calcitonin levels, pathologic N stage, resected lymph nodes, LNM, LNR, and the American Joint Committee on Cancer (AJCC) clinical stage were significant (P < 0.05) prognostic factors influencing biochemical cure. In univariable analyses, gross extrathyroidal extension, preoperative calcitonin levels, pathologic T classification, pathologic N stage, resected lymph nodes, LNM, LNR, AJCC clinical stage, and biochemical cure were significant (P < 0.05) factors of DFS. When the multivariable analysis was performed, LNR was identified as predictor of DFS (HR = 4.818, 95% CI [1.270-18.276]). Univariable Cox regression models reflected that tumor size, pathologic N stage, and LNR were predictor of OS. Furthermore, multivariable analysis manifested that LNR was predictor of OS (HR = 10.061, 95% CI [1.222-82.841]). This study illustrated that LNR was independent prognostic factor of DFS and OS in MTC. In addition, LNR influenced biochemical cure. Further investigations are needed to determine the optimal cut-off value for predicting prognosis.

Early calcitonin levels in medullary thyroid carcinoma: Prognostic role in patients without distant metastases at diagnosis.

Calcitonin is the most specific marker for medullary thyroid carcinoma, thus, low detectable calcitonin values after surgery can conceal persistent disease. The present study aimed to explore the prognostic role of pre-operative and early calcitonin levels in patients without distant metastases at diagnosis. A retrospective cohort of patients suffering from medullary thyroid carcinoma was considered (N=55). The final disease status, i.e. complete response (undetectable calcitonin levels and negative radiological assessments) or persistent disease (detectable calcitonin levels and/or positive radiological assessments), was deduced from the last available follow-up. Pre-operative and early calcitonin levels (i.e. six months after surgery) have been correlated to several clinical and histological features, according to the final disease status. Persistent disease patients showed higher pre-operative and early calcitonin values (p=0.028 and p<0.001, respectively), compared to complete response sub-cohort. Cox-regression models show that early detectable calcitonin increases up to 18-fold the risk of persistent disease, independently from tumour size and pre-operative calcitonin levels (p=0.006). Of note, when considering only patients who finally developed distant metastasis, ROC curve analysis shows that an early calcitonin level ≥16 pg/ml predicts the final disease status with a sensitivity of 89% and a specificity of 82% (AUC=0.911, CI95%: 0.819-1000, p<0.001). Calcitonin levels six months after surgery represents an easy and effective predictor of persistent disease for medullary thyroid carcinoma without distant metastasis at diagnosis.

Prophylactic and Early Thyroidectomy in RET Germline Mutation Carriers in Pediatric and Adult Population: Long-Term Outcomes of a Series of 63 Patients

Prophylactic and early thyroidectomy in RET germline mutation carriers allows the removal of the thyroid before medullary thyroid carcinoma (MTC) develops, or while it is still confined to the gland. This study was aimed to assess the clinicopathological features in RET carriers according to the age at surgery and the long-term outcomes after prophylactic and early thyroidectomy. A retrospective analysis of 63 operated asymptomatic RET carriers diagnosed after familial genetic screening was performed. Twenty-one RET carriers were operated at pediatric (<18 yrs) and 42 at adult (≥18 yrs) age. Serum preoperative calcitonin levels were significantly lower in pediatric compared to adult patients (p = 0.04); moreover, adult RET carriers had a greater frequency of microMTC at pathology (p = 0.009). Permanent postoperative morbidity occurred in 9.5% of patients, without differences between the two groups. Biochemical postoperative cure was achieved in all patients. At a median follow-up of 14 years, all C-cell hyperplasia patients are disease-free; conversely, biochemical, and structural recurrence of disease occurred in three adults and one pediatric patient with microMTC. The independent predictive factors of MTC were the age at surgery, the preoperative calcitonin level and the RET mutational risk profile (p < 0.02). In conclusion, prophylactic and early thyroidectomy are safe and effective procedures in achieving definitive cure in most RET carriers. However, since recurrences may occur at long-term in case of microMTC, thyroidectomy should be possibly performed earlier to prevent microMTC development.

Surgical selection and prognostic analysis in patients with unilateral sporadic medullary thyroid carcinoma.

The extent of thyroid surgery and cervical lymph node dissection of unilateral sporadic medullary thyroid carcinoma (sMTC) is still controversial, and the aim of this study was to investigate whether hemithyroidectomy was adequate as a locally curative surgery for patients with unilateral sMTC. This study is a retrospective case series of patients with sMTC who underwent curative total thyroidectomy or hemithyroidectomy in our institution from January 2011 to December 2019. In total, 129 patients who met the inclusion criteria were enrolled including 49 (38.0%) patients who underwent total thyroidectomy and 80 (62.0%) patients who underwent hemithyroidectomy. About 80 (62.0%) patients achieved a biochemical cure (BC), whereas there was no significant difference between two groups in biochemical cure rate (61.2% versus 62.5%, P = 0.885). A logistic regression analysis showed a strong negative correlation between the factors of preoperative calcitonin level and pTNM stage and biochemical cure. In the log-rank test, no significant difference in OS (P = 0.314) and DFS (P = 0.409) was found between the two surgical groups. Lateral cervical lymph node metastasis and pTNM stage were significant prognostic factors affecting DFS in univariate analysis; moreover, absence of biochemical cure, tumor size ≥ 4cm and lateral cervical lymph node metastasis were independent risk factors of unilateral sMTC patients in our analysis. For patients with unilateral sMTC, hemithyroidectomy was adequate as a locally curative surgery, because the patients underwent total thyroidectomy did not benefit more from it in the aspects of BC/OS/RFS, while the postoperative increasing incidence rate of postoperative hypocalcemia could not improve patients' quality of life.

Construction of the prognostic model for assessing the risk of medullary thyroid cancer metastases using binary logistic regression

Background. Medullary thyroid cancer is a topical disease that is often accompanied by metastases. The danger of this pathology requires timely and adequate surgery. Objective to assess the prognostic value and informativeness of some clinical indicators with the selection of the most optimal and reliable potential factors in the development of the mathematical equation for calculating the personal probability of detecting metastases of medullary thyroid cancer in the absence of clinical and instrumental signs in the preoperative stage. Materials and methods. Patients with medullary thyroid carcinoma with and without locoregional metastases participated in this study. To verify metastatic deposits, a pathomorphological study was performed using the TNM classification (UICC). StatPlus Pro v.7.6, EpiTools and MedCalc statistical calculators were used for statistical processing of results. Data Mining technologies were used to assess the degree of impact of potential predictors using the data mining add-on for MS Office. To assess the diagnostic value of the test, ROC analysis was performed and the corresponding characteristic curve was constructed with the calculation of the area under it (according to the DeLong method). For the operational characteristics of the tests, 95 % confidence interval was calculated according to the Wilson method. The results were considered statistically significant at p &lt; 0.05. Results. Basal calcitonin, patient sex, multifocality, and total tumor size have been shown to be significant in the a priori of the medullary thyroid cancer metastatic risk assessment. These indicators can be used not only as predictors of unfavourable prognosis, but also as indicators for individual determination of the surgery scope. Conclusions. The method of binary logistic regression to assess latent metastasis showed lower sensitivity (0.77 vs 0.89) and higher specificity (0.90 vs 0.64) in contrast to the monofactorial prognosis based on preoperative calcitonin levels. Further improvement of the model requires additional analysis of erroneous test results in the applied training sample. The proposed prognostic model due to calculations in MS Excel allows you to easily and quickly obtain information, so it can be used as an additional diagnostic tool when choosing a method of surgical treatment.

Does shear wave elastography for medullary thyroid carcinoma predict lateral cervical lymph node metastasis?

PurposeTo assess whether shear wave elastography (SWE) for medullary thyroid carcinoma (MTC) can independently predict lateral cervical lymph node metastasis (LNM). MethodPatients with MTC who were treated via primary surgery between January 2015 and May 2020 and who had undergone preoperative SWE and ultrasound (US) examinations in the Harbin Medical University Cancer Hospital were retrospectively studied. The relationships between lymphatic status and the clinicopathological and imaging characteristics were evaluated. Afterwards, associations between lateral cervical LNM and SWE parameters, as well as sex, age, invasive size, extrathyroidal extension (ETE), preoperative calcitonin levels, and US features were assessed by using multivariable logistic regressions. ResultsA total of 76 patients (31 men and 45 women, 48.1 ± 11.8 years) were evaluated. The following factors demonstrated significant associations with lateral cervical LNM: the male sex (P = 0.015), an age ≤ 35 years (P = 0.049), an invasive size > 1.0 cm (P = 0.028), ETE (P = 0.005), a preoperative calcitonin level > 60 pg/ml (P < 0.001), irregular shape on the US (P = 0.001), the presence of a non-circumscribed margin on the US (P = 0.009), an Emax > 66 kPa (P < 0.001), an Emean > 37.5 kPa (P < 0.001), and an ER > 1.65 (P = 0.002). In the multivariable analysis, an age ≤ 35 years (P = 0.049), a preoperative calcitonin level > 60 pg/ml (P = 0.004), an irregular shape on the US (P = 0.036), and an Emax > 66 kPa (P = 0.011) maintained independent significance. ConclusionEmax was demonstrated to be an independent predictor for lateral cervical LNM of MTC. SWE may serve as a noninvasive method of preoperative lateral cervical LNM risk assessment for MTC.

Serum Calcitonin-Negative Medullary Thyroid Carcinoma: A Case Series of 19 Patients in a Single Center.

IntroductionMedullary 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.MethodFrom 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.ResultNineteen 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%.ConclusionSince 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.

Medullary thyroid cancer: What is the optimal management of the lateral neck in a node negative patient at index operation?

BackgroundMedullary thyroid cancer is a neuroendocrine malignancy that can occur sporadically or as the result of genomic rearranged during transfection mutations. Medullary thyroid cancer has a higher rate of metastasis than well-differentiated thyroid cancer. Lateral neck dissection is often performed, and its prophylactic use is controversial. MethodsSingle-center, retrospective review (2000–2017) of patients undergoing primary surgical treatment for medullary thyroid cancer who had negative lateral neck imaging preoperatively. Demographics, genetic associations, clinical, and imaging findings were analyzed. Locoregional recurrence, overall recurrence, and overall survival were examined. ResultsA total of 110 patients were identified, of which 18 underwent prophylactic lateral neck dissection and 92 did not. Age, sex distribution, preoperative calcitonin levels, and follow-up were similar among groups. Overall recurrence was 20% for no prophylactic lateral neck dissection and 39% for prophylactic lateral neck dissection (P = .46). Most recurrences were locoregional recurrence, 7.6% for no prophylactic lateral neck dissection versus 22% for prophylactic lateral neck dissection (P = .08), half of it being to the lateral neck in both groups. A total of 7 patients from the no prophylactic lateral neck dissection group required treatment for recurrences versus 4 patients in prophylactic lateral neck dissection group (P = .57). Overall survival at 5 years was similar, 43% the no prophylactic lateral neck dissection group and 31% for prophylactic lateral neck dissection group (P = .52). ConclusionLateral neck dissection has no effect in decreasing locoregional or overall recurrences in medullary thyroid cancer and has no effect in overall survival when performed prophylactically at index surgical intervention.

Correlation between preoperative ultrasonic features of medullary thyroid carcinoma and postoperative recurrence

BackgroundTo investigate the factors that affect postoperative recurrence in medullary thyroid carcinoma (MTC) patients, including preoperative ultrasonic characteristics and other factors.MethodA retrospective analysis of 7 MTC patients who underwent the first thyroid surgery from 2009 to 2018 and who had complete follow-up data was conducted. According to the follow-up results, these patients were divided into the recurrence group (17 cases) and non-recurrence group (57 cases). The preoperative ultrasound characteristics, preoperative and postoperative calcitonin levels, and general informations of the two groups were recorded, respectively. Univariate and multivariate analyses were performed.ResultsSingle factor Kaplan-Meier (K-M) analysis showed that: ① Preoperative ultrasonic characteristics including tumor size > 40.0 mm, capsular invasion, and metastatic cervical lymph nodes, as well as preoperative calcitonin level > 565.8 pg/ml, and postoperative calcitonin (within one week) level > 45.0 pg/ml were positively correlated with the risk of postoperative recurrence of MTC (P < 0.05); ② There was no evidence to show that sex and age had a statistically significant effect on postoperative recurrence of MTC (P > 0.05). Multivariate Cox regression analysis showed that metastatic lymph nodes shown by ultrasound (HR = 5.368, 95%CI 1.063–27.104, P = 0.042) was an independent risk factor for postoperative recurrence of MTC.ConclusionsMTC patients with metastatic lymph nodes shown by ultrasound are prone to postoperative recurrence of MTC. In addition, MTC patients with a tumor > 40.0 mm, capsular invasion, preoperative calcitonin level > 565.8 pg/ml, and postoperative calcitonin level > 45.0 pg/ml are more likely to have postoperative recurrence.

Prophylactic Lateral Neck Dissection for Medullary Thyroid Carcinoma is not Associated with Improved Survival.

Patients with medullary thyroid carcinoma (MTC) often receive lateral lymph node dissection with total thyroidectomy when calcitonin levels are elevated, even in the absence of structural disease, but the effect of this intervention on disease-specific outcomes is not known. We retrospectively reviewed patients from 1986 to 2017 who underwent thyroidectomy with curative intent for MTC at our institution. The association of disease-specific survival and clinicopathologic features was examined using univariate and multivariate Cox regression. We identified 316 patients who underwent curative resection for MTC. Overall and disease-specific survival were 76% and 86%, respectively, at 10years. To investigate the effect of prophylactic ipsilateral lateral lymph node dissection, we analyzed 89 patients without known structural disease in the neck lymph nodes at the time of resection and preoperative calcitonin > 200pg/ml, of whom 45 had an ipsilateral lateral lymph node dissection (LND) and 44 did not. There were no differences in tumor size or preoperative calcitonin levels. There was no difference at 10years in cumulative incidence of recurrence in the neck (20.9% LND vs. 30.4% no LND, p = 0.46), cumulative incidence of distant recurrence (18.3% vs. 18.4%, p = 0.97), disease-specific survival (86% vs. 93%, p = 0.53), or overall survival (82% vs. 90%, p = 0.6). Lateral neck dissection in the absence of clinical or radiologic abnormal lymph nodes is not associated with improved survival in patients with MTC.

Correlation between Ultrasonic Features of Medullary Thyroid Carcinoma and Cervical Lymph Node Metastasis

The aim of this study was to investigate the factors that affect cervical lymph node metastasis (CLNM) in individuals with medullary thyroid carcinoma (MTC) in terms of ultrasonic characteristics and other parameters. Single-factor χ2 analysis showed that the ultrasonic characteristics of tumor size >10 mm, unclear boundary, irregular pattern and capsular invasion, as well as pre-operative calcitonin level >302.50 pg/mL (p < 0.001) and age ≤52.50 y (p = 0.036), were risk factors for CLNM in individuals with MTC. Multivariate logistic regression analysis showed that age ≤52.50 y (odds ratio = 3.796; 95% confidence interval, 1.010–14.259; p = 0.048), irregular pattern (odds ratio = 5.262; 95% confidence interval, 1.200–23.084; p = 0.028) and tumor size >10 mm (odds ratio = 7.789; 95% confidence interval, 1.123–54.005; p = 0.038) were independent risk factors for CLNM in individuals with MTC. Individuals with MTC aged ≤52.50 y with an irregular pattern and tumor size >10 mm were more likely to develop CLNM. In addition, those with a pre-operative calcitonin level >302.50 pg/mL were more likely to have CLNM.

Preoperative Serum Calcitonin and Its Correlation with Extent of Lymph Node Metastasis in Medullary Thyroid Carcinoma.

Simple SummarySurgery is the only curative treatment for medullary thyroid carcinoma (MTC), but the initial surgical extent is still controversial. We examined whether the preoperative serum calcitonin level reflects the extent of lymph node metastasis (LNM), and therefore might be used to predict the optimal initial surgical extent for MTC. Furthermore, positive and negative likelihood ratios for preoperative serum calcitonin were calculated for calcitonin concentration categories, revealing that serum calcitonin levels can be of diagnostic value and might be applicable to surgical decision-making.The optimal initial surgical extent for medullary thyroid carcinoma (MTC) remains controversial. Previous studies on serum calcitonin are limited to reporting the calcitonin threshold according to anatomical disease burden. Here, we evaluated whether preoperative calcitonin levels can be used to predict optimal surgical extent. We retrospectively reviewed the 170 patients with MTC at a tertiary Korean hospital from 1994 to 2019. We extracted data on preoperative calcitonin level, primary tumor size and the number and location of lymph node metastases (LNMs). To evaluate disease extent, we divided the patients into five groups: no LNM, central LNM, ipsilateral lateral LNM, contralateral lateral LNM, and distant metastasis. We calculated the positive and negative likelihood ratios (LRs) for multiple categories of preoperative calcitonin levels. Preoperative calcitonin level positively correlated with primary tumor size (rho = 0.744, p < 0.001) and LNM number (rho = 0.537, p < 0.001). Preoperative calcitonin thresholds of 20, 200, and 500 pg/mL were associated with the presence of ipsilateral lateral LNM, contralateral lateral LNM, and distant metastasis, respectively. The negative LRs were 0.1 at a preoperative calcitonin cut-off of 100 pg/mL in the central LNM, 0.18 at a cut-off of 300 pg/mL in the ipsilateral lateral LNM, and 0 at a cut-off of 300 pg/mL in the contralateral lateral LNM. The preoperative calcitonin level correlates with disease extent and has diagnostic value for predicting LNM extent. Our results suggest that the preoperative calcitonin level can be used to determine optimal initial surgical extent.

Prediction of lateral neck lymph node metastasis according to preoperative calcitonin level and tumor size for medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) accounts up to 10% of all thyroid cancers, but is responsible for a disproportionate number of deaths. While surgery is the only curative treatment for MTC, indications for lateral neck lymph node (LLN) dissection are controversial. We performed a retrospective review to describe clinical outcomes in 93 MTC patients from July 1995 to March 2015. We analyzed their clinicopathologic factors, and cut-off values of tumor size and calcitonin levels were calculated using a receiver operating characteristic curve. Using the instances of lymph node metastases, the tumor size cut-off value was 0.95 cm (area under curve, AUC = 0.697) in patients with ipsilateral central lymph node (CLN) metastases, 2.25 cm (AUC = 0.793) in contralateral CLN metastases, and 1.75 cm (AUC = 0.753) in ipsilateral LLN metastases. The cut-off values of preoperative calcitonin levels were 226.6 pg/mL (AUC = 0.746) in ipsilateral CLN, 755.0 pg/mL (AUC = 0.840) in contralateral CLN metastases, and 237.0 pg/mL (AUC = 0.775) in ipsilateral LLN metastases. This study supports the notion that ipsilateral LLN metastases occur before contralateral CLN metastases. Therefore, ipsilateral LLN dissection should be considered in patients with contralateral CLN metastases. The extent of surgery should be based on the status of LN metastases, preoperative basal calcitonin level, and tumor size to help individualize the extent of surgery.

MON-561 Medullary Thyroid Cancer in a Single Institution: Factors Associated With Biochemical Failure

Background: Medullary thyroid carcinoma (MTC) is a rare thyroid cancer with a disproportionate high mortality and can be sporadic or familial. Surgery is the only potentially curative treatment. Our aim was to access demographic, clinical and pathological characteristics of MTC patients associated with biochemical failure after surgery. Methods: Retrospective observational study of patients with MTC diagnosed between 1984 and 2018 and followed-up in our institution. Results: We evaluated 76 individuals with MTC, 27.6% with hereditary MTC, 69.7% female, median of age 49 years-old (IQR 33.50-60.00). The median of preoperative calcitonin levels was 1121 pg/mL (IQR 445-4383), being ≥500 pg/mL in 72.3%. Preoperative calcitonin levels, when performed, had a sensitivity of 97.9%. According to TNM staging (AJCC 8th ed.), 35.9% were in stage I, 15.6% in stage II, 1.6% in stage III and 46.9% in stage IV. One patient had poor functional status, contraindicating surgery. A total of 75 patients were submitted to thyroidectomy (or completion thyroidectomy when indicated) with lymph node dissection at our institution (n=50) or an outside one (n=25). Biochemical cure (BC) was achieved in 48 (64%) patients after surgery; of these, 7 (14.58%) relapsed. BC was 95.7% in stage II, 100% in stages II/III and 24.1% in stage IV (p<0.001). Biochemical failure occurred in 36% of patients, all of them with preoperative calcitonin levels ≥500 pg/mL (p<0.001). There were no significant differences in sex, age, presence of germline RET mutation and results of fine-needle aspiration cytology between groups. Regarding histological features, patients with biochemical failure had higher tumor size (2.5 cm vs. 1.9 cm, p=0.025), multifocality (66.7% vs. 37.5%, p=0.024), vascular invasion (76.5% vs. 43.8%, p=0.028), perineural invasion (23.4 % vs. 0%, p=0.024), capsular invasion (82.4% vs. 12.1%, p<0.001), extrathyroidal extension (57.9% vs. 7.9%, p<0.001), surgical margin positivity (57.9% vs. 7.9%, p<0.001) and lymph node positivity (100% vs. 33.3%, p<0.001). Preoperative calcitonin levels (OR per increments of 500 pg/mL=1.183; p=0.012), tumor size in cm (OR=2.093; p=0.003), multifocality (OR=2.769; p=0.049), vascular invasion (OR=4.250; p=0.024), capsular invasion (OR=27.000; p<0.001), extrathyroidal extension (OR=85.000; p<0.001), surgical margins positivity (OR=17.455; p=0.001) and lymph nodes positivity (OR=62.500; p<0.001) were predictors of biochemical failure. The 5-year survival rate was higher in the BC group (91.7% vs. 74.1%; p=0.049). Conclusions: Several tumor histological characteristics were the best predictors for biochemical failure and preoperative calcitonin level was the only significant predictor performed before surgery. Demographic data, RET mutation and cytology were not associated with BC. These findings highlight that early detection is important to achieve BC in MTC.

Time to calcitonin normalization after surgery for node-negative and node-positive medullary thyroid cancer

It remains unclear when postoperative serum calcitonin levels should be measured in patients with medullary thyroid cancer (MTC) and, specifically, whether this decision should be based on the preoperative calcitonin level or nodal status. A cohort of patients with previously untreated MTC was studied. Kaplan-Meier analyses, stratified by preoperative calcitonin level, nodal status and number of nodal metastases, were performed to determine time to calcitonin normalization after initial surgery, with statistical analysis by means of the log rank test. Some 213 patients with node-negative and 182 with node-positive MTC were included in the study. Postoperative calcitonin levels normalized in a mean of 3·5 versus 3·7 days respectively among patients with preoperative calcitonin levels of 10-100 pg/ml (P = 0·815); 4·8 versus 5·3 days in those with preoperative calcitonin levels of 100·1-500 pg/ml (P = 0·026); 5·3 versus 9·9 days in patients with preoperative calcitonin levels of 500·1-1000 pg/ml (P = 0·004); and 6·6 versus 57·7 days among those with preoperative calcitonin levels exceeding 1000 pg/ml (P < 0·001). Calcitonin levels normalized in a mean of 4·7 days when nodal metastasis was not present, 5·2 days in those with one to five nodal metastases, 7·0 days in patients with six to ten nodal metastases, and 57·1 days among patients with more than ten nodal metastases. Postoperative calcitonin normalization curves paralleled each other in patients with node-negative MTC, but diverged in those with node-positive disease and with more nodal metastases. Calcitonin levels typically normalize within 1 week; and within a fortnight in those with node-positive MTC and preoperative calcitonin levels of 500·1-1000 pg/ml. With node-positive MTC and preoperative calcitonin levels exceeding 1000 pg/ml, and with more than ten nodal metastases, calcitonin normalization takes longer.

Carcinoembryonic antigen levels correlated with advanced disease in medullary thyroid cancer

BackgroundMedullary thyroid cancer (MTC) cells are capable of secreting various tumor markers including calcitonin and carcinoembyronic antigen (CEA). The purpose of this study is to determine whether abnormal CEA levels may be used as a tumor marker to predict the severity of disease in MTC.MethodsA retrospective analysis was completed for 33 patients with MTC who had preoperative serum CEA levels. Univariate and multivariate analyses were used to quantify the relationship between serum CEA levels and tumor stage and prognosis.ResultsOn multivariate analysis, elevated preoperative CEA levels were significantly associated with the size and stage of tumor, distant metastasis, decreased biochemical cure, and mortality. There was a significant association between tumor size greater than 37 mm and elevated CEA levels (> 271 ng/ml). There was also a positive correlation with increased cancer stage (> 377 ng/ml), distant metastasis (> 405 ng/ml), and contralateral compartment location of lymph node metastasis (> 162 ng/ml). When pre-operative CEA levels are > 500 ng/ml, patient mortality was 67%.ConclusionIn this study, both pre-operative calcitonin and CEA levels were significantly correlated with the extent of disease in MTC. While calcitonin has a linear relationship with disease progression, abnormal CEA levels were a better indicator of advanced disease. CEA levels > 271 ng/ml are significant for advanced tumor size and staging, metastasis to the central compartment, and decreased chance of biochemical cure. CEA levels greater than 500 ng/ml are associated with significant patient mortality.