Predictive Value of a Prognostic Model Based on Lymphocyte-to-Monocyte Ratio Before Radioiodine Therapy for Recurrence of Papillary Thyroid Carcinoma.

BACKGROUND: The aim of this study was to investigate the predictive value of a prognostic model based on the lymphocyte-to-monocyte ratio (LMR) before radioiodine treatment for the recurrence of papillary thyroid carcinoma (PTC). METHODS: Clinicopathological data of 441 patients with papillary thyroid cancer were collected retrospectively. The Receiver operating characteristic (ROC) was used to determine the optimal cut-off value for predicting PTC recurrence by LMR before radioiodine treatment. Recurrence was the endpoint of the study, and survival was estimated by the Kaplan-Meier method, and any differences in survival were evaluated with a stratified log-rank test. Univariate and multifactorial analyses were performed using Cox proportional-hazards models to identify risk factors associated with PTC recurrence. RESULTS: The ROC curve showed that the best cut-off value of LMR before radioiodine treatment to predict recurrence in patients with PTC was 6.61, with a sensitivity of 54.1%, a specificity of 73%, and an area under the curve of 0.628. The recurrence rate was significantly higher in the low LMR group (16%) than in the high LMR group (5%) (P = 0.001, χ2 = 12.005). Multifactorial analysis showed that LMR < 6.61 (P = 0.006; HR = 2.508) and risk stratification (high risk) (P = 0.000; HR = 5.076) before radioiodine treatment were independent risk factors predicting recurrence in patients with PTC. Patients with preoperative LMR < 6.61 and high risk stratification had the lowest recurrence-free survival rate and the shortest recurrence-free survival time. CONCLUSIONS: The LMR-based prognostic model before radioactive iodine treatment is valuable for early prediction of PTC recurrence and it can be used in clinical practice as a supplement to risk stratification and applied in combination to help screen out patients with poorer prognosis early.

Blood prognostic predictors of treatment response for patients with papillary thyroid cancer.

BACKGROUND: Papillary thyroid cancer (PTC) is a very common malignant disease with high morbidity. We needed some pretreatment indicators to help us predict prognosis and guide treatment. We conducted a study about some pretreatment prognostic indicators. METHODS: This clinical study recruited 705 postoperative PTC patients (211 males, 494 females). Clinical data before radioactive iodine (RAI) treatment were collected. Patients' response to therapy were classified into two categories: 'Good Prognosis Group' (GPG) and 'Poor Prognosis Group' (PPG), according to '2015 American Thyroid Association Guidelines'. Differences of indicators between different prognosis groups were compared. Odds ratios (ORs) were calculated by univariate/multiple binary logistic regression models. Difference of body mass index (BMI) changes before and after RAI treatment between different prognosis groups was also compared. RESULTS: A total of 546 (77.45%) belonged to GPG, and 159 (22.55%) belonged to PPG. Platelet (PLT), neutrophil (NEUT), PLT subgroups, and combination of red blood cell distribution width (RDW) and BMI (COR-BMI) were different between two prognosis groups. The significance of the difference between the two groups of BMI disappeared after the Bonferroni correction. PLT and PLT subgroups had detrimental effects on the risk of PPG; T stage had a positive effect on the risk of PPG. PLT subgroup showed a detrimental effect on the risk of PPG when we included additional covariates. CONCLUSIONS: We found that lower pretreatment PLT levels may indicate a poor prognosis for PTC. The relationship between platelet-derived growth factor (PDGF) and radiation sensitivity may be the key to this association.

Association between clinical and tumor features with postoperative thyroglobulin in pediatric papillary thyroid cancer.

BACKGROUND: Why certain patients after total thyroidectomy for thyroid cancer who do not have distant metastasis have increased serum stimulated thyroglobulin (s-Tg) is unknown. The aim of our study was to systematically investigate the associations of preablation s-Tg with clinical and tumor characteristics in children and young adults less than 20 years old after total thyroidectomy for papillary thyroid cancer. METHODS: We performed a retrospective analysis of 93 children and young adults younger than 20 years old who had undergone total thyroidectomy and were without known distant metastases who underwent remnant ablation. Before any remnant preablation, we assessed the association of s-Tg after thyroid hormone withdrawal with the clinical and histopathologic characteristics according to the American Thyroid Association pediatric initial risk classification system. RESULTS: The median age was 18 years, and the majority of patients were female (80%). The preablation s-Tg ranged from 0.02 to 902.00 ng/mL, with a median of 9.2 ng/mL. Forty-five (48%) patients had an increased preablation s-Tg >10 ng/mL. In multivariate analyses of clinical and tumor characteristics, high-risk stratification and high neck uptake (>2%) were the independent predictive factors for the presence of an increased preablation s-Tg. CONCLUSION: Children and young adults younger than 20 years old with high-risk stratification and high neck uptake are likely to present a high level of preablation s-Tg after total thyroidectomy for papillary thyroid cancer. Continued long-term surveillance is necessary in this cohort of patients to confirm the role of preablation s-Tg as a biomarker for monitoring postoperative residual disease.

Serum Matrix metalloproteinase-9 (MMP-9) can help identify patients with papillary thyroid cancer at high risk of persistent disease: Value and limitations of a potential marker of neoplasia.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is an important mediator of invasion and metastasis in neoplasia. In thyroid cancer expression levels correlate with aggressiveness but data on peripheral MMP-9 levels are less definitive. OBJECTIVE: Prospective study evaluating serum MMP-9 in the diagnosis and prognosis of papillary thyroid cancer. METHODS: Serum samples of MMP-9 were drawn before surgery in 185 consecutively enrolled patients with nodular thyroid disease, stratified on pathology as benign disease (N= 88) and papillary thyroid cancer (N= 97). Serum MMP-9 was measured by an immunometric assay. RESULTS: MMP-9 levels were not different between benign vs malignant pathology (p= 0.3). In papillary thyroid cancer there was no significant difference in MMP-9 levels between histologies, TNM stage and invasive/non-invasive cancers. High-risk patients with multiple features of aggressiveness had significantly higher MMP-9 levels compared to low-intermediate risk patients (767.5 ± 269.2 ng/ml vs 563.7 ± 228.4 ng/ml, p= 0.019). A cut-off of 806 ng/ml distinguished high from low-intermediate risk patients with a sensitivity of 60% and a specificity of 87.36%, p= 0.018. In patients with available follow-up data (N= 78), MMP-9 was higher in patients who required ⩾ 2 doses of 131I therapy (p= 0.009) and in those with biochemical evidence of persistent disease/who required additional therapy to achieve disease-free status (p= 0.017). CONCLUSION: Serum MMP-9 is not useful in the diagnosis of PTC, but preliminary data shows that high pre-surgical serum MMP-9 levels may identify patients at higher risk of persistent disease who require intensive treatment. Large volume prospective studies are required to confirm this observation.

Associations of telomerase reverse transcriptase rs10069690 and rs2736100 polymorphisms with papillary thyroid carcinoma.

Papillary thyroid carcinoma is one of the most common endocrine malignancies. Telomerase reverse transcriptase rs10069690 and rs2736100 polymorphisms have been studied in thyroid carcinomas with different ethnicity, but the results were inconsistent. Therefore, we evaluated the relationship between rs10069690 and rs2736100 polymorphisms and papillary thyroid carcinoma risk and furtherly investigated the associations of these polymorphisms with stimulated thyroglobulin (sTg) positivity and adverse reactions of I treatment in papillary thyroid carcinoma. Four hundred thirty-six papillary thyroid carcinoma patients and 345 controls of Chinese Han population were included in our study. Rs10069690 and rs2736100 were genotyped using improved multiple ligase detection reactions. Analysis of inheritance model was performed using the unconditional logistic regression. In our study, rs10069690 and rs2736100 were associated with papillary thyroid carcinoma risk, especially in females over 45 years of age (P = 0.002 and P = 0.032, respectively). Rs10069690 was associated with sTg positivity and with an rs10069690-related occurrence risk order of thyroglobulin antibody (Tg-Ab)(+) + Tg(+) > Tg-Ab(+) + sTg(-) > Tg-Ab(-) + sTg(+). Patients with the homozygous TT genotype of rs10069690 had an increased risk of neck discomfort (P = 0.033), while the homozygous CC genotype of rs2736100 had a decreased risk of gastrointestinal toxicity (P = 0.048). Our data demonstrated that rs10069690 and rs2736100 might be bio-indicators related to papillary thyroid carcinoma risk in females over 45 years of age and I treatment-related toxicity. In addition, rs10069690 may be a predictor of bad clinicopathological features and poor prognosis from a serological point of view.

Estimating the Growth Rate of Lung Metastases in Differentiated Thyroid Carcinoma: Response Evaluation Criteria in Solid Tumors or Doubling Time?

Background: Estimating the growth rate of lung metastases for the treatment of patients with metastases of differentiated thyroid carcinoma (DTC) is important. This study aimed to evaluate survival outcomes according to different criteria for estimating the growth rate of lung metastases. Methods: Patients with macronodular (≥1 cm) lung metastases of DTC who underwent total thyroidectomy and high-dose radioactive iodine therapy between 1995 and 2013 were enrolled. The time to progressive disease (PD) by the Response Evaluation Criteria in Solid Tumors (RECIST), average tumor volume doubling time of the two dominant target lung lesions (midDT), and thyroglobulin doubling time (TgDT) were measured in each patient, and their association with disease-specific survival (DSS) was evaluated. Results: Forty-four patients with target lung metastatic nodules with an initial maximal diameter of 1.3 cm (median) were followed-up for a median of 6.8 years after the diagnosis of lung metastases. Based on RECIST, 12 patients (27.3%) showed fast tumor progression, with time to PD <1 year. When assessed by midDT, nine patients (20.5%) had midDT ≤1 year, showing rapid tumor progression. Seven of 33 patients (21.2%) who were negative for thyroglobulin antibody had midDT <1 year. Growth rates assessed by all three criteria were significantly associated with DSS. However, midDT had the highest predictive value for DSS, with a proportion of variation explained of 33.6%. Five-year DSS was 29.6% in patients with midDT ≤1 year, 50.0% in patients with time to PD <1 year, and 42.9% in patients with TgDT <1 year. Conclusions: Among the different criteria for estimating the growth rate of metastases in patients with lung metastases of DTC, midDT was the most powerful for predicting DSS, in comparison with RECIST and TgDT. Performing at least three serial chest computed tomography scans during the first year from the diagnosis of lung metastases can facilitate early detection of patients with rapid tumor progression and provide objective guidance for initiation of systemic therapy.

The most reliable time point for intact parathyroid hormone measurement to predict hypoparathyroidism after total thyroidectomy with central neck dissection to treat papillary thyroid carcinoma: a prospective cohort study.

PURPOSE: We assessed the optimal time for intact parathyroid hormone (iPTH) measurement for early detection of post-total thyroidectomy (TT) hypocalcemia in patients with papillary thyroid carcinoma (PTC). METHODS: In this single-center prospective cohort study, 143 patients who underwent TT with central neck dissection with or without lateral neck dissection for PTC were included. Biochemical profiles including iPTH, corrected total calcium, and ionized calcium within 24 h after surgery were analyzed. RESULTS: The 4-h postoperative iPTH was the most reliable predictor of post-TT transient or permanent hypoparathyroidism (cutoff for hypocalcemia was 3.75 pg/mL, AUC = 0.885, P < 0.001, sensitivity 81.6%, specificity 86.0%; cutoff for permanent hypocalcemia was 2.48 pg/mL, AUC = 0.819, P < 0.001, sensitivity 100%, specificity 57.8% calculated using ROC curves). CONCLUSIONS: The 4-h postoperative iPTH can most accurately predict hypoparathyroidism after TT with central neck dissection to treat PTC and facilitate the early discharge of low-risk postoperative hypoparathyroidism patients and decrease unnecessary overnight observation and calcium supplementation.

Papillary Thyroid Carcinoma Recurrence: Low Yield of Neck Ultrasound With an Undetectable Serum Thyroglobulin Level.

OBJECTIVES: To assess the yield of neck ultrasound (US) when serum thyroglobulin (Tg) is undetectable (<0.1 ng/mL) compared to elevated serum Tg in patients with differentiated papillary thyroid carcinoma (PTC) treated with thyroidectomy and radioactive iodine 131 (RAI) ablation. METHODS: A retrospective chart review was conducted from 2010 through 2015 at an academic institution evaluating US results in patients with serum Tg levels obtained within 6 months of a neck US examination after thyroidectomy and RAI. The reference standard for recurrence was pathologic results from US-guided fine-needle aspiration (FNA) or follow-up for at least 1 year. RESULTS: Among 76 patients with undetectable serum Tg levels, there were 19 examinations in 18 patients in which US raised the possibility of recurrence. None of these 18 patients had recurrence by FNA (n = 8) or clinical follow-up of at least 1 year (n = 10). Among 65 patients with elevated serum Tg levels, there were 24 examinations in 22 patients in which US raised the possibility of recurrence. Twelve patients underwent FNA, with 9 patients (34.6%) showing PTC; 7 patients had follow-up neck US examinations showing stability of findings; and 3 patients were lost to follow up. The yield of neck US was significantly lower when serum Tg was undetectable compared to when levels were elevated (P = .001). CONCLUSIONS: Neck US did not identify recurrent PTC when the serum Tg level was undetectable in patients who underwent total thyroidectomy and RAI therapy. Eliminating neck US when serum TG levels are undetectable could decrease unnecessary imaging examinations without negatively affecting the ability to detect recurrent disease.