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The Delayed Risk Stratification System in the Risk of Differentiated Thyroid Cancer Recurrence.

ABSTRACT: There has been a marked increase in the detection of differentiated thyroid carcinoma (DTC) over the past few years, which has improved the prognosis. However, it is necessary to adjust treatment and monitoring strategies relative to the risk of an unfavourable disease course.This retrospective study examined data from 916 patients with DTC who received treatment at a single centre between 2000 and 2013. The utility of the American Thyroid Association (ATA) and the European Thyroid Association (ETA) recommended systems for early assessment of the risk of recurrent/persistent disease was compared with that of the recently recommended delayed risk stratification (DRS) system.The PPV and NPV for the ATA (24.59% and 95.42%, respectively) and ETA (24.28% and 95.68%, respectively) were significantly lower than those for the DRS (56.76% and 98.5%, respectively) (p<0.0001). The proportion of variance for predicting the final outcome was 15.8% for ATA, 16.1% for ETA and 56.7% for the DRS. Recurrent disease was rare (1% of patients), and was nearly always identified in patients at intermediate/high risk according to the initial stratification (9/10 cases).The DRS showed a better correlation with the risk of persistent disease than the early stratification systems and allows personalisation of follow-up. If clinicians plan to alter the intensity of surveillance, patients at intermediate/high risk according to the early stratification systems should remain within the specialized centers; however, low risk patients can be referred to endocrinologists or other appropriate practitioners for long-term follow-up, as these patients remained at low risk after risk re-stratification.

SUBMITTER: Kowalska A

PROVIDER: S-EPMC4831829 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Project description:ContextAlthough response to therapy assessment is a validated tool for dynamic risk stratification in patients with differentiated thyroid cancer (DTC) treated with total thyroidectomy (TT) and radioactive iodine therapy (RAI), it has not been well studied in patients treated with lobectomy or TT without RAI. Because these responses to therapy definitions are heavily dependent on serum thyroglobulin (Tg) levels, modifications of the original definitions were needed to appropriately classify patients treated without RAI.ObjectiveThis study aimed to validate the response to therapy assessment in patients with DTC treated with lobectomy or TT without RAI.Design and settingThis was a retrospective study, which took place at a referral center.PatientsA total of 507 adults with DTC were treated with lobectomy (n = 187) or TT (n = 320) without RAI. They had a median age of 43.7 y, 88% were female, 85.4% had low risk, and 14.6% intermediate risk.Main outcome measureMain outcome measured was recurrent/persistent structural evidence of disease (SED) during a median followup period of 100.5 months (24-510).ResultsRecurrent/persistent SED was observed in 0% of the patients with excellent response to therapy (nonstimulated Tg for TT < 0.2 ng/mL and for lobectomy < 30 ng/mL, undetectable Tg antibodies [TgAb] and negative imaging; n = 326); 1.3% with indeterminate response (nonstimulated Tg for TT 0.2-5 ng/mL, stable or declining TgAb and/or nonspecific imaging findings; n = 2/152); 31.6% of the patients with biochemical incomplete response (nonstimulated Tg for TT > 5 ng/mL and for lobectomy > 30 ng/mL and/or increasing Tg with similar TSH levels and/or increasing TgAb and negative imaging; n = 6/19) and all (100%) patients with structural incomplete response (n = 10/10) (P < .0001). Initial American Thyroid Association risk estimates were significantly modified based on response to therapy assessment.ConclusionsOur data validate the newly proposed response to therapy assessment in patients with DTC treated with lobectomy or TT without RAI as an effective tool to modify initial risk estimates of recurrent/persistent SED and better tailor followup and future therapeutic approaches. This study provides further evidence to support a selective use of RAI in DTC.

Project description:The concept of response to therapy in differentiated thyroid cancer (DTC) was introduced as a dynamic risk stratification used to assess the status of the disease at the time of the evaluation during the follow-up and the risk of recurrence in the future. Our aim in this study was to evaluate the natural course over time of different response to therapy statuses.MethodsWe studied 501 nonselected DTC patients (102 males and 399 females) with a median age of 37 years (interquartile range [IQR] 29-48). All patients underwent near-total or total thyroidectomy followed by I-131 ablation (initial management).ResultsOf the 501 patients, 387 patients (77.2%) did not have any additional therapuetic interventions after the initial management. In this group, the response to therapy status at the time of the first evaluation after I-131 (median 17 months, IQR 14-22) was an excellent response in 258 (66.7%), an indeterminate response in 101 (26.1%), biochemically incomplete in 17 (4.4%), and structurally incomplete in 11 patients (2.8%). The status changed spontaneously without any intervention in many of them. At the last follow-up visit (median duration 101 months, IQR 71-126), 357 patients (92.2%) achieved an excellent response, 4 (1%) an indeterminate response, 8 (2.1%) a biochemically incomplete status, 16 (4.1%) a structurally incomplete status, and 2 (0.5%) died secondary to DTC with a structurally incomplete status. The response to therapy in the other 114 patients who underwent additional interventions changed from before intervention to the last evaluation as follows: excellent response, 0 to 60 patients (52.6%), indeterminate response, 20 (17.5%) to 1 patient (0.9%), biochemically incomplete 25 (21.9%) to 10 patients (9%), and structurally incomplete 69 (60.5%) to 43 patients (37.7%). Overall, at the last evaluation, 417 (83.2%) were in an excellent response, 5 (1%) in an indeterminate response, 18 (3.6%) in a biochemically incomplete status, 50 (10.2%) in a structurally incomplete status, and 11 (2.2%) died secondary to DTC with a structurally incomplete status.ConclusionsThe response to therapy at the initial evaluation is predictive of the long-term outcome. Most patients with the indeterminate response and some in the biochemically incomplete statuses spontaneously regress to an excellent status. Mortality and progression of DTC occur mostly in the structurally incomplete status.

Project description:BackgroundSurgical extent in the management of well-differentiated thyroid cancer (DTC) remains a recurrent subject of debate. This is especially relevant in low-risk DTC of 1-4 cm, which represent the majority of new thyroid cancer diagnoses. With trends towards treatment de-escalation and recent guidelines from the American Thyroid Association and British Thyroid Association endorsing hemithyroidectomy (HT) alone for low-risk DTC of 1-4 cm, we sought to systematically appraise the literature to examine recurrence rate outcomes after HT in this low-risk group.SummarySearching PubMed, Cochrane Library, and Ovid MEDLINE, we conducted a systematic review to assess the survival and recurrence rate data presented in all published studies that had a cohort of patients treated with HT for the treatment of DTC. Pooled 10-year survival and recurrence rates, odds ratios, and 95% confidence intervals were calculated for meta-analysis. We identified 31 studies (with a total of 228,746 patients (HT: 36,129, total thyroidectomy, TT: 192,617), which had published recurrence and/or survival data for patients having had HT for DTC. We discovered a pooled recurrence rate of 9.0% for HT, which is significantly higher than in previously published reports. Further, this rate is maintained when examining patients within low-risk cohorts established with recognised risk classifications. We also discovered that of those patients who develop recurrent disease, 48% recur outside the central neck.Key messagesOur study provides a comprehensive systematic review of evidence aimed primarily at defining the recurrence rate in DTC after HT, and more specifically within the low-risk subgroup. We describe pooled recurrence and 10-year survival rates from a larger, broader, and more contemporary patient population than has been previously reported. Our findings indicate that there is a small but significantly higher recurrence rate after HT than TT, but the evidence base is heterogenous and subject to confounding factors and would ultimately benefit from prospective randomised trials to overcome these deficiencies.

Project description:IntroductionDifferentiated thyroid cancer (DTC) is the most common of endocrine cancers. Many studies have focused on recurrence-free survival of DTC patients, however, few studies have addressed overall survival rates. Given its very good prognosis, estimating overall or long-term survival in patients with DTC seems rational. So far, neither the impact of pre- and post-ablation thyroglobulin, nor that of initial American Thyroid Association (ATA) risk stratification on long-term disease-specific survival, have been sufficiently studied.ObjectiveThe aim of this study was to determine the factors that influence long-term disease-specific survival and thyroglobulin levels in patients with DTC who have been previously treated with thyroidectomy and radioactive iodine (RAI) remnant ablation.Patients and methodsThis observational retrospective study included 1093 patients who were treated for DTC between 1995 and 2010 and are still monitored in our tertiary center. Only patients who needed RAI ablation after thyroidectomy were included in this study. Patients who were treated with RAI following rhTSH stimulation, patients who presented positive anti-thyroglobulin antibodies, and patients who had micro-cancers were excluded. Pre-ablation stimulated thyroglobulin (Pre-ablation sTg) was measured after thyroid hormone withdrawal (THW), just before RAI.ResultsAccording to ATA standards, 29 patients (2.7%) were classified as high-risk patients. Initial ATA high-recurrence risk rating (HR 21.9; 95% CI: 8.5-56.3), age>55 years (HR 23.8; 95%-CI: 7.5-75.3) and pre-ablation sTg?30 ?g/l (HR 8.4; 95% CI: 4.6-15.3) significantly impacted ten-year survival. Moreover, age over 45 years, ATA moderate-risk and follicular DTC were also significant. Ten-year survival was lower in ATA high-risk patients (51% vs 95% and 93% for the low and intermediate risk; p<10-7), patients older than 55 years (82% vs 98%; p<10-7), and in patients with pre-ablation sTg?30 (78% vs 95%; p<10-7). Three rates of long-term survival were distinguished: excellent (survival rate of 99% in patients<55 years with pre-ablation sTg <30?g/l) representing 59% of the cohort, moderate (survival rate of 94.5% in patients <55 years with pre-ablation sTg ?30?g/l or ?55 years with pre-ablation sTg <30 ?g/l) representing 38% of the cohort, and low (survival rate of 49% in patients ?55 years with pre-ablation sTg ?30?g/l) representing 3% of the cohort.ConclusionInitial ATA high-risk classification, age over 55 years old and pre-ablation sTg ?30 ?g/l are the main negative factors that influence the ten-year survival in DTC. We suggest three categories of overall survival rates. Patients older than 55 years with pre-ablation sTg ?30 ?g/l have the worst survival rate.

Project description:Differentiated thyroid cancer (DTC) is a common type of cancer among women with an increasing worldwide incidence rate. However, there are no specific and sensitive molecular biomarkers for DTC diagnosis or prognosis. Angiopoietin-like protein 1 (ANGPTL1) may be a novel tumor suppressor in lung, breast, colorectal and hepatocellular carcinoma. However, little is known about the influence of ANGPTL1 on the malignant properties of thyroid cancer cells or DTC recurrence in patients. Thus, the present study aimed to investigate the effects of ANGPTL1 on thyroid cancer malignancy or recurrence. The present study examined the mRNA levels of ANGPTL1 in thyroid cancer and paracancerous tissues using RNA sequencing data from The Cancer Genome Atlas. The present study also determined the effects of ANGPTL1 on thyroid cancer cell proliferation using the Cell Counting Kit-8 assay. Associations were identified among ANGPTL1 expression levels and thyroid cancer proliferation, migration and metastasis using The Cancer Genome Atlas data set and by Gene Set Enrichment Analysis. The expression of ANGPTL1 in patients with DTC and without recurrence was compared in order to assess its potential as a prognostic biomarker for DTC. In addition, ANGPTL1 concentrations in the serum of patients with DTC and individuals with benign thyroid nodules were compared to evaluate the sensitivity and specificity of ANGPTL1 as a predictive biomarker for DTC. The results of the present study demonstrated that ANGPTL1 expression levels were lower in thyroid cancer compared with those in adjacent normal thyroid tissues. ANGPTL1 expression was observed to decrease with thyroid cancer progression. In addition, ANGPTL1 was demonstrated to inhibit thyroid cancer cell proliferation, migration and invasion and ANGPTL1 expression levels were reduced in patients with DTC with recurrence compared with those in patients with non-recurrent DTC. Additionally, serum concentrations of ANGPTL1 in patients with DTC were decreased compared with those in individuals with benign thyroid nodules. In conclusion, ANGPTL1 may be a novel predictive biomarker for DTC diagnosis and recurrence in patients with DTC.

Project description:Neck ultrasonography, a mainstay of long-term surveillance for recurrence of differentiated thyroid cancer (DTC), is routinely used by endocrinologists, general surgeons, and otolaryngologists; however, physician confidence in their ability to use ultrasonography to identify lymph nodes suggestive of cancer recurrence remains unknown. To evaluate physicians' posttreatment surveillance practices for DTC recurrence, specifically their use of and confidence in ultrasonography. Cross-sectional study of 448 physicians in private and academic hospitals who completed a survey on DTC posttreatment practices from October 2018 to August 2019 (response rate, 69%) and self-reported involvement in long-term surveillance for thyroid cancer recurrence. Physicians were identified by patients affiliated with the Surveillance, Epidemiology, and End Results Program registries in Georgia State and Los Angeles County. Of the respondents, 320 physicians who reported involvement with DTC surveillance were included in the analysis. Physician-reported long-term surveillance practices for DTC, including frequency of use and level of confidence in ultrasonography for detecting lymph nodes suggestive of cancer recurrence. In the cohort of 320 physicians who reported involvement with DTC surveillance, 186 (60%) had been in practice for 10 years to less than 30 years; 209 (68%) were White; and 212 (66%) were men. The physicians included 170 (56%) endocrinologists, 67 (21%) general surgeons, and 75 (23%) otolaryngologists. Just 84 (27%) physicians reported personally performing bedside ultrasonography. Only 57 (20%) had high confidence (rated quite or extremely confident) in their ability to use bedside ultrasonography to identify lymph nodes suggestive of recurrence; 94 (33%) did not report high confidence in either their ability or a radiologist's ability to use ultrasonography to detect recurrence. Higher confidence in ultrasonography was associated with the general surgery subspecialty (odds ratio [OR], 5.7; 95% CI, 2.2-14.4; reference endocrinology) and with treating a higher number of patients per year (>50 patients: OR, 14.4; 95% CI, 4.4-47.4; 31-50 patients: OR, 8.4; 95% CI, 2.6-26.7; 11-30 patients: OR, 4.3; 95% CI, 1.5-12.1; reference 0-10 patients). Given the importance of neck ultrasonography in long-term surveillance for thyroid cancer, these findings of physicians' low confidence in their own ability and that of radiologists to use ultrasonography to detect recurrence point to a major obstacle to standardizing long-term DTC surveillance practices.

Project description:BackgroundStudies have reported differing factors associated with poor outcomes in patients with differentiated thyroid cancer (DTC). We aimed to describe our 20 years of experience in the management of thyroid cancer (TC) and identify predictors of treatment outcomes.MethodsWe conducted a retrospective review of medical records of patients with TC seen in the Thyroid Center at King Saud University Medical City (KSUMC) in Riyadh, Saudi Arabia, between the years 2000 and 2020. Demographic and clinical data including pathological characteristics were collected. The American Thyroid Association (ATA) risk stratification was determined for all patients at the postoperative period as well as the response to therapy at the final follow-up visit.ResultsA total of 674 patients (mean age: 47.21 years) with TC, 571 (84.7%) of which were women, were included. There were 404 (60.0%) patients with ATA low risk, 127 (18.8%) with intermediate risk, and 143 (21.2%) with high-risk histology. Overall, 461 patients (68.4%) had an excellent response to treatment, 65 (9.6%) had an indeterminate response, 83 (12.3%) had a biochemical incomplete response, and 65 (9.6%) had a structural incomplete response. Patients who had an excellent response were mostly ATA low risk (n = 318 of 431, 68.1%), whereas 40 of 65 patients (61.5%) of those with ATA high-risk histology had a structural incomplete response to treatment. There were significantly more women who had an excellent response compared with men. Obesity, lymphovascular invasion, and size of the tumor were significant predictors of worse outcomes to therapy.ConclusionTumor size, lymphovascular invasion, and obesity are strong predictors of a worse response to therapy among patients with TC. Patients with obesity should be carefully followed up regardless of their risk stratification in light of the recent compelling evidence associating obesity with thyroid cancer and its higher risk of a worse disease outcome. ATA risk stratification is well correlated with patient long-term outcomes.

Project description:ObjectiveTo evaluate the computed tomography (CT) features for diagnosing metastatic cervical lymph nodes (LNs) in patients with differentiated thyroid cancer (DTC) and validate the CT-based risk stratification system suggested by the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) guidelines.Materials and methodsA total of 463 LNs from 399 patients with DTC who underwent preoperative CT staging and ultrasound-guided fine-needle aspiration were included. The following CT features for each LN were evaluated: absence of hilum, cystic changes, calcification, strong enhancement, and heterogeneous enhancement. Multivariable logistic regression analysis was performed to identify independent CT features associated with metastatic LNs, and their diagnostic performances were evaluated. LNs were classified into probably benign, indeterminate, and suspicious categories according to the K-TIRADS and the modified LN classification proposed in our study. The diagnostic performance of both classification systems was compared using the exact McNemar and Kosinski tests.ResultsThe absence of hilum (odds ratio [OR], 4.859; 95% confidence interval [CI], 1.593-14.823; P = 0.005), strong enhancement (OR, 28.755; 95% CI, 12.719-65.007; P < 0.001), and cystic changes (OR, 46.157; 95% CI, 5.07-420.234; P = 0.001) were independently associated with metastatic LNs. All LNs showing calcification were diagnosed as metastases. Heterogeneous enhancement did not show a significant independent association with metastatic LNs. Strong enhancement, calcification, and cystic changes showed moderate to high specificity (70.1%-100%) and positive predictive value (PPV) (91.8%-100%). The absence of the hilum showed high sensitivity (97.8%) but low specificity (34.0%). The modified LN classification, which excluded heterogeneous enhancement from the K-TIRADS, demonstrated higher specificity (70.1% vs. 62.9%, P = 0.016) and PPV (92.5% vs. 90.9%, P = 0.011) than the K-TIRADS.ConclusionExcluding heterogeneous enhancement as a suspicious feature resulted in a higher specificity and PPV for diagnosing metastatic LNs than the K-TIRADS. Our research results may provide a basis for revising the LN classification in future guidelines.

Project description:BackgroundIt is difficult to reliably distinguish between American Thyroid Association (ATA) low-risk and intermediate-risk differentiated thyroid cancer (DTC) before surgery. Therefore, physicians are faced with a dilemma regarding the necessity and timing of completion total thyroidectomy (CT) after thyroid lobectomy (TL). We evaluated proper surgical methods by analyzing oncologic outcomes of TL in patients with DTC whose risk had been upgraded after surgery.MethodsWe retrospectively reviewed the medical records of 1,702 patients with DTC who underwent TL and ipsilateral central lymph node (LN) dissection between January 2006 and December 2011. The patients were classified into Group A (n=1,159; low risk; ≤5 central LN metastases or the absence of pathologic microscopic capsular invasion) and Group B (n=543; upgraded intermediate risk after surgery; >5 central LN metastases or the presence of pathologic microscopic capsular invasion). We analyzed their clinicopathological characteristics and recurrence-free survival.ResultsAll 32 patients who experienced recurrence underwent CT. After the first operation, the duration until reoperation in Groups A and B were 8.00±2.74 (range, 3.42-12.17) and 5.10±3.09 (range, 1.25-11.67) years, respectively. There was no significant difference in recurrence rates, disease-related mortality rates, or 10-year recurrence-free survival rates between the two groups. The mean follow-up durations in Groups A and B were 10.22±1.58 and 10.13±1.47 years, respectively. Univariate analysis showed that sex, age, tumor size, multifocality, extrathyroidal extension (ETE), and number of central LN metastases were not associated with recurrence after TL, although the rate of central LN metastases was. Multivariate analysis showed that sex, age, tumor size, multifocality, ETE, central LN metastases, and the number of central LN metastases were not associated with recurrence after TL, although multifocality was.ConclusionsTL with prophylactic central compartment neck dissection (CCND) is sufficient for patients with DTC whose risk is upgraded after surgery because they have a good prognosis at long-term follow-up. Larger-scale randomized clinical trials are required to confirm our findings.

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The Delayed Risk Stratification System in the Risk of Differentiated Thyroid Cancer Recurrence.

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