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Updates on the Management of Advanced, Metastatic, and Radioiodine Refractory Differentiated Thyroid Cancer.

ABSTRACT: Differentiated thyroid cancer (DTC) accounts for 95% of all thyroid cancers and is generally an indolent tumor, treated effectively with surgery, radioactive iodine, and thyroid-stimulating hormone suppressive therapy. However, 5-10% of patients have advanced disease, with aerodigestive tract invasion, distant metastases, or radioiodine refractory disease, with poor prognosis. This review focuses on the approaches for treating advanced DTC, including management of gross extra-thyroidal extension, recurrent loco-regional or distant metastatic disease, the role of external beam radiation therapy and systemic treatment. Locally ablative treatment modalities, including surgery, radiation therapy, and thermal ablation are evolving and can be used in selected patients. In recent years, new therapeutic agents with molecular targets have become available and two multi-kinase inhibitors, Sorafenib and Lenvatinib, have been licensed for iodine refractory DTC showing an advantage in terms of progression-free survival, although an impact on overall survival has not been proven yet. Management of advanced thyroid cancer can be challenging but a multidisciplinary approach can significantly improve outcomes for this patient population.

SUBMITTER: Tumino D

PROVIDER: S-EPMC5702018 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Updates on the Management of Advanced, Metastatic, and Radioiodine Refractory Differentiated Thyroid Cancer.

Tumino Dario D Frasca Francesco F Newbold Kate K

Frontiers in endocrinology 20171120

Differentiated thyroid cancer (DTC) accounts for 95% of all thyroid cancers and is generally an indolent tumor, treated effectively with surgery, radioactive iodine, and thyroid-stimulating hormone suppressive therapy. However, 5-10% of patients have advanced disease, with aerodigestive tract invasion, distant metastases, or radioiodine refractory disease, with poor prognosis. This review focuses on the approaches for treating advanced DTC, including management of gross extra-thyroidal extension ...[more]

PMID: 29209273

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Project description:BackgroundIt has been shown that a subgroup of patients with differentiated thyroid cancer (DTC) and medullary thyroid carcinoma (MTC) would progress to advanced stages of thyroid cancer. Therefore, the present study was done to systematically review available evidence in order to investigate efficacy and safety of peptide receptor radionuclide therapy (PRRT) in the patients with advanced radioiodine refractory differentiated thyroid cancer (RR-DTC) and metastatic MTC.MethodsFor this purpose, relevant studies investigated safety and efficacy of PRRT in the patients with advanced RR-DTC and metastatic MTC were identified by searching Medline (Pubmed, Ovid, and Ebsco), Scopus, Embase, Web of Science, and Cochrane Library databases (from database inception to March 24, 2021). The review was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Searching was done independently by two investigators. Two researchers independently extracted the data and any disagreement was adjudicated by consensus. Quality of the studies was assessed using the tool of case reports/series in systematic reviews.ResultsAmong 2284 related papers, 41 papers met the inclusion criteria. A total of 157 patients with RR-DTC were treated with PPRT. Biochemical and objective responses (partial and complete) were observed in 25.3 and 10.5% of patients, respectively. Among 220 patients with metastatic MTC, biochemical and objective responses were observed in 37.2 and 10.6% of the patients, respectively. Forty-six deaths were reported in 95 patients with advanced RR-DTC. In addition, 63 deaths were observed in 144 patients with metastatic MTC. Major side effects were reported in 124 patients treated with 90Y -based agent. In the patients treated with 177Lu-DOTA-TATE and 111In-Octreotide, mild and transient hematologic or renal complications were reported.ConclusionFindings of the study revealed that in the absence of the established treatment for the patients with RR-DTC and metastatic MTC, PRRT could be effective with few adverse events.Trial registrationPROSPERO registration number: CRD42019125245 .

Project description:BackgroundThe diagnosis of radioiodine refractory differentiated thyroid cancer (RAIR-DTC) is primarily based on clinical evolution and iodine uptake over the lesions, which is still time-consuming, thus urging a predictive model for timely RAIR-DTC informing. The aim of this study was to develop a nomogram model for RAIR prediction among DTC patients with distant metastases (DM).MethodsData were extracted from the treatment and follow-up databases of Peking Union Medical College Hospital between 2010 and 2021. A total of 124 patients were included and divided into RAIR (n=71) and non-RAIR (n=53) according to 2015 ATA guidelines. All patients underwent total thyroidectomy followed by at least two courses of RAI treatment. Serological markers and various clinical, pathological, genetic status, and imaging factors were integrated into this study. The pre-treatment stimulated Tg and pre- and post-treatment suppressed Tg at the first and second course RAI treatment were defined as s-Tg1, s-Tg2, sup-Tg1, and sup-Tg2, respectively. Δs-Tg denoted s-Tg1/s-Tg2, and Δs-TSH denoted s-TSH1/s-TSH2. Multivariate logistic regression and correlation analysis were utilized to determine the independent predictors of RAIR. The performance of the nomogram was assessed by internal validation and receiver operating characteristic (ROC) curve, and benefit in clinical decision-making was assessed using decision curve.ResultsIn univariate logistic regression, nine possible risk factors were related to RAIR. Correlation analysis showed four of the above factors associated with RAIR. Through multivariate logistic regression, Δs-Tg/Δs-TSH<1.50 and age upon diagnosis were obtained to develop a convenient nomogram model for predicting RAIR. The model was internally validated and had good predictive efficacy with an AUC of 0.830, specificity of 0.830, and sensitivity of 0.755. The decision curve also showed that if the model is used for clinical decision-making when the probability threshold is between 0.23 and 0.97, the net benefit of patients is markedly higher than that of the TreatAll and TreatNone control groups.By using 1.50 as a cut-off ofΔs-Tg/Δs-TSH, differing biochemical progression among the generally so-called RAIR can be further stratified as meaningfully rapidly or slowly progressive patients (P=0.012).ConclusionsA convenient user-friendly nomogram model was developed with good predictive efficacy for RAIR. The progression of RAIR can be further stratified as rapidly or slowly progressive by using 1.50 as a cut-off value of Δs-Tg/Δs-TSH.

Project description:While there is a clear consensus for defining radioiodine-refractory differentiated thyroid cancer (RR-DTC), it is unknown whether these criteria are equally valid for determining when radioiodine (RAI) therapy is no longer beneficial and systemic treatment should be considered. Lenvatinib, a multikinase inhibitor, significantly prolonged progression-free survival (PFS) compared to placebo in a Phase 3 trial in RR-DTC (SELECT; hazard ratio [HR]: 0.21 [99% confidence interval (CI) 0.14-0.31]; p?<?0.001). This sub-analysis compared clinical outcomes of lenvatinib-treated patients in SELECT stratified by RR-DTC inclusion criteria.In SELECT, patients with measurable RR-DTC and radiologic evidence of disease progression ?13 months prior to study entry were randomized 2:1 to lenvatinib (24?mg/day; 28-day cycle) or placebo. In this analysis, patients were stratified based on the following RR-DTC inclusion criteria: no RAI uptake, disease progression within 12 months of RAI therapy despite RAI avidity at the time of treatment, and extensive (>600?mCi) cumulative RAI exposure. All had disease progression as an inclusion criterion for SELECT.Of 392 patients (261 lenvatinib; 131 placebo) enrolled, 275, 235, and 73 patients met the inclusion criteria for no RAI uptake, disease progression despite RAI avidity, and extensive RAI exposure, respectively. There was significant overlap between the patient groups, with 167 (42.6%) patients meeting more than one inclusion criterion. Lenvatinib improved median PFS compared to placebo in all groups ("no RAI uptake": lenvatinib not quantifiable [NQ; CI 14.8-NQ] vs. placebo, 3.7 months [CI 2.5-5.3]; "disease progression despite RAI avidity": lenvatinib 16.5 months [CI 12.8-NQ] vs. placebo, 3.7 months [CI 1.9-5.4]; "extensive RAI exposure": lenvatinib 18.7 months [CI 10.7-NQ] vs. placebo, 3.6 months [CI 1.9-5.5]). Objective response rates were 71.8%, 60.0%, and 56.0% for patients with no RAI uptake, disease progression despite RAI avidity, and extensive RAI exposure, respectively. Lenvatinib-related adverse events were similar across groups.Comparable efficacy and safety profiles were observed in lenvatinib-treated patients regardless of RR-DTC criteria, possibly because of a large overlap among patients fulfilling each criterion. However, differing definitions for RR-DTC may be equally valid because both lenvatinib and placebo arms exhibited similar PFS outcomes across groups.

Project description:BackgroundOutcomes vary among patients with radioiodine refractory (RR) differentiated thyroid cancer (DTC). The prognostic factors for survival are not well-known, resulting in difficulty in selecting patients for new targeted therapies. We assessed overall survival (OS) and cancer-specific survival (CSS) from RR-DTC to identify prognostic factors associated with survival.Patients and methodsThe data on all cases of metastatic RR-DTC treated in our center from 1990 to 2011 were retrospectively reviewed. Survival was estimated using the Kaplan-Meier method; associated prognostic factors were assessed using Cox's model.ResultsOf 153 cases of metastatic DTC, 59% (n = 91) met a criterion for RR: that is, 60% (n = 55) had at least 1 metastasis without (131)I uptake; 21% (n = 19) had progressive disease (PD) despite (131)I; 19% (n = 17) had persistent disease despite a cumulative activity of (131)I of ≥600 mCi. After the diagnosis of RR, median OS was 8.9 years (95% confidence interval [CI]: 5.4-NR); median CSS was 9.6 years (95% CI: 6.01-NR). In multivariate analyses, PD despite (131)I as a criterion for RR disease and the time from initial diagnosis of DTC to diagnosis of RR <3 years were the only independent prognostic factors for poor OS and CSS. Thyroglobulin doubling time (Tg-DT) was assessed in 31 of 91 cases. Among the 11 patients with Tg-DT for <1 year or undetectable Tg, 6 deaths occurred, whereas only 3 died of 20 patients with Tg-DT >1 year or negative Tg-DT.ConclusionThe identification of prognostic factors for decreased survival in RR-DTC may improve the selection of patients for targeted agents.Implications for practiceThis study shows a great heterogeneity in terms of prognosis in radioiodine refractory differentiated thyroid carcinoma. Poorer prognosis is observed in patients with tumor progression or with a diagnosis of radioiodine resistance within 3 years after the initial diagnosis of thyroid cancer. Those findings could lead to improvements in the selection of patients for targeted therapies.

Dataset Information

Updates on the Management of Advanced, Metastatic, and Radioiodine Refractory Differentiated Thyroid Cancer.

Publications

Updates on the Management of Advanced, Metastatic, and Radioiodine Refractory Differentiated Thyroid Cancer.

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