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Radioiodine Treatment and Thyroid Hormone Suppression Therapy for Differentiated Thyroid Carcinoma: Adverse Effects Support the Trend toward Less Aggressive Treatment for Low-Risk Patients.

ABSTRACT: Over the past decades, the incidence of differentiated thyroid carcinoma (DTC) has steadily increased, with especially a growing number of low-risk patients. Whereas DTC used to be treated rather aggressively, it is now acknowledged that aggressive treatment does not affect outcome for low-risk patients and that it can induce adverse effects. In this review an overview of the most clinically relevant adverse effects of radioiodine treatment and thyroid hormone suppression therapy (THST) is presented, and the trend toward less aggressive treatment for low-risk patients is outlined. Salivary gland dysfunction occurs in roughly 30% of patients, and is probably due to the concentration of radioiodine in the salivary glands by the sodium/iodide symporter. Beta radiation from radioiodine can result in sialoadenitis and eventually fibrosis and loss of salivary function. Furthermore, patients can experience bone marrow dysfunction following radioiodine treatment. Although this is in general subclinical and transient, patients that receive very high cumulative radioiodine doses may be at risk for more severe bone marrow dysfunction. THST can induce adverse cardiovascular effects in patients with DTC, such as diastolic and systolic dysfunction, and also adverse vascular and prothrombotic effects have been described. Finally, the effects of THST on bone formation and resorption are outlined; especially postmenopausal women with DTC on THST seem to be at risk of bone loss. In the past years, advances have been made in preventing low-risk patients from being overtreated. Improved biomarkers are still needed to further optimize risk stratification and personalize medicine.

SUBMITTER: Klein Hesselink EN

PROVIDER: S-EPMC4521066 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Radioiodine Treatment and Thyroid Hormone Suppression Therapy for Differentiated Thyroid Carcinoma: Adverse Effects Support the Trend toward Less Aggressive Treatment for Low-Risk Patients.

Klein Hesselink E N EN Links T P TP

European thyroid journal 20150611 2

Over the past decades, the incidence of differentiated thyroid carcinoma (DTC) has steadily increased, with especially a growing number of low-risk patients. Whereas DTC used to be treated rather aggressively, it is now acknowledged that aggressive treatment does not affect outcome for low-risk patients and that it can induce adverse effects. In this review an overview of the most clinically relevant adverse effects of radioiodine treatment and thyroid hormone suppression therapy (THST) is prese ...[more]

PMID: 26279993

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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.

Project description:BackgroundIn the phase 3 SELECT study, lenvatinib significantly improved prognostic outcomes vs. placebo in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). However, toxicity of lenvatinib is sometimes considerable and requires frequent dose interruptions and modifications. Recently, planned drug holidays have been proposed as a means of avoiding severe adverse events (AEs).MethodsWe retrospectively reviewed medical records to compare the efficacy and safety of lenvatinib in RR-DTC patients who underwent planned drug holidays (planned holiday group) vs. those who received conventional daily oral administration (daily group).ResultsThe subjects were 25 patients in the planned holiday group and 21 in the daily group. Median age was 73 years (range 43-84) and 62 years (range 42-75), and histologic subtype of papillary/follicular was 21/4 cases and 15/6 cases, respectively. Time to treatment failure (TTF) and overall survival (OS) were significantly longer in the planned holiday group than the daily group (not reached [NR] vs. 14.9 months, hazard ratio [HR] 0.25, 95% confidence interval [Cl] 0.11-0.58, p<0.001; NR vs. 26.6 months, HR 0.20, 95% CI 0.073-0.58, p=0.001, respectively). Median progression-free survival (PFS) was NR in the planned holiday group vs. 15.1 months in the daily group (HR 0.31, 95% CI 0.14-0.68, p=0.002). Duration of the period with lenvatinib dose ≥10 mg was significantly longer in the planned holiday group (NR vs. 6.5 months, HR 0.22, 95% CI 0.10-0.49, p<0.001), and the frequency of drug interruption due to intolerable AEs was lower (68.0% vs. 95.2%, p=0.027).ConclusionPlanned drug holidays for lenvatinib demonstrated significantly longer PFS, TTF, and OS than daily oral administration, and less intolerable toxicity leading to further unplanned treatment interruption. These benefits were apparently associated with a more extended period of lenvatinib administration at ≥10 mg. These findings might contribute to a favorable patient prognosis and safer toxicity profile.

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.

Dataset Information

Radioiodine Treatment and Thyroid Hormone Suppression Therapy for Differentiated Thyroid Carcinoma: Adverse Effects Support the Trend toward Less Aggressive Treatment for Low-Risk Patients.

Publications

Radioiodine Treatment and Thyroid Hormone Suppression Therapy for Differentiated Thyroid Carcinoma: Adverse Effects Support the Trend toward Less Aggressive Treatment for Low-Risk Patients.

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