Dynamic Immune Function Changes Before and After the First Radioactive Iodine Therapy After Total Resection of Differentiated Thyroid Carcinoma
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SUBMITTER: Shi Z
PROVIDER: S-EPMC9280633 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
| S-EPMC6287503 | biostudies-literature
Project description:Until recently, no truly effective treatment options have existed for patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), a serious disease with poor prognosis. In November 2013, the targeted multikinase inhibitor, sorafenib, was approved for use in these patients based on substantially improved progression-free survival compared with placebo. A number of other targeted agents, including lenvatinib, are being investigated in phase II and phase III trials. With the advent of these new treatment options, practitioners are faced with making important decisions in determining which patients are candidates for systemic treatment and the optimal timing for treatment initiation. Since patients may remain asymptomatic for a protracted period of time, tumor size and growth rate are the primary considerations for making these choices. Proactive management of side effects is also critical in optimizing the effectiveness of treatment. Here we review targeted systemic agents that are either in use or are under investigation for RAI-refractory DTC and provide recommendations on the rationale for initiating systemic treatment and on managing adverse events. Four illustrative case studies are provided.
| S-EPMC4206652 | biostudies-literature
Project description:Radioactive iodine (RAI) is a key component in the treatment of differentiated thyroid cancer. RAI has been recommended more selectively in recent years as guidelines evolve to reflect risks and utility in certain patient subsets. In this study we sought to evaluate the survival impact of radioactive iodine in specific thyroid cancer subgroups. Nationwide retrospective cohort study of patients using the National Cancer Database (NCDB) from 2004 to 2012 and Surveillance, Epidemiology, and End Results (SEER) database from 1992 to 2009 examining patients with differentiated thyroid cancer treated with or without RAI. Primary outcomes included all-cause mortality (NCDB and SEER), and cancer-specific mortality (SEER). Cox multivariate survival analyses were applied to each dataset, and in 135 patient subgroups based on clinical and non-clinical parameters. A total of 199,371 NCDB and 77,187 SEER patients were identified. RAI was associated with improved all-cause mortality (NCDB: RAI hazard ratio (HR) 0.55, P < 0.001; SEER: HR 0.64, P < 0.001); and cancer-specific mortality (SEER: HR 0.82, P = 0.029). Iodine therapy showed varied efficacy within each subgroup. Patients with high-risk disease experienced the greatest benefit in all-cause mortality, followed by intermediate-risk, then low-risk subgroups. Regarding cancer-specific mortality, radioactive iodine therapy was protective in high-risk patients, but did not achieve statistical significance in most intermediate-risk subgroups. Low-risk T1a subgroups demonstrated an increased likelihood of cancer-specific mortality with iodine therapy. The efficacy of RAI in patients with differentiated thyroid cancer varies by disease severity. A negative cancer-specific survival association was identified in patients with T1a disease. These findings warrant further evaluation with prospective studies.
| S-EPMC6994333 | biostudies-literature
Project description:The treatment of differentiated thyroid cancer refractory to radioactive iodine (RAI) had been hampered by few effective therapies. Recently, tyrosine kinase inhibitors (TKIs) have shown activity in this disease. Clinical guidance on the use of these agents in RAI-refractory thyroid cancer is warranted.Molecular mutations found in RAI-refractory thyroid cancer are summarized. Recent phase II and III clinical trial data for TKIs axitinib, lenvatinib, motesanib, pazopanib, sorafenib, sunitinib, and vandetinib are reviewed including efficacy and side effect profiles. Molecular targets and potencies of these agents are compared. Inhibitors of BRAF, mammalian target of rapamycin, and MEK are considered.Routine testing for molecular alterations prior to therapy is not yet recommended. TKIs produce progression-free survival of approximately 1 year (range: 7.7-19.6 months) and partial response rates of up to 50% by Response Evaluation Criteria in Solid Tumors. Pazopanib and lenvatinib are the most active agents. The majority of patients experienced tumor shrinkage with TKIs. Common adverse toxicities affect dermatologic, gastrointestinal, and cardiovascular systems.Multiple TKIs have activity in RAI-refractory differentiated thyroid cancer. Selection of a targeted agent should depend on disease trajectory, side effect profile, and goals of therapy.
| S-EPMC4319630 | biostudies-literature
Project description:The incidence of differentiated thyroid cancer (DTC) has increased over the last few decades, though it remains to be a rare disease. The prognosis of DTC is excellent; its treatment includes surgery (near-/total thyroidectomy), which is usually followed by remnant thyroid bed ablation using radio-iodine, as well as a risk-stratified follow-ups, including hormone replacement. Treatment of patients who are non-responsive to radioactive iodine (RAI) remains a challenge. Targeted therapies for RAI refractory DTC act primarily through inhibition of cell proliferation, survival and angiogenesis. Tyrosine kinase inhibitors (TKI) have achieved prolonged responses and improved progression-free survival, thereby representing a shift in the treatment of advanced thyroid cancer. There will be number of targeted treatment options for this patient population in the near future. Evidence regarding which drug should be used first and whether there is crossover drug resistance between these drugs is still lacking. Clinicians should be able to choose precisely which patients should be treated with novel targeted therapies after taking into account the following facts: i) TKIs have still not demonstrated a survival benefit. ii) The adverse effects of long-lasting treatment with TKIs could worsen quality of life, which is mostly excellent in these patients before starting treatment with these agents.
| S-EPMC7788563 | biostudies-literature
Project description:ObjectivePulmonary function test (PFT) is a useful tool for an objective assessment of respiratory function. Impaired pulmonary function is critical for the survival and quality of life in patients with pulmonary metastases of solid cancers including thyroid cancer. This study aimed to evaluate clinical factors associated with severely impaired pulmonary function by serial assessment with PFT in patients with pulmonary metastasis of differentiated thyroid cancer (DTC) who received radioactive iodine treatment (RAIT).PatientsThis retrospective study enrolled 31 patients who underwent serial PFTs before and after RAIT for pulmonary metastasis of DTC. We evaluated the risk factors for severe impairment of pulmonary function.ResultsThe median age of the patients was 44.1 years and 18 of them were female patients. Severe impairment of pulmonary function was observed in five patients (16%) after a median of three RAITs (cumulative I-131 activity = 20.4 GBq). These patients were older and more frequently had mild impairment of baseline pulmonary function, respiratory symptoms, or progressive disease compared with patients with stable pulmonary function. Neither cumulative dose nor number of RAIT was associated with decreased pulmonary function. Coexisting pulmonary diseases, presence of respiratory symptoms, and metastatic disease progression were significantly associated with severe decrease in forced vital capacity during follow-up (p =.047, p =.011, and p =.021, respectively).ConclusionsPulmonary function was severely impaired during follow-up in some patients with pulmonary metastasis of DTC after a high-dose RAITs. Neither the number of RAIT nor the cumulative I-131 activity was associated with decreased pulmonary function. Serial PFT might be considered for some high-risk patients during follow-up.
| S-EPMC4414613 | biostudies-literature
Project description:Context. Radioiodine (RAI) administration has adverse effects in patients treated for thyroid cancer (DTC), but there is scarce information regarding their intensity and duration. Objective. To evaluate frequency and intensity of early and late RAI-related symptoms in patients with DTC. Design. Observational prospective study. Patients. DTC patients who underwent thyroidectomy, with or without RAI. Measurements. Patients answered 2 surveys: (1) from 0 to 6 months and (2) between 6 and 18 months after initial treatment. Results. 110 patients answered the first survey and 61 both. Nearly 80 percent received RAI. Among early symptoms, periorbital edema, excessive tearing, salivary gland disturbances, dry mouth, taste disorders, and nausea were more frequent and intense among RAI patients. Regarding late symptoms, periorbital edema, salivary gland pain and swelling, and dry mouth were more frequent and intense in RAI patients. Frequency and intensity of adverse effects were not different between low and high RAI doses (50 versus ?100?mCi). Conclusion. RAI-related symptoms are frequent and usually persist after 6 months of administration, even when low doses are given. This finding must be considered when deciding RAI administration, especially in low risk patients, among whom RAI benefit is controversial.
| S-EPMC5102728 | biostudies-literature
Project description:ObjectiveOur study aimed to analyse temporal trends in radioactive iodine (RAI) treatment for thyroid cancer over the past decade; to analyse key factors associated with clinical decisions in RAI dosing; and to confirm lower activities of RAI for low-risk patients were not associated with an increased risk of recurrence.MethodsRetrospective analysis of 1,323 patients who received RAI at a quaternary centre in Australia between 2008 and 2018 was performed. Prospectively collected data included age, gender, histology, and American Joint Committee on Cancer stage (7th ed). American Thyroid Association risk was calculated retrospectively.ResultsThe median activities of RAI administered to low-risk patients decreased from 3.85 GBq (104 mCi) in 2008-2016 to 2.0 GBq (54 mCi) in 2017-2018. The principal driver of this change was an increased use of 1 GBq (27 mCi) from 1.3% of prescriptions in 2008-2011 to 18.5% in 2017-2018. In patients assigned as low risk per ATA stratification, lower activities of 1 GBq or 2 GBq (27 mCi or 54 mCi) were not associated with an increased risk of recurrence. In patients assigned to intermediate- or high-risk categories who received RAI as adjuvant therapy, there was no difference in risk of recurrence between 4 GBq (108 mCi) and 6 GBq (162 mCi).ConclusionsOur data demonstrate an evolution of RAI activities consistent with translation of ATA guidelines into clinical practice. Use of lower RAI activities was not associated with an increase in recurrence in low-risk thyroid cancer patients. Our data also suggest lower RAI activities may be as efficacious for adjuvant therapy in intermediate- and high-risk patients.
| S-EPMC8406251 | biostudies-literature
Project description:BackgroundWe identified differentiated thyroid cancer (DTC) survivors from SEER registries and performed Poisson regression to calculate the relative risks (RRs) of subsequent malignancies (SMs) by different sites associated with radioactive iodine (RAI) treatment, and the attributable risk proportion of RAI for developing different SMs.ResultsWe identified 4628 of 104,026 DTC patients developing a SM after two years of their DTC diagnosis, with a medium follow-up time of 113 months. The adjusted RRs of developing SM associated with RAI varied from 0.98 (0.58-1.65) for neurologic SMs to 1.37 (1.13-1.66) for hematologic SMs. The RRs of developing all cancer combined SMs generally increased with age at DTC diagnosis and decreased with the latency time. We estimated that the attributable risk proportion of RAI treatment is only 0.9% for all cancer combined SMs and 20% for hematologic SMs, which is the highest among all SMs. The tumor features and mortalities in patients treated with and without RAI are generally comparable.ConclusionWith the large population based analyses, we concluded that a low percentage of DTC survivors would develop SMs during their follow-up. Although the adjusted RR of SMs development increased slightly in patients receiving RAI, the attributable risk proportion associated with RAI was low, suggesting the absolute number of SMs induced by RAI in DTC survivors would be low. The attributable risk proportion of RAI treatment is the highest in hematological SMs, but when in consideration of its low incidence among all DTC survivors, the absolute number of hematological SMs was low.
| S-EPMC8117631 | biostudies-literature
Project description:Objective To investigate the cardiometabolic effects of a severe hypothyroid state induced by withdrawal of thyroid hormone replacement before radioactive iodine therapy. Methods Patients with thyroid cancer who were scheduled to receive radioactive iodine ablation were enrolled. Cardiometabolic parameters were measured using blood samples taken immediately before levothyroxine withdrawal, 4 weeks following withdrawal (on radiotherapy day), and 4 weeks following reinstitution of levothyroxine. Results Out of 48 patients (age 49.4?±?10.5 years; 77.1% [37/48] female), the severe hypothyroid state induced by levothyroxine withdrawal significantly aggravated the majority of lipid parameters, particularly in patients with a greater number of metabolic syndrome components. Fasting plasma glucose levels and homeostatic model assessment values for insulin resistance and ?-cell function significantly decreased following levothyroxine withdrawal. Serum high-sensitivity C-reactive protein, fibrinogen and cystatin C levels significantly decreased, and homocysteine levels increased during the severe hypothyroid state. All of these changes were reversed by levothyroxine reinstitution. Conclusions Severe hypothyroid state induced pronounced changes in cardiometabolic parameters. Further studies should identify the long-term effects of changes in these parameters on cardiovascular morbidity and mortality in relation to thyroid disease.
| S-EPMC5536594 | biostudies-literature