Radioactive iodine does not improve overall survival for patients with aggressive variants of papillary thyroid carcinoma less than 2 cm.

BACKGROUND: Tall cell and diffuse sclerosing variants of papillary thyroid cancer are associated with aggressive features. Radioactive iodine after total thyroidectomy is poorly studied. METHODS: Patients ≥18 years in the National Cancer Data Base from 2004 to 2016 with classic papillary thyroid cancer, tall cell, or diffuse sclerosing 1 mm to 40 mm were identified. Logistic regression identified factors associated with aggressive features. Overall survival was assessed using Kaplan-Meier method and log-rank tests, after propensity score matching for clinicopathological and treatment variables. RESULTS: A total of 155,940 classic papillary thyroid cancer patients, 4,011 tall cell, and 507 diffuse sclerosing were identified. Tall cell patients represented an increasing proportion of the study population during the analysis period, whereas diffuse sclerosing and classic papillary thyroid cancer patients showed a statistically significant decline. Extrathyroidal extension and nodal involvement were more prevalent among tall cell and diffuse sclerosing patients when compared to those diagnosed with classic papillary thyroid cancer (P < .01). Adjuvant radioactive iodine was less frequently used in patients with classic papillary thyroid cancer when compared to tall cell and diffuse sclerosing patients (42.6% vs 62.4%, 59.0%; P < .001, respectively). Aggressive variants receiving total thyroidectomy versus total thyroidectomy + radioactive iodine propensity score matched across clinicopathologic variables were analyzed. There was no difference in overall survival between the 2 treatment groups for tumors <2 cm (01-1.0 cm, 92.2% vs 84.8%; P = .98); (1.0-2.0 cm, 72.7% vs 88.1%; P = .82). However, overall survival was improved for total thyroidectomy + radioactive iodine propensity score matched patients with tumor sizes 21 to 40 mm versus total thyroidectomy (83.4% vs 70.0%, P = .004). CONCLUSION: For aggressive tumor variants ≤2 cm treated with total thyroidectomy, there is no overall survival advantage provided by the addition of adjuvant radioactive iodine.

Insurance type is associated with appropriate use of surgical and adjuvant care for differentiated thyroid carcinoma.

BACKGROUND: We aimed to characterize the association between differentiated thyroid cancer (DTC) patient insurance status and appropriateness of therapy (AOT) regarding extent of thyroidectomy and radioactive iodine (RAI) treatment. METHODS: The National Cancer Database was queried for DTC patients diagnosed between 2010 and 2016. Adjusted odds ratios (AOR) for AOT, as defined by the American Thyroid Association guidelines, and hazard ratios (HR) for overall survival (OS) were calculated. A difference-in-differences (DD) analysis examined the association of Medicaid expansion with outcomes for low-income patients aged <65. RESULTS: A total of 224,500 patients were included. Medicaid and uninsured patients were at increased risk of undergoing inappropriate therapy, including inappropriate lobectomy (Medicaid 1.36, 95% confidence interval [CI]: 1.21-1.54; uninsured 1.30, 95% CI: 1.05-1.60), and under-treatment with RAI (Medicaid 1.20, 95% CI: 1.14-1.26; uninsured 1.44, 95% CI: 1.33-1.55). Inappropriate lobectomy (HR 2.0, 95% CI: 1.7-2.3, P < .001) and under-treatment with RAI (HR 2.3, 95% CI: 2.2-2.5, P < .001) were independently associated with decreased survival, while appropriate surgical resection (HR 0.3, 95% CI: 0.3-0.3, P < .001) was associated with improved odds of survival; the model controlled for all relevant clinico-pathologic variables. No difference in AOT was observed in Medicaid expansion versus non-expansion states with respect to surgery or adjuvant RAI therapy. CONCLUSION: Medicaid and uninsured patients are at significantly increased odds of receiving inappropriate treatment for DTC; both groups are at a survival disadvantage compared with Medicare and those privately insured.

Overall survival is improved with total thyroidectomy and radiation for male patients and patients older than 55 with T2N0M0 Stage 1 classic papillary thyroid cancer.

BACKGROUND: We examine whether surgery extent and radiation administration affect overall survival for cT2N0M0 classic papillary thyroid cancer according to age and sex. METHODS: Patients with cT2N0M0 classic papillary thyroid cancer tumors in the National Cancer Data Base (2004-2016) were selected. Multivariable Cox regression analysis compared patients (combined male + female cohorts) having lobectomy to those having total thyroidectomy with or without radiation (primarily radioactive iodine) for ages: 18 to 45, 46 to 55, and >55 years. In addition, 1:1 propensity score matching and Kaplan-Meier curves with 10-year overall survival estimates, and log-rank test were stratified by age and sex. RESULTS: Lobectomy had equivalent overall survival to total thyroidectomy without and with radiation for patients (combined male + female cohorts) aged 18 to 45 and 46 to 55 years on multivariable analysis. On propensity score matching there was overall survival advantage for total thyroidectomy with radiation over both lobectomy and total thyroidectomy for men (ages 18-90+ combined) and overall survival advantage in patients (combined male + female cohort) aged >55 years having total thyroidectomy with radiation versus lobectomy. On propensity score matching there were no overall survival differences in women (ages 18-90+ combined) or patients (combined male + female cohort) aged 18 to 45 and 46 to 55 years having either lobectomy, total thyroidectomy, or total thyroidectomy with radiation. CONCLUSION: For cT2N0M0 classic papillary thyroid cancer, total thyroidectomy with radiation improves 10-year overall survival for patients (combined male + female cohort) aged >55 years and men (ages 18-90+ combined).

Real-World Efficacy and Safety of Multi-Tyrosine Kinase Inhibitors in Radioiodine Refractory Thyroid Cancer.

Background: The management of patients with locally advanced or metastatic differentiated thyroid cancer (DTC) that is refractory to radioiodine (RAI) remains a therapeutic challenge. The multi-tyrosine kinase inhibitors (TKIs) sorafenib and lenvatinib have been approved based on phase 3 clinical trials. Patients and Methods: We aimed at describing the efficacy and safety of TKI treatment of RAI-refractory DTC in a real-world setting at six German referral centers. One hundred and one patients with locally advanced or metastatic RAI-refractory DTC treated with sorafenib, lenvatinib, and/or pazopanib were included. Progression-free survival (PFS) and overall survival (OS) probabilities were estimated by using the Kaplan-Meier method. Results: Ninety-seven of 101 patients had progressive disease before TKI initiation. The median PFS for first-line treatment with sorafenib (n = 33), lenvatinib (n = 53), and pazopanib (n = 15) was 9 (95% confidence interval 5.2-12.8), 12 (4.4-19.6), and 12 months (4.4-19.6), respectively. The median OS for first-line treatment was 37 (10-64) for sorafenib, 47 (15.5-78.5) for lenvatinib, and 34 months (20.2-47.8) for pazopanib. Serious complications (e.g., hemorrhage, acute coronary syndrome, and thrombosis/venous thromboembolism) occurred in 16 out of 75 (21%) patients taking lenvatinib, in 3 out of 42 (7%) patients taking sorafenib, and in 3 out of 24 (13%) patients taking pazopanib. Conclusions: Sorafenib, lenvatinib, and pazopanib are effective treatment options in the majority of patients with RAI-refractory DTC. The PFS and six-month survival rate in patients treated with lenvatinib und pazopanib appear to compare favorably with sorafenib in the first-line treatment setting. However, a more advanced disease stage at treatment initiation in sorafenib- and pazopanib-treated patients in the era before TKI-approval and the retrospective nature of this study precludes a direct comparison of TKIs.

PSMA Expression in Differentiated Thyroid Cancer: Association With Radioiodine, 18FDG Uptake, and Patient Outcome.

CONTEXT: Little is known about prostate-specific membrane antigen (PSMA) expression in patients with cervical involvement of differentiated thyroid cancer (DTC). OBJECTIVE: We investigated PSMA expression in neck persistent/recurrent disease (PRD) using immunohistochemistry and the association with radioiodine (RAI) or 18-fluorodeoxyglucose (18FDG) uptake, and patient outcome. DESIGN, SETTING, AND PATIENTS: Data from 44 consecutive DTC patients who underwent neck reoperation from 2006 to 2018 in a comprehensive cancer center. MAIN OUTCOME MEASURE(S): Immunostaining was performed with vascular endothelial marker CD31 and PSMA. PSMA expression was quantified using the immunoreactive score (IRS). RAI and 18FDG uptake were assessed before surgery using posttherapeutic RAI scintigraphy and 18FDG positron emission tomography with computed tomography. Mean follow-up after reintervention was 6.5 ±â€…3.7 years. RESULTS: Thirty patients (68%) showed at least 1 PSMA-positive lesion (IRS ≥ 2) with similar proportions in RAI-positive and RAI-negative patients (75% vs 66%). In RAI-negative patients, however, the proportion of PSMA-positive disease (79% vs 25%, P < 0.01) and the mean IRS (4.0 vs 1.0, P = 0.01) were higher in 18FDG-positive than in 18FDG-negative patients. Furthermore, mean IRS was higher in patients ≥ 55 years, large primary tumors (>40 mm) or aggressive subtypes, and was correlated with structural disease at last follow-up. Strong PSMA expression (IRS ≥ 9) was associated with shorter progression-free survival (PFS). CONCLUSIONS: Our findings show that PSMA expression was present in two-thirds of patients with neck PRD, that it was related to poor prognostic factors and that very high expression was associated with poorer PFS. This preliminary study may offer new perspectives for the management of RAI-refractory DTC.

Adjuvant radiotherapy and radioiodine treatment for locally advanced differentiated thyroid cancer: systematic review and meta-analysis.

BACKGROUND: Treatment for locally advanced differentiated thyroid cancer is surgery followed by radioiodine while the role of adjuvant external beam radiotherapy (EBRT) is debated. METHODS: The panel of the Italian Association of Radiotherapy and Clinical Oncology developed a clinical recommendation on the addition of EBRT to radioiodine after surgery for locally advanced differentiated thyroid cancer by using the Grades of Recommendation, Assessment, Development, and Evaluation methodology and the Evidence to Decision framework. A systematic review with meta-analysis about this topic was conducted with a focus on outcome of benefits and toxicity. RESULTS: Locoregional control was improved by EBRT while no considerable toxicity impact was reported. CONCLUSION: The panel judged uncertain the benefit/harms balance; final recommendation was conditional both for EBRT + radioiodine and radioiodine alone in the adjuvant setting.

Association between quality of life and patient-reported complications from surgery and radioiodine in early-stage thyroid cancer survivors: A matched-pair analysis.

BACKGROUND: Remnant radioiodine ablation is discouraged in low-risk differentiated thyroid cancer because it confers no survival advantage. The impact of remnant radioiodine ablation on health-related quality of life in these patients is not well described. We hypothesized remnant radioiodine ablation is associated with lower health-related quality of life in early-stage differentiated thyroid cancer survivors. METHODS: A retrospective matched-pair analysis was conducted in stage I differentiated thyroid cancer survivors recruited from a thyroid cancer support group. Respondents self-reported via online survey. Dysphonia and dysphagia were reported via Likert scale. Health-related quality of life was evaluated using Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item profile. Respondents who received remnant radioiodine ablation were matched for age, sex, race, and years since diagnosis with respondents who did not receive remnant radioiodine ablation. PROMIS t-scores were compared between remnant radioiodine ablation and nonremnant radioiodine ablation groups, and among those with or without surgical complications. RESULTS: One hundred and twenty-two pairs were matched. There was no significant difference in incidence of self-reported hypocalcemia, infection, dysphonia, or dysphagia between remnant radioiodine ablation and no remnant radioiodine ablation groups. There was no significant difference in mean PROMIS t-scores. Of respondents reporting normal preoperative voice and swallowing, there were no significant differences in postprocedural outcomes or PROMIS scores. Regardless of remnant radioiodine ablation treatment, those with surgical complications of hypocalcemia, dysphonia, or dysphagia reported worse PROMIS scores across multiple domains. Remnant radioiodine ablation-associated xerostomia was associated with worse PROMIS scores across multiple domains. CONCLUSION: This is the first study to use PROMIS measures to evaluate the association between remnant radioiodine ablation and health-related quality of life in early-stage differentiated thyroid cancer survivors treated surgically. Surgical and remnant radioiodine ablation-associated complications were associated with significantly worse PROMIS scores across multiple domains.

Questions and Controversies in the Clinical Application of Tyrosine Kinase Inhibitors to Treat Patients with Radioiodine-Refractory Differentiated Thyroid Carcinoma: Expert Perspectives.

Notwithstanding regulatory approval of lenvatinib and sorafenib to treat radioiodine-refractory differentiated thyroid carcinoma (RAI-R DTC), important questions and controversies persist regarding this use of these tyrosine kinase inhibitors (TKIs). RAI-R DTC experts from German tertiary referral centers convened to identify and explore such issues; this paper summarizes their discussions. One challenge is determining when to start TKI therapy. Decision-making should be shared between patients and multidisciplinary caregivers, and should consider tumor size/burden, growth rate, and site(s), the key drivers of RAI-R DTC morbidity and mortality, along with current and projected tumor-related symptomatology, co-morbidities, and performance status. Another question involves choice of first-line TKIs. Currently, lenvatinib is generally preferred, due to greater increase in progression-free survival versus placebo treatment and higher response rate in its pivotal trial versus that of sorafenib; additionally, in those studies, lenvatinib but not sorafenib showed overall survival benefit in subgroup analysis. Whether recommended maximum or lower TKI starting doses better balance anti-tumor effects versus tolerability is also unresolved. Exploratory analyses of lenvatinib pivotal study data suggest dose-response effects, possibly favoring higher dosing; however, results are awaited of a prospective comparison of lenvatinib starting regimens. Some controversy surrounds determination of net therapeutic benefit, the key criterion for continuing TKI therapy: if tolerability is acceptable, overall disease control may justify further treatment despite limited but manageable progression. Future research should assess potential guideposts for starting TKIs; fine-tune dosing strategies and further characterize antitumor efficacy; and evaluate interventions to prevent and/or treat TKI toxicity, particularly palmar-plantar erythrodysesthesia and fatigue.

Trends in the Diagnosis and Treatment of Patients with Medullary Thyroid Carcinoma in Korea.

BACKGROUND: Thyroid cancer is becoming increasingly common worldwide, but little is known about the epidemiology of medullary thyroid carcinoma (MTC). This study investigated the current status of the incidence and treatment of MTC using Korean National Health Insurance Service (NHIS) data for the entire Korean population from 2004 to 2016. METHODS: This study included 1,790 MTC patients identified from the NHIS database. RESULTS: The age-standardized incidence rate showed a slightly decreasing or stationary trend during the period, from 0.25 per 100,000 persons in 2004 to 0.19 in 2016. The average proportion of MTC among all thyroid cancers was 0.5%. For initial surgical treatment, 65.4% of patients underwent total thyroidectomy. After surgery, external-beam radiation therapy (EBRT) was performed in 10% of patients, a proportion that increased from 6.7% in 2004 to 11.0% in 2016. Reoperations were performed in 2.7% of patients (n=49) at a median of 1.9 years of follow-up (interquartile range, 1.2 to 3.4). Since November 2015, 25 (1.4%) patients with MTC were prescribed vandetanib by December 2016. CONCLUSION: The incidence of MTC decreased slightly with time, and the proportion of patients who underwent total thyroidectomy was about 65%. EBRT, reoperation, and tyrosine kinase inhibitor therapy are additional treatments after initial surgery for advanced MTC in Korea.

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.

Contemporary considerations in adjuvant radioiodine treatment of adults with differentiated thyroid cancer.

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy with a growing incidence worldwide. The initial conventional management is surgery, followed by consideration of 131 I treatment that includes three options. These are termed remnant ablation (targeting benign thyroid remnant), adjuvant (targeting presumed microscopic DTC) and known disease (targeting macroscopic DTC) treatments. Some experts mostly rely on clinicopathologic assessment for recurrence risk to select patients for the 131 I treatment. Others, in addition, apply radioiodine imaging to guide their treatment planning, termed theranostics (aka theragnostics or radiotheragnostics). In patients with low-risk DTC, remnant ablation rather than adjuvant treatment is generally recommended and, in this setting, the ATA recommends a low 131 I activity. 131 I adjuvant treatment is universally recommended in patients with high-risk DTC (a primary tumor of any size with gross extrathyroidal extension) and is generally recommended in intermediate-risk DTC (primary tumor >4 cm in diameter, locoregional metastases, microscopic extrathyroidal extension, aggressive histology or vascular invasion). The optimal amount of 131 I activity for adjuvant treatment is controversial, but experts reached a consensus that the 131 I activity should be greater than that for remnant ablation. The main obstacles to establishing timely evidence through randomized clinical trials for 131 I therapy include years-to-decades delay in recurrence and low disease-specific mortality. This mini-review is intended to update oncologists on the most recent clinical, pathologic, laboratory and imaging variables, as well as on the current 131 I therapy-related definitions and management paradigms, which should optimally equip them for individualized patient guidance and treatment.

The optimal surgical approach for papillary thyroid carcinoma with pathological n1 metastases: An analysis from the SEER database.

OBJECTIVES/HYPOTHESIS: The definition of large-volume pathologic N1 metastases has been changed in the 2017 version 2 of the National Comprehensive Cancer Network guidelines, leading to a controversy over the optimal surgical approach selection for patients with biopsy-proven papillary thyroid carcinoma (PTC). The aim of this study was to investigate the therapeutic efficacy of total thyroidectomy (TT) and thyroid lobectomy (TL) for these patients. STUDY DESIGN: Retrospective population-based database analysis. METHODS: A total of 906 consecutive PTC patients with pathologic N1 metastases (>5 involved nodes with metastases ≤5 mm in the largest dimension) were retrieved from the Surveillance, Epidemiology, and End Results database, and divided into two groups (≤2 mm, >2-5 mm) based on the size of the extent of disease. Overall survival (OS) was then compared between patients treated with TT and TL, followed by Cox proportional hazards regression analysis to explore multiple prognostic factors. RESULTS: OS favored TT compared with TL in patients with more than five involved nodes and metastases >2 to 5 mm in the largest dimension (P < .05). Cox analysis showed that the TL was not an independent factor associated with poorer OS than TT in these patients (P > .05). CONCLUSIONS: TT showed better survival than TL for patients with more than five involved nodes and metastases >2 to 5 mm in the largest dimension. For patients with more than five involved nodes and metastases ≤2 mm in the largest dimension, either TT or TL can be recommended because there was no difference in survival. LEVEL OF EVIDENCE: NA Laryngoscope, 130:269-273, 2020.

Age, thyroglobulin levels and ATA risk stratification predict 10-year survival rate of differentiated thyroid cancer patients.

INTRODUCTION: Differentiated 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. OBJECTIVE: The 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 METHODS: This 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. RESULTS: According 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 µg/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 <30µg/l) representing 59% of the cohort, moderate (survival rate of 94.5% in patients <55 years with pre-ablation sTg ≥30µg/l or ≥55 years with pre-ablation sTg <30 µg/l) representing 38% of the cohort, and low (survival rate of 49% in patients ≥55 years with pre-ablation sTg ≥30µg/l) representing 3% of the cohort. CONCLUSION: Initial ATA high-risk classification, age over 55 years old and pre-ablation sTg ≥30 µg/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 µg/l have the worst survival rate.

The medical treatment of radioiodine-refractory differentiated thyroid cancers in 2019. A TUTHYREF® network review.

Patients with radioiodine-refractory (RAIR) differentiated thyroid carcinoma (DTC) represent a challenging subgroup of DTC because they are at higher risk of cancer-related death. Multidisciplinary discussions can assess the role and the nature of local treatments, but also determine the optimal timing for first-line antiangiogenic therapy as some of these patients can be followed for several months or years without any treatment. In this review, we will examine the definition of RAIR-DTC, the different treatment options and finally some of the most recent cancer research breakthroughs for RAIR-DTC.

Disparity in the use of adjuvant radioactive iodine ablation among high-risk papillary thyroid cancer patients.

BACKGROUND: We sought to identify treatment disparities existing prior to publication of the 2015 American Thyroid Association Management Guidelines in order to identify patients with papillary thyroid cancer (PTC) at risk for receiving inadequate treatment. METHODS: Patients diagnosed with PTC from 2011 to 2013 were identified using Surveillance, Epidemiology and End Results database. High-risk disease was defined as T4, N1, or M1. Chi-square tests compared characteristics of patients with and without high-risk disease and characteristics of high-risk patients who did and did not receive radioactive iodine ablation (RAI). Likelihoods of having high-risk disease, of receiving RAI, and of cause-specific death were calculated using regression analyses. RESULTS: Sample included 32,229 individuals; 7894 (24.5%) had high-risk disease. Mean age was 50.0 years, 24,815 (77.0%) were female, and 21,318 (66.2%) were white. Odds of high-risk disease were greater among males (OR:2.04; 95% CI:1.92-2.16), Hispanics (OR:1.67; 95% CI:1.56-1.79) and Asians (OR:1.49; 95% CI:1.37-1.62), and uninsured (OR:1.24; 95% CI:1.07-1.43), and lower among patients ages 45-64 (OR:0.57; 95% CI:0.53-0.60), and ≥65 years (OR:0.54; 95% CI:0.50-0.59), and Blacks (OR:0.46; 95% CI:0.40-0.53). Most (69.3%) high-risk patients received RAI. Odds of receiving RAI were lower among patients age ≥65 years (OR:0.67; 95% CI:0.58-0.77), uninsured (OR:0.52; 95% CI:0.41-0.67), or with Medicaid (OR:0.58; 95% CI:0.50-0.69). RAI use reduced the risk of cause-specific mortality (HR:0.29; 95% CI:0.18-0.47). CONCLUSION: Knowledge of these treatment disparities will allow recognition of groups at risk for high-risk disease and receiving inadequate treatment.

Recombinant Thyrotropin vs Levothyroxine Withdrawal in 131I Therapy of N1 Thyroid Cancer: A Large Matched Cohort Study (ThyrNod).

CONTEXT: Recombinant human thyrotropin (rhTSH) has been shown to be an effective stimulation method for radioactive iodine (RAI) therapy in differentiated thyroid cancer, including in those with nodal metastases (N1 DTC). OBJECTIVES: To demonstrate the noninferiority of rhTSH vs thyroid hormone withdrawal (THW) in preparation to RAI regarding disease status at the first evaluation in the real-life setting in patients with N1 DTC. DESIGN: This was a French multicenter retrospective study. Groups were matched according to age (<45/≥45 years), number of N1 nodes (≤5/>5 lymph nodes), and stage (pT1-T2/pT3). RESULTS: The cohort consisted of 404 patients pT1-T3/N1/M0 DTC treated with rhTSH (n = 205) or THW (n = 199). Pathological characteristics and initially administrated RAI activities (3.27 ± 1.00 GBq) were similar between the two groups. At first evaluation (6 to 18 months post-RAI), disease-free status was defined by thyroglobulin levels below threshold and a normal ultrasound. Disease-free rate was not inferior in the rhTSH group (75.1%) compared with the THW group (71.9%). The observed difference between the success rates was 3.3% (-6.6 to 13.0); rhTSH was therefore considered noninferior to THW because the upper limit of this interval was <15%. At the last evaluation (29.7 ± 20.7 months for rhTSH; 36.7 ± 23.8 months for THW), 83.5% (rhTSH) and 81.5% (THW) of patients achieved a complete response. This result was not influenced by any of the known prognostic factors. CONCLUSIONS: A preparation for initial RAI treatment with rhTSH was noninferior to that with THW in our series of pT1-T3/N1/M0-DTC on disease-free status outcomes at the first evaluation and after 3 years.

Safety and efficacy of ultrasound-guided percutaneous thermal ablation in treating low-risk papillary thyroid microcarcinoma: A pilot and feasibility study.

OBJECTIVE: This study aimed to evaluate the safety and efficacy of thermal ablation in treating low-risk unifocal papillary thyroid microcarcinoma (PTMC). MATERIALS AND METHODS: Patients with unifocal PTMC were enrolled in this study, and thermal ablations were performed. Contrast-enhanced ultrasound was used to estimate the extent of ablation immediately after thermal ablation; complications were recorded. The size and volume of the ablated area and thyroid hormones were measured, and the clinical evaluations were performed at 1, 3, 6, 12, and 18 months after thermal ablation. From July 2016 to July 2017, the prospective study was conducted involving 107 patients. Thermal ablation was well tolerated without serious complications. RESULTS: Compared with the volume immediately after thermal ablation, the mean volume reduction ratio (VRR) of ablated lesions was 0.457 ± 0.218 (range: 0.040-0.979), 0.837 ± 0.150 (range: 0.259-1), 0.943 ± 0.090 (range: 0.491-1), 0.994-0.012 (range: 0.938-1), and 0.999 ± 0.002 (range: 0.992-1) at 1, 3, 6, 12, and 18 months after thermal ablation, respectively. Significant differences in the VRR were found between every two follow-up visits (P < 0.01). Results of patients' thyroid function test before thermal ablation and at 1 month after thermal ablation were normal, and no significant differences were observed (P > 0.05). No tumor regrowth, local recurrence, or distant metastases were detected during follow-up visits. CONCLUSION: Thermal ablation is a short-term safe and effective method in treating low-risk small PTMCs, which can be considered a potential alternative therapy for patients with PTMC.

Association of adjuvant radioactive iodine therapy with survival in node-positive papillary thyroid cancer.

PURPOSE: To assess the effect of adding radioactive iodine (RAI) therapy to total thyroidectomy (TT) on overall survival (OS) in patients presenting with papillary thyroid cancer (PTC) and cervical pathologically proven LN metastases (pN1). METHODS AND MATERIALS: We identified a cohort of patients with PTC and nodal metastases treated with TT alone or TT plus RAI in the Surveillance, Epidemiology and End Results database between 2004 and 2013. Propensity score 1-to-1 matching was used to balance baseline characteristics. Cox proportional hazards regression models and Kaplan-Meier survival analysis were used to test the relationship between RAI and OS. RESULTS: In all, 15,953 patients were identified. After propensity score matching, 12,128 patients remained in each group. Based on multivariate Cox analysis, patients treated with TT + RAI had a statistically significant improvement in OS compared with those treated with TT alone [hazard ratio (HR) = 0.54, P < 0.001)], and significance persisted in the matched cohort (HR = 0.41, P < 0.001). In a subgroup analysis, the survival benefit was observed among patients ≥55 years but not among those <55 years (age < 55: HR = 1.06, P = 0.72; age ≥ 55: HR = 0.33, P < 0.001). Patients with stage T4 benefited most from RAI treatment (HR = 0.29, P < 0.001). CONCLUSION: This propensity-matched analysis suggests that RAI therapy after TT was associated with improved OS in PTC patients with pN1 disease. Adjuvant RAI therapy needs to be considered in this patient group.

Effect of Tumor Size and Minimal Extrathyroidal Extension in Patients with Differentiated Thyroid Cancer.

INTRODUCTION: Risk-stratified treatment strategies have become a focus in the treatment of differentiated thyroid cancer (DTC). In the 2015 American Thyroid Association treatment guidelines, adjuvant treatment with radioactive iodine (RAI) is considered in the presence of minimal extrathyroidal extension (mETE). This study aimed to investigate the prognostic significance of mETE and tumor size in patients with DTC. METHODS: A retrospective review was undertaken of 2323 consecutive patients treated surgically for T1-T3 (defined per seventh edition of the American Joint Committee on Cancer staging criteria) and M0 DTC from 2000 to 2015 at The University of Texas MD Anderson Cancer Center. Patients were divided into four groups according to the size of the tumor (≤4 cm vs. >4 cm) and the presence of mETE. Predictors of disease-free survival (DFS), disease-specific survival, locoregional failure (LRF), and distant metastatic failure (DMF) were compared using the log-rank test and Cox's proportional hazards models. RESULTS: There were only seven DTC-related deaths, limiting the clinical significance of the analysis, especially of overall and disease-specific survival. Following multivariate analysis, patients with tumors >4 cm did worse than patients with tumors ≤4 cm with respect to DFS (group 3 [>4 cm without mETE] adjusted hazard ratio (HRadj) = 2.1 [confidence interval (CI) 1.1-3.8]; group 4 [>4 cm with mETE] HRadj = 2.9 [CI 1.6-5.1]). However, patients did not differ according to DFS, regardless of the presence of mETE within each size category (group 2 [≤4 cm with mETE] vs. group 1 [≤4 cm without mETE] HRadj = 1.3 [CI 0.9-1.8]; group 4 [>4 cm without mETE] vs. group 3 [>4 cm with mETE] HRadj = 1.0 [CI 0.5-2.3]). For LRF and DMF, size but not mETE was also an independent risk factor. CONCLUSION: Tumor size, but not the presence of mETE, was an independent predictor of DFS, LRF, and DMF in DTC.

Treatment-emergent hypertension and efficacy in the phase 3 Study of (E7080) lenvatinib in differentiated cancer of the thyroid (SELECT).

BACKGROUND: Hypertension (HTN) is an established class effect of vascular endothelial growth factor receptor (VEGFR) inhibition. In the phase 3 Study of (E7080) Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, HTN was the most frequent adverse event of lenvatinib, an inhibitor of VEGFR1, VEGFR2, VEGFR3, fibroblast growth factor receptor 1 (FGFR1), FGFR2, FGFR3, FGFR4, platelet-derived growth factor receptor α (PDGFRα), ret proto-oncogene (RET), and stem cell factor receptor (KIT). This exploratory analysis examined treatment-emergent hypertension (TE-HTN) and its relation with lenvatinib efficacy and safety in SELECT. METHODS: In the multicenter, double-blind SELECT trial, 392 patients with progressive radioiodine-refractory differentiated thyroid cancer (RR-DTC) were randomized 2:1 to lenvatinib (24 mg/d on a 28-day cycle) or placebo. Survival endpoints were assessed with Kaplan-Meier estimates and log-rank tests. The influence of TE-HTN on progression-free survival (PFS) and overall survival (OS) was analyzed with univariate and multivariate Cox proportional hazards models. RESULTS: Overall, 73% of lenvatinib-treated patients and 15% of placebo-treated patients experienced TE-HTN. The median PFS for lenvatinib-treated patients with (n = 190) and without TE-HTN (n = 71) was 18.8 and 12.9 months, respectively (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.39-0.88; P = .0085). For lenvatinib-treated patients, the objective response rate was 69% with TE-HTN and 56% without TE-HTN (odds ratio, 1.72; 95% CI, 0.98-3.01). The median change in tumor size for patients with and without TE-HTN was -45% and -40%, respectively (P = .2). The median OS was not reached for patients with TE-HTN; for those without TE-HTN, it was 21.7 months (HR, 0.43; 95% CI, 0.27-0.69; P = .0003). CONCLUSIONS: Although HTN is a clinically significant adverse event that warrants monitoring and management, TE-HTN was significantly correlated with improved outcomes in patients with RR-DTC, indicating that HTN may be predictive for lenvatinib efficacy in this population. Cancer 2018;124:2365-72. © 2018 American Cancer Society.