Received Radioactive Iodine Therapy Research Articles

Implementation of the 2015 American Thyroid Association guideline changes across a health system: A quality improvement opportunity

BackgroundWith the release of the 2015 management guidelines, the American Thyroid Association narrowed the indications for postoperative radioactive iodine (RAI) in well-differentiated thyroid cancer. However, the adoption of new guidelines varies between healthcare entities. The goal of this study was to characterize the appropriateness of RAI use within our health system, before and after the 2015 guideline changes. MethodsIn this retrospective cohort study, we identified patients who were treated for well-differentiated thyroid cancer between 2011–2020. Patients were characterized as “undertreated,” “appropriately treated,” or “overtreated” with RAI. Variation in RAI use was assessed using interrupted time series and multivariable logistic regression analyses. ResultsAmong 6310 patients, the mean age was 50 ± 15 years, and 74% were female. There was an immediate drop in the likelihood of receiving RAI after the release of the 2015 guidelines (p = 0.016), and the likelihood of receiving RAI therapy continued to significantly decline over time (OR 0.83, p < 0.001). Despite this trend in the absolute rate of RAI use, there was a significant increase in overtreatment with RAI after the release of the 2015 guidelines (p < 0.001), indicating imperfect uptake of the new criteria. Two hospitals within the health system were identified as disproportionate contributors to overtreatment (Hospital 4: OR 6.50, p < 0.001; Hospital 6: OR 8.63, p < 0.001). ConclusionsWhile the use of postoperative RAI was largely appropriate across our health system, rates of guideline adherence differed between hospitals. Efforts to standardize treatment protocols systemwide may enable more rapid and consistent uptake of new management guidelines.

Risk Stratification of Differentiated Thyroid Cancer at King Abdullah Specialized Children's Hospital Endocrinology Clinic in Riyadh, Saudi Arabia.

Background Papillary thyroid cancer (PTC), a well-differentiated form of cancer, accounts for the majority of thyroid malignancies, and the incidence of PTC is on the rise. While the rate of PTC recurrence is considered to be low, there are broad spectrums of clinical and biological behavior that can lead to disease recurrence. The American Thyroid Association (ATA) risk stratification system for differentiated thyroid cancer is used as a prognostic tool to guide decision-making and management strategies most likely to achieve a favorable outcome. Aim This study aimed to estimate the prevalence of PTC recurrence in each category of the ATA risk stratification system and determine the appropriate iodine dose to be administered at the King Abdulaziz Medical City Endocrinology Clinic in Riyadh, Saudi Arabia. Methods A cross-sectional retrospective chart review was conducted on adult patients with PTC who underwent thyroidectomy procedures at the King Abdullah SpecializedChildren'sHospital(KASCH) Endocrinology Clinic in Riyadh between 2015 and 2023. IBM SPSS (Statistical Package for the Social Sciences) version 25 (IBM Corp., Armonk, NY) was used for data analysis. Results Of the 697 patients included in the study, 82.4% were females. About 5% had suffered from PTC recurrence, and 54.4% had low-risk stratification. In addition, more than half (52.1%) had received radioactive iodine (RAI). The recurrence of PTC was significantly associated with age (P = 0.019), ATA risk stratification (P = 0.0001), RAI therapy (P = 0.001), and iodine dosage (P = 0.013). Conclusion Both low PTC recurrence rates and low-risk stratification were observed among the PTC patients. The risk factors relating to PTC recurrence included high-risk stratification, advanced age, RAItherapy, and the dosage of RAI administered.

How Radioactive Iodine Treatment Affects the Retina.

Objective The aim of this study was to quantitatively assess the macular and retinal nerve fiber layer thicknesses in patients with hyperthyroidism and thyroid cancer undergoing radioactive iodine (RAI) therapy. Study Design This prospective study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the Bagcilar Training and Research Hospital Clinical Research Ethics Committee. Written informed consent was obtained from the patients following a detailed explanation of the study objectives and protocol. Patient selection was randomized. Patients scheduled for RAI treatment in the Nuclear Medicine Clinic were referred to the ophthalmology clinic, respectively. Patients without additional ocular pathology were included in the study. Methods All patients had received RAI therapy using Iodine-131 for hyperthyroidism or thyroid cancer. A complete ophthalmological examination and measurement of macular and retinal nerve fiber layer thickness using optical coherence tomography were performed on all patients before and at the first and sixth months and in first year after RAI treatment. The results were prospectively evaluated. Results The study included 80 eyes of 40 patients. The hyperthyroid group was group 1, and the thyroid cancer group was group 2. There were 25 patients in group 1 and 15 patients in group 2. The mean age was 43.76 ± 11.85 years (range: 22-65 years) in group 1 and 39.87 ± 9.13 years (range: 30-58 years) in group 2. There was no significant difference between the two groups regarding age and sex ( p > 0.05). In both groups, no significant difference was found in the macular thickness and retinal nerve fiber layer thicknesses values obtained in both eyes before and after the RAI treatment. Conclusion As a result of our study, we observed that RAI intake did not harm the retinal layer.

Effect of Radioactive Iodine Therapy on Cancer-Specific Survival of Papillary Thyroid Cancer Tall Cell Variant.

Radioactive iodine (RAI) therapy is often used as an adjuvant treatment to reduce the risk of recurrence in patients with papillary thyroid cancer (PTC). However, the effect of RAI therapy on cancer-specific survival (CSS) in patients with tall cell variant (TCV) remains controversial. This study aimed to investigate the impact of RAI therapy on CSS in patients with TCV-PTC by analyzing data from the Surveillance, Epidemiology, and End Results database. We identified 1281 patients with TCV-PTC in the SEER database who underwent total thyroidectomy between 2004 and 2019. Of these, 866 (67.6%) patients received RAI therapy and 415 (32.4%) did not. Propensity score matching was conducted to balance the baseline characteristics between the 2 groups. Cox proportional hazards regression models were used to estimate the hazard ratio (HR) and 95% CI for the effect of RAI therapy on CSS. After propensity score matching, 373 pairs of patients were included in the analysis. The results showed no significant difference in CSS between the RAI therapy group and the non-RAI therapy group (HR 0.54, 95% CI 0.25-1.17, P = .120). Subgroup analyses indicated similar results. RAI therapy may not improve CSS in patients with TCV-PTC after total thyroidectomy. Future studies with larger sample sizes, longer follow-up periods, and better study designs are needed to confirm or refine our research findings.

FRI494 Ischemic Stroke After Radioactive Iodine Therapy In Graves Disease

Abstract Disclosure: T. Rave: None. J. Giunta: None. Hyperthyroidism is defined as excess thyroid hormone, most commonly due to Graves Disease. Thiomides are first line therapy, however more definitive options are radioactive iodine (RAI) or thyroidectomy. RAI enters thyroid follicular cells and destroys the thyroid tissue with beta ray emissions. Patients with Graves disease, toxic multinodular goiter, and thyroid cancer can benefit from RAI, but it is contraindicated in pregnancy, breast feeding, and severely uncontrolled thyrotoxicosis. Early side effects are pancytopenia, thyrotoxicosis, and later complications are bone marrow suppression and cancer. There are several reports of cerebral vascular accidents (CVA) after RAI therapy, however, there is limited research demonstrating whether CVA is a direct consequence of RAI or secondary to thyrotoxicosis. This case describes a possible RAI-induced CVA. A 60-year-old female with a past medical history of type 2 Diabetes Mellitus, hypertension, obesity, and Graves disease presented with altered mental status and gait instability for 1 day. She received RAI therapy 1 day prior to symptom onset for uncontrolled Graves disease. She was previously on Methimazole and PTU, however, both were discontinued due to an intolerable rash. As a result, she was maintained on a beta blocker prior to RAI. On presentation, she was afebrile, normotensive with a heart rate of 79. She was oriented only to person and place and had an unbalanced gait. Her Burch-Wartofsky score was 30, which was concerning for thyrotoxicosis. Her TSH was undetectable and EKG showed normal sinus rhythm. She was placed on atenolol, PTU and hydrocortisone. Her CT head was negative for acute disease, however, her MRI brain diagnosed an acute ischemic stroke. During admission, she had episodes of atrial fibrillation with rapid ventricular response. This patient presented with thyrotoxicosis after RAI therapy complicated by a CVA. It is important to note that on presentation she was reliably taking a beta blocker outpatient and her EKG was normal sinus rhythm making atrial fibrillation a less likely culprit of her CVA. Research has found that hyperthyroidism alone can lead to a prothrombotic state, however, additional literature reports that both hyperthyroid and euthyroid patients have an increased risk of CVA following RAI. Whether a CVA is secondary to thyrotoxicosis or a direct effect of RAI, this potentially life-threatening complication should be discussed with patients prior to treatment. Presentation: Friday, June 16, 2023

Radioactive iodine therapy strategies for distinct types of differentiated thyroid cancer: a propensity score-matched analysis.

The management guidelines of radioactive Iodine (RAI) therapy for distinct types of differentiated thyroid carcinoma (DTC) were the same in clinical practice. However, in distinct types DTC, differences in RAI avidity and response existed and the effect of RAI therapy could not be equated. DTC patients' data in SEER database were extracted to perform retrospective analysis. The differences between case group and control group were compared by chi-square tests. We used Kaplan-Meier statistics and Cox regression analyses to investigate cancer-specific survival (CSS). Propensity score-matched was performed to make 1:1 case-control matching. 105195 patients who receiving total thyroidectomy were identified in SEER database. Compared to papillary thyroid carcinoma (PTC) (52.3%), follicular thyroid carcinoma (FTC) (63.8%) and oncocytic carcinoma of thyroid (OCA) (64.4%) had higher rates of RAI therapy. In the multivariable Cox regression model, RAI therapy was independent prognosis factor in PTC but not in OCA and FTC. In subgroup analysis, RAI therapy could improve prognosis in PTC when gross extrathyroidal extension or lymph node metastases or early survival when distant metastases (DM) were presented. However, OCA and FTC patients with DM rather than regional lesions only could benefit from RAI therapy. High-risk patients receiving RAI therapy showed a better prognosis in PTC but not in OCA and FTC. RAI therapy was an effective treatment for DTC and should be considered individually in PTC, OCA and FTC patients. Our results provided further guideline for treatment selection in DTC.

Outcomes of ATA Low-Risk Pediatric Thyroid Cancer Patients Not Treated With Radioactive Iodine Therapy.

The American Thyroid Association (ATA) Pediatric Guidelines recommend patients not receive radioactive iodine therapy (RAIT) for differentiated thyroid cancer (DTC) confined to the thyroid. Since publication, there is ongoing concern whether withholding RAIT will result in a lower rate of remission. This study explores whether ATA low-risk patients treated with and without RAIT achieved similar remission rates. Medical records of patients <19 years old diagnosed with DTC and treated with total thyroidectomy between 2010 and 2020 were reviewed. Multivariate logistic regression was performed to evaluate factors influencing RAIT administration and remission rate. Ninety-five patients with ATA low-risk DTC were analyzed: 53% (50/95) and 47% (45/95) were treated with and without RAIT, respectively. RAIT was used to treat 82% of patients before 2015 compared with 33% of patients after 2015 (P < .01). No significant difference in 1-year remission rate was found between patients treated with and without RAIT, 70% (35/50) vs 69% (31/45), respectively. With longer surveillance, remission rates increased to 82% and 76% for patients treated with and without RAIT, respectively. Median follow-up was 5.8 years (IQR 4.3-7.9, range 0.9-10.9) and 3.6 years (IQR 2.7-6.6; range 0.9-9.3) for both cohorts. No risk factors for persistent or indeterminate disease status were found, including RAIT administration, N1a disease, and surgery after 2015. Withholding RAIT for pediatric patients with ATA low-risk DTC avoids exposure to radiation and does not have a negative impact on remission rates. Dynamic risk stratification at 1-year after initial treatment is a suitable time point to assess the impact of withholding RAIT for these patients.

Abstract #1399287: New-Onset Thyroid Eye Disease After COVID-19 Infection in Patient with Graves’ Disease Post-Radioactive Iodine Treatment

Coronavirus disease 2019 (COVID-19) has been associated with dysregulation of the immune system and abnormal thyroid function. The aim of this novel case report is to inform physicians of the possibility that COVID-19 infection may precipitate thyroid eye disease (TED) in patients with Graves’ Disease (GD) even after treatment with radioactive iodine (RAI). In this report, we describe a patient with GD treated with RAI who developed TED after COVID-19 infection. The patient was initially diagnosed with GD in 2018. A thyroid uptake scan (I-123) was consistent with GD with moderately elevated uptake. She was initially managed with methimazole and atenolol and was eventually treated with RAI (16.32 millicurie I-131) in February 2021. She had post-ablative hypothyroidism managed with levothyroxine. The patient contracted COVID-19 in January 2022. In February 2022, the patient started experiencing eye irritation, dryness, protrusion of eyes, eyelid swelling, and visual disturbances. Thyroid stimulating hormone (TSH) receptor auto-antibodies (7.33 IU/L, normal < /=1.00 IU/L) and thyroid stimulating immunoglobulin (4.30 IU/L, normal < /=1.00 IU/L) were elevated. TSH was normal (2.180 mIU/L, normal 0.270 - 4.200 mIU/L) on levothyroxine 125 mcg daily. She was later diagnosed with TED. GD is an autoimmune thyroid disorder related to the presence of TSH receptor-stimulating antibodies and is often associated with ocular symptoms. Activation of an autoimmune response during COVID-19 infection, may induce onset or relapse of GD. A study using the national health insurance service database in South Korea noted an increase in the incidence of subacute thyroiditis in 2020 in association with the COVID-19 pandemic. TED is usually seen in patients with GD. Radioactive iodine is widely used in the treatment of GD and has been associated with development or worsening of TED. There are published cases of TED occurring in patients with GD after receiving COVID-19 vaccine. It is thought that the inflammatory syndrome induced by the adjuvants could induce molecular mimicry, which could trigger TED. In most cases this adverse effect was transient, lasting a few months after treatment. There have been case reports of TED occurring after 3 to 21 days of COVID-19 vaccination in patients with controlled GD. Symptoms improved in 4-8 months. Development of TED in patients with GD who have been treated with RAI typically occurs soon after RAI therapy. For TED to occur in a GD patient 11 months after receiving RAI therapy is unusual. COVID-19 infection appears to have been the trigger for this patient's eye disease. This is highly unusual and has not been published to our knowledge.

Papillary thyroid carcinoma with fibromatosis-like stroma: a case report and review of the literature

BackgroundPapillary thyroid carcinoma (PTC) is a common neoplasia with multiple variants. One of these extremely rare and poorly described variants is PTC with fibromatosis-like stroma (PTC-FMS), a peculiar entity distinguished by its predominant mesenchymal component. This paper reviews the literature, discusses the diagnostic challenges, and the clinical and surgical implications of this type of tumor which has fewer than 30 cases reported in the literature.Case presentationWe reported a case of PTC-FMS found in a 41-year-old Italian woman, who came to our Institute with a recent growth in the form of a mass on the neck. Further immunohistochemical examination showed β-catenin aberrant staining both in the nuclei and cytoplasm of the mesenchymal cells. The patient underwent total thyroidectomy and received radioactive iodine (RAI) 2 months after surgery.ConclusionGiven the possibility of recurrence of PTC-FMS and the ineffectiveness of RAI therapy, complete surgical resection represents the main treatment for this type of tumor. Despite the fact that the specific nature of these lesions has yet to be determined, guidelines for classical PTC should be followed.

Linear association between radioactive iodine dose and second primary malignancy risk in thyroid cancer.

We aimed to investigate whether the risk of second primary malignancy (SPM) in patients with thyroid cancer (TC) receiving radioactive iodine (RAI) therapy rises in a cumulative, dose-dependent manner compared with those not undergoing RAI. Using the Korean National Health Insurance Service National Health Information Database (2002-2019), we investigated hazard ratios of SPM associated with RAI in TC. SPM was defined as a second primary malignancy diagnosed at least 1 year after TC diagnosis. Of 217 777 patients with TC (177 385 women and 40 392 men; mean [SD] age, 47.2 [11.6] years), 100 448 (46.1%) received RAI therapy. The median (IQR) follow-up duration was 7.7 (5.5-10.3) years, and the median (IQR) cumulative RAI dose was 3.7 (1.9-5.6) GBq. From 2004 to 2019, SPM incidence rates were 7.30 and 6.56 per 1000 person-years in the RAI and non-RAI groups, respectively, with an unadjusted hazard ratio of 1.09 (95% confidence interval = 1.05 to 1.13); this rate remained at 1.08 (95% confidence interval = 1.04 to 1.13) after adjustment for multiple clinical confounding factors. Notably, SPM risk increased significantly, from 3.7 GBq with full adjustments, and a strong linear association between cumulative RAI dose and SPM was observed in the restricted cubic spline analysis. Regarding cancer subtypes, myeloid leukemia and salivary gland, trachea, lung and bronchus, uterus, and prostate cancers were the most significantly elevated risks in patients who underwent RAI therapy. This study identified that SPM risk increased linearly in a dose-dependent manner in patients with TC undergoing RAI therapy compared with those not undergoing RAI therapy.

Late Breaking Abstracts

Late Breaking Abstracts

Factors Associated With Radioactive Iodine Therapy–Acquired Nasolacrimal Duct Obstruction

ObjectiveTo identify factors associated with radioactive iodine (RAI)-acquired nasolacrimal duct obstruction (NLDO). MethodsRetrospective chart review and telephone surveys of patients who received RAI therapy for thyroid carcinoma at an academic institution were conducted. Telephone surveys were used to screen for post-RAI NLDO diagnoses. Databases were reviewed for documented NLDO, demographics, RAI dose, total number of RAI treatments, and sialadenitis. Routine post-RAI whole-body scintigraphy (WBS) images were analyzed for the presence or absence of 131I sodium iodide (I-131) in the nasolacrimal duct. Intranasal I-131 activity was graded as none, low, moderate, and high; those with moderate or high activity were considered to have “increased” activity. Logistic and ordinal logistic regression models were used to evaluate the associations with NLDO while adjusting for I-131 dose. ResultsOf the 209 patients who completed the survey, 15 (7%) had NLDO diagnoses. Increased intranasal I-131 activity on WBS, presence of nasolacrimal I-131 WBS activity, presence of documented post-RAI sialadenitis, and history of >1 RAI treatment were associated with the development of NLDO from univariate analyses (P ≤ .013). After adjusting for the administered dose of I-131, the presence of sialadenitis and nasolacrimal I-131 activity on WBS were the remaining 2 factors significantly associated with NLDO development (P < .001 and P = .01, respectively). ConclusionsThe presence of sialadenitis and nasolacrimal I-131 activity on WBS are I-131 dose-independent correlative factors for RAI-associated NLDO. Patients with these characteristics should be counseled on their increased risk of NLDO after RAI therapy for thyroid carcinoma.

Proposed Risk Stratification and Patterns of Radioactive Iodine Therapy in Malignant Struma Ovarii.

Introduction: Malignant struma ovarii (MSO) is a rare thyroid cancer arising within an ovarian teratoma. While surgical excision of the primary tumor is widely accepted as standard of care, recommendations for adjuvant treatment of MSO-whether or not to administer radioactive iodine (RAI)-are based largely on case reports and remain debated. In this study, we aimed to propose a risk stratification and analyze RAI utilization patterns in MSO cases. Methods: The National Cancer Database (NCDB) was queried for patients with MSO between 2004 and 2016. Demographic, oncological, and clinicopathologic data were compared between groups using Fisher's exact test. Kaplan-Meier curves were used to estimate overall survival (OS), and variables associated with OS were assessed via univariate Cox regression. We adapted the 2015 American Thyroid Association risk guidelines for MSO patients. We stratified patients into low-, intermediate-, and high-risk groups using metastasis, extraovarian extension, lymphovascular invasion, lymph node status, surgical margins, tumor size, and grade. Risk stratification, demographic, oncological, and clinicopathologic data were compared between the groups receiving and not receiving RAI therapy. We then queried the Surveillance, Epidemiology, and End Results (SEER) 18 registry for patients with MSO between 2000 and 2018 to confirm our risk stratification analysis. Results: In the NCDB analysis, a total of 158 patients were identified, and 19 received RAI. RAI therapy was associated with distant metastasis (p = 0.005) and lymph node status (p = 0.012). Twenty-one NCDB patients were stratified as high risk, and 30% of high-risk patients received RAI. High-risk stratification was associated with decreased OS via univariate Cox regression (hazard ratio = 4.0 [95% confidence interval 1.11-14.26], p = 0.034). In our subsequent analysis using the SEER registry, there were 95 MSO patients, and 18 received RAI. Again, the majority of high-risk patients did not receive RAI, with only 41% of high-risk patients receiving RAI. Conclusions: MSO is a rare malignancy with apparently variable and inconsistent patterns of postoperative RAI administration. The risk stratification described here provides a framework to identify patients potentially at risk for mortality, and utilization of RAI in this group should be studied further.

Efficacy of Radioiodine Therapy in Patients With Primary Hyperthyroidism: An Institutional Review From Pakistan.

BackgroundRadioactive iodine (RAI) is the treatment of choice for most patients with primary hyperthyroidism. The most common etiologies of hyperthyroidism are Graves' disease (GD), toxic adenoma (TA), and toxic multinodular goiter (TMNG). A single dose of RAI is usually sufficient to cure hyperthyroidism. The aim of this study was to assess the effectiveness of RAI therapy for patients diagnosed with primary hyperthyroidism.Methods and materialsPatients diagnosed with hyperthyroidism who received RAI therapy between 2008 and 2018 were included in the study. The data was acquired from the hospital's electronic medical record system. Following the RAI treatment, a cure was defined as the development of euthyroidism or hypothyroidism after a single fixed-dose without antithyroid medication within one year of RAI therapy. In addition, a simple logistics regression model was used to identify the prognostic factors that may lead to better outcomes.ResultsA total of 112 patients diagnosed with hyperthyroidism with a mean age of 47 ± 14 were included in this study. The majority of the patients were female, 79 (70.5%). Within one year of RAI therapy, 84 (75%) patients achieved a cure that is either hypothyroid or euthyroid status. RAI dose was higher in responsive patients (18.50 ± 4.10 millicurie [mCi] versus 16.50 ± 4.10 mCi) than in non-responsive patients. The mean RAI doses were 16.05 ± 2.99 mCi in GD, 19.81 ± 4.40 mCi in TMNG, and 20.50 ± 3.30 mCi in TA, with a statistically significant p-value of 0.001. In the univariable logistic regression model, RAI dose was a significant prognostic factor of the responsive group (OR: 1.15, CI [1.01-1.31], p-value 0.03).ConclusionOur data presented that RAI therapy is effective for primary hyperthyroidism. We achieved remission with a single fixed-dose in the majority of patients. Most of our patients were cured within three months of RAI therapy. In addition, the RAI dose was higher in the responsive group as compared to the non-responsive group.

Abstract 730: Annual hazard rate of recurrence in Middle-Eastern papillary thyroid cancer over a long-term follow-up

Abstract Predicting the pattern of recurrence is necessary to establish optimal surveillance and treatment strategies. We identified patient population that remain at risk for an event and clarify changes in the hazard rate (HR) for tumor recurrence overtime in Middle Eastern patients with Papillary Thyroid Cancer (PTC). Data for 1201 PTC patients from single institute with median follow-up of 9.5 years were analyzed. Estimated HR were plotted overtime for the entire cohort, as well as for radioactive iodine (RAI) ablation in patients separately. The changes in risk were further analyzed according to clinical variable and factors predictive of early (≤ 5years) and late (&amp;gt;5 years) recurrence were explored using Cox regression analysis. Tumor recurrence was noted in 18.4% (221/1201) patients. The annualized hazard of PTC recurrence was highest during the first 5 years (2.8%), peaking between 1 - 2 years (3.7%), with a second smaller peak between 13 - 14 years (3.2%). Patients receiving RAI therapy had a lower hazard of recurrence compared to those who did not receive RAI therapy (1.5% vs 2.7%, p = 0.0001). Importantly, this difference was significant even in the intermediate-risk PTC patients (0.7% vs 2.3%; p = 0.0001). Interestingly, PTC patients who were male, aged ≥ 55 years, with lymph node involvement and advanced stage disease were still at high risk for late recurrence. In conclusion, we confirmed the validity of double-peaked time-varying pattern for risk of recurrence in Middle-Eastern PTC patients. Furthermore, according to the time distribution of recurrence hazard, we could formulate individualized treatment and surveillance plans in PTC patients. Citation Format: Abdul K. Siraj, Sandeep K. Parvathareddy, Zeeshan Qadri, Saud Azam, Felisa De Vera, Maha Al-Rasheed, Wael Haqawi, Hassan AlDossari, Khawla S. Al-Kuraya. Annual hazard rate of recurrence in Middle-Eastern papillary thyroid cancer over a long-term follow-up [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 730.

Usefulness of albumin–globulin ratio as a clinical prognostic factor in patients with thyroid cancer treated with radioiodine

Albumin-globulin ratio (AGR), which is calculated by dividing serum albumin by serum globulin, is considered as a cancer-related inflammation biomarker. Although the prognosis of many solid cancers has been shown to be associated with AGR, there are no studies to demonstrate the association between the prognosis of thyroid cancer and AGR. The purpose of this study is to reveal the relationship between AGR and overall survival (OS) in patients with thyroid cancer who received radioactive iodine therapy (RIT). Eighty-eight patients with thyroid cancer who had received RIT for the first time in our institution were included. The values before RIT were adopted as initial measurements for serum albumin, globulin, and thyroglobulin (Tg) and used for analysis. Patients were divided into two groups based on the AGR value. We analyzed the relationship between clinical factors and treatment outcome. The median follow-up period was 92.4months (range: 30.1-173.9months). The 5-year OS and progression-free survival (PFS) were 94% and 54%, respectively. Seventeen patients (< 65years, 8; and ≥ 65years, 9) died during the follow-up period. Low AGR was significantly associated with OS in both univariate and multivariate analyses (p = 0.0059 and p = 0.0120, respectively). As the 5-year OS was as high as 94%, there was no significant difference in survival rate between the two groups during the first 5years. However, there seemed to be a remarkable difference in 10years after the first RIT. On the other hand, Tg was significantly associated with PFS in both univariate and multivariate analyses (p = 0.0016 and p = 0.0441, respectively). In patients under the age of 65, the PFS rate was significantly lower in the low AGR group (p < 0.0001), while there was no difference in PFS rate between the two AGR groups in patients aged 65years or older. AGR may be used as a prognostic factor in relatively younger patients with thyroid cancer treated with radioiodine, while it may be less useful in the older. Overall, it may be an independent prognostic factor for long-term survival in those with thyroid cancer.

Clinical Outcomes of Differentiated Thyroid Cancer With Gross Extrathyroidal Extension Into the Strap Muscles: A Case Control Study

Background: The 8th edition of the American Joint Committee on Cancer/tumor-node-metastasis (AJCC/TNM) staging system for differentiated thyroid cancer (DTC), implemented in January 2018, classifies patients >/= 55 years of age with gross extrathyroidal extension (ETE) of the primary tumor into the overlying strap muscles as prognostic stage II. However, it remains controversial as to whether or not gross ETE into the strap muscles is an independent predictor of recurrence, response to therapy, need for additional therapies, or overall survival. Using a case control study design, we evaluated the prognostic significance of gross ETE among adults. Methods: After obtaining IRB approval, we used the tumor registry at our institution to retrospectively identify 51 AJCC stage II patients with DTC aged >/= 55 years with gross ETE into only the strap muscles (51/2,225 patients). For each of the 51 cases, we identified one control who matched on all of the following important prognostic factors: age at diagnosis (± 5 years), sex, histology, size of tumor (± 1 cm), lymph node metastases, distant metastases, completeness of resection, receipt of radioactive iodine (RAI) therapy, and duration of follow-up (± 5 years). The controls (n=51) had no gross ETE. Results: In the 51 patients with gross ETE into only the strap muscles, the mean age at diagnosis was 64 years, 77% were female, 37% had lymph node metastases, and none had distant metastases. The average tumor size was 2.1 cm with the majority of patients (49/51) demonstrating papillary thyroid carcinoma (1 follicular thyroid carcinoma and 1 Hurthle cell thyroid carcinoma). Only 6% of patients (3/51) had incomplete resections and 92% (47/51) received RAI therapy. The mean duration of follow-up was 8 years.There were no statistically significant differences between the cases and controls on each of the pre-specified prognostic variables described in the methods. In addition, there were no statistically significant differences between the groups in terms of rates of recurrence: cases 18% (9/51) and controls 29% (15/51) (p=0.24), best response to initial therapy (excellent, biochemical incomplete, structural incomplete, or indeterminate response to therapy), and need for subsequent interventions including surgery, RAI, external beam radiation, or systemic therapy. Furthermore, there were no statistically significant differences between the cases and controls with respect to 10-year disease-free survival (cases 83% and controls 68%, p=0.90) and 10-year overall survival (cases 97% and controls 89%, p=0.10). Conclusions: In a case control analysis with a mean follow up of 8 years, the presence of ETE into the strap muscles was not an independent predictor of worse clinical outcomes in adults >/= 55 years old with DTC. These findings can be used to inform the future editions of the AJCC/TNM and American Thyroid Association staging systems for DTC.

Effects of radioactive iodine treatment on cardiovascular disease in thyroid cancer patients: a nationwide cohort study.

BackgroundRadioactive iodine (RAI) treatment is a standard treatment in differentiated thyroid cancer (TC). However, its adverse effects on cardiovascular diseases (CVDs) have not been clearly elucidated.MethodsIn this retrospective cohort study based on the Korean National Health Insurance Service-National Health Screening Cohort (2002–2015), we analyzed 4,845 patients with TC with a median follow-up of 66 months. We evaluated and compared the risk of CVD between patients treated with and without RAI therapy. The primary CVD outcome was defined as a composite of ischemic stroke (IS), ischemic heart disease (IHD), hemorrhagic stroke (HS), or heart failure (HF).ResultsOverall, 2,533 patients (52.3%) received RAI treatment with a median cumulative dosage of 103 mCi [interquartile range (IQR), 40–162 mCi]. The incidence of the primary CVD outcome in patients who did not receive RAI therapy and those who did was 17.32 [95% confidence interval (CI), 15.07–19.90] and 13.96 (95% CI, 12.17–16.01) per 1,000 person-years, respectively, indicating an adjusted hazard ratio (HR) of 0.87 (95% CI, 0.71–1.07) after multivariate adjustments for variable confounding factors. The risks of IS (HR, 0.83; 95% CI, 0.51–1.34), IHD (HR, 0.90; 95% CI, 0.71–1.13), HS (HR 1.01; 95% CI, 0.49–2.09), and HF (HR 0.89; 95% CI, 0.49–1.63) were comparable between the patients who received RAI therapy and those who did not. There was no cumulative dose-dependent risk for CVD in TC patients who received RAI treatment.ConclusionsRAI treatment is a prevalent and crucial treatment for TC, and has been used in more than half of TC patients in Korea from 2004 to 2015. This study found no significant between-group difference for the CVD risk in patients with TC who received RAI treatment and those who did not, giving further evidence to allay concerns related to the adverse effects of RAI.

Evaluation of the response levels of non-metastatic thyroid cancer patients in the postoperative twelfth month

Objective: Radioactive iodine (RAI) is used to ablate residual thyroid tissue after total thyroidectomy. The aim of this study was to evaluate the response according to the12th-month results of thyroid cancer patients and to investigate the changes in response level during follow-up.&#x0D; Materials and Methods: The study included 97 patients, comprising 88 (90.7%) females and 9 (9.3%) males, with a mean age of 41.68±13.25 years. None of the patients had lymph node or distant metastasis and all received RAI therapy. Thyroid-stimulating hormone (TSH), thyroglobulin (TG), and anti-TG levels and neck USG were examined in the 12th-month. Response to therapy was evaluated as an excellent response, biochemical incomplete response, structural incomplete response, or indeterminate response.&#x0D; Results: In the 12th month, 80 patients (82.47%) had excellent response, 13 patients (13.40%) had an indeterminate response, 3 patients (3.09%) had structural incomplete response and 1 patient (1.03 %) had biochemical incomplete response. Of the 80 patients with excellent response, 15 had no follow-up after the 12th month. The remaining 65 patients were followed up for 31.11±9.58 months. The response changed to indeterminate in the 18th month in 1 (1.54%) patient and to structural incomplete response in the 35th month in 1 (1.54%) patient. The 13 patients with indeterminate responses were followed up for 20.61±6.28 months.&#x0D; Conclusion: The TG level at 12th months provides accurate data about the course of the disease especially in patients with excellent responses. Patients with excellent response in the 12th month may be followed up less often and those with the indeterminate or incomplete responses should be followed up more often.

Unexpected radioactive iodine accumulation on whole-body scan after I-131 ablation therapy for differentiated thyroid cancer.

ABSTRACTWe retrospectively evaluated the frequency of unexpected accumulation of radioactive iodine on the post-therapy whole-body scan (Rx-WBS) after radioactive iodine (RAI) ablation therapy in patients with differentiated thyroid cancer (DTC). We searched our institutional database for Rx-WBSs of DTC patients who underwent RAI ablation or adjuvant therapy between 2012 and 2019. Patients with distant metastasis diagnosed by CT or PET/CT before therapy, and those had previously received RAI therapy were excluded. In total, 293 patients (201 female and 92 male, median age 54 years) were selected. Two nuclear medicine physicians interpreted the Rx-WBS images by determining the visual intensity of radioiodine uptake by the thyroid bed, cervical and mediastinal lymph nodes, lungs, and bone. Clinical features of the patients with and without the metastatic accumulation were compared by chi-square test and median test. Logistic regression analyses were performed to compare the association between the presence of metastatic accumulation and these clinical factors. Eighty-four of 293 patients (28.7%) showed metastatic accumulation. Patients with metastatic RAI accumulation showed a significantly higher frequency of pathological N1 (pN1) and serum thyroglobulin (Tg) > 1.5 ng/ml under TSH stimulation (p = 0.035 and p = 0.031, respectively). Logistic regression analysis indicated that a serum Tg > 1.5 ng/ml was significantly correlated with the presence of metastatic accumulation (odds ratio = 1.985; p = 0.033). In conclusion, Patients with Tg > 1.5 ng/ml were more likely to show metastatic accumulation. In addition, the presence of lymph node metastasis at the initial thyroid surgery was also associated with this unexpected metastatic accumulation.