Differentiated thyroid cancer patients potentially benefitting from postoperative I-131 therapy: a review of the literature of the past decade.

BACKGROUND: Since the last major review of literature on the benefit of I-131 therapy, the continued debate on postoperative radioiodine treatment (RIT) in differentiated thyroid carcinoma (DTC) has led to a number of further studies being published on this topic. AIM: The aim of the present paper is to report the results of an updated structured review of the literature pertaining to the prognostic benefits of postoperative RIT in DTC in terms of recurrence-free and disease-specific survival. METHODS: A systematic search of the literature was performed using the Medline and Cochrane Library database. The search period started in August 2007 and ended on December 6, 2017. Search terms used included "differentiated thyroid cancer" and "radioiodine therapy" amended by specific terms for recurrence/disease-free survival or overall and/or cancer-specific survival. Included in the search were systematic reviews, randomized clinical trials, or cohort studies consisting of both patients who underwent postoperative RIT and patients treated by surgery alone. RESULTS: Eleven retrospective cohort studies met the defined inclusion criteria and were included in the present review. Results of the studies were mixed, with some showing a benefit of RIT even in microcarcinoma whereas others showed no benefit at all. CONCLUSION: Literature published in the last decade offers data that support adjuvant postoperative RIT in DTC patients with a tumor diameter exceeding 1 cm. Therefore, at least until randomized prospective studies prove otherwise, the prescription of adjuvant I-131 treatment to all DTC patients with a primary tumor diameter exceeding 1 cm remains a reasonable option.

Advanced differentiated thyroid cancer: when to stop radioiodine?

Radioiodine (RAI) is a pivotal important treatment for patients with metastatic differentiated thyroid cancer (DTC). In order to determine when a patient will no longer respond to RAI, multiple classifications have been described to categorize a patient as RAI refractory (RAI-R). Current classifications, although very useful, are problematic and controversial and cannot be merely applied in the context of individualized patient management. In addition, classifications on how to define RAI-R disease are continuously evolving as more studies are published and managing physicians better understand the limitations and confounding factors of present classifications. Accordingly, each patient should be individually managed with a good understanding of the limitations of the various classifications, assessing the many other factors that affect the patient's specific clinical situation and delivering appropriate individualized patient care.

Poor patient compliance with instructions for continuous sialogogues after 131 I therapy.

OBJECTIVES: To analyze the role of patient compliance as a factor in evaluating the effectiveness of continuous sialogogues to prevent salivary side effects from 131 I therapy in differentiated thyroid cancer patients. METHODS: Differentiated thyroid cancer patients who were clinically scheduled for an 131 I therapy at MedStar Washington Hospital Center between 2012 and 2013 were given instructions for continuous sialogogues per standard clinical protocol. The prospective survey was given at multiple time points. RESULTS: Ninety-nine patients consented to participate of whom 94 participants had complete data. The mean prescribed 131 I activity was 121 ± 50 mCi (4.5 ± 1.9 GBq), range 27.5-288 mCi (1.0-10.7 GBq ). Overall, only 10% (9/94) of patients were compliant with continuous sialogogues. Even though all patients took sialogogues on the first day of post-therapy, 17% of participants did not continuously take sialogogues during the first day, 60% during the first night, and 72% on the second day despite rigorous instructions to continue for two days. CONCLUSION: Despite repetitive instructions to use sialogogues continuously, most patients (90%) were not compliant. In future studies, strict monitoring and evaluation of patient compliance will be crucial when assessing the effect of continuous versus intermittent or delayed initiation of sialogogues.

Redifferentiation of Differentiated Thyroid Cancer: Clinical Insights from a Narrative Review of Literature.

Background: Patients who have metastatic differentiated thyroid cancer (mDTC) frequently have negative diagnostic and/or post-therapy radioiodine scans. As a result, 131I therapy is frequently no longer considered a therapeutic option for these patients. However, with the knowledge of genomic alterations of patients with mDTC, the use of selected agents in specific patient groups may be used with the intention to re-establish 131I uptake (i.e., redifferentiation) and additional 131I therapy. The objectives of this narrative review are to present definitions of related terminology, a brief overview of the molecular mechanisms of redifferentiating agents, and a narrative review of the literature for redifferentiation in patients who have radioiodine refractory mDTC. Summary: We searched multiple electronic databases and reviewed the relevant English-language literature reported after 2010. Fourteen articles were included in this narrative review. Conclusions: Preliminary data suggest that select agents may offer potential for re-establishing 131I uptake in selected patients with radioiodine refractory mDTC (e.g., negative diagnostic and/or post-therapy radioiodine scans). These agents may also enhance uptake (e.g., uptake enhancement) in patients who have 131I uptake in mDTC on a diagnostic and/or post-therapy radioiodine scan. As a result, this may facilitate higher absorbed dose delivered (Gy (rad]) per 131I activity administered [GBq (mCi)]. This in turn may increase the likelihood of a better therapeutic effect for the planned administered 131I activity or a reduction in the originally planned administered 131I activity, while achieving the same intended therapeutic effect with potentially less untoward effects. Further studies are warranted to confirm these preliminary observations and to confirm acceptable subsequent 131I therapy responses after redifferentiation and/or uptake enhancement.

I-124 PET/CT image-based dosimetry in patients with differentiated thyroid cancer treated with I-131: correlation of patient-specific lesional dosimetry to treatment response.

PURPOSE: The objective of this study is to evaluate the lesion absorbed dose (AD), biological effective dose (BED), and equivalent uniform dose (EUD) to clinical-response relationship in lesional dosimetry for 131I therapy. METHODS: Nineteen lesions in four patients with metastatic differentiated thyroid cancer (DTC) were evaluated. The patients underwent PET/CT imaging at 2 h, 24 h, 48 h, 72 h, and 96 h post administration of ~ 33-65 MBq (0.89-1.76 mCi) of 124I before undergoing 131I therapy. The 124I PET/CT images were used to perform dosimetry calculations for 131I therapy. Lesion dose-rate values were calculated using the time-activity data and integrated over the measured time points to obtain AD and BED. The Geant4 toolkit was used to run Monte Carlo on spheres the same size as the lesions to estimate EUD. The lesion AD, BED, and EUD values were correlated with response data (i.e. change in lesion size pre- and post-therapy): complete response (CR, i.e. disappearance of the lesion), partial response (PR, i.e. any decrease in lesion length), stable disease (SD, i.e., no change in length), and progressive disease (PD, i.e., any increase in length). RESULTS: The lesion responses were CR and PR (58%, 11/19 lesions), SD (21%, 4/19), and PD (21%, 4/19). For CR and PR lesions, the ADs, BEDs and EUDs were > 75 Gy for 82% (9/11) and < 75 Gy for 18% (2/11). The ADs and BEDs were < 75 Gy for SD and PD lesions. CONCLUSION: By performing retrospective dosimetry calculations for 131I therapy based on 124I PET/CT imaging, we evaluated the correlation of three dosimetric quantities to lesional response. When lesion AD, BED, and EUD values were > 75 Gy, 47% (9/19) of the lesions had a CR or PR. The AD, BED, and EUD values for SD and PD lesions were < 75 Gy. The data presented herein suggest that the greater the lesion AD, BED, and/or EUD, the higher the probability of a therapeutic response to 131I therapy.

Metastatic Differentiated Thyroid Cancer Survival Is Unaffected by Mode of Preparation for 131I Administration.

Context: Recombinant human thyrotropin (rhTSH) is currently not Food and Drug Administration approved for the treatment of high-risk patients with differentiated thyroid cancer (DTC). Objective: The goal of our study was to compare the outcomes in higher-risk patients with metastatic DTC prepared for radioiodine (RAI) therapy with rhTSH vs thyroid hormone withdrawal (THW). Methods: A retrospective chart review was performed of patients with metastatic DTC in follow-up at MedStar Washington Hospital Center and MedStar Georgetown University Hospital from 2009 to 2017. Patients were divided according to their preparation for RAI therapy, with assessment of progression-free survival (PFS) and overall survival (OS). Results: Fifty-five patients with distant metastases (16 men, 39 women) were prepared for RAI therapy exclusively either with rhTSH (n = 27) or with THW (n = 28). There were no statistically significant differences between the groups regarding clinicopathological features and history of RAI therapies. The median follow-up time for patients with rhTSH-aided therapies was 4.2 years (range, 3.3-5.5 years) and for patients with THW-aided therapies was 6.8 years (range, 4.2-11.6 years) (P = .002). Multivariate analysis showed that the method of thyrotropin stimulation was not associated with a difference in PFS or OS. Conclusion: As has been shown previously for low-risk DTC, this study indicates that the mode of preparation for RAI therapy does not appear to influence the outcomes of patients with metastatic DTC. PFS and OS were similar for patients with THW-aided or rhTSH-aided RAI therapies.

Does an undetectable rhTSH-stimulated Tg level 12 months after initial treatment of thyroid cancer indicate remission?

OBJECTIVES: Routine monitoring after the initial treatment of differentiated thyroid cancer (DTC) includes periodic cervical ultrasonography (US) and measurement of serum thyroglobulin (Tg) during thyrotrophin (TSH) suppression and after recombinant human TSH (rhTSH) stimulation. The aim of our study was to evaluate the utility of repeated rhTSH-stimulated Tg measurements in patients with DTC who have had no evidence of disease at their initial rhTSH stimulation test performed 1 year after the treatment. MATERIAL AND METHODS: A retrospective chart review of 278 patients with DTC who had repeated rhTSH stimulation testing after an initial undetectable rhTSH-stimulated serum Tg level. RESULTS: The number of rhTSH stimulation tests performed on individual patients during the follow-up period (3-12 years, mean 6·3) varied from two to seven. Biochemical and/or cytological evidence of potential persistent/recurrent disease based on detectable second or third rhTSH-stimulated Tg values and US findings was observed in 11 (4%) patients. Subsequent follow-up data revealed that in five cases, the results of the second stimulation were false positive, in one case - false negative. Combined with the negative neck US, the negative predictive value for disease-free survival was 98% after the first undetectable rhTSH-stimulated Tg and 100% after the second one. CONCLUSIONS: In patients with DTC, the intensity of follow-up should be adjusted to new risk estimates evolving with time. The first rhTSH-stimulated Tg is an excellent predictor for remission, independent of clinical stage at presentation. Second negative rhTSH-Tg stimulation is additionally reassuring and can guide less aggressive follow-up by the measurement of nonstimulated Tg and neck US every few years.

Three-dimensional radiobiological dosimetry (3D-RD) with 124I PET for 131I therapy of thyroid cancer.

Radioiodine therapy of thyroid cancer was the first and remains among the most successful radiopharmaceutical (RPT) treatments of cancer although its clinical use is based on imprecise dosimetry. The positron emitting radioiodine, (124)I, in combination with positron emission tomography (PET)/CT has made it possible to measure the spatial distribution of radioiodine in tumors and normal organs at high resolution and sensitivity. The CT component of PET/CT has made it simpler to match the activity distribution to the corresponding anatomy. These developments have facilitated patient-specific dosimetry (PSD), utilizing software packages such as three-dimensional radiobiological dosimetry (3D-RD), which can account for individual patient differences in pharmacokinetics and anatomy. We highlight specific examples of such calculations and discuss the potential impact of (124)I PET/CT on thyroid cancer therapy.

Optimal Time for 124I PET/CT Imaging in Metastatic Differentiated Thyroid Cancer.

BACKGROUND: The objective of this study was to determine the optimal time for 124I PET/CT imaging to maximize the detection of locoregional and/or distant metastases of differentiated thyroid cancer. METHODS: Differentiated thyroid cancer patients suspected of having metastatic disease were prepared with low-iodine diet and appropriate thyroid-stimulating hormone stimulation. 124I PET and low-dose localization CT were performed over 4 days after oral administration of 31.5 or 62.9 MBq (0.85 or 1.7 mCi) of 124I. Each scan was independently reviewed by 2 nuclear medicine physicians. All foci of activity were categorized, and the visual intensity of uptake was scored by a semiquantitative 3-point grading system (1: mild uptake, 2: moderate uptake, 3: intense uptake). Lesion volumes were determined on the CT image or on the PET images. Background (bkg) was also measured for each lesion and on each individual PET image. For each lesion, the mean activity concentration rate per unit administered activity (ACRmean/AA) and lesion-to-bkg ratios were compared across the 5 different time points. The semiquantitative grade and the quantitative measurements were compared. RESULTS: A total of 45 124I PET/CT scans were reviewed for 9 patients. In the visual assessment, a total of 31 foci suggestive for or highly suggestive of metastasis were identified on 124I PET/CT. Of these, 6 were seen on the 2-h, 18 on the 24-h, 27 on the 48-h, 24 on the 72-h, and 20 on the 96-h scan. There was a significant difference between the 24- and 48-h scans in the total number of foci (ie, locoregional and distant metastasis) (P < 0.05) and in the number of distant metastases (P < 0.05). The 24-, 48-, and 72-h scans identified the same number of locoregional foci. The 48-h scan visualized more of the distant metastases than any other time point. 124I PET/CT with dual-time-point imaging was superior to single-time-point imaging (97% vs 87%). In the quantitative analysis, the median ACRmean/AA was highest at 24 and 48 h, and the median lesion-to-bkg ratio was variable for different lesion locations. For lung metastases, the highest median lesion-to-bkg ratio was at 72 and 96 h. CONCLUSIONS: 124I PET/CT with dual-time-point imaging was superior to any single-time-point imaging (P < 0.10). Based on the visual assessment, dual time points at 48 + 72 h or 48 + 96 h yielded the highest lesion detection rate, whereas for single-time-point imaging, the 48-h images had the highest lesion detection rate. If the 48-h scan is completely negative or has negative 124I uptake in the region of interest, then a 72- or 96-h scan may be valuable. If lung metastases are suspected, then one should consider additional imaging at 72 or 96 h.

The spectrum of 124I uptake in the lacrimal gland and nasolacrimal sac/duct on PET/CT imaging.

METHODS: 124I PET/CT in 31 DTC patients was performed at 2, 24, 48, 72, and 96 h after oral administration of 31.5 or 62.9 MBq (0.85 or 1.7 mCi) of 124I after either recombinant human thyroid-stimulating hormone injections or thyroid hormone withdrawal. All but two patients had a history of prior 131I therapy. Patterns of 124I uptake in the lacrimal glands and nasolacrimal sac/ducts (NLD) were assessed. RESULTS: A total of 173 individual 124I PET/CT scans (forming 35 sets of scans) were reviewed for 31 patients. Lacrimal glands were visualized bilaterally in only 4 patients. The focal mild uptake (grade 2), best seen on the 2-h images, was crescent-shaped and located in the lateral upper quadrant of the orbit. In contrast, the NLDs were identified in all patients (bilateral in 29 of 31 patients) with high focal uptake (grade 4) peaking on the 2- and 24-h timepoints; however, the overall pattern of uptake was variable. Of the 29 patients with prior 131I therapy, three patients had a relatively fixed and unchanging pattern of uptake on at least one side of the NLDs. CONCLUSIONS: In patients with DTC, 124I activity in the NLDs is more frequently visualized, more intense, more prolonged, and more variable than in the lacrimal glands. The lack of clearance may suggest possible obstruction or stasis of an NLD.

30 mCi exploratory scan for two-step dosimetric 131I therapy in differentiated thyroid cancer patients: A novel approach and case report.

Differentiated thyroid cancer patients with significantly elevated or rapidly rising serum thyroglobulin (Tg) levels and negative diagnostic radioiodine scans (DxScan) often present a therapeutic dilemma in deciding whether or not to administer an 131I treatment. In this report, we describe a novel two-step approach of a 30 mCi 131I exploratory scan before a dosimetric 131I therapy to help "un-blind" the treating physician of the benefit/risk ratio of a further "blind" 131I treatment. A 51-year-old man presented with rising Tg levels, a negative DxScan, and a history of widely metastatic follicular thyroid cancer. He had undergone total thyroidectomy, remnant ablation with 3.8 GBq (103.5 mCi) of 131I, Gammaknife®, and treatment with 12.1 GBq (326 mCi) of 131I for multiple metastases. However, at 19 months after the treatments, his Tg levels continued to rise, and scans demonstrated no evidence of radioiodine-avid metastatic disease. In anticipation of a "blind" 131I treatment, the medical team and the patient opted for a 30 mCi exploratory scan. The total dosimetrically guided prescribed activity (DGPA) was decided based on the whole-body dosimetry. The patient was first given 30 mCi of 131I, and the exploratory scan was performed 22 h later, which demonstrated 131I uptake in the left lung, left humeral head, T10, and right proximal thigh muscle. Based on the positive exploratory scan, the remainder of the DGPA was administered within several hours after the scan. On the post-DGPA treatment scan performed at 5-7 days, the lesions seen on the ~ 22 h exploratory scan were confirmed, and an additional lesion was observed in the left kidney. The 30 mCi exploratory scan suggested the potential for a response in the radioiodine-avid lesions despite a negative diagnostic scan. This method allows 131I treatment to be administered to patients who may have a greater potential for a therapeutic response while avoiding unwarranted side effects in those patients with nonavid disease.

Nationwide Survey on Implementation of 2011 Nuclear Regulatory Commission Policy on Release of Patients After 131I Therapy for Thyroid Cancer.

The objective of this nationwide survey was to evaluate whether there has been a change in the practice regarding hospital release of differentiated thyroid cancer patients treated with 131I since the publication of Nuclear Regulatory Commission Regulatory Issue Summary 2011-01 addressing patient release. Methods: A survey was emailed to approximately 25,000 members of ThyCa: Thyroid Cancer Survivors' Association, Inc., and was available online from March to August 2018. Responses were included from adult patients regarding their most recent 131I therapy received between 2011 and 2018 ("after 2011"). Responses to this survey were compared with those of a similar previous survey for 131I therapies received between 1997 and 2009 ("before 2009"). Results: Of the 2,136 responses, 1,111 met the inclusion criteria. A similar percentage (∼98%) of patients were given oral or written radiation safety instructions (RSIs) after 2011 and before 2009, with a shift away from nuclear medicine physicians providing instructions after 2011 (43%) in comparison with before 2009 (54%; P < 0.001). More patients were able to discuss and individualize the RSIs after 2011 (67%) than before 2009 (29%; P < 0.001). However, 2% of patients do not recall ever receiving RSIs after 2011. After 2011, more patients were treated as outpatients (87%) than before 2009 (66%; P < 0.001). For outpatients, more patients were discharged within 30 min after receiving 131I therapy after 2011 (78%) than before 2009 (72%; P = 0.002). The same percentage (0.6%) of patients traveled more than 2 h with at least 2 occupants in the vehicle within approximately 1 m of the patient after 2011 and before 2009. Immediately after therapy, a similar percentage of patients stayed in a nonprivate residence after 2011 (4%) and before 2009 (5%; P = 0.28). Of the 27 outpatients released within 30 min to nonprivate residences, 2 patients received 5.55-11.1 GBq (150-299 mCi) of 131I. Conclusion: This survey suggests that since publication of the Nuclear Regulatory Commission Regulatory Issue Summary 2011-01 on patient release after radioiodine therapy, there have been improvements in some radiation safety practices on release of outpatients, as well as improvements in patient compliance on travel and lodging.

Radioiodine Imaging for Differentiated Thyroid Cancer: Not All Radioiodine Images Are Performed Equally.

Background: Radioiodine scanning may help risk stratify patients with differentiated thyroid carcinoma (DTC) during initial and subsequent restaging. To maximize the information obtained from radioiodine scanning, image quality and interpretation should be optimized. However, not all radioiodine scans are performed equally. This illustrated article reviews seven techniques that may significantly improve the information obtained from a radioiodine scan in patients with DTC, which in turn may alter management such as showing regional or distant metastases that were otherwise unknown and/or help classify whether a metastasis is radioiodine avid. Summary: The first of the techniques is spot imaging of anatomical areas of interest using a gamma camera with a parallel-hole collimator. Spot images typically provide superior spatial resolution and enhanced lesion detection compared with whole-body scans using the same equipment. The second technique is spot imaging of the thyroid bed and neck with a pin-hole collimator, further improving spatial resolution. Two other techniques, delayed image acquisition and longer acquisition time, may clarify the nature of indeterminate foci of uptake or areas with negative initial findings. Delayed image acquisition may increase tumor-to-background ratio and thus improves lesion detectability. Longer acquisition times also increase contrast resolution between lesions and background activity, again increasing the detectability of malignant lesions. The fifth technique, adjustment of image brightness/contrast on film or on the computer screen, may reveal previously unobserved subtle differences in counts. The sixth technique, focus-specific history, comprises additional patient information that is specific to a focus of radioiodine uptake and elicited by the nuclear medicine physician or technologist. The goal is to help determine if the focus represents a metastasis or an artifact, which in turn decreases false positives and increases specificity. The seventh technique, single-photon emission computed tomography/computed tomography, improves contrast resolution and helps localize foci of uptake to anatomical structures. Conclusions: Technique is important to maximize information obtained from radioiodine scans in patients with DTC. With the greater usage and understanding of these seven techniques, physicians will significantly improve the information obtained from a radioiodine scan in patients with DTC, which in turn may alter management and potentially outcomes.

Conventional Radioiodine Therapy for Differentiated Thyroid Cancer.

This article presents an overview of the use of radioactive iodine (131-I) in the treatment of patients with differentiated thyroid cancer. Topics reviewed include definitions; staging; the 2 principal methods for selection of 131-I dosage; the indications for ablation, adjuvant treatment, and treatment; the recommendations for the use of 131-I contained in the guidelines of the American Thyroid Association and the Society of Nuclear Medicine and Molecular Imaging; the dosage recommendations and selection of dosage approach for 131-I by these organizations; the use of recombinant human thyrotropin for radioiodine ablation, adjuvant therapy, or treatment; and the MedStar Washington Hospital Center approach.

124I Positron Emission Tomography/Computed Tomography Versus Conventional Radioiodine Imaging in Differentiated Thyroid Cancer: A Review.

Background: Studies report a wide spectrum of 124I positron emission tomography (PET)/computed tomography (CT) sensitivity and specificity in the detection of differentiated thyroid cancer (DTC) lesions. This study reviews the lesion detection rate of pretherapy 124I PET/CT in different patient populations and further analyzes the factors necessary for a better detection on 124I PET/CT. Methods: A literature search was performed using multiple different databases (MEDLINE, EMBASE, Northern Lights, and handsearching) covering 1996 to April 2018. Two reviewers reviewed and extracted study data for 124I, 123I, and 131I scans in DTC. Results: This review includes 4 retrospective and 10 prospective studies in which 495 DTC patients underwent 124I and 131I imaging; no studies made comparisons with 123I. In the reports that compared 124I PET/CT with diagnostic 131I scans, there were a total of 72 patients in whom 120 lesions were detected on 124I imaging, whereas only 52 were detected on diagnostic 131I scans. In publications that compared 124I with post-therapy 131I scans in 266 patients, 410 lesions were detected with 124I PET, whereas 390 were detected on post-therapy 131I scans. Based on 124I PET/CT in six studies, TNM staging was revised in 15-21% of patients, and disease management was altered in 5-29% of patients. Conclusions:124I PET/CT is able to identify a greater number of foci compared with diagnostic 131I scans. 124I PET may have better detection compared with post-therapy 131I scans in patients who are 131I therapy naive, have less aggressive pathology, or do not have disseminated lung metastases. Additional metastatic lesion detection by 124I PET may have a significant clinical impact in the management of patients before 131I therapy in some patients.

Detection at Public Facilities of 131I in Patients Treated for Differentiated Thyroid Cancer: Frequency, Sites, Management by Security Agents, and Physician Documentation Recommended for Patients.

Patients treated with 131I may be identified at security checkpoints at various public facilities. The objective of this survey was to determine the frequency of detection, the spectrum of public facilities, the various methods of management of the situation by security agents, and the spectrum of physician documentation for patients regarding their 131I therapy. Methods: Data were tabulated from a Thyroid Cancer Survivors' Association, Inc., survey emailed to approximately 15,000 associates and available online from December 2013 to December 2014. Responses were tabulated from respondents who reported that they were 18 y old or older, had received at least 1 131I treatment for differentiated thyroid cancer, and were responding regarding their last 131I treatment. Results: Of 621 respondents, 595 reported an attempt to pass through a public facility security checkpoint. Of these 595 patients, approximately 10% (57) were identified as being radioactive. The facility reported by 43 respondents was an airport for 35% (15), border crossing for 33% (14), government building for 19% (8), shopping mall for 7% (3), train station for 5% (2), and steel recycling plant for 2% (1). The security agent's management of the situation reported by 47 respondents included questioning for 81% (38), allowing them to proceed without a change in travel plans for 57% (27), requesting documentation of the therapy for 55% (26), rescanning for 55% (26), calling a member of the treating team for validation for 17% (8), "strip" searching for 4% (2), detaining such that a change in travel plans was required for 6% (3), and prohibiting continued travel for 4% (2). The period of detainment reported by these 47 respondents was less than 30 min for 57% (27), 30 to less than 60 min for 21% (10), 1 to less than 1.5 h for 15% (7), 1.5 to less than 2 h for 2% (1), 2-4 h for 0% (0), and greater than 4 h for 4% (2). Data regarding physician documentation are presented. Conclusion: The detection of radioactivity at a variety of security checkpoints at public facilities after131I therapy occurred in approximately 10% of respondents. Travel inconvenience is not infrequent and may require alteration of travel plans. Physicians should take steps to ensure that patients not only have appropriate documentation of their 131I therapy with them but also have instructions regarding how security agents may verify their 131I therapy.

Improved Survival After Multimodal Approach with 131I Treatment in Patients with Bone Metastases Secondary to Differentiated Thyroid Cancer.

Background: The objective of this study was to evaluate the overall survival (OS) of radioiodine (131I) treatments alone or combined with non-131I treatments in patients with bone metastases (BM) of differentiated thyroid cancer (DTC). Methods: This was a retrospective study of patients who were evaluated between 2001 and 2018 at MedStar Washington Hospital Center and who had DTC, BM, and at least one 131I treatment after the diagnosis of BM. The OS was analyzed by Kaplan-Meier survival curves and was compared by log-rank test between two groups: patients who received 131I treatments alone and those who received treatments combining 131I with non-131I treatments (CombTx). Non-131I treatments include surgery, radiofrequency ablation, cryotherapy, arterial embolization, external beam radiation, Cyberknife, systemic targeted therapy, and anti-resorptive medication. Results: A total of 77 patients met the above criteria and were followed up to 41 years. Thirty percent (23/77) of patients received 131I treatment alone, and 70% (54/77) received CombTx. For 131I treatment alone, the median survival was 3.9 years, and the 1-, 2-, 3-, 5-, and 10-year OS rates were 86%, 81%, 61%, 35%, and 23%, respectively. For CombTx, the median survival was 7.7 years, and the 1-, 2-, 3-, 5-, and 10-year OS rates were 96%, 92%, 86%, 69%, and 30%, respectively. Patients who had undergone initial 131I therapy within six months post thyroidectomy demonstrated a better median survival after BM diagnosis than those whose initial 131I therapy was six months or more after thyroidectomy (6.5 vs. 0.5 years; p < 0.001). Patients who received external beam radiation therapy demonstrated a better median survival than those who did not (7.8 vs. 4.4 years; p = 0.016). Patients who received denosumab demonstrated a better median survival than those who did not (7.7 vs. 5.2 years; p = 0.03). Patients who were <55 years of age at the initial diagnosis of DTC or at the initial diagnosis of BM had a better median OS than those diagnosed at ≥55 years of age (both p = 0.01). In the multivariate analysis, only age at initial diagnosis of DTC and initial 131I therapy within six months post thyroidectomy, and multiple 131I treatments were independent prognostic factors. Conclusions: In patients with DTC with BM, 131I treatment in combination with one or more non-131I direct and systemic treatments was associated with a significant increase in OS compared with those patients who were treated by 131I treatment alone.

Brain Metastases From Differentiated Thyroid Carcinoma: Prevalence, Current Therapies, and Outcomes.

BACKGROUND AND OBJECTIVE: The brain is an unusual site for distant metastases of differentiated thyroid carcinoma (DTC). The aim of this study was to document the prevalence of brain metastases from DTC at our institutions and to analyze the current therapies and the outcomes of these patients. METHODS: We performed a retrospective chart review of patients with DTC and secondary neoplasia of the brain. RESULTS: From 2002 to 2016, 9514 cases of thyroid cancer were evaluated across our institutions and 24 patients met our inclusion criteria, corresponding to a prevalence of 0.3% of patients with DTC. Fourteen (58.3%) were female and 10 (41.7%) were male. Fifteen patients had papillary thyroid cancer (PTC) (62.5%). Brain metastases were diagnosed 0 to 37 years (mean ± SD, 10.6 ± 10.4 years) after the initial diagnosis of thyroid cancer. Patients undergoing surgery had a median survival time longer than those that did not undergo surgery (27.3 months vs 6.8 months; P = 0.15). Patients who underwent stereotactic radiosurgery (SRS) had a median survival time longer than those that did not receive SRS (52.5 months vs 6.7 months; P = 0.11). Twelve patients (50%) were treated with tyrosine kinase inhibitors (TKIs), and they had a better survival than those who have not used a TKI (median survival time, 27.2 months vs 4.7 months; P < 0.05). CONCLUSION: The prevalence of brain metastases of DTC in our institutions was 0.3% over 15 years. The median survival time after diagnosis of brain metastases was 19 months. In our study population, the use of TKI improved the survival rates.

Controversies, Consensus, and Collaboration in the Use of 131I Therapy in Differentiated Thyroid Cancer: A Joint Statement from the American Thyroid Association, the European Association of Nuclear Medicine, the Society of Nuclear Medicine and Molecular Imaging, and the European Thyroid Association.

BACKGROUND: Publication of the 2015 American Thyroid Association (ATA) management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer was met with disagreement by the extended nuclear medicine community with regard to some of the recommendations related to the diagnostic and therapeutic use of radioiodine (131I). Because of these concerns, the European Association of Nuclear Medicine and the Society of Nuclear Medicine and Molecular Imaging declined to endorse the ATA guidelines. As a result of these differences in opinion, patients and clinicians risk receiving conflicting advice with regard to several key thyroid cancer management issues. SUMMARY: To address some of the differences in opinion and controversies associated with the therapeutic uses of 131I in differentiated thyroid cancer constructively, the ATA, the European Association of Nuclear Medicine, the Society of Nuclear Medicine and Molecular Imaging, and the European Thyroid Association each sent senior leadership and subject-matter experts to a two-day interactive meeting. The goals of this first meeting were to (i) formalize the dialogue and activities between the four societies; (ii) discuss indications for 131I adjuvant treatment; (iii) define the optimal prescribed activity of 131I for adjuvant treatment; and (iv) clarify the definition and classification of 131I-refractory thyroid cancer. CONCLUSION: By fostering an open, productive, and evidence-based discussion, the Martinique meeting restored trust, confidence, and a sense of collegiality between individuals and organizations that are committed to optimal thyroid disease management. The result of this first meeting is a set of nine principles (The Martinique Principles) that (i) describe a commitment to proactive, purposeful, and inclusive interdisciplinary cooperation; (ii) define the goals of 131I therapy as remnant ablation, adjuvant treatment, or treatment of known disease; (iii) describe the importance of evaluating postoperative disease status and multiple other factors beyond clinicopathologic staging in 131I therapy decision making; (iv) recognize that the optimal administered activity of 131I adjuvant treatment cannot be definitely determined from the published literature; and (v) acknowledge that current definitions of 131I-refractory disease are suboptimal and do not represent definitive criteria to mandate whether 131I therapy should be recommended.