Frank Atkins

Dosimetrically determined doses of radioiodine for the treatment of metastatic thyroid carcinoma.

In the absence of definitive studies relating radioiodine dose to outcomes, selection of a dose of radioiodine to treat metastatic thyroid carcinoma is problematic, and several approaches have been used. These include empiric fixed doses and doses used on dosimetric approaches specific for each patient. This paper is a review of the rationale and technique for dosimetrically-determined doses of radioiodine for the treatment of metastatic thyroid carcinoma. This review (1) discusses the alternatives for selection of a dose, (2) discusses the two major approaches for determining radioiodine doses dosimetrically, (3) briefly reviews several modifications of these approaches, (4) reviews the literature regarding the results, (5) discusses the side effects of these different approaches, and (6) concludes with recommendations for patient management and future research. This review does not address use of dosimetrically-determined doses of radioiodine for the initial ablation of thyroid tissue postoperatively.

124I Positron Emission Tomography Versus 131I Planar Imaging in the Identification of Residual Thyroid Tissue and/or Metastasis in Patients Who Have Well-Differentiated Thyroid Cancer

BACKGROUND AND OBJECTIVE (124)I emits a positron and can be imaged with a positron emission tomography (PET) scanner. The objective of this study was to compare the ability of diagnostic (124)I PET images versus (131)I planar whole-body imaging in detecting residual thyroid tissue and/or metastatic well-differentiated thyroid cancer (WDTC). METHODS Patients were recruited prospectively for this study who (i) had WDTC, (ii) were suspected of having metastatic WDTC, and (iii) were referred for (131)I whole-body dosimetry. The prescribed activity was 1-2 mCi (37-74 MBq) and 1.7 mCi (62.9 MBq) for (131)I and (124)I, respectively. For each image, one blinded reader (D.V.N.) categorized every focus of (131)I and (124)I radioiodine uptake as 1 = definite physiological uptake/artifact, 2 = most likely physiological uptake/artifact, 3 = indeterminate, 4 = residual thyroid tissue/metastases in the neck/bed, 5 = most likely metastases, or 6 = definite metastases. Foci categorized as 4, 5, or 6 were considered positive. When available, foci categorized as 4, 5, or 6 were correlated with other diagnostic studies. RESULTS Of the 25 patients, 8 patients (32%) had more positive foci on (124)I images than on (131)I, of which 3 patients to date have had metastases confirmed in one or more of the additional positive (124)I foci. (124)I demonstrated the same number of foci as on (131)I in 16 patients (14 with no positive foci, and 2 with two positive and five positive foci each). One patient had one additional positive focus on (131)I not seen on (124)I, which has not yet been confirmed as a metastasis. A total of 97 positive foci were identified on either (124)I or (131)I. (124)I identified 49 positive foci not seen with (131)I, and (131)I identified one positive focus not seen with (124)I. CONCLUSION Relative to (131)I planar whole-body imaging, (124)I PET identified as many as 50% more foci of radioiodine uptake suggestive of additional residual thyroid tissue and/or metastases in as many as 32% more patients who had WDTC.

The Utility of Radioiodine Scans Prior to Iodine 131 Ablation in Patients with Well-Differentiated Thyroid Cancer

BACKGROUND The utility of radioiodine (RAI) scans prior to (131)I ablation is controversial. The objective of this study was to evaluate the utility of RAI scans prior to (131)I ablation in patient with well-differentiated thyroid cancer. METHOD All RAI scans performed prior to (131)I ablation from July 2000 to November 2006 at Washington Hospital Center were reviewed retrospectively. Patients were excluded who were suspected of having 1) loco-regional disease, 2) distant metastases, and/or 3) physiological uptake that might alter management prior to the pre-ablation RAI scans. RAI scans were performed either 24 hours after dosing with 37-148 MBq of (123)I or 48 hours after dosing with 37-148 MBq of (131)I with imaging of the whole body, the thyroid bed/neck with a pinhole collimator, and the neck and chest with a parallel-hole collimator. One reviewer blindly evaluated each set of scans using six criteria, and for the purpose of this study, the thresholds for each criterion for which the patients management may have been altered prior to (131)I ablation are noted in parentheses: 1) the number of foci of RAI uptake in thyroid bed/neck (0 or > or =6), 2) the location(s) of these foci in the thyroid bed/neck (outside the thyroid bed), 3) the size of the largest foci in thyroid bed/neck (> or =1 lobe), 4) the percent uptake in the thyroid bed/neck (> or =15%), 5) uptake suggestive of distant metastases, and 6) significant altered biodistribution (e.g., any breast, marked salivary gland, or marked gastrointestinal uptake). RESULTS Of 355 sets of scans reviewed, 53% of patients had findings on the RAI scans that might have altered the patients management prior to their (131)I ablation. The data grouped by the criteria noted above were 1) 12% with six or more foci suggesting local metastases and 6% (22) with no focal uptake, 2) 14% with suggestion of lymph node metastases, 3) 1.1% with at least one focus > or =1 lobe, 4) 8% with > or =15% uptake, 5) 4% with distant metastases, 6) 16% demonstrating altered distribution with 6% breast, 3% salivary, 10% GI, and 0.3% urinary bladder. CONCLUSION Pre-ablation RAI scans demonstrate a significant number of findings that may alter the management of patients with well-differentiated thyroid cancer prior to (131)I ablation.

Efficacy of dosimetric versus empiric prescribed activity of 131I for therapy of differentiated thyroid cancer.

Abstract Background: The optimal management of high-risk patients with differentiated thyroid cancer (DTC) consists of thyroidectomy followed by radioiodine (131I) therapy. The prescribed activity of 131I can be determined using two approaches: 1) empiric prescribed activity of 131I (E-Rx); and 2) dosimetry-based prescribed activity of 131I (D-Rx). Aim: The aim of the study was to compare the relative treatment efficacy and side effects of D-Rx vs. E-Rx. Methods: A retrospective analysis was performed of patients with distant metastases and/or locoregionally advanced radioiodine-avid DTC who were treated with either D-Rx or E-Rx. Response to treatment was based on RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 criteria. Results: The study group consisted of 87 patients followed for 51 ± 35 months, of whom 43 were treated with D-Rx and 44 with E-Rx. Multivariate analysis, controlling for age, gender, and status of metastases revealed that the D-Rx group tended to be 70% less likely to progress (odds ratio, 0.29; 95% confidence interval, 0.087–1.02; P = 0.052) and more likely to obtain complete response (CR) compared to the E-Rx group (odds ratio, 8.2; 95% confidence interval, 1.2–53.5; P = 0.029). There was an association in the D-Rx group between the observed CR and percentage of maximum tolerable activity given as a first treatment of 131I (P = 0.030). The advantage of D-Rx was specifically apparent in the locoregionally advanced group because CR was significantly higher in D-Rx vs. E-Rx in this group of patients (35.7 vs. 3.3%; P = 0.009). The rates of partial response, stable disease, and progression-free survival, as well as the frequency of side effects, were not significantly different between the two groups. Conclusion: Higher efficacy of D-Rx with a similar safety profile compared to E-Rx supports the rationale for employing individually prescribed activity in high-risk patients with DTC.

Utility of the Radioiodine Whole-Body Retention at 48 Hours for Modifying Empiric Activity of 131-Iodine for the Treatment of Metastatic Well-Differentiated Thyroid Carcinoma

BACKGROUND Dosimetry has been used to help identify when empiric dosages of 131-I treatment for suspected metastatic well-differentiated thyroid carcinoma (WDTC) may be increased or should be decreased, but dosimetry is complex, and easier approaches would be useful. The three objectives of this study were to assess the utility of the percent whole-body retention of 131-I at 48 hours (%WBR(48hr)) in identifying patients with WDTC in whom the therapeutic empiric prescribed activity of 131-I might be increased/decreased, to evaluate the thresholds proposed by Sisson et al. in 2003 for increasing or decreasing activity, and to determine the relationship between %WBR(48hr) and maximum tolerated activity (MTA). METHOD A retrospective review was conducted of patients who had WDTC, total thyroidectomy, suspected metastatic disease, thyroid hormone withdrawal, and 131-I dosimetry. The %WBR(48hr) was determined based on the Benua-Leeper dosimetry protocol, and the four thresholds and recommendations of Sisson et al., 2003 for the use of %WBR(48hr) were evaluated relative to an empiric activity (EA) of 7.4 GBq of 131-I. A biexponential equation was determined from the %WBR(48hr) data. RESULTS Of 142 patients, 47 patients had a %WBR(48hr) of <9%, and all could have received more than the EA of 7.4 GBq with an average of 21.0 GBq (incremental range of 6.8-23.2 GBq). Ten patients had a %WBR(48hr) < or = 5%, and all could have had their EA of 7.4 GBq safely increased by at least 250%. Conversely, if the %WBR(48hr) was >24.8%, then 7 of 14 of these patients would have exceeded the MTA by 0.37-3.18 GBq with an EA of 7.4 GBq. Finally, for patients with a %WBR(48hr) > 40%, five of six patients would have exceeded the MTA by 0.85-3.18 GBq. A biexponential regression equation is presented. CONCLUSION We conclude that, with respect to the treatment of metastatic epithelial cell thyroid cancer, the %WBR(48hr) of 131-I helps identify those patients in whom the empiric therapeutic prescribed activity of 131-I may be increased or should be decreased so as not to exceed the MTA and that Sisson et al.s thresholds published in 2003 are applicable. We favor a biexponential regression model using the %WBR(48hr) and a lower limit threshold as a potentially useful method for determining how much an empiric therapeutic prescribed activity of 131-I can be increased or decreased.

Utility of PET/Neck MRI Digital Fusion Images in the Management of Recurrent or Persistent Thyroid Cancer

BACKGROUND Approximately 30% of thyroid cancer patients present with reappearing disease within 40 years of initial diagnosis. Hence, sensitive postsurgical monitoring techniques are imperative to successful long-term care. The objective of this study was to assess the added clinical utility of a combined positron emission tomography/magnetic resonance imaging (PET/MRI) of the neck in conjunction with standard imaging in the detection of recurrent thyroid carcinoma. We define standard imaging as a neck sonogram, 131I scan, computed tomography, and MRI. METHODS This study included 34 patients treated for thyroid cancer at Washington Hospital Center. All patients had previously undergone near-total or total thyroidectomy, standard follow-up imaging studies, and laboratory studies. Twenty-nine of thirty-four patients had received at least one 131I treatment prior to the study. Each patient received a PET and MRI scan, and these images were subsequently digitally fused. RESULTS Individually and blinded, four endocrinologists retrospectively reviewed all information in patient charts prior to PET and PET/MRI coregistration. A clinical assessment and treatment plan were devised with these data. Following the initial assessment, the endocrinologists were provided results from the PET and PET/MRI fusion studies and asked to make a revised assessment and treatment plan. For each patient, the physicians categorized PET/MRI fusion results as providing new information that altered the initial treatment plan, providing new information that confirmed the initial treatment plan, or providing no additional information. On average, PET/MRI coregistration provided additional information that altered the treatment plan in 46% of the cases, provided additional information that confirmed the treatment plan in 36% of cases, and did not provide any additional information in 18% of cases. CONCLUSION The combination of structural and functional data that PET/neck MRI fusion offers provided further information in an overwhelming majority of thyroid cancer patients in this study. Thus PET/MRI can be a useful tool in surgical planning, radioactive iodine therapy decisions, and determining the level of follow-up necessary for each patient.

Salivary Gland Protection with Sialagogues: A Case Study

BACKGROUND To decrease the severity and frequency of radiation sialoadenitis, postponement of the use of sialagogues has been proposed for the first 24 hours after (131)I treatment for well-differentiated thyroid cancer. One proposed mechanism is that sialagogues increased salivation and salivary blood flow resulting in greater radioiodine uptake in the salivary glands-a rebound effect. This case study demonstrates no rebound effect. METHODS A 33-year-old woman with well-differentiated thyroid cancer desired to know whether she would have a rebound effect if she used sialagogues during the 24-hour period after her (131)I treatment. Salivary images of the parotid glands were initiated 2 hours after the administration of (131)I for her whole body scan. Lemon juice was administered. Background corrected time-activity curves were obtained for both parotid glands. The potential reduction in radiation absorbed dose to the parotid glands secondary to the administration of lemon juice was calculated. RESULTS The time-activity curves demonstrated that the (131)I in the right and left parotid glands decreased rapidly after lemon juice by 87% and 83%, respectively, with return to pre-lemon juice levels by 30 and 13 minutes in the right and left parotid glands, respectively. However, at no time during the 1 hour of imaging did the uptake in either parotid gland significantly exceed the pre-lemon juice levels of activity. The potential reduction of radiation absorbed dose to the parotid glands secondary to the use of lemon juice ranged from as much as 30% to 67%. CONCLUSION This case study demonstrates 1) an approach to assess whether an individual patient will have increased or decreased radioiodine uptake in the salivary glands after administration of sialagogues without the administration of any additional radioiodine, 2) a decrease of radioiodine uptake in the salivary glands after lemon juice without a rebound effect, and 3) a potential reduction of radiation absorbed dose with administration of sialagogues.

Radiopharmacokinetics of Radioiodine in the Parotid Glands After the Administration of Lemon Juice

BACKGROUND The ability of sialagogues to increase or decrease radiation induced-sialoadenitis and/or xerostomia after therapeutic administration of ¹³¹I is controversial. To evaluate this we measured the radiopharmacokinetics of ¹²³I in the parotid glands (PGs) after its administration of lemon juice (LJ). METHODS A retrospective review was performed on all patients who had a salivary gland scan performed before ¹³¹I therapy between July 2008 and April 2009 at the Washington Hospital Center. Two hours after ¹²³I was given orally, dynamic scintigraphy was initiated. Five milliliters of LJ was given 5 minutes later. Then, the patient was imaged for 1 hour (phase 1) at which point the sequence was repeated (phase 2). Twenty-three patients were studied. For each PG, the presence or absence of uptake was assessed, and based on background corrected counts, the mean, range, and standard deviation were determined for multiple radiopharmacokinetic parameters such as (i) percent radioiodine washout, (ii) time from LJ administration to re-accumulation of radioiodine to pre-LJ activity, and (iii) percent reduction in radiation absorbed dose to the PGs if LJ had been re-administered at the time the radioiodine activity re-accumulated to the pre-LJ activity. RESULTS The mean  ± one standard deviation and range for percent washout were 84%  ± 18% (35%-100%) and 83%  ±  21% (37%-100%) in phase 1 and 2, respectively. The times from LJ to re-accumulation of the radioiodine to the pre-LJ activity were 21  ± 10 minutes (4-45 minutes) and 40  ± 14 minutes (12-62 minutes) for phase 1 and 2, respectively. The estimated percent reduction in radiation absorbed dose to the PGs following the first and second administration of LJ was 37%  ± 14% (13%-93%) and 47% ± 16% (21%-97%), respectively. CONCLUSIONS The washout of radioiodine from the PGs is rapid but transient. Early repeat administration may result in continued and cumulative reduction of radiation absorbed dose in the PGs.

Recombinant human thyroid-stimulating hormone versus thyroid hormone withdrawal in 124I PET/CT-based dosimetry for 131I therapy of metastatic differentiated thyroid cancer

Patients with metastatic differentiated thyroid cancer (DTC) may be prepared using either thyroid-stimulating hormone withdrawal (THW) or recombinant human thyroid-stimulating hormone (rhTSH) injections before 131I administration for treatment. The objective of this study was to compare the absorbed dose to the critical organs and tumors determined by 124I PET/CT–based dosimetry for 131I therapy of metastatic DTC when the same patient was prepared with and imaged after both THW and rhTSH injections. Methods: Four DTC patients at MedStar Washington Hospital Center were first prepared using the rhTSH method and imaged by 124I PET/CT at 2, 24, 48, 72, and 96 h after administration of approximately 30–63 MBq of 124I. After 5–8 wk, the same patients were prepared using the THW method and imaged as before. The 124I PET/CT images acquired as part of a prospective study were used to perform retrospective dosimetric calculations for 131I therapy for the normal organs with the dosimetry package 3D-RD. The absorbed doses from 131I for the lungs, liver, heart, kidneys, and bone marrow were obtained for each study (rhTSH and THW). Twenty-two lesions in 3 patients were identified. The contours were drawn on each PET image of each study. Time-integrated activity coefficients were calculated and used as input in OLINDA/EXM sphere dose calculator to obtain the absorbed dose to tumors. Results: The THW-to-rhTSH organ absorbed dose ratio averaged over 5 organs for the first 3 patients was 1.5, 2.5, and 0.64, respectively, and averaged over 3 organs for the fourth patient was 1.1. The absorbed dose per unit administered activity to the bone marrow was 0.13, 0.086, 0.33, and 0.068 mGy/MBq after rhTSH and 0.11, 0.14, 0.22, and 0.080 mGy/MBq after THW for each patient, respectively. With the exception of 3 lesions of 1 patient, the absorbed dose per unit administered activity of 131I was higher in the THW study than in the rhTSH study. The ratio of the average tumor absorbed dose after stimulation by THW compared with stimulation by rhTSH injections was 3.9, 27, and 1.4 for patient 1, patient 2, and patient 3, respectively. The ratio of mean tumor to bone marrow absorbed dose per unit administered activity of 131I, after THW and rhTSH, was 232 and 62 (patient 1), 12 and 0.78 (patient 2), and 22 and 11 (patient 3), respectively. Conclusion: The results suggest a high patient variability in the overall absorbed dose to the normal organs per MBq of 131I administered, between the 2 TSH stimulation methods. The tumor–to–dose-limiting-organ (bone marrow) absorbed dose ratio, that is, the therapeutic index, was higher in the THW-aided than rhTSH-aided administrations. Additional comparison for tumor and normal organ absorbed dose in patients prepared using both methods is needed before definitive conclusions may be drawn regarding rhTSH versus THW patient preparation methods for 131I therapy of metastatic DTC.

Pediatric differentiated thyroid cancer: can the prescribed activity of I-131 be increased?

The two primary methods for selecting the prescribed activity of I-131 for the therapy of locoregional and/or metastatic differentiated thyroid carcinoma are empiric and dosimetry. Empiric is defined by Webster’s New World Dictionary as “. . . relying on or based on practical experience without reference to scientific principles.” Dosimetry is based on the calculation of the radiation absorbed dose to the tumor to maximize the likelihood of control of that tumor (1, 2) and/or the calculation of the maximum prescribed activity that can be administered to limit damage of normal tissue to acceptable levels (3–5). Because these calculations are based on one or both of the fundamental principles of radiation therapy planning, multiple authorsbelievethatdosimetricallydeterminedprescribedac