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.

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.

Validation of a Simple Thyroid Cancer Dosimetry Model Based on the Fractional Whole-Body Retention at 48 Hours Post-Administration of (131)I.

BACKGROUND: Standard dosimetric methods to determine the maximum tolerated activity (MTA) of (131)I for the treatment of metastatic, well-differentiated thyroid cancer (DTC) are time-consuming and require complex analysis. As a result, reliable, accurate, and simplified methods are desirable. The objective of this study was to evaluate the validity of a simple regression dosimetry model. METHOD: Previously, the authors reported a bi-exponential model for estimating the MTA of (131)I for the treatment of metastatic DTC based on a limit of 2 Gy to the blood. This model uses the patient's body surface area (BSA) along with the fractional whole-body retention (WBR) at 48 hours following oral administration of a diagnostic dosage of (131)I. A bi-exponential regression model was developed between the MTA normalized to the patient's BSA and the percent retention value at the 48-hour time point (R): MTA (GBq)/BSA (m(2)) = (13.91 · e(-0.0387R) + 42.33 · e(-0.8522R)). In this study, the same model was applied to a different set of adult patients referred for dosimetry and possible (131)I treatment of DTC under conditions of thyroid hormone withdrawal or recombinant human thyrotropin (rhTSH) stimulation. All patients (n = 170; 96 female) referred to the authors' clinic for dosimetry and possible (131)I treatment for metastatic DTC during the collection period were included in this study, apart from those undergoing renal dialysis. The MTA predicted (MTAp) using the model described above was compared to the measured MTA (MTAm), with statistical analysis performed using ProStat v4.5. RESULTS: In this group, the MTAm ranged from 2.3 to 41.1 GBq. The linear correlation between the MTAp and MTAm was excellent (r = 0.96), with an average deviation of only ± 1.2%. However, to avoid overdosing a patient on the basis of the MTAp, a weighting factor (<1.0) should be applied (e.g., using a value of 0.7 would result in only one patient receiving a prescribed activity of (131)I that exceeded the MTAm [<3%]). CONCLUSIONS: The % 48-hour WBR as determined by the bi-exponential function noted herein with reasonable restrictions has been validated as a reliable simplified dosimetry model.

Do negative 124I pretherapy positron emission tomography scans in patients with elevated serum thyroglobulin levels predict negative 131I posttherapy scans?

BACKGROUND: The management of patients with differentiated thyroid cancer (DTC) who have elevated serum thyroglobulin (Tg) levels and negative (131)I or (123)I scans is problematic, and the decision regarding whether or not to administer (131)I therapy (a "blind" therapy) is also problematic. While (124)I positron emission tomography (PET) imaging has been shown to detect more foci of residual thyroid tissue and/or metastases secondary to DTC than planar (131)I images, the utility of a negative (124)I PET scan in deciding whether or not to consider performing blind (131)I therapy is unknown. The objective of this study was to determine whether a negative (124)I pretherapy PET scan in patients with elevated serum Tg levels and negative (131)I or (123)I scans predicts a negative (131)I posttherapy scan. METHODS: Several prospective studies have been performed to compare the radiopharmacokinetics of (124)I PET versus (131)I planar imaging in patients who 1) had histologically proven DTC, 2) were suspected to have metastatic DTC (e.g., elevated Tg, positive recent fine-needle aspiration cytology, suspicious enlarging mass), and 3) had (131)I planar and (124)I PET imaging performed. Using these criteria, we retrospectively identified patients who had an elevated Tg, a negative diagnostic (131)I/(123)I scan, a negative diagnostic (124)I PET scan, therapy with (131)I, a post-therapy (131)I scan, and a prior (131)I therapy with a subsequent positive post-(131)I therapy scan. For each scan, two readers categorized every focus of (131)I and (124)I uptake as positive for thyroid tissue/metastases or physiological. RESULTS: Twelve patients met the above criteria. Ten of these 12 patients (83%) had positive foci on (131)I posttherapy scan. CONCLUSION: In our selected patient population, (131)I posttherapy scans are frequently positive in patients with elevated serum Tg levels, a negative diagnostic (131)I or (123)I scan, and a negative (124)I PET scan. Thus, for a patient with elevated serum Tg level, negative diagnostic (131)I planar scan, and a prior post-(131)I therapy scan that was positive, a negative (124)I PET scan will have a low predictive value for a negative post-(131)I therapy scan and should not be used to exclude the option of blind (131)I therapy.

Recombinant human thyroid-stimulating hormone versus thyroid hormone withdrawal in the identification of metastasis in differentiated thyroid cancer with 131I planar whole-body imaging and 124I PET.

UNLABELLED: Various studies have compared the detection of functioning residual thyroid tissue after thyroidectomy using radioiodine whole-body (WB) imaging following preparation of patients with injections of recombinant human thyroid-stimulating hormone (rhTSH) and thyroid hormone withdrawal (THW). However, metastases may have radiopharmacokinetics different from normal thyroid tissue. The objective of this study was to evaluate these 2 methods of patient preparation for the detection of metastases from differentiated thyroid cancer (DTC) using (131)I WB imaging and (124)I PET. METHODS: A prospective study approved by the institutional review board was conducted at Washington Hospital Center from 2006 to 2010 recruiting patients who had DTC, were suspected of having metastasis from DTC (e.g., elevated thyroglobulin level without thyroglobulin antibodies, positive results on recent fine-needle aspiration, suspected enlarging mass, and abnormal findings suggesting metastasis on a diagnostic study) and were referred for (131)I WB dosimetry. All patients subsequently underwent both (131)I WB imaging and (124)I PET performed using the same preparation. All foci of uptake identified on these scans were categorized in a masked manner by consensus of 2 physicians in the following manner: 1, definite physiologic uptake or artifact; 2, most likely physiologic uptake or artifact; 3, indeterminate; 4, most likely locoregional metastases in the neck bed; 5, most likely distant metastases; or 6, definite distant metastases. Foci categorized as 4, 5, and 6 were considered positive for functioning metastases. RESULTS: Of 40 patients evaluated, 24 patients were prepared with rhTSH and 16 with THW. No statistical difference was noted between the 2 groups for any of the parameters evaluated, including serum thyroglobulin. The percentages of patients with positive foci detected on the rhTSH (131)I and THW (131)I WB scans were 4% (1/24) and 63% (10/16), respectively (P < 0.02). The number of foci detected on the rhTSH (131)I and THW (131)I WB scans were 2 and 58, respectively (P < 0.05). When (124)I PET was used for imaging, the percentages of patients with foci detected on the rhTSH and THW scans were 29% (7/24) and 63% (10/16), respectively (P < 0.03). The number of foci detected on the rhTSH and THW scans were 17 and 117, respectively (P < 0.03). CONCLUSION: Significantly more foci of metastases of DTC may be identified in patients prepared with THW than in patients prepared with rhTSH.

(124)I positron emission tomography versus (131)I 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 patient's 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 patient's 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.

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.

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.

Doxorubicin-induced cardiac toxicity and cardiac rest gated blood pool imaging.

Anthracyclines are one of the most commonly used and potent chemotherapeutic agents. Doxorubicin (Adriamycin) is one common anthracycline used to treat many solid tumors including breast, sarcomas, gynecologic and hematological malignancies, such as leukemias and lymphomas. However, its use is often limited due to dose-dependent cardiotoxicity. As a result, patients receiving doxorubicin should have close monitoring of their left ventricular function. The gated cardiac blood pool (GBP) study is one of the most accurate and reproducible methods of assessing left ventricular function. This report presents an overview of (1) the incidence, clinical course, mechanisms, pathology, prevention, and monitoring of doxorubicin-induced cardiotoxicity (DIC), (2) the use of GBP studies in monitoring for DIC, and (3) 2 algorithms for the use of GBP studies in monitoring for DIC. This report concludes with a proposed algorithm for the use of GBP studies in DIC. With an understanding of DIC, GBP studies, and various algorithms, the interpreting physician may help the oncologist identify DIC earlier, more accurately, and before it becomes clinically apparent.