Radioiodine Therapy For Thyroid Cancer Research Articles

Radioiodine therapy for thyroid cancer in the era of risk stratification and alternative targeted therapies.

Differentiated thyroid cancers are typically iodine-avid and can be effectively treated with radioiodine. In most patients, radioiodine treatment is done for ablation of residual tissue, and in these cases the focus should be on using the minimum effective dose. Adjuvant therapy can be done to reduce the risk of recurrence, but optimal patient selection and dose are unclear. Patients with advanced disease benefit most from treatment with the maximum-tolerated dose. Recent research has focused on better patient selection and reduced radioiodine doses for remnant ablation. There are emerging targeted therapeutic approaches in patients who are appropriately shown to have iodine-refractory disease, with 1 drug approved by the Food and Drug Administration. Numerous trials are ongoing to assess targeted therapeutics alone or in combination with radioiodine.

A randomized controlled trial for the use of Thymus Honey in decreasing Salivary Gland Damage following Radioiodine Therapy for Thyroid cancer: research protocol

To test the effectiveness of thymus honey as a complementary intervention for decreasing the salivary gland damage due to Radioiodine ((131) I) therapy. Radioiodine is the treatment of choice in people diagnosed with thyroid cancer following total thyroidectomy. Although its value has been acknowledged in eradicating remnant thyroid tissue and treating residual disease in patients with visible, inoperable, iodine-avid metastases, it has been associated with various salivary gland side effects. This is a randomized controlled trial with a 2 × 3 mixed between-within subjects design. In total, 120 participants of postsurgical differentiated thyroid cancer, who will be referred to this centre for (131) I therapy to ablate the remnant thyroid tissue or to treat metastatic tumour, will be prospectively studied under varying regimens of lemon candy (standard treatment) and thymus honey mouthwashes (experimental intervention). Patients will be randomized in four equally numbered groups based on the assumptions and hypothesis of the study. The recruiting process will be informed by predefined inclusion and exclusion criteria. Mixed statistical modelling will be adopted taking into consideration between and within subjects' effects and repeated measures. The recommended intervention protocol is expected to improve the comprehensive management of salivary gland-related side effects induced by the radioiodine treatment in people diagnosed with thyroid cancer. Through the methodological approach chosen, the ideal intervention protocol in terms of the time to initiate the intervention and the frequency of the intervention to acquire optimal results in minimizing salivary glands damage will be tested.

The evaluation of urine activity and external dose rate from patients receiving radioiodine therapy for thyroid cancer

The aim of this study was to determine the external dose rate of iodine retention as a function of time in the bodies of thyroid cancer patients during their isolation period in the hospital. Urine samples were collected at 6th, 12th, 18th, 24th h and 2nd, 3rd, 4th, 5th d from 83 patients after oral administration of (131)I and counted. The external dose rates were also simultaneously determined at the same time points. Then, it was expressed as retained radioiodine body activity versus dose rate. Effective half life calculated from urine sample measurements was found as 18.4±1.8 h within the first 24 h and 64±2.7 h between 48 and 120 h. According to this results, the external dose rate (<20 µSv h(-1)), which patients could be discharged, was achieved after 48 h for 3700 and 5550 MBq, and after 72 h for 7400 MBq of (131)I treatments.

Methods and Clinical Efficacy of Dosimetry-Based Treatment in Radioiodine Therapy of Thyroid Cancer

Methods and Clinical Efficacy of Dosimetry-Based Treatment in Radioiodine Therapy of Thyroid Cancer

A rare case of laryngotracheal chondrosarcoma in a patient with past history of radioiodine therapy for thyroid cancer

Tracheal chondrosarcoma is a rare malignant mesenchymal tumor and there are less than 15 reports in the literature. We report a rare case of laryngotracheal chondrosarcoma in a 74-year-old man. He gave a history of radioiodine therapy for thyroid papillary carcinoma about 24 years ago. Diagnostic steps, histological presentation, and therapy are described in detail.

일부 대학병원 방사성옥소 치료병실의 안전관리로 본 실태 고찰

방사성옥소를 이용한 갑상선 암의 치료는 지난 수 십년 동안 사용되어 왔으며 많은 치료효과를 보이면서 앞으로 지속적으로 사용되어 질 전망이고 현재 우리나라의 옥소치료병실 수는 2010년 기준 124개의 치료병실이 운영되고 있으나 아직도 부족한 실정이다. 그래서 많은 병원들이 치료병실을 개설하고 있으나 중요한건 치료병실의 수적 증가보단 현재 치료병실의 올바른 관리가 선행되어야 한다는 것이다. 따라서 병실증설에 대한 논의에 앞서 현재 적용되고 있는 치료병실의 안전관리 기준과 일부 대학병원에서 기준으로 삼고 있는 안전관리기준을 조사하여 얼마나 잘 지켜지고 있는지, 치료병실의 이용에 따른 전반적인 안전관리실태여부를 조사하여 고찰 하였다. Using Radioiodine therapy of thyroid cancer in the past have been used for decades as many look forward to continuing treatment be used, and the current outlook of in korea 2010 based on the number of Iodine therapy room is operated by 124, but still is lacking. So many hospitals opened their therapy room, but importantly, increasing number of treatment rather than therapy room current treatment is that it must be preceded by the proper administration of the. Therefore therapy room expansion, discussions about before now being applied therapy room safety management standards, and a part university hospital based safety management standards by examining how well kept and that the therapy room to the use of the overall safety management research on the actual condition were discussed.

The pituitary tumor transforming gene in thyroid cancer.

The pituitary tumor transforming gene (PTTG) is a multifunctional proto-oncogene that is over-expressed in various tumors including thyroid carcinomas, where it is a prognostic indicator of tumor recurrence. PTTG has potent transforming capabilities in vitro and in vivo, and many studies have investigated the potential mechanisms by which PTTG contributes to tumorigenesis. As the human securin, PTTG is involved in critical mechanisms of cell cycle regulation, whereby aberrant expression induces aneuploidy. PTTG may further contribute to tumorigenesis through its role in DNA damage response pathways and via complex interactions with hormones and growth factors. Furthermore, PTTG over-expression negatively impacts upon the efficacy of radioiodine therapy in thyroid cancer, through repression of expression and function of the sodium iodide symporter. Given its various roles at all disease stages, PTTG appears to be an important oncogene in thyroid cancer. This review discusses the current knowledge of PTTG with particular focus on its role in thyroid cancer.

The Utility of I-123 Pretherapy Scan in I-131 Radioiodine Therapy for Thyroid Cancer

There is a growing belief that a pretherapy scan yields little or no additional information that would impact on radioiodine ablation dosing. In addition, there is some concern regarding on the stunning effect of a pretherapy scan, especially when I-131 radioisotope is used for imaging. We hypothesized that a pretherapy scan provides invaluable information on the amount of thyroid remnant, sometimes indicating the need for two-step I-131 ablation. It may also detect unsuspected local lymph node involvement or distant metastases, indicating the requirement for a higher I-131 dose after thyroidectomy. The aim of this study was to evaluate how effective pretherapy scans are for guiding I-131 therapy planning and augmenting information provided in the pathology reports for thyroidectomy specimens. We reviewed 122 patients who underwent I-123 pretherapy scan and I-131 radioablation at Yale New Haven Hospital between January 2006 and August 2007. The percentage of neck uptake and whole-body images were acquired 24 hours following the administration of 51.8 MBq (1.4 mCi) of I-123 NaI. A 24-hour uptake of >3% was used as the cutoff to determine whether there was a greater than desired quantity of thyroid remnant, which would require a two-step treatment protocol. Furthermore, attention was paid to identifying cervical lymph nodes, which may not have presented themselves in the euthyroid state at the time of thyroidectomy. Additional clinical information provided by pretherapy scans was computed as percentages with 95% confidence intervals by using adjusted Wald intervals. Overall, the pretherapy scans provided additional critical information in 25% of the cases (31/122; 95% CI: 18%-34%). For cases demonstrating >3% uptake with midline lymph nodes, the pretherapy scan provided additional information in 50% of the cases (8/16; 95% CI: 28%-72%). Our study demonstrated that I-123 pretherapy scans provide valuable information with regard to unsuspected lymph nodes or distant metastases, indicating the requirement for a significantly higher I-131 dose, and unexpected large thyroid remnants, suggesting the need for two-step ablation. We should take advantage of stimulated pretherapy scans and adjust the treatment dosing accordingly.

Microarray analysis of genes associated with cell surface NIS protein levels in breast cancer

BackgroundNa+/I- symporter (NIS)-mediated iodide uptake allows radioiodine therapy for thyroid cancer. NIS is also expressed in breast tumors, raising potential for radionuclide therapy of breast cancer. However, NIS expression in most breast cancers is low and may not be sufficient for radionuclide therapy. We aimed to identify biomarkers associated with NIS expression such that mechanisms underlying NIS modulation in human breast tumors may be elucidated.MethodsPublished oligonucleotide microarray data within the National Center for Biotechnology Information Gene Expression Omnibus database were analyzed to identify gene expression tightly correlated with NIS mRNA level among human breast tumors. NIS immunostaining was performed in a tissue microarray composed of 28 human breast tumors which had corresponding oligonucleotide microarray data available for each tumor such that gene expression associated with cell surface NIS protein level could be identified.Results and DiscussionNIS mRNA levels do not vary among breast tumors or when compared to normal breast tissues when detected by Affymetrix oligonucleotide microarray platforms. Cell surface NIS protein levels are much more variable than their corresponding NIS mRNA levels. Despite a limited number of breast tumors examined, our analysis identified cysteinyl-tRNA synthetase as a biomarker that is highly associated with cell surface NIS protein levels in the ER-positive breast cancer subtype.ConclusionsFurther investigation on genes associated with cell surface NIS protein levels within each breast cancer molecular subtype may lead to novel targets for selectively increasing NIS expression/function in a subset of breast cancers patients.

Iodine kinetics and dosimetry in the salivary glands during repeated courses of radioiodine therapy for thyroid cancer

The present study was conducted to investigate salivary iodine kinetics and dosimetry during repeated courses of radioiodine ((131)I) therapy for differentiated thyroid cancer (DTC). Such data could provide a better understanding of the mechanisms of (131)I induced salivary toxicity and help to develop appropriate methods to reduce this injury. Seventy-eight consecutive DTC patients (mean age 45 ± 17 years, 60%, female) undergoing (131)I therapy for remnant ablation or metastatic tumors were prospectively recruited. Planar quantitative scintigraphy of head-neck images was serially acquired after administration of 2.9-7.4 GBq of (131)I to assess kinetics in the salivary glands of patients. Salivary absorbed doses were calculated based on the schema of Medical Internal Radiation Dosimetry. The maximum uptakes in percentage of administered (131)I activity per kilogram of gland tissue (%/kg) were 12.9% ± 6.5%/kg (range, 0.4%-37.3%/kg) and 12.3% ± 6.2%/kg (range, 0.4%-35.1%/kg) for the parotid and submandibular glands, respectively. Statistically significant correlations of maximum uptake versus cumulative activity (r = -0.74, P < 0.01, for the parotid glands; r = -0.71, P < 0.01, for the submandibular glands) and treatment cycle (P < 0.001, for both gland types) were found. The effective half-lives of (131)I in the parotid and submandibular glands were 9.3 ± 3.5 h (range, 1.5-19.8 h) and 8.6 ± 3.2 h (range, 0.8-18.0 h), respectively. A statistically significant correlation was observed between effective half-life with cumulative activity (r = 0.37, P < 0.01) and treatment cycle (P = 0.03) only for the parotid glands. The calculated absorbed doses were 0.20 ± 0.10 mGy/MBq (range, 0.01-0.92 mGy/MBq) and 0.25 ± 0.09 mGy/MBq (range, 0.01-1.52 mGy/MBq) for the parotid and submandibular glands, respectively. The photon contribution to the salivary absorbed dose was minimal in relation to the beta dose contribution. Photon-absorbed dose fractions of total absorbed dose were 4.9% ± 1.3% (range, 1.1%-8.7%) and 3.7% ± 2.5% (range, 0.8%-7.9%) for the parotid and submandibular glands, respectively. The iodine uptake of salivary glands is continuously reduced during the courses of therapy. The phenomenon of hyper-radiosensitivity may to some extent account for the occurrence of salivary gland hypofunction at very low radiation doses with low dose rates in (131)I therapy. On the other hand, failure to incorporate a nonuniform and preferential uptake by salivary gland ductal cells may result in underestimating the actual dose for the critical tissue. Other methods, including (124)I voxel-based dosimetry, are warranted to further investigate the (131)I-induced salivary gland toxicity.

Outpatient Radioiodine Therapy for Thyroid Cancer

To evaluate the dosimetric effect of outpatient radioiodine therapy for thyroid cancer in members of a patient's family and their living environment, when using iodine-131 doses reaching 7.4 GBq. The following parameters were thus defined: (a) whole-body radiation doses to caregivers, (b) the production of contaminated solid waste, and (c) radiation potential and surface contamination within patients' living quarters. In total, 100 patients were treated on an outpatient basis, taking into consideration their acceptable living conditions, interests, and willingness to comply with medical and radiation safety guidelines. Both the caregivers and the radiation dose potentiality inside patients' residences were monitored by using thermoluminescent dosimeters. Surface contamination and contaminated solid wastes were identified and measured with a Geiger-Müller detector. A total of 90 monitored individuals received a mean dose of 0.27 (±0.28) mSv, and the maximum dose registered was 1.6 mSv. The mean value for the potential dose within all living quarters was 0.31 (±0.34) mSv, and the mean value per monitored surface was 5.58 Bq/cm(2) for all the 1659 points measured. The overall production of contaminated solid wastes was at a low level, being about 3 times less than the exemption level indicated by the International Atomic Energy Agency. This study indicates that the treatment of thyroid cancer by applying radioiodine activities up to 7.4 GBq, on an outpatient basis, is a safe procedure, especially when supervised by qualified professionals. This alternative therapy should be a topic for careful discussion considering the high potential for reducing costs in healthcare and improving patient acceptance.

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.

KT5823 Differentially Modulates Sodium Iodide Symporter Expression, Activity, and Glycosylation between Thyroid and Breast Cancer Cells

Na(+)/I(-) symporter (NIS)-mediated iodide uptake into thyroid follicular cells serves as the basis of radioiodine therapy for thyroid cancer. NIS protein is also expressed in the majority of breast tumors, raising potential for radionuclide therapy of breast cancer. KT5823, a staurosporine-related protein kinase inhibitor, has been shown to increase thyroid-stimulating hormone-induced NIS expression, and thus iodide uptake, in thyroid cells. In this study, we found that KT5823 does not increase but decreases iodide uptake within 0.5 h of treatment in trans-retinoic acid and hydrocortisone-treated MCF-7 breast cancer cells. Moreover, KT5823 accumulates hypoglycosylated NIS, and this effect is much more evident in breast cancer cells than thyroid cells. The hypoglycosylated NIS is core glycosylated, has not been processed through the Golgi apparatus, but is capable of trafficking to the cell surface. KT5823 impedes complex NIS glycosylation at a regulatory point similar to brefeldin A along the N-linked glycosylation pathway, rather than targeting a specific N-glycosylated site of NIS. KT5823-mediated effects on NIS activity and glycosylation are also observed in other breast cancer cells as well as human embryonic kidney cells expressing exogenous NIS. Taken together, KT5823 will serve as a valuable pharmacological reagent to uncover mechanisms underlying differential NIS regulation between thyroid and breast cancer cells at multiple levels.

The influence of saliva flow stimulation on the absorbed radiation dose to the salivary glands during radioiodine therapy of thyroid cancer using 124I PET(/CT) imaging

A serious side effect of high-activity radioiodine therapy in the treatment of differentiated thyroid cancer is radiogenic salivary gland damage. This damage may be diminished by lemon-juice-induced saliva flow immediately after 131I administration. The aim of this study was to assess the effect of chewing lemon slices on the absorbed (radiation) doses to the salivary glands. Ten patients received (pretherapy) 124I PET(/CT) dosimetry before their first radioiodine therapy. The patients underwent a series of six PET scans at 0.5, 1, 2, 4, 48 and ≥96 h and one PET/CT scan at 24 h after administration of 27 MBq 124I. Blood samples were also collected at about 2, 4, 24, 48, and 96 h. Contrary to the standard radioiodine therapy protocol, the patients were not stimulated with lemon juice. Specifically, the patients chewed no lemon slices during the pretherapy procedure and neither ate food nor drank fluids until after completion of the last PET scan on the first day. Organ absorbed doses per administered 131I activity (ODpAs) as well as gland and blood uptake curves were determined and compared with published data from a control patient group, i.e. stimulated per the standard radioiodine therapy protocol. The calculations for both groups used the same methodology. A within-group comparison showed that the mean ODpA for the submandibular glands was not significantly different from that for the parotid glands. An intergroup comparison showed that the mean ODpA in the nonstimulation group averaged over both gland types was reduced by 28% compared to the mean ODpA in the stimulation group (p=0.01). Within each gland type, the mean ODpA reductions in the nonstimulation group were statistically significant for the parotid glands (p=0.03) but not for the submandibular glands (p=0.23). The observed ODpAs were higher in the stimulation group because of increased initial gland uptake rather than group differences in blood kinetics. The 124I PET(/CT) salivary gland dosimetry indicated that lemon juice stimulation shortly after 131I administration in radioiodine therapy increases the absorbed doses to the salivary glands.

Salivary Gland Malignancy and Radioiodine Therapy for Thyroid Cancer

The risk of second primary malignancies in patients with well-differentiated thyroid cancer is of special interest because of the common use of radioactive iodine (RAI) ablation and/or treatment of these patients and the theoretical risk of subsequent nonthyroid malignancies associated with the radiation exposure. This brief report focuses specifically on the occurrence of second primary malignancies of the salivary glands. RAI residency within salivary tissues is known to have both acute and chronic consequences on salivary function, but secondary neoplasia is quite unusual. We present a very rare case of a patient with papillary thyroid cancer treated with 600 mCi of RAI, who subsequently developed salivary gland cancer. We recommend salivary gland protection to diminish potential side effects after the exposure to radioiodine. On the basis of our experience we suggest administration of sialogogues (such as lemon juice) continuously, every 30-60 minutes for 24 hours, after RAI administration.

Radioiodine Therapy for Thyroid Cancer Depicted Uterine Leiomyoma

A 55-year-old woman underwent radioiodine therapy for papillary carcinoma of the thyroid. Post-therapeutic I-131 scan revealed radioiodine uptake in the pelvic region and in the thyroid bed. CT revealed a huge mass connected to the uterus. The tumor was operated on and histologically proven to be a leiomyoma of the uterus. Some physiological conditions or nonthyroidal diseases can cause false positives in patients with postoperative thyroid cancer. We suggest that uterine leiomyoma might be added to the pitfall list, although the mechanism of I-131 uptake remains unclear.

The Dental Safety Profile of High-Dose Radioiodine Therapy for Thyroid Cancer: Long-Term Results of a Longitudinal Cohort Study

The long-term dental safety profile of high-dose radioiodine therapy remained elusive despite more than 6 decades of clinical use. In a cohort study, we investigated the incidence of sialadenitis, xerostomia, caries, and tooth extractions after high-dose radioiodine therapy for differentiated thyroid cancer and explored risk factors by multiple regression models. One hundred seventy-six participants were recruited (median follow-up, 6.6 y; range, 1.1-32.6 y; patient-years: 8,472 before and 1,421 after radioiodine therapy). Scintigraphic salivary gland uptake during radioiodine treatment predicted development of sialadenitis (odds ratio: 1.31 [1.05-1.63], P = 0.015) and xerostomia (odds ratio: 1.58 [1.16-2.16], P = 0.004). The caries risk increased by postradioiodine xerostomia (% increase: 98.8 [26.5-212], P = 0.003). The long-term risk for postradioiodine tooth extractions increased with increasing cumulative radioiodine activities (% increase [per gigabequerel]: 8.14 [1.07, 15.7], P = 0.02). High-dose radioiodine treatment can impair the long-term dental health, depending on the cumulative radioiodine activity and individual salivary gland radioiodine uptake.

Salivary Gland Toxicity after Radioiodine Therapy for Thyroid Cancer

Aims Salivary gland toxicity is a common, but not widely appreciated, adverse effect of high-dose radioiodine ( 131I). This study was carried out to determine the incidence of symptoms of salivary gland damage after 131I treatment for differentiated thyroid cancer. Materials and methods This was a prospective study of 76 consecutive patients attending thyroid cancer treatment. Symptoms of salivary gland damage (dry mouth, pain and swelling) were assessed during hospital admission and at follow-up visits. Additionally, a retrospective analysis was carried out of patients recorded in our database as having chronic salivary gland swelling after 131I ablation. Results Twenty patients (26%) developed salivary gland toxicity, 11 (15%) had symptoms within the first 48 h, continuing for 12 months in seven of these patients. The onset of toxicity in a further nine (12%) patients with persistent symptoms did not occur until 3 months after therapy. In total, 16 (21%) patients had evidence of chronic toxicity, typically xerostomia, at 12 months. Toxicity was more common after repeated 131I administration. After searching our thyroid cancer database, we identified an additional five patients to have chronic salivary gland swelling (chronic sialadenitis or pleomorphic adenoma) 20 months to 23 years after 131I. Conclusions Pain, swelling and dry mouth occurred frequently after 131I, with some developing symptoms months or years after administration. Early recognition of salivary gland complications may help to reduce morbidity in these patients.

Relationship between cumulative radiation dose and salivary gland uptake associated with radioiodine therapy of thyroid cancer

To estimate the individual absorbed dose to the parotid and submandibular salivary glands in radioiodine therapy and its dependence from the previous cumulative therapy. Fifty-five patients with differentiated thyroid carcinoma after thyroidectomy received 1-21 GBq (131)I using single activities of 1-6 GBq. The patients were stratified according to the cumulative activities into low-activity (1-2 GBq), middle-activity (3-7 GBq), and high-activity groups (9-21 GBq). The time-activity curves over the respective salivary glands were derived from multiple static calibrated images measured for each patient up to 48 h after ingestion of the radioiodine therapy capsule with a gamma camera. Manually drawn regions of interests were used to determine the background activities and the activities arising from the salivary glands. The gland volumes were determined by ultrasonography using appropriate volume models. The median absorbed dose per administered activity of each single parotid and submandibular gland was about 0.15 Gy.GBq (range, 0.1-0.3 Gy.GBq(-1)) and 0.48 Gy.GBq(-1) (range, 0.2-1.2 Gy.GBq(-1)), respectively. The maximum uptake of both gland types was significantly lower for the high-activity than for the low-activity groups and correlated with the mean cumulative administered activity of the activity groups. The iodine uptake of salivary glands is significantly reduced, whereas the absorbed dose per administered (131)I activity was not significantly decreased during the course of therapy. Comparing the well-known dose-effect relationships in external radiation therapy, the absorbed dose per administered (131)I activity is too low to induce comparable radiation damage, suggesting an inhomogeneous distribution of (131)I in human salivary glands.

Pilocarpine for the treatment of salivary glands’ impairment caused by radioiodine therapy for thyroid cancer

To study the effect of single-dose pilocarpine hydrochloride 5 mg on the whole unstimulated and stimulated salivary flow in patients suffering from thyroid cancer treated with radioiodine therapy, and to investigate the changes in vital signs during the treatment. Five such patients were referred with complaints of dry mouth, rampant caries, and pain in the parotid gland region or history of chronic recurrent suppurative sialodenitis. A single dose of 5 mg pilocarpine hydrochloride was administered to each patient and blood pressure, heart rate, body temperature and salivary secretion rate were monitored at 1, 2 and 3 h. A significant elevation of unstimulated and stimulated saliva flow rate was observed in four patients without significant alteration of the monitored vital signs. Treatment with pilocarpine hydrochloride may be beneficial in the case of impaired salivary function in patients treated with radioiodine.