Dosimetry-based treatment for Graves' disease.

OBJECTIVE: The aim of this retrospective study was to assess the long-term outcome of a personalized dosimetry approach in Graves' disease aiming to render patients euthyroid from a planned thyroid absorbed dose of 60 Gy. PATIENTS AND METHODS: A total of 284 patients with Graves' disease were followed prospectively following administration of radioiodine calculated to deliver an absorbed dose of 60 Gy. Patients with cardiac disease were excluded. Outcomes were analysed at yearly intervals for up to 10 years with a median follow-up of 37.5 months. RESULTS: A single radioiodine administration was sufficient to render a patient either euthyroid or hypothyroid in 175 (62%) patients, the remainder requiring further radioiodine. The median radioactivity required to deliver 60 Gy was 77 MBq. Less than 2% patients required 400-600 MBq, the standard activity administered in many centres. In the cohort receiving a single administration, 38, 32 and 26% were euthyroid on no specific thyroid medication at 3, 5 and 10 years, respectively. Larger thyroid volumes were associated with the need for further therapy. The presence of nodules on ultrasonography did not adversely affect treatment outcome. CONCLUSION: A personalized dosimetric approach delayed the long-term onset of hypothyroidism in 26% of patients. This was achieved using much lower administered activities than currently recommended. Future studies will aim to identify those patients who would benefit most from this approach.

Excretion and whole-body retention of radium-223 dichloride administered for the treatment of bone metastases from castration resistant prostate cancer.

OBJECTIVE: The aim of the study was to determine the fraction of administered activity that was excreted and retained by a small cohort of patients who each received treatment with radium-223 dichloride (Ra). Ra is an α-emitting radionuclide that has been approved for use in the treatment of bone metastases that are secondary to castration resistant prostate cancer. PATIENTS AND METHODS: Six patients received two weight-based administrations of Ra 6 weeks apart. Activity excreted in the urine and faeces during the first 48 h following each treatment was assessed by direct counting of the excreta. During the same period the whole-body retention of Ra was also determined using a single probe counting system. The results of the excreta counting and the whole-body counting were compared to determine whether whole-body counting was a suitable surrogate for assessing excretion. Further whole-body retention counts were made at around 3, 4, 7 and 42 days following treatment. RESULTS: Patterns of excretion and retention of Ra varied significantly between patients, but were similar for each patient's pair of treatments. The cumulative maximum activity excreted in the initial 8-h period following the Ra administration was 2.6% that increased to 39% at 48 h. The median excreted activity at ~1 and 6 weeks after treatment was 70 and 86%, respectively. Skeletal retention of Ra at 6 weeks ranged from 11 to 60% of the administered activity.

InfuShield: a shielded enclosure for administering therapeutic radioisotope treatments using standard syringe pumps.

The administration of radionuclide therapies presents significant radiation protection challenges. The aim of this work was to develop a delivery system for intravenous radioisotope therapies to substantially moderate radiation exposures to staff and operators. A novel device (InfuShield) was designed and tested before being used clinically. The device consists of a shielded enclosure which contains the therapeutic activity and, through the hydraulic action of back-to-back syringes, allows the activity to be administered using a syringe pump external to the enclosure. This enables full access to the pump controls while simultaneously reducing dose to the operator. The system is suitable for use with all commercially available syringe pumps and does not require specific consumables, maximising both the flexibility and economy of the system. Dose rate measurements showed that at key stages in an I mIBG treatment procedure, InfuShield can reduce dose to operators by several orders of magnitude. Tests using typical syringes and infusion speeds show no significant alteration in administered flow rates (maximum of 1.2%). The InfuShield system provides a simple, safe and low cost method of radioisotope administration.

Effect of Playground Environments on the Physical Activity of Children With Ambulatory Cerebral Palsy.

PURPOSE: To compare the effect of 2 different playground environments on the physical activity of children with ambulatory cerebral palsy during their playground play. METHODS: Five 7- to 8-year-old children with cerebral palsy (Gross Motor Functional Classification System [GMFCS] level II) participated. Using an alternating treatment, single-subject design, stride patterns were obtained using an activity monitor on an Americans with Disabilities Act (ADA)-compliant and noncompliant playground. Visual and statistical analysis of the stride data was used to analyze the effect of the playground environments. RESULTS: Four of the 5 participants increased the number of strides on an ADA-compliant playground. CONCLUSION: Children with cerebral palsy (GMFCS II) may benefit from an ADA-compliant playground to increase their physical activity.

A Phase 1, Open-Label Study of the Biodistribution, Pharmacokinetics, and Dosimetry of 223Ra-Dichloride in Patients with Hormone-Refractory Prostate Cancer and Skeletal Metastases.

UNLABELLED: The aim of this single-site, open-label clinical trial was to determine the biodistribution, pharmacokinetics, absorbed doses, and safety from 2 sequential weight-based administrations of (223)Ra-dichloride in patients with bone metastases due to castration-refractory prostate cancer. METHODS: Six patients received 2 intravenous injections of (223)Ra-dichloride, 6 wk apart, at 100 kBq/kg of whole-body weight. The pharmacokinetics and biodistribution as a function of time were determined, and dosimetry was performed for a range of organs including bone surfaces, red marrow, kidneys, gut, and whole body using scintigraphic imaging; external counting; and blood, fecal, and urine collection. Safety was assessed from adverse events. RESULTS: The injected activity cleared rapidly from blood, with 1.1% remaining at 24 h. The main route of excretion was via the gut, although no significant toxicity was reported. Most of the administered activity was taken up rapidly into bone (61% at 4 h). The range of absorbed doses delivered to the bone surfaces from α emissions was 2,331-13,118 mGy/MBq. The ranges of absorbed doses delivered to the red marrow were 177-994 and 1-5 mGy/MBq from activity on the bone surfaces and from activity in the blood, respectively. No activity-limiting toxicity was observed at these levels of administration. The absorbed doses from the second treatment were correlated significantly with the first for a combination of the whole body, bone surfaces, kidneys, and liver. CONCLUSION: A wide range of interpatient absorbed doses was delivered to normal organs. Intrapatient absorbed doses were significantly correlated between the 2 administrations for any given patient. The lack of gastrointestinal toxicity is likely due to the low absorbed doses delivered to the gut wall from the gut contents. The lack of adverse myelotoxicity implies that the absorbed dose delivered from the circulating activity may be a more relevant guide to the potential for marrow toxicity than that due to activity on the bone surfaces.

Long-term outcomes following low-dose radioiodide ablation for differentiated thyroid cancer.

CONTEXT: Randomized trials show that low-dose (1.1 GBq [30 mCi]) radioiodide (RAI) has efficacy equivalent to high-dose RAI (3.7 GBq [100 mCi]) in thyroid remnant ablation (TRA) for differentiated thyroid cancer. Long-term follow-up is required to ensure detection of late recurrences and to confirm equivalence in terms of survival end points. However, median follow-up duration within randomized trials is currently limited. PATIENTS AND SETTING: We studied 53 patients undergoing TRA for differentiated thyroid cancer with long-term follow-up in the Thyroid Unit of The Royal Marsden Hospital (Sutton, United Kingdom). INTERVENTION: Patients were treated with TRA using low-dose (1.1 GBq) RAI. MAIN OUTCOME MEASURES: Disease-free survival, overall survival, and the incidence of second malignancies were measured. Multivariable analysis was used to determine clinical risk factors for failure to achieve TRA after low-dose RAI. RESULTS: Median follow-up was 24 (range, 4-34) years. Low-dose RAI TRA was successful in 26 (49%) patients (successful ablation [SA] group), whereas 27 (51%) patients required further treatment (unsuccessful ablation [UA] group). Thirty-year disease-free survival was 92% in the SA group vs 87% in the UA group (P = .601). Thirty-year overall survival was 81% in the SA group vs 62% in the UA group (P = .154). Nine (17%) patients developed second malignancies (4 in the SA group and 5 in the UA group). Predictors of failure to achieve TRA with low-dose RAI were male sex and stage pT4 disease. CONCLUSIONS: There is no evidence from long-term follow-up of our cohort that treatment outcomes are compromised for patients that fail TRA with low-dose RAI and subsequently receive high-dose RAI.

PLFA analyses of microbial communities associated with PAH-contaminated riverbank sediment.

Sediment contaminated with polycyclic aromatic hydrocarbons (PAHs) is widely distributed in aquatic ecosystems. The microbial community structure of riverbank PAH-contaminated sediments was investigated using phospholipid-derived fatty acid (PLFA) analysis. Surface and subsurface riverbank sediment was collected from a highly contaminated site and from an uncontaminated site along the Mahoning River, OH. PAH concentrations, physical sediment characteristics, and other microbial community parameters (biomass as phospholipid phosphate (PLP) and activity) were also measured. PAHs were detected in all samples but were only quantifiable in the contaminated (250 µg/g g(-1)) subsurface sediment. Subsurface samples from both locations showed very similar PLP values and distribution of PLFAs, with 27-37 % of the microbial community structure being composed of sulfate reducing and other anaerobic bacteria. Principal components analysis indicated no correlation between PAH contamination and PLFA diversity. Although PLP and phospholipid fatty acid measurements of bacterial communities did not reflect the environmental differences among sites, the highly PAH-contaminated sediment showed the highest measured microbial activity (reduction of 1,200 nmol INT g(-1) h(-1)), likely from a population adapted to environmental pollutants, rates that are much higher than measured in many uncontaminated soil and sediment systems. These data warrant further investigation into community structure at the genetic level and indicate potential for bioremediation by indigenous microbes.

Outcome of Pregnancy After Exposure to Radioiodine In Utero.

OBJECTIVE: Radioiodine (131I) therapy is absolutely contraindicated in pregnancy yet reports of inadvertent exposure continue to appear in the literature. In this review, we discuss the risks of fetal exposure and prevention strategies in the light of current guidelines. METHODS: We performed a literature search on MEDLINE using the terms radioiodine, I-131, toxicity, complications and pregnancy and chose the most relevant studies for this review. RESULTS: Before implantation, the major concern is miscarriage and death of the embryo above a radiation threshold of 100mGy (10 rads). Exposure to 131I at this very early stage of pregnancy is unlikely to result in major malformations or thyroid dysfunction in surviving embryos. Exposure later in pregnancy i.e. during thyroidogenesis (from 10 weeks gestation) and organogenesis (from 2 weeks gestation) at similar radiation thresholds may result in fetal thyroid ablation, birth defects and in later life, growth retardation and reduction in IQ. In addition to these deterministic effects, radiation at any dose may increase the risk of cancer (stochastic effect) and recent evidence indicates an increased risk of thyroid cancer many years after in utero exposure. CONCLUSIONS: Clinicians treating women of child-bearing age with radioiodine need to be aware of the risks of fetal exposure to radioiodine and take all measures to avoid inadvertent exposure during pregnancy.

Participation of the child with cerebral palsy in the home, school, and community: A review of the literature.

Improving participation of children with cerebral palsy is an important outcome in the practice of pediatric rehabilitation. Current knowledge of how a child's interactions with various environments influence participation can affect care provision to children with cerebral palsy. The literature was searched using electronic databases and reference lists from 1991 to 2008. Studies included reports on one or more factors influencing a child's participation. Using the International Classification of Function, Disability, and Health (ICF) as a framework, factors that influence participation are summarized.

Optimization of equipment and methodology for whole body activity retention measurements in children undergoing targeted radionuclide therapy.

Accurate measurements of whole-body activity retention of patients during radionuclide therapy are essential for two reasons: First, they enable the correct radiation protection advice to be given and second, they permit the accurate determination of the absorbed whole-body dose delivered during therapy. This, in turn, allows treatment planning to be carried out for future radionuclide therapy on an individual patient basis, and also enables the investigation of the potential correlation of absorbed dose with treatment outcome in groups of patients. There are significant difficulties associated with taking whole-body retention measurements of children, especially when they are very young and/or unwell. It is essential to carry these out in a way that minimises disturbance to the child while still providing good quality data. To accomplish this, we have aimed to optimize the following aspects of the procedure: (i) the environment in which the measurements are performed; (ii) the equipment--which includes the recent installation of a specially designed whole-body activity monitoring system for these patients; and (iii) the methodology for calculating the absorbed dose. These improvements have allowed large numbers of accurate and reproducible whole-body measurements to be collected following patient administrations. This has enabled the identification of more phases of radionuclide excretion during therapy than had previously been observed. These data have been used for radiation protection advice and treatment planning. Two (2) patients were given multiple radionuclide treatments and we were able to compare the whole-body doses delivered.

Diagnostic 131I whole body scanning after thyroidectomy and ablation for differentiated thyroid cancer.

OBJECTIVE: To assess the value of the diagnostic whole body (131)I scan after thyroidectomy and (131)I ablation. DESIGN: Retrospective analysis of all patients with differentiated thyroid cancer treated in one centre between 1990 and 2000. RESULTS: A total of 153 consecutive patients who underwent diagnostic scanning following ablative therapy were identified. This diagnostic scan was positive in 20 patients (13%) and faintly positive in 16 patients (11%). The majority (117 patients) had negative scans. Of the 20 patients with positive scans, four received no further treatment, nine showed no abnormal uptake following a second ablative (131)I dose and seven had uptake in the thyroid bed (six) or in neck nodes (one) after repeat ablation. OUTCOME: In the group with positive scans, the four patients who received no further treatment and the nine with a negative second ablation scan remained disease free during follow-up. No patient with a positive diagnostic scan received additional (131)I therapy which would not otherwise have been given based on the clinical findings, serum thyroglobulin (Tg) values or the presence of anti-Tg antibodies. Ten of the patients with negative scans developed recurrent disease which was always detected clinically or by a rising serum Tg value. CONCLUSIONS: Diagnostic whole body (131)I scans add little extra information and in our experience do not influence patient management. They should be reserved for patients in whom serum Tg levels are unreliable because of the presence of antibodies or when there is clinical suspicion of tumour.

Testicular dose and fertility in men following I(131) therapy for thyroid cancer.

OBJECTIVE: Young adults with differentiated thyroid cancer are treated with high doses of radioiodine and have an excellent long-term prognosis. However, there is limited information on the effects of this treatment on the gonads and fertility in male patients. We have reviewed the outcome of treatment in our centre with respect to male fertility. We have also assessed directly the radiation dose received by the testes. DESIGN: Retrospective analysis of males attending the thyroid clinic at the Royal Marsden Hospital for treatment of differentiated thyroid cancer. A prospective study was also performed to assess radiation dose to testes in 14 consecutive patients attending for thyroid cancer treatment. PATIENTS: Males under the age of 40 years at the time of treatment with a minimum of 3 years follow-up. MEASUREMENTS: Number of children fathered by patients and number of congenital malformations. For the prospective study: gonadal function assessed by serum FSH, LH and testosterone measurements; radiation dose to the testes (Gy) measured by thermoluminescent dosimetry. RESULTS: Fertility was assessed in 122 men with a median follow-up of 21 years (range 3-39) of whom 93 were under active follow-up. One hundred and six children were fathered by 59 patients; the remainder had no wish to have children. No major malformations were reported. Of these 59 patients, 12 had received a single 3 GBq ablation dose, 19 had been treated with up to 14 GBq radioiodine and 28 had received up to 44 GBq. In 14 patients followed prospectively, the median estimated radiation dose to each testis was 6.4 cGy following 3 GBq, 14.1 cGy following 5.5 GBq and 21.2 cGy following 9.2 GBq. There was a transient elevation in serum FSH after radioiodine which normalized within 9 months from the last administration. CONCLUSIONS: Radioiodine treatment for thyroid cancer may result in transient impairment of gonadal function. The radiation dose absorbed by the testis after a single ablative dose of radioiodine is well below that associated with permanent damage to germinal epithelium and the risk of infertility in these patients is minimal. Patients requiring multiple administrations for persistent or metastatic thyroid cancer may be at greater risk of gonadal damage although even in this group, we found no evidence of infertility.