Brenda Pratt

Testicular dose and fertility in men following I131 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.

Imaging metastatic testicular germ cell tumours with 18FDG positron emission tomography: prospects for detection and management

The aim of this study was to investigate the role of positron emission tomography (PET) with [18F]fluoro-2-deoxyglucose (18FDG) in metastatic testicular germ cell tumours. Twenty-one patients with stage II–IV testicular germ cell tumours were imaged by PET with a multiwire proportional chamber PET system and18FDG. Avid18FDG uptake was seen in metastatic disease from primary seminoma and malignant teratoma. Normal tissue uptake was seen in differentiated teratoma or necrotic, fibrotic tissue.18FDG standard uptake values and tumour to normal tissue ratios were 6.0±1.4 and 1.7±0.4 (mean ± 1SD), respectively, for malignant tissue. Reduction of18FDG tumour to normal tissue ratios from pre-treatment to on-treatment scans was predictive of response (n=3). No significant reduction in18FDG uptake was seen in patients not responding to therapy (n=2). These results suggest a role for18FDG PET in the detection and management of metastatic testicular germ cell tumours.

Thyroid volume measurement in thyrotoxic patients: comparison between ultrasonography and iodine-124 positron emission tomography

Abstract. The aim of this paper was to compare ultrasound (US) assessment of thyroid volume with that obtained by positron emission tomography (PET), in patients scheduled for adaptive radioiodine therapy, in which 50 Gy was prescribed to the functional PET volume. Firstly a pilot study was performed to ascertain the optimum method for US assessment of thyroid volume. Then 17 comparative measurements of thyroid volume by US and PET were made on 15 patients (two male and thirteen female, ages 28–73 years) with suspected Graves’ disease. This comparison showed that in normal sized and enlarged thyroid glands (n=13), the ratio of functional PET to anatomical US volume was approximately 2:3. However, using the same ellipsoid model, PET and US assessment of anatomical volume agreed within the measurement errors. Owing to the presence of nodules and non-uniform distribution of radioiodine, the functional PET volume and anatomical US volume are often not equivalent. If high-resolution emission tomography (e.g. PET) is unavailable, the comparative data presented in this paper could be used to derive the functional volume from the US volume for calculating functional thyroid dose in hyperthyroid patients undergoing radioiodine therapy.

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

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 223Ra-dichloride in patients with bone metastases due to castration-refractory prostate cancer. Methods: Six patients received 2 intravenous injections of 223Ra-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

CONTEXTnRandomized 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.nnnPATIENTS AND SETTINGnWe 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).nnnINTERVENTIONnPatients were treated with TRA using low-dose (1.1 GBq) RAI.nnnMAIN OUTCOME MEASURESnDisease-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.nnnRESULTSnMedian 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.nnnCONCLUSIONSnThere 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.

Outcome of Pregnancy After Exposure to Radioiodine In Utero.

OBJECTIVEnRadioiodine (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.nnnMETHODSnWe 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.nnnRESULTSnBefore 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.nnnCONCLUSIONSnClinicians 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.

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 (223Ra). 223Ra is an &agr;-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 223Ra 6 weeks apart. Activity excreted in the urine and faeces during the first 48u2009h following each treatment was assessed by direct counting of the excreta. During the same period the whole-body retention of 223Ra 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 223Ra 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 223Ra administration was 2.6% that increased to 39% at 48u2009h. The median excreted activity at ~1 and 6 weeks after treatment was 70 and 86%, respectively. Skeletal retention of 223Ra at 6 weeks ranged from 11 to 60% of the administered activity.

Whole-body and blood dosimetry for radioiodine treatment of differentiated thyroid cancer

IntroductionIdeally, the administration of radioiodine (RAI) therapy for the treatment of differentiated thyroid cancer (DTC) would be carried out on a patient-specific basis. This requires individual dosimetry calculations. AimTo calculate whole-body absorbed doses (WBD) and blood doses (BD) resulting from different levels of administration, to determine whether a correlation exists between the levels of administered activity and these toxicity criteria. MethodsEighty-two patients underwent 110 treatments. Serial whole-body activity measurements were taken following administration of 3, 5.5 and 9 GBq RAI. Blood samples were taken at 48, 72 and 144u2009h for similar evaluations. WBD and BD were calculated using standard MIRD methodology with interpolated S values. ResultsWBD and BD values are expressed as mean±SD Gy. After 3 GBq, WBD=0.18±0.04, BD=0.31±0.08; after 5.5 GBq, WBD=0.34±0.14, BD=0.64±0.38; and after 9 GBq, WBD=0.66±0.39, BD=0.94±0.44. Whilst higher administered activities resulted in higher absorbed whole-body and blood doses, no adverse haematological toxicity was observed throughout the study. ConclusionThe determination of absorbed whole-body and blood doses can be used as a guide to the safe prescription of administered activity up to 9 GBq. These methods can help predict and minimize potential toxicity.