Course Of Radioiodine Therapy Research Articles

Results of treatment of patients with poorly differentiated carcinoma of the thyroid gland

Introduction. Poorly differentiated carcinoma of the thyroid gland (PDTC) is characterised by aggressive, high rate of tumor growth, massive infiltration, early lymphogenous and hematogenous dissemination. Ways to improve treatment outcomes include developing individual treatment programmes. Given the unsatisfactory results of the treatment, the search for combined treatment options is well founded.Materials and methods. An analysis was made of the treatment of PDTC in patients from May 2014 to July 2021. The study included 24 patients aged 22 to 81 years (9 (37.5 %) men and 15 (62.5 %) women). Surgical treatment was performed in 14 (58.3 %) cases. In 8 (33.3 %) cases, a course of radioiodine therapy with a total dose of 3–4 Gbq was performed in the postoperative period. Seven (29.2 %) patients underwent external beam radiation therapy. In 2 (8.3 %) cases, chemotherapy with carboplatin was performed simultaneously with external beam radiation therapy. Four (16.7 %) patients were prescribed lenvatinib. For one reason or another, 9 (37.5 %) patients did not receive treatment.Results. For patients not treated, the overall survival rate was 5.8 ± 0.5 months, for patients treated – 9.6 ± 1.0 months (p <0.00095). According to the index Lenvatinib showed a significant increase in the general group of patients – up to 15 months.Conclusion. Combined treatment in the form of a combination of surgical, radiation and chemotherapeutic methods at PDTC, allows to achieve much higher survival. In order to achieve longer-term stabilization, further research is needed on new ways to enhance the anti-tumor effect of modern drugs.

Euthyroidism: following a course of radio iodine therapy for Graves' disease

Euthyroidism: following a course of radio iodine therapy for Graves' disease

Predictive Value of Clinical and Pathological Characteristics for Metastatic Radioactive Iodine-Refractory Differentiated Thyroid Carcinoma: A 16-year Retrospective Study.

PurposeTo assess predictive value of clinical and pathological characteristics for metastatic radioactive iodine-refractory differentiated thyroid carcinoma (RAIR-DTC) in early stage retrospectively.MethodsWe studied 199 metastatic DTC patients who were divided into two groups (TgAb negative and TgAb positive). The stimulated Tg (Sti-Tg) at the first and second radioiodine therapy (RIT) were defined as Sti-Tg1 and Sti-Tg2, the suppressed Tg (Sup-Tg) were designated as Sup-Tg1 and Sup-Tg2, while the TgAb were defined as TgAb1 and TgAb2, respectively. Univariate analysis and Logistic regression were used to investigate the effects of 13 observed factors to predict RAIR-DTC.ResultsIn TgAb negative group, ROC curve analysis showed that cut-off values of age, Sti-Tg2/Sti-Tg1 and Sup-Tg2/Sup-Tg1 to predict RAIR-DTC were 40 years old, 57.0% and 81.0%, respectively. Age, extrathyroid invasion, Sti-Tg2/Sti-Tg1, Sup-Tg2/Sup-Tg1 and BRAF gene mutation were proved to be independent factors predicting RAIR-DTC. In TgAb-positive group, ROC curve analysis showed that cut-off values of age, TgAb1 and TgAb2/TgAb1 to predict RAIR-DTC were 55 years old, 297 IU/ml (14.8 times higher than the upper limit) and 53.6%, respectively.ConclusionsFor TgAb-negative DTC, age over 40, extraglandular invasion, mutated BRAF gene, Sti-Tg decreased less than 43%, and Sup-Tg decreased less than 19% after the first two courses of RIT were independent predictors for RAIR-DTC. For TgAb-positive DTC, age over 55, extraglandular invasion, mutated BRAF gene, distant metastasis before RIT, TgAb level 14.8 times higher than the upper limit, TgAb dropped less than 46.4% after two courses of RIT were influencing factors.

DOSE RELATIONSHIP DURING RADIOABLATION OF THYROID RESIDUAL IN PATIENTS WITH THYROID DIFFERENTIATED CANCER.

to study relationship between the focal adsorbed doses (FAD) in the residual thyroid tissue (RTT) atradioiodine therapy (RIT) in patients with differentiated thyroid cancer (DTC) and efficacy of radioablation (RA). FAD in RTT in 221 patients aged 25-74 years were analyzed. Scintigraphic investigations were executed using gamma-camera «МВ 9200» and single photon emission tomograph «Е. САМ 180». FAD in RTT were determined according to recommendation of the Committee on Medical Internal Radiation Dose. Mean FAD in RTT was consisted (125.9 ± 8.6) Gy with range 1.8-1373.4 Gy. Positive effect after first course of RIT was in 77.4 % of patients complete RA of 78 % of RTT was achieved. Mean FAD in cases with complete RA was (147.0 ± 13.3) Gy with range 1.8-1373.4 Gy. Efficacy of RIT constantly increased from 68.2 to 93.7 % with increasing mean FAD from 30 to 370 Gy. Feather enlarging of FAD did not lead to any significant increasing of efficacy of RIT:enlarging mean FAD from 370 to 776 Gy increased efficacy of RA on 0.4 % only. Repeated RIT decreased FAD in RTTafter each course. Using regression analysis was established type of relationship between efficacy of RA and FAD in RTT, according it efficacy of first RA consists at 40 Gy 72.8 %, 150 Gy - 84.9 %, 300 Gy - 91.2 %, 400 Gy - 93.7 %,500 Gy - 95.7 %. FAD in RTT at RIT differ in large range, it can be explained different anatomical and functional condition of iodine accumulate thyroid tissue after surgical treatment and its radioresistance. Efficacy of RA increases with enlarging of FAD, this relationship is nonlinear. Efficacy of RA has the upper dose threshold in range 350-400 Gy. The frequency of thyroid tissue with high radioresistance is approximately 6 %.

Статеві й вікові особливості змін імунологічних показників у хворих на рак щитоподібної залози і хворих на токсичний зоб після радіойодотерапії

Мета: провести порівняльний аналіз цитотоксичної активності NK-клітин і метаболічної активності нейтрофілів (НФ) до і після радіойодотерапії (РЙТ) у хворих на диференційований рак щитоподібної залози (ДРЩЗ) залежно від статі, віку, наявності віддалених метастазів і у хворих на токсичний зоб (ТЗ) залежно від статі. Матеріали та методи. Визначили імунологічні показники в трьох групах тиреоїдектомованих хворих із ДРЩЗ. У групу 1 ввійшли 48 осіб (30 жінок, 18 чоловіків) молодого віку (від 11 до 39 років) без віддалених метастазів ДРЩЗ. Групу 2 становили 40 хворих (23 жінки, 17 чоловіків) молодого віку (від 16 до 40 років) із віддаленими метастазами ДРЩЗ. Групу 3 становили 55 хворих (30 жінок, 25 чоловіків) старшого віку (від 41 до 75 років) із віддаленими метастазами ДРЩЗ. Середня кількість курсів РЙТ у жінок групи 1 становила 1,10 ± 0,04, у чоловіків — 1,50 ± 0,24, у жінок групи 2 — 5,4 ± 0,7, у чоловіків — 6,3 ± 0,8. У хворих старшого віку (група 3) середня кількість курсів РЙТ у жінок становила 5,4 ± 0,3, у чоловіків — 5,5 ± 0,7. Визначали імунологічні показники в 30 хворих (22 жінки, 8 чоловіків) із ТЗ віком від 23 до 67 років. Хворі на ТЗ отримали курс РЙТ. Імунологічне дослідження проводили напередодні й у ранній термін (5 чи 6 діб) після РЙТ. Цитотоксичну активність NК-клітин проти індикаторних клітин-мішеней визначали, використовуючи спектрофотометрію. Метаболічну активність НФ досліджували в стандартному тесті відновлення нітросинього тетразолію. Результати. У ранній термін після РЙТ активність NK-клітин знижується в чоловіків молодого віку групи 1. У чоловіків молодого віку групи 2 активність NК-клітин після РЙТ знижується більшою мірою, ніж у групі 1. Активність NК-клітин у чоловіків старшого віку (група 3) і до, і після РЙТ істотно нижча, ніж у жінок, і значно нижча, ніж у чоловіків молодого віку. Після РЙТ метаболічна активність НФ у хворих на ДРЩЗ чоловіків і жінок збільшується в групі 1 і в чоловіків групи 2. У жінок групи 1 цей показник значно більший, ніж у чоловіків. У чоловіків і жінок групи 2 метаболічна активність НФ після РЙТ істотно менша, ніж у хворих групи 1. У хворих на ТЗ осіб чоловічої статі активність NK-клітин напередодні РЙТ нижча, а метаболічна активність НФ значно вища, ніж у жінок. Після РЙТ збільшення активності NК-клітин у хворих на ТЗ більшою мірою відбувається в осіб жіночої статі, а метаболічної активності НФ — в осіб чоловічої статі. Висновки. Порівняльний аналіз результатів дослідження раннього впливу 131І на цитотоксичну активність NK-клітин і метаболічну активність НФ виявив особливості змін цих показників у хворих на ДРЩЗ залежно від віку, статі, наявності віддалених метастазів, у хворих на ТЗ — залежно від статі.

Value of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography in staging of patients with differentiated thyroid cancer after thyroidectomy during the first course of radioiodine therapy

The study objective is to evaluate value of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (PET-CT) and whole-body scintigraphy (131I-WBS) performed during the first course of radioiodine therapy for its ability to detect persistence metastatic foci and for its role in the management of differentiated thyroid cancer patients.Materials and methods. Forty patients with DTC underwent both post-therapeutic 131I-WBS and PET-CT. PET-CT performed on a positron emission tomograph combined with a 16-slice computer tomograph. Post-therapeutic 131I-WBS performed during radioiodine therapy on the single-detector gamma camera.Results. Sensitivity in detecting of the tumor persistence for PET-CT was 84 %, for post-therapeutic 131I-WBS 66 % (р >0.05). In 17 (42.5 %) patients additional PET-CT foci were found that negative on 131I-WBS, including 11 (27.5 %) cases of distant metastases. Fifteen percent of patients had metastatic foci visualized only on 131I-WBS, including 4 (10 %) cases of distant metastases. In 17 (44 %) patients tumor foci were identified by both methods. A high pre-ablative level of stimulated thyroglobulin was the only independent predictor of the presence of PET-CTpositive metastatic foci (p = 0.001).Conclusion. 18F-fluorodeoxyglucose PET-CT can be recommended during the first radioiodine therapy in differentiated thyroid cancer patients with a high risk progression group, as well as with suspected the tumor persistence in case of a high pre-ablation thyroglobulin level, to complete staging, improve the quality of management and ongoing risk stratification.

Значимость персональных клинико-диагностических показателей при оценке побочного радиационного воздействия для больных раком щитовидной железы, получающих радиойодтерапию

The radioiodine therapy is the most well-known branch of radionuclide therapy. The therapy composed of thyroidectomy and iodine-131 radiopharmaceutical is the “gold standard” for treat-ment of differentiated thyroid cancer patients (DTC). Given metastases in lymph nodes such therapy is absolutely exclusive treatment mode. At the same time, despite the targeted effect of radioiodine on pathological foci a side internal exposure of healthy organs and tissues is noted in the course of radioiodine therapy. Therefore, a reliable assessment of the side exposure is nec-essary taking into account the individual characteristics of patients considering that the side dose varies significantly from patient to patient. For this reason, the identification of significance of personal clinic-diagnostic factors determined the side whole body exposure is the vital and im-portant task. In this aspect, the cytogenetic examination of DTC patients by means of the analysis of chromosomal aberrations in peripheral blood lymphocytes is the goal of essential importance. The certain types of chromosomal aberrations are specific radiation markers that unequivocally indicate radiation exposure. Using the frequency of radiation markers the side absorbed dose can be reliably estimated. In the present work, the statistical analysis of the significance of vari-ous clinic-diagnostic factors in relation to the induction of radiation markers in the blood lympho-cytes was performed. For that end the results of the cytogenetic examination of the group com-prised of 38 DTC patients have been used. The examined patients underwent a course of radio-iodine therapy in the department of radionuclide therapy of the A.F. Tsyb MRRC, Obninsk. The slide preparation and cytogenetic analysis were carried out in the laboratory of radiation cytoge-netic of the same Center. The performed analysis of the correlation matrix with respect to the dependence of the increased frequency of stable and unstable markers resulted from a one-time course of radioiodine therapy showed no meaningfulness at the level R>0.3 for all the studied factors. For the absolute value of the frequency of radiation markers, both before and after radioiodine therapy, the meaningful relationship was found at the level R>0.7 for unsta-ble and at the level R>0.8 for stable markers with a total administered activity of radioiodine dur-ing all the previous courses of radioiodine therapy.

Гістопатологічний аналіз випадкових папілярних тиреоїдних карцином за хвороби Грейвса на тлі дифузного зоба та результати післяопераційного спостереження за пацієнтами

Мета — порівняти гістопатологічні характеристики випадкових папілярних тиреоїдних карцином (ВПТК) за хвороби Грейвса (ХГ) з дифузним зобом (ДЗ), виявлених під час макроскопічного опису післяопераційного матеріалу (макровипадкові папілярні тиреоїдні карциноми — МВПТК) і виключно за мікроскопічного дослідження гістологічних препаратів (справжні окультні папілярні тиреоїдні карциноми — СОПТК); з’ясувати можливі відмінності в післяопераційному перебігу захворювання в пацієнтів із МВПТК і СОПТК. Матеріал і методи. Проведено порівняльний гістопатологічний аналіз 16 МВПТК та 31 СОПТК, виявлених у 47 хворих із ХГ на тлі ДЗ, яких було прооперовано протягом періоду з 2008 по 2019 рік. Порівняно результати післяопераційного спостереження пацієнтів щодо застосування радіойодтерапії (РЙТ) та наявності рецидивів ВПТК. Результати. Усі досліджені ВПТК не перевищували за розміром 10 мм. Частота МВПТК була вірогідно нижчою, ніж СОПТК (34% проти 66%, р=0,0036; шанс ризику (OR)=0,26). Середній розмір пухлини, навпаки, був більшим у першій групі, ніж у другій (5,8±1,2 проти 2,8±1,2 мм, р<0,0001). Жодних істотних відмінностей у домінантнійархітектоніці пухлин чи їхніх інвазійних характеристиках між двома групами не простежувалося, окрім вірогідно частіших ознак інтратиреоїдного розповсюдження МВПТК порівняно із СОПТК (37,5% проти 6,5%, р<0,0130; OR=8,70). Жодна з пухлин в обох групах не мала ознак екстратиреоїдного розповсюдження, усі ВПТК належали до рТ1а категорії відповідно до 8-го видання TNM класифікації. Тривалість післяопераційного спостереженняпацієнтів вірогідно не відрізнялася в обох групах і становила 3,9±2,7 проти 4,2±3,3 року (р=0,9999). Тринадцять із 47 пацієнтів (27,7%) пройшли курс післяопераційної РЙТ, за якої в жодного пацієнта не було виявлено регіонарних чи віддалених метастазів. Також не зафіксовано випадків локальних чи регіонарних рецидивів ВПТК. Висновки. Усі ВПТК за ХГ на тлі ДЗ були мікрокарциномами розміром до 10 мм. МВПТК і СОПТК характеризувалися подібними структурними характеристиками та низькими інвазійними властивостями. Під час післяопераційного спостереження (від 0,2 до 11,2 року) у жодного пацієнта не зафіксовано локальні або реґіонарні рецидиви, незалежно від того, пройшли пацієнти курс РЙТ чи ні, що ставить під сумнів доцільність застосування РЙТ за наявності ВПТК у пацієнтів із ХГ на тлі ДЗ.

Thyroid carcinoma in woman. gynecologist view

Over the past decade the incidence of thyroid cancer in Ukraine has increased 1.5 times, and the average age of diagnosis among women is 36 years. Thyroid cancer is the most common endocrine cancer, occurs in 5–10% of patients with thyroid nodules. Papillary carcinoma is 80% of all thyroid malignant neoplasms and is three times more common in women than in men. The peak incidence in women is observed in 40–49 years, while in men the peak is 60–69 years. In addition to established risk factors such as female sex, exposure to ionizing radiation, a history of benign thyroid disease, deficiency or excess of iodine in the diet, somatic mutations BRAFV600E, RET/PTC, NTRK, remain relevant studies of the role of estrogen imbalance and progesterone and progesterone expression of their receptors sensitive in the development of thyroid carcinogenesis. Recent studies devoted to improving the diagnosis of thyroid cancer, surgical intervention techniques, subsequent radioactive iodine therapy and duration of thyroid stimulating hormone suppression. Thanks to this patients with thyroid papillary carcinoma have favorable prognoses, because the 5-year survival rate is more than 98%. According to the American Thyroid Association a modern approach to the treatment of papillary thyroid cancer has several stages and depends on the recurrence risk in a patient. Thus, patients in accordance with the tumor size, the presence of local, distant metastases, BRAF V600E mutations, etc. are divided into three groups: low, medium and high risk of developing a relapse. At the first stage of treatment surgical intervention (thyroidectomy or lobectomy) is performed, followed by histopathological verification of the diagnosis, radioiodine diagnosis of the presence of metastases, evaluation of risk factors for recurrence, and the decision to conduct a course of radioiodine therapy during the second stage of treatment. The further management of these patients also depends on the risk group and includes the long-term suppressive treatment of thyroid stimulating hormone with levothyroxine.

Medullary thyroid cancer. Returning to the need to determine the preoperative basal calcitonin level in patients with thyroid nodular pathology

There are International and Russian guidelines for the diagnosis and treatment of medullary thyroid carcinoma. There is a recommendation to determine the basal level of calcitonin for all patients with nodular thyroid disease at the all of these documents. However, this test is not performed for this category of patients routinely even in large clinics for a number of reasons, the main one, which seems to be an economic issue. Six months ago a patient addressed to our clinic who underwent surgical treatment for a papillary carcinoma (follicular variant) of the thyroid gland in the volume of thyroidectomy with pre-tracheal lymphodissection and subsequent course of radioiodine therapy at the place of residence. A relapse of the disease was suspected on the control examination at the place of residence and the patient was sent for consultation to the polyclinic of the N.N. Blokhin National Medical Research Center of Oncology. In our clinic, diagnostic studies were carried out, including a revision of the finished cytological and histological preparations and a conclusion was obtained – medullary carcinoma of the thyroid. Determination of basal level of calcitonin in serum showed a value of 1292 pg/ml. The level of basal calcitonin significantly decreased after repeated surgical treatment. This case shows that in order to avoid such mistake, which is described in our clinical case, it seems necessary to follow the national recommendations, international standards to determine the level of basal calcitonin for all patients with thyroid nodal pathology who consulted and treated in medical institutions.

Lenvatinib complementary with radioiodine therapy for patients with advanced differentiated thyroid carcinoma: case reports and literature review

BackgroundThe prognosis for patients with advanced differentiated thyroid carcinoma (ADTC) with disseminated distant metastases is very poor. Tyrosine kinase inhibitors targeting tumor angiogenesis have been shown to improve progression-free survival in patients with advanced thyroid carcinoma and progressive radioiodine-refractory thyroid carcinoma. Tyrosine kinase inhibitor has been reported as a successful neoadjuvant for total thyroidectomy to reduce tumor burden. However, the special indications for prompt treatment with lenvatinib as a rescue therapy to reduce tumor burden and prolong a durable response to radioiodine therapy have not been explored.Case presentationHere, we present two ADTC cases with distant metastases who were effectively treated by total thyroidectomy combined with lenvatinib to prolong a durable response to radioiodine therapy. Case 1 was a 66-year-old male diagnosed with ADTC and disseminated brain, lung, and bone metastases. Lenvatinib was initiated via compassionate access because of rapidly progressive tumor growth even after second doses of radioiodine therapy and external beam radiation therapy for his brain metastases. The result was a durable response to lenvatinib, slowing progressive tumor growth for 3 years and allowing a third course of radioiodine therapy to treat the bone metastases. Case 2 was a 45-year-old male diagnosed with ADTC and diffuse disseminated lung metastases. Respiratory failure ensued after total thyroidectomy, requiring mandatory support by respirator. Lenvatinib was started as a rescue therapy to reduce tumor burden rapidly. The patient was successfully weaned off the respirator only 1 week after using lenvatinib. The patient was then maintained on a low dose of lenvatinib, allowing three subsequent courses of radioiodine therapy. Currently, his lung metastasis remains well controlled with decreased lung infiltrating nodules and the patient can tolerate exercise well.ConclusionOur case experience indicated that lenvatinib has significant value as salvage therapy, reducing tumor burden, producing a durable response and maintaining quality of life. For ADTC patients with progressive life-threatening metastases, our experience suggests that lenvatinib treatment can be used as an urgent rescue therapy as well as a complement to radioiodine therapy to improve tumor eradication.

RADIOIODINE THERAPY OF PAPILLARY THYROID CANCER, COMPLICATED BY A RADIAL MYELITIS. CLINICAL CASE

Over the past decades, there has been an increase in the incidence of thyroid cancer in most countries, and the most common form of thyroid cancer is papillary thyroid cancer. Application of radioiodine therapy for papillary thyroid cancer depends on the degree of postoperative risk of the disease recurrence. Radioactive iodine is recommended after radical thyroidectomy in case of intermediate or high risk of recurrence, that reduces the probability of disease progression and increases survival. The aim of radioiodine therapy is the ablation of thyroid tissue left after thyroidectomy and metastases, accumulating radioactive iodine. The recommended activity of the drug for radioablation is 30 mCi in the intermediate risk group and 30 to 150 mCi with a high risk of recurrence, but total doses and multiplicity of courses varies widely. The acute side effects of radioiodine therapy, the probability of which increases with a radioiodine dose of more than 100 mCi, include allergic reactions to iodine, post-radiation parotitis and sialadenitis, gastritis, cystitis, pulmonitis (with lung metastases), myelodepression, transient amenorrhea and hypo-spermia. The listed violations are transient and last from several days to several months. In the presented article the clinical case of papillary thyroid cancer with metastases in the lymph nodes of the neck was examined. The patient underwent thyroidectomy, central lymphadenectomy and radiotherapy. One year after the third course of radioiodine therapy the patient experienced the development of post-radiation gastritis, myelodepression and myelitis, manifested by a marked pain syndrome in the cervical spine and sensory and movement disorder of hands and legs. Pulse therapy with glucocorticoids in combination with drugs that improve microcirculation, neuromuscular conduction and reduce the severity of neuropathic disorders allowed to stop post-radiation complications.

Potential of the drug-regulation iodide uptake in patients for prevention of radioiodine-refractory papillary thyroid cancer

Objective To evaluate the efficacy and feasibility of retinoic acid derivatives and lithium salts for radioiodine-refractory prevention in patients with differentiated thyroid cancer during multistage radioiodine therapy. Materials and methods The retrospective analysis was performed using the diagnostic and treatment results of 40 patients with differentiated thyroid cancer that underwent 131 I therapy, which on the basis of posttherapy whole-body scan had direct indications for subsequent course of radioiodine therapy. The patients were divided into two groups: the control group (20 patients), which conducted a second course of radioiodine therapy on the standard template and without special training$ the main group (20 patients), who were administered Sedalia (900 mg per day for 8 days, p.o.) and isotretinoin (1.2 mg/kg body weight for 60 days, p.o.) to prevention of the 131 I resistance. To evaluate the effectiveness of a repeated course of radioiodine therapy following parameters were used: the thyroglobulin (Tg) and antibodies to thyroglobulin (Tg-Ab) level in the serum, the posttherapy whole body scan in combination with SPECT-CT. Results We have found, that radioactive iodine treatment was effective in 75% of the main group and 90% of patients in the control group. The remission was observed in 10% and 40% in the main and control group, respectively. The partial regression was considered as Tg and TG-Ab reduction, and was observed more in the study group. The resistance to 131 I therapy was found in 20% and 10% in the main and control group, respectively, which was based on the fact of permanent Tg/Tg-Ab serum level and absence of the pathological foci iodine uptake on the whole-body scans. The disease progress was found in one patient in the main group. Conclusion The use of retinoic acid derivatives and lithium salts, in an effort to prevent the resistance to 131 I-theraphy pretend to be unjustified, because it does not lead to significant improvement in long-term results and reduce the number of 131 I-resistance.

Nabothian cyst associated with high false-positive incidence of iodine-131 uptake in whole-body scans after treatment for differentiated thyroid cancer

ObjectiveThis study aimed to analyze the focal uptake of iodine-131 (131I) in the upper pelvis superior to the urinary bladder on whole-body images of patients who underwent this treatment after thyroidectomy for differentiated thyroid cancer.MethodsBetween June 2012 and March 2013, 205 patients (72 men and 133 women, with an average age of 47.9±11.7 years) who underwent 131I radioactive treatment after thyroid cancer surgery were analyzed retrospectively. Pathological findings confirmed papillary thyroid carcinoma. A whole-body scan was acquired 5 days after 100–120 mCi sodium iodide was administered orally to the patients. Single-photon emission computed tomography/computed tomography (SPECT/CT) scanning was carried out to locate the lesion; this showed abnormal intense activity in the upper pelvis superior to the urinary bladder, which was further evaluated by ultrasonography.ResultsUsing 131I-SPECT scanning, five (3.76%) female patients were shown to have abnormal focal radioactivity in the lower abdomen. Subsequent SPECT/CT examination showed that the radioactivity was located in the cervix in four of the five patients and in the sigmoid colon in one patient. Transvaginal ultrasonography was performed in the former four patients, which revealed several echo-free regions in the cervix. These findings are consistent with the diagnosis of a nabothian cyst. Three of these patients were administered a second course of radioiodine therapy. Radioactive uptake was still visible at the same sites on whole-body imaging.ConclusionNabothian cyst should be considered in cases in which abnormal uptake in the upper pelvis superior to the urinary bladder is detected on 131I whole-body scans after differentiated thyroid cancer resection.

Approach to the Patient: Role of Dosimetric RAI Rx in Children With DTC

Pediatric differentiated thyroid cancer (DTC) patients frequently present with lymph node and/or distant (lung) metastases. Such patients warrant an aggressive treatment consisting of surgical removal of all surgically accessible local metastases as well as further treatment with one or more courses of radioiodine therapy (RAI). It is still a subject of debate in literature how much I-131 should be administered to pediatric patients. Patients can either be given a fixed (possibly body weight adjusted) activity or a dosimetry based activity, which is often considerably higher. Here, we will present a typical case of a pediatric patient who was treated using a dosimetric approach. Then we will discuss the basis of dosimetry and the procedures involved, followed by a discussion of when to use dosimetric RAI as well as the pros and cons of the various approaches in pediatric patients. In general, two opposite approaches to dosimetry exist: either the activity that is as high as safely administrable (AHASA) is determined based on the radiation exposure to the critical organs at risk (in pediatric patients these are the bone marrow and, in patients with lung metastases, the lungs), or a lesion-based approach in which the activity that is required to deliver a certain radiation dose to the metastatic lesion(s) is determined. Because the latter approach requires an accurate volumetry of the target lesion(s), which is not possible in children with disseminated pulmonary metastases, which are often not visible with morphologic imaging techniques, we advocate using the AHASA approach in children with extensive metastatic DTC.

Risk of second primary malignancy in differentiated thyroid carcinoma treated with radioactive iodine therapy

Differentiated thyroid cancer survivors are at increased risk of nonsynchronous second primary malignancy, but the cause remains unclear. This study aimed to evaluate the association between radioiodine therapy and risk of nonsynchronous second primary malignancy and to examine whether the risk of nonsynchronous second primary malignancy in differentiated thyroid cancer survivors treated with radioiodine therapy is increased relative to the general population. Among 895 radiation-naïve patients with differentiated thyroid cancer, 643 (71.8%) received ≥1 course of radioiodine therapy (radioiodine therapy-positive group) and 252 (28.2%) received no radioiodine therapy (radioiodine therapy-negative group). After a median follow-up of 93.5 months (range, 23.4-570.8), 64 (7.2%) patients developed ≥1 nonsynchronous second primary malignancy. Potential risk factors for nonsynchronous second primary malignancy were entered into a multivariable regression model and cancer incidence in the radioiodine therapy-positive and -negative groups were compared to that of the general population by estimating the standardized incidence ratios. The 20-year cumulative nonsynchronous second primary malignancy risk in radioiodine therapy-positive group was significantly higher than radioiodine therapy-negative group (13.5% vs 3.1%; P = .015). Cumulative radioiodine therapy activity of 3.0 to 8.9 GBq (relative risk, 2.77; 95% CI, 1.079-7.154; P = .034) was the only independent risk factor for nonsynchronous second primary malignancy after adjusting for age, sex, period of differentiated thyroid cancer diagnosis, and stage of differentiated thyroid cancer. For females, the standardized incidence ratio in the radioiodine therapy-positive group was 1.54 (95% CI, 1.11-2.08) and in the radioiodine therapy-negative group it was 0.92 (95% CI, 0.37-1.90). Differentiated thyroid cancer female survivors treated by radioiodine therapy appeared to be at elevated risk of nonsynchronous second primary malignancy when compared to the general population and this risk was not apparent in those not previously treated by radioiodine therapy.

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.

Benefit and side effects of radioiodine therapy in radiation-induced childhood thyroid carcinoma

Abstract. After the Chernobyl reactor accident on April 26, 1986, the incidence of thyroid cancer in children and adolescents living in contaminated areas of the Ukraine and Belarus increased significantly. In total, 4600 cases of thyroid cancer have been observed between 1986 and 2002 among those aged 0–18 years at the time of the reactor accident. It is estimated that approximately 40% of those cases are associated with radiation exposure and 60% are spontaneous cases. Starting April 1, 1993, a joint Belarussian–German project on the combined treatment with surgery and radioiodine was launched. Thyroid surgery was performed in the Center for Thyroid Tumors in Minsk, Belarus, and radioiodine therapy followed in Germany at the Universities of Essen (until the end of 1994) and afterwards the University of Wurzburg. Until March 31, 2006, 245 selected children and adolescents with advanced disease had received a total of 995 one-week courses of radioiodine therapy. The number of girls was 147 and the number of boys 98. The age at the time of radioiodine therapy ranged from 7 to 19 years with a mean age of 12.7 ± 2.5 years. Histologically, 243 of the cancers had been classified as papillary and only 2 as follicular cancers. 152 out of those 245 patients suffered from locally advanced tumor stage pT4 (62%). In nearly all of the children (238 out of 245 = 97%) neck lymph node metastases were detected during surgery or follow-up. 104 out of 245 children (42%) revealed distant metastases (nearly all of them to the lungs). Up to now, 234 patients received more than one course of radioiodine therapy so that the effectivity of the preceding treatment course could be checked by a consecutive radioiodine whole-body scan. In total, 131 children (56%) are in complete remission, 70 children (30%) in stable partial remission and 33 children (14%) in partial remission. With respect to the subgroup of children with distant metastases, the rate of complete remissions is 35%, stable partial remissions 34% and partial remissions 31%. All of the children and adolescents treated with radioiodine responded to treatment and are alive. Concerning transient side effects, gastritis with nausea and vomiting is usual especially in small children immediately after application of radioiodine. In 20–30% of the children, acute sialadenitis occurs because of high radioiodine uptake in the salivary glands. In 20% of the children, reversible leuco- and or thrombopenia is observed. Concerning late side effects approximately 10% of female and male adolescents show signs of impairment of gonadal function. In up to 30% of the males oligo- or asthenozoospermia occurs. A permanent Sicca syndrome is to be seen in less than 10% of the patients and in up to 5% of patients with lung metastases radiological signs of pulmonary fibrosis. Fortunately, no single case of leukemia, a secondary solid malignancy, has been observed during the 13-year follow-up of our treatment program.

Efficacy of radioiodine therapy in the treatment of elevated serum thyroglobulin in patients with differentiated thyroid carcinoma and negative whole-body iodine scan

In the management of patients with differentiated thyroid carcinoma, serum thyroglobulin levels are often well correlated with whole-body radioiodine scanning (WBS) results. However, occasionally, a mismatched result - increased thyroglobulin with negative WBS - is observed. Radioiodine therapy has been suggested as a therapeutic choice with controversial results. We studied 32 differentiated thyroid carcinoma patients with elevated thyroglobulin level and negative WBS who had been treated with high-dose radioiodine. With a mean follow-up of 25.6 months (all follow-ups >11 months), thyroglobulin and thyroid-stimulating hormone levels, WBS, clinical, radiographic and pathological findings following treatment were recorded. The mean pre-therapy off-treatment thyroglobulin was 152 +/- 119.0 ng.ml(-1). Although there was a mild trend towards an increase in thyroglobulin in the first post-treatment year, the difference was not significant. At the end of the follow-ups, 22 patients (68.7%) were categorized as non-responders to radioiodine therapy (any change or elevation of thyroglobulin or radiological and pathological evidences of progression), four patients (12.5%) as partial responders (transient reduction but not a normalization of thyroglobulin) and six patients (18.7%) as responders (normalization of thyroglobulin with no evidence of remnant disease). In nine of 10 partial and complete responders, reduction or normalization of thyroglobulin had occurred in the first post-treatment year. We recommend that in differentiated thyroid carcinoma patients with elevated thyroglobulin and negative WBS, at least one course of radioiodine therapy should be undertaken and if reduction or normalization of serum thyroglobulin is not achieved, repeated courses of radioiodine therapy are not logical and other therapeutic methods should be applied.

Respective Roles of Thyroglobulin, Radioiodine Imaging, and Positron Emission Tomography in the Assessment of Thyroid Cancer

Depending on the iodine supply of an area, the incidence of thyroid cancer ranges between 4 and 12/100,000 per year. To detect thyroid cancer in an early stage, the assessment of thyroid nodules includes ultrasonography, ultrasonography-guided fine-needle aspiration biopsy, and conventional scintigraphic methods using (99m)Tc-pertechnetate, (99m)Tc-sestamibi or -tetrofosmin, and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in selected cases. After treatment of thyroid cancer, a consequent follow-up is necessary over a period of several years. For following up low-risk patients, recombinant thyroid-stimulating hormone-stimulated thyroglobulin and ultrasonography is sufficient in most cases. After total thyroidectomy and radioiodine ablation therapy, thyroid-stimulating hormone-stimulated thyroglobulin should be below the detection limit (eg, <0.5 ng/mL, R: 70-130). An increase of thyroglobulin over time is suspicious for recurrent or metastatic disease. Especially in high-risk patients, aside from the use of ultrasonography for the detection of local recurrence and cervial lymph node metastases, nuclear medicine methods such as radioiodine imaging and FDG-PET are the methods of choice for localizing metastatic disease. Radioiodine imaging detects well-differentiated recurrences and metastases with a high specificity but only moderate sensitivity. The sensitivity of radioiodine imaging depends on the activity administered. Therefore a low activity diagnostic (131)I whole-body scan (74-185 MBq) has a lower detection rate than a high activity post-therapy scan (3700-7400 MBq). In patients with low or dedifferentiated thyroid cancer and after several courses of radioiodine therapy caused by metastatic disease, iodine negative metastases may develop. In these cases, despite clearly elevated levels of thyroglobulin, radioiodine imaging is negative or demonstrates only faint iodine uptake. The method of choice to image these iodine negative metastases is FDG-PET. In recent years the combination of PET and computed tomography has been introduced. The fusion of the metabolic and morphologic information was able to increase the diagnostic accuracy, reduces pitfalls and changes therapeutic strategies in a reasonable number of patients.