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Oncology 2023Therapy-related leukemia is a term that describes the occurrence of leukemia following exposure to hematotoxins and radiation to emphasize the difference from leukemia... (Review)
Review
BACKGROUND
Therapy-related leukemia is a term that describes the occurrence of leukemia following exposure to hematotoxins and radiation to emphasize the difference from leukemia that arises de novo. Many agents and host factors contribute to this entity of leukemias. Therapy-related acute myeloid leukemia has an extensive literature review in contrast to therapy-related chronic myeloid leukemia (t-CML). Radioactive iodine (RAI), an established agent in the management of differentiated thyroid carcinomas, has raised concern due to its possible carcinogenic effects.
SUMMARY
In this article, we reviewed all the reports from the 1960s to date related to t-CML following RAI on Google Scholar and PubMed. We have identified 14 reports and found that most reports were for men under the age of 60 years with primary papillary thyroid carcinoma and mixed follicular-papillary thyroid carcinoma who developed t-CML mainly between 4 and 7 years after exposure to varying doses of I131. However, the mean dose was 287.78 millicuries (mCi). It was reported that a statistically significant increase in leukemia following RAI therapy (relative risk of 2.5 for I131 vs. no I131). Also, there was a linear relationship between the cumulative dose of I131 and the risk of leukemia. Doses higher than 100 mCi were associated with a greater risk of developing secondary leukemia, and most of the leukemias developed within the initial 10 years of exposure. The precise mechanism through which RAI provokes leukemia is largely unclear. A few mechanisms have been proposed.
KEY MESSAGES
Although the risk for t-CML appears to be low based on current reports and does not represent a contraindication to RAI therapy, it should not be disregarded. We suggest including it in the risk-benefit discussion before initiating this therapy. Long-term follow-up for patients is advisable for those who received doses over 100 mCi with a complete blood count, possibly yearly, for the first 10 years. The new onset of significant leukocytosis post RAI exposure should raise the suspicion for t-CML. Further studies are needed to establish or refute a causal relationship.
Topics: Male; Humans; Middle Aged; Thyroid Neoplasms; Iodine Radioisotopes; Thyroid Cancer, Papillary; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Risk Assessment
PubMed: 37231874
DOI: 10.1159/000530463 -
Journal of Veterinary Internal Medicine Mar 2017Radioiodine ( I) is effective treatment for hyperthyroidism in cats, but optimal dose to restore euthyroidism without inducing hypothyroidism is unclear....
BACKGROUND
Radioiodine ( I) is effective treatment for hyperthyroidism in cats, but optimal dose to restore euthyroidism without inducing hypothyroidism is unclear. Treatment-induced hypothyroidism can lead to azotemia and reduced duration of survival.
OBJECTIVE
To compare efficacy and short-term outcomes of low-dose I versus higher, standard-dose I as treatment for hyperthyroidism.
ANIMALS
A total of 189 client-owned cats undergoing I treatment for mild-to-moderate hyperthyroidism (serum T ≥ 4.0 μg/dL and <13.0 μg/dL).
METHODS
Prospective, nonrandomized, cohort study comparing treatment with either low-dose (2 mCi, n = 150) or standard-dose (4 mCi, n = 39) I. Serum T , thyroid-stimulating hormone (TSH), and creatinine concentrations were measured after 1, 3, and 6 months to determine persistent hyperthyroidism, overt hypothyroidism (low T , high TSH), subclinical hypothyroidism (normal T , high TSH), and azotemia.
RESULTS
There was no significant difference in prevalence of cats with persistent hyperthyroidism between standard- and low-dose treatment groups at 3 (0% versus 5.3%; P = .34) and 6 (0% versus 3.3%; P = .51) months. Overt (18% versus 1%; P = .0005) or subclinical (46% versus 21%; P = .004) hypothyroidism was more common in cats at 6 months after standard-dose I. No difference in incidence of azotemia existed between groups, but cats treated with standard-dose I had higher creatinine concentrations (P < .05) and higher percent rises in creatinine (P < .0001).
CONCLUSIONS AND CLINICAL IMPORTANCE
Low-dose I is safe and effective for cats with mild-to-moderate hyperthyroidism, as evidenced by a cure rate of >95% with reduced frequency of iatrogenic hypothyroidism and azotemia.
Topics: Animals; Azotemia; Cat Diseases; Cats; Creatinine; Female; Hyperthyroidism; Hypothyroidism; Iodine Radioisotopes; Male; Prospective Studies; Thyrotropin; Thyroxine; Treatment Outcome
PubMed: 28158908
DOI: 10.1111/jvim.14646 -
Clinical and Molecular Hepatology Jun 2016Iodine-131 is a radioisotope that is routinely used for the treatment of differentiated thyroid cancer after total or near-total thyroidectomy. However, there is some...
Iodine-131 is a radioisotope that is routinely used for the treatment of differentiated thyroid cancer after total or near-total thyroidectomy. However, there is some evidence that iodine-131 can induce liver injury . Here we report a rare case of drug-induced liver injury (DILI) caused by iodine-131 in a patient with regional lymph node metastasis after total thyroidectomy. A 47-year-old woman was admitted with elevated liver enzymes and symptoms of general weakness and nausea. Ten weeks earlier she had undergone a total thyroidectomy for papillary thyroid carcinoma and had subsequently been prescribed levothyroxine to reduce the level of thyroid-stimulating hormone. Eight weeks after surgery she underwent iodine-131 ablative therapy at a dose of 100 millicuries, and subsequently presented with acute hepatitis after 10 days. To rule out all possible causative factors, abdominal ultrasonography, endoscopic ultrasonography (on the biliary tree and gall bladder), and a liver biopsy were performed. DILI caused by iodine-131 was suspected. Oral prednisolone was started at 30 mg/day, to which the patient responded well.
Topics: Abdomen; Chemical and Drug Induced Liver Injury; Female; Humans; Iodine Radioisotopes; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Prednisolone; Thyroid Neoplasms; Thyroidectomy; Thyroxine; Ultrasonography
PubMed: 27209646
DOI: 10.3350/cmh.2015.0037 -
Blood Feb 2018Pretargeted radioimmunotherapy (PRIT) has demonstrated remarkable efficacy targeting tumor antigens, but immunogenicity and endogenous biotin blocking may limit clinical...
Pretargeted radioimmunotherapy (PRIT) has demonstrated remarkable efficacy targeting tumor antigens, but immunogenicity and endogenous biotin blocking may limit clinical translation. We describe a new PRIT approach for the treatment of multiple myeloma (MM) and other B-cell malignancies, for which we developed an anti-CD38-bispecific fusion protein that eliminates endogenous biotin interference and immunogenic elements. In murine xenograft models of MM and non-Hodgkin lymphoma (NHL), the CD38-bispecific construct demonstrated excellent blood clearance and tumor targeting. Dosimetry calculations showed a tumor-absorbed dose of 43.8 Gy per millicurie injected dose of Y, with tumor-to-normal organ dose ratios of 7:1 for liver and 15:1 for lung and kidney. In therapy studies, CD38-bispecific PRIT resulted in 100% complete remissions by day 12 in MM and NHL xenograft models, ultimately curing 80% of mice at optimal doses. In direct comparisons, efficacy of the CD38 bispecific proved equal or superior to streptavidin (SA)-biotin-based CD38-SA PRIT. Each approach cured at least 75% of mice at the highest radiation dose tested (1200 µCi), whereas at 600- and 1000-µCi doses, the bispecific outperformed the SA approach, curing 35% more mice overall ( < .004). The high efficacy of bispecific PRIT, combined with its reduced risk of immunogenicity and endogenous biotin interference, make the CD38 bispecific an attractive candidate for clinical translation. Critically, CD38 PRIT may benefit patients with unresponsive, high-risk disease because refractory disease typically retains radiation sensitivity. We posit that PRIT might not only prolong survival, but possibly cure MM and treatment-refractory NHL patients.
Topics: ADP-ribosyl Cyclase 1; Animals; Antibodies, Bispecific; CHO Cells; Cell Line, Tumor; Cricetinae; Cricetulus; Female; Humans; Leukemia, B-Cell; Lymphoma, B-Cell; Mice, Nude; Molecular Targeted Therapy; Multiple Myeloma; Radioimmunotherapy; Xenograft Model Antitumor Assays
PubMed: 29158362
DOI: 10.1182/blood-2017-09-807610 -
Pharmaceutics Jul 2019Trans-nasal pulmonary aerosol delivery using high flow nasal cannula (HFNC) devices is described with the administration of high gas flows exceeding patient inspiratory...
BACKGROUND
Trans-nasal pulmonary aerosol delivery using high flow nasal cannula (HFNC) devices is described with the administration of high gas flows exceeding patient inspiratory flow (HF) and with lower flows (LF). The aim of this pilot clinical trial was to compare deposition and distribution of radiolabeled aerosol via nasal cannula in healthy adults across three rates of gas flow delivered with active heated humidification, and to further identify the impact of aerosol administration without heated humidity.
METHODS
Twenty-three (23) healthy adults (16F) were randomized to receive aerosol with active heated humidification or unheated oxygen at gas flows of 10 L/min ( = 8), 30 L/min ( = 7), or 50 L/min ( = 8). Diethylenetriaminepentaacetic acid labeled with 1 millicurie (37 MBq) of Technetium-99m (DTPA-Tc99m) was mixed with NaCl to a fill volume of 1 mL, and administered via mesh nebulizer placed at the inlet of the humidifier. Radioactivity counts were performed using a gamma camera and the regions of interest (ROIs) were delimited with counts from the lungs, upper airways, stomach, nebulizer, circuit, and expiratory filter. A mass balance was calculated and each compartment was expressed as a percentage of the total.
RESULTS
Lung deposition (mean ± SD) with heated humidified gas was greater at 10 L/min than 30 L/min or 50 L/min (17.2 ± 6.8%, 5.71 ± 2.04%, and 3.46 ± 1.24%, respectively; = 0.0001). Using unheated carrier gas, a lung dose of aerosol was similar to the active heated humidification condition at 10 L/min, but greater at 30 and 50 L/min ( = 0.011). Administered gas flow and lung deposition were negatively correlated ( = -0.880, < 0.001).
CONCLUSIONS
Both flow and active heated humidity inversely impact aerosol delivery through HFNC. Nevertheless, aerosol administration across the range of commonly used flows can provide measurable levels of lung deposition in healthy adult subjects (NCT02519465).
PubMed: 31284680
DOI: 10.3390/pharmaceutics11070320 -
Journal of Veterinary Internal Medicine Nov 2018Radioiodine is the treatment of choice for hyperthyroidism in cats. The ideal method of dose determination of radioiodine remains controversial.
BACKGROUND
Radioiodine is the treatment of choice for hyperthyroidism in cats. The ideal method of dose determination of radioiodine remains controversial.
OBJECTIVE
To compare a method of radioiodine dose determination that utilized thyroid scintigraphy with a standard fixed dose for treatment of hyperthyroidism.
ANIMALS
Fifty-seven and 23 client-owned hyperthyroid cats in the variable and fixed dose groups, respectively.
METHODS
Cats with a percent dose uptake using Tc-pertechnetate uptake on thyroid scintigraphy <5%, 5%-10%, and >10% were to receive 3, 3.5, or 4.5 millicuries (mCi) of radioiodine, respectively, administered SC. Radioiodine dose was adjusted according to thyroid gland size as determined by the thyroid:salivary size ratio and categorized as <5:1, 5-10:1, and >10:1. If the thyroid size fell into a higher dosing category than the percent dose uptake, the dose was increased accordingly. Cats in the fixed dose group received 4.5 mCi. Six months after treatment, cats were determined to be euthyroid, hypothyroid, or hyperthyroid based on serum thyroxine and thyroid stimulating hormone concentrations.
RESULTS
No difference in outcome was found between the variable and fixed dose treatment groups. Euthyroidism, hypothyroidism, and persistent hyperthyroidism developed in 61, 30, and 9% of cats in the fixed dose group compared to 58, 26, and 16%, respectively, in the variable dose group.
CONCLUSIONS
A variable dosing method of radioiodine based on percent dose uptake primarily and thyroid gland size secondarily did not improve outcome compared to a standard fixed dose method.
Topics: Animals; Cat Diseases; Cats; Drug Dosage Calculations; Female; Hyperthyroidism; Iodine Radioisotopes; Male; Treatment Outcome
PubMed: 30328158
DOI: 10.1111/jvim.15296 -
AACE Clinical Case Reports 2019The objective of this report is to present an unusual case of intramedullary spinal cord metastasis (ISCM) as the presenting feature of papillary thyroid carcinoma (PTC).
OBJECTIVE
The objective of this report is to present an unusual case of intramedullary spinal cord metastasis (ISCM) as the presenting feature of papillary thyroid carcinoma (PTC).
METHODS
The presented case includes clinical, biochemical, and imaging findings as well as surgical and pathology reports. Treatment with radioactive iodine (RAI) and the response to this treatment are presented.
RESULTS
A 71-year-old woman was evaluated for debilitating low back pain and walking disability. Magnetic resonance imaging demonstrated an oval, lumbar, intramedullary mass with benign features and surgery was scheduled. On preoperative evaluation for the lumbar mass, a multinodular thyroid goiter (unfortunately overlooked previously) was noticed, causing severe narrowing of the trachea. Total thyroidectomy was performed with a pathology diagnosis of PTC. In a second operation, the lumbar lesion was removed and proved to represent metastatic PTC. External beam radiation was subsequently administered to the thyroid bed, lumbar spine, and other skeletal metastases, followed by 150 milliCurie of RAI. A post-treatment scan showed high uptake over the lumbar spine, and skeletal and lung lesions. Clinically, the patient restored her walking ability and back pain improved.
CONCLUSION
ISCM rarely is the presenting feature of PTC. Our patient presented with back pain which is the typical, though non-specific symptom, of ISCM. She showed good clinical response to multimodal treatment which is in line with the few other differentiated thyroid cancer patients with ISCM reported in the literature. Prompt surgical resection, followed by external beam radiation and RAI, may improve neurological signs, alleviate pain, and improve quality of life.
PubMed: 31967051
DOI: 10.4158/ACCR-2019-0072 -
Cureus May 2022Background Radioactive iodine (RAI) is the treatment of choice for most patients with primary hyperthyroidism. The most common etiologies of hyperthyroidism are Graves'...
Background Radioactive iodine (RAI) is the treatment of choice for most patients with primary hyperthyroidism. The most common etiologies of hyperthyroidism are Graves' disease (GD), toxic adenoma (TA), and toxic multinodular goiter (TMNG). A single dose of RAI is usually sufficient to cure hyperthyroidism. The aim of this study was to assess the effectiveness of RAI therapy for patients diagnosed with primary hyperthyroidism. Methods and materials Patients diagnosed with hyperthyroidism who received RAI therapy between 2008 and 2018 were included in the study. The data was acquired from the hospital's electronic medical record system. Following the RAI treatment, a cure was defined as the development of euthyroidism or hypothyroidism after a single fixed-dose without antithyroid medication within one year of RAI therapy. In addition, a simple logistics regression model was used to identify the prognostic factors that may lead to better outcomes. Results A total of 112 patients diagnosed with hyperthyroidism with a mean age of 47 ± 14 were included in this study. The majority of the patients were female, 79 (70.5%). Within one year of RAI therapy, 84 (75%) patients achieved a cure that is either hypothyroid or euthyroid status. RAI dose was higher in responsive patients (18.50 ± 4.10 millicurie [mCi] versus 16.50 ± 4.10 mCi) than in non-responsive patients. The mean RAI doses were 16.05 ± 2.99 mCi in GD, 19.81 ± 4.40 mCi in TMNG, and 20.50 ± 3.30 mCi in TA, with a statistically significant p-value of 0.001. In the univariable logistic regression model, RAI dose was a significant prognostic factor of the responsive group (OR: 1.15, CI [1.01-1.31], p-value 0.03). Conclusion Our data presented that RAI therapy is effective for primary hyperthyroidism. We achieved remission with a single fixed-dose in the majority of patients. Most of our patients were cured within three months of RAI therapy. In addition, the RAI dose was higher in the responsive group as compared to the non-responsive group.
PubMed: 35719786
DOI: 10.7759/cureus.24992 -
Indian Journal of Surgical Oncology Mar 2022The real-world patterns of TKI use in differentiated thyroid cancer (DTC) are largely governed by the accessibility and financial feasibility of the patient with more...
The real-world patterns of TKI use in differentiated thyroid cancer (DTC) are largely governed by the accessibility and financial feasibility of the patient with more sorafenib use compared to lenvatinib. There are limited data available on the toxicity profile, safety and tolerance of sorafenib and lenvatinib in DTC. Hence, we audited our practice on DTC. This is a retrospective single-centre analysis of patients with DTC who were referred to the Department of Medical Oncology for systemic therapy. Baseline demographics (age, sex, ECOG PS, comorbidities, substance use), tumour details (site of metastasis), previous treatment details, clinical features at metastasis (symptoms), the pattern of treatment, adverse events and outcomes including progression and death were extracted. There were 67 patients with DTC referred for systemic therapy; the median age was 56 (33-81) with a male preponderance (55.6%). The most common reason to start TKI therapy was radioactive iodine (RAI) cumulative dose > 600 milliCurie, followed by low iodine uptake in the RAI low-dose scan done at progression. The most common TKI used in the first line was sorafenib in 56 (83.6%) patients followed by lenvatinib in 9 (13.4%) patients. Papillary thyroid carcinoma was the most common histology (51, 76.1%), and the rest were follicular carcinoma (16, 23.9%). With a median follow-up of 36 months, the median PFS was 13.2 months (95% CI 10.4-16.0). The median OS was 18.8 months (95% CI 10.0-27.6). Among variables tested, no factors had a significant impact on the PFS or OS. The most common adverse events were hand-foot syndrome (54, 80.5%), diarrhoea (23, 33.3%) and transaminitis (24, 34.4%). The pattern of care of patients with RAI-refractory DTC is TKI therapy, especially sorafenib and lenvatinib in the real-world settings with comparable efficacy and safety profile compared to international literature.
PubMed: 35462674
DOI: 10.1007/s13193-021-01445-y -
Journal of Labelled Compounds &... Sep 2016The radiosynthesis of [(18) F]DCFPyL on 2 distinct automated platforms with full regulatory compliant quality control specifications is described. The radiotracer...
The radiosynthesis of [(18) F]DCFPyL on 2 distinct automated platforms with full regulatory compliant quality control specifications is described. The radiotracer synthesis was performed on a custom-made radiofluorination module and the Sofie Biosciences ELIXYS. The radiofluorination module synthesis was accomplished in an average of 66 minutes from end of bombardment with an average specific activity at end of synthesis (EOS) of 4.4 TBq/μmol (120 Ci/μmol) and an average radiochemical yield of 30.9% at EOS. The ELIXYS synthesis was completed in an average of 87 minutes with an average specific activity of 2.2 TBq/μmol (59.3 Ci/μmol) and an average radiochemical yield of 19% at EOS. Both synthesis modules produced large millicurie quantities of [(18) F]DCFPyL while conforming to all standard US Pharmacopeia Chapter <823> acceptance testing criteria.
Topics: Antigens, Surface; Chemistry Techniques, Synthetic; Enzyme Inhibitors; Glutamate Carboxypeptidase II; Humans; Isotope Labeling; Lysine; Radiochemistry; Urea
PubMed: 27470935
DOI: 10.1002/jlcr.3430