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1.
Contemporary considerations in adjuvant radioiodine treatment of adults with differentiated thyroid cancer.
Juweid, ME, Tulchinsky, M, Mismar, A, Momani, M, Zayed, AA, Al Hawari, H, Albsoul, N, Mottaghy, FM
International journal of cancer. 2020;(9):2345-2354
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Abstract
Differentiated thyroid cancer (DTC) is the most common endocrine malignancy with a growing incidence worldwide. The initial conventional management is surgery, followed by consideration of 131 I treatment that includes three options. These are termed remnant ablation (targeting benign thyroid remnant), adjuvant (targeting presumed microscopic DTC) and known disease (targeting macroscopic DTC) treatments. Some experts mostly rely on clinicopathologic assessment for recurrence risk to select patients for the 131 I treatment. Others, in addition, apply radioiodine imaging to guide their treatment planning, termed theranostics (aka theragnostics or radiotheragnostics). In patients with low-risk DTC, remnant ablation rather than adjuvant treatment is generally recommended and, in this setting, the ATA recommends a low 131 I activity. 131 I adjuvant treatment is universally recommended in patients with high-risk DTC (a primary tumor of any size with gross extrathyroidal extension) and is generally recommended in intermediate-risk DTC (primary tumor >4 cm in diameter, locoregional metastases, microscopic extrathyroidal extension, aggressive histology or vascular invasion). The optimal amount of 131 I activity for adjuvant treatment is controversial, but experts reached a consensus that the 131 I activity should be greater than that for remnant ablation. The main obstacles to establishing timely evidence through randomized clinical trials for 131 I therapy include years-to-decades delay in recurrence and low disease-specific mortality. This mini-review is intended to update oncologists on the most recent clinical, pathologic, laboratory and imaging variables, as well as on the current 131 I therapy-related definitions and management paradigms, which should optimally equip them for individualized patient guidance and treatment.
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The role of radioactive iodine in the management of patients with differentiated thyroid cancer - An oncologic surgical perspective.
Nixon, IJ, Shah, JP, Zafereo, M, Simo, RS, Hay, ID, Suárez, C, Zbären, P, Rinaldo, A, Sanabria, A, Silver, C, et al
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2020;(5):754-762
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Abstract
With improved understanding of the biology of differentiated thyroid carcinoma its management is evolving. The approach to surgery for the primary tumour and elective nodal surgery is moving from a "one-size-fits-all" recommendation to a more personalised approach based on risk group stratification. With this selective approach to initial surgery, the indications for adjuvant radioactive iodine (RAI) therapy are also changing. This selective approach to adjuvant therapy requires understanding by the entire treatment team of the rationale for RAI, the potential for benefit, the limitations of the evidence, and the potential for side-effects. This review considers the evidence base for the benefits of using RAI in the primary and recurrent setting as well as the side-effects and risks from RAI treatment. By considering the pros and cons of adjuvant therapy we present an oncologic surgical perspective on selection of treatment for patients, both following pre-operative diagnostic biopsy and in the setting of a post-operative diagnosis of malignancy.
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High-specific-activity iodine 131 metaiodobenzylguanidine for the treatment of metastatic pheochromocytoma or paraganglioma: a novel therapy for an orphan disease.
Jimenez, C, Núñez, R, Wendt, R
Current opinion in endocrinology, diabetes, and obesity. 2020;(3):162-169
Abstract
PURPOSE OF REVIEW Pheochromocytomas and paragangliomas represent less than 1% of all endocrine tumors. Approximately 15-20% of these tumors are malignant. The definition of malignancy relies on the presence of metastasis. Metastatic pheochromocytomas and paragangliomas are usually advanced, incurable tumors with limited therapeutic options. About 50-60% of these tumors express the noradrenaline transporter in their cell membranes. Recently, the United States Food and Drug Administration approved high-specific-activity iodine 131 metaiodobenzylguanidine (HSA-I-131-MIBG) for the treatment of metastatic pheochromocytomas and paragangliomas that express the noradrenaline transporter. This review reports the benefits and toxicity of HSA-I-131-MIBG, its physical and dosimetric aspects, and radiation safety precautions, as well as its potential therapeutic value for other malignancies (neuroblastoma, gastroenteropancreatic neuroendocrine tumors, and medullary thyroid carcinoma). RECENT FINDINGS A phase 2 clinical trial with HSA-I-131-MIBG reported an impressive clinical benefit rate, acceptable toxicity and long-term benefits. SUMMARY HSA-I-131-MIBG is an effective medication for metastatic pheochromocytomas and paragangliomas that express the noradrenaline transporter.
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Radioactive Iodine Therapy in Differentiated Thyroid Cancer: 2020 Update.
Ciarallo, A, Rivera, J
AJR. American journal of roentgenology. 2020;(2):285-291
Abstract
OBJECTIVE. The paradigm of theranostics is based on tailoring therapy for the purpose of optimizing outcomes. This principle is being applied to radioactive iodine therapy. Consequently, thyroid cancer therapy protocols are evolving. The purpose of this article is to promote a modern approach to radioiodine therapy. CONCLUSION. This article highlights guidelines and position statements, summarizes the prognostication systems of thyroid cancer, and reviews which prescribed activities of 131I.
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Current controversies in the management of Graves' hyperthyroidism.
Francis, N, Francis, T, Lazarus, JH, Okosieme, OE
Expert review of endocrinology & metabolism. 2020;(3):159-169
Abstract
Introduction: The management of Graves' disease centers on the use of effective and well-established therapies, namely thionamide antithyroid drugs, radioactive iodine, and thyroidectomy. Optimal treatment strategies are however controversial and vary significantly across centers.Areas covered: This review addresses specific controversies in Graves' disease management including the choice of primary therapy, the approach to women planning pregnancy, and optimal strategies for antithyroid drug and radioiodine therapy.Expert opinion: Important considerations in choosing therapy include treatment efficacy, adverse effects, patient convenience, and resource settings. Recent data suggest that early and effective control of hyperthyroidism is key to improving cardiovascular morbidity and mortality. Studies addressing cancer risk in radioiodine-treated patients face methodological challenges and require clarification in appropriately designed studies. Remission rates with antithyroid drugs are comparable when thionamides are used alone (titration-regimen) or in combination with levothyroxine (block and replace) and can be optimized by extending treatment for at least 12-18 months. Fixed and calculated radioiodine activity regimens are both effective but entail a trade-off between convenience and precision in the administered activity. Optimal preconception strategies are still evolving but ablative treatment in advance of pregnancy offers the most pragmatic means of reducing adverse effects of hyperthyroidism in subsequent pregnancy.
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Managing radioiodine refractory thyroid cancer: the role of dosimetry and redifferentiation on subsequent I-131 therapy.
Dotinga, M, Vriens, D, van Velden, F, Heijmen, L, Nagarajah, J, Hicks, R, Kapiteijn, E, de Geus-Oei, LF
The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of.... 2020;(3):250-264
Abstract
Poor responses to iodine-131 (I-131) therapy can relate to either low iodine uptake and retention in thyroid cancer cells or to increased radioresistance. Both mechanisms are currently termed radioactive iodine (RAI)-refractory (RAI-R) thyroid cancer but the first reflects unsuitability for I-131 therapy that can be evaluated in advance of treatment, whereas the other can only be identified post hoc. Management of both represents a considerable challenge in clinical practice as failure of I-131 therapy, the most effective treatment of metastatic thyroid cancer, is associated with a poor overall prognosis. The development of targeted therapies has shown substantial promise in the treatment of RAI-R thyroid cancer in progressive patients. Recent studies show that selective tyrosine kinase inhibitors (TKIs) targeting B-type rapidly accelerated fibrosarcoma kinase (BRAF) and mitogen-activated protein kinase (MEK) can be used as redifferentiation agents to re-induce RAI uptake, thereby (re)enabling I-131 therapy. The use of dosimetry prior- and post-TKI treatment can assist in quantifying RAI uptake and improve identification of patients that will benefit from I-131 therapy. It also potentially offers the prospect of calculating individualized therapeutic administered activities to enhance efficacy and limit toxicity. In this review, we present an overview of the regulation of RAI uptake and clinically investigated redifferentiation agents, both reimbursed and in experimental setting, that induce renewed RAI uptake. We describe the role of dosimetry in redifferentiation and subsequent I-131 therapy in RAI-R thyroid cancer, explain different dosimetry approaches and discuss limitations and considerations in the field.
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Brachytherapy for meningiomas.
Magill, ST, Schwartz, TH, Theodosopoulos, PV, McDermott, MW
Handbook of clinical neurology. 2020;:303-307
Abstract
Interstitial intracranial radiotherapy implants, or brachytherapy, is an adjuvant option for treatment of recurrent high-grade meningiomas after resection. The implants are placed in the resection cavity following tumor resection. The most commonly used isotope is Iodine-125 (I-125). While there are no controlled studies comparing treatment of meningiomas with or without brachytherapy, several case series report good long-term survival, suggesting that this may be a useful adjuvant for recurrent high-grade tumors. Complications can occur including radiation necrosis, impaired wound healing, hydrocephalus and infection. In the future, new isotopes are being explored that may have fewer complications and better safety profiles.
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Lenvatinib complementary with radioiodine therapy for patients with advanced differentiated thyroid carcinoma: case reports and literature review.
Sheu, NW, Jiang, HJ, Wu, CW, Chiang, FY, Chiou, HC, Hsiao, PJ
World journal of surgical oncology. 2019;(1):84
Abstract
BACKGROUND The 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 PRESENTATION Here, 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. CONCLUSION Our 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.
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Radioactive Iodine-Refractory Differentiated Thyroid Cancer and Redifferentiation Therapy.
Liu, J, Liu, Y, Lin, Y, Liang, J
Endocrinology and metabolism (Seoul, Korea). 2019;(3):215-225
Abstract
The retained functionality of the sodium iodide symporter (NIS) expressed in differentiated thyroid cancer (DTC) cells allows the further utilization of post-surgical radioactive iodine (RAI) therapy, which is an effective treatment for reducing the risk of recurrence, and even the mortality, of DTC. Whereas, the dedifferentiation of DTC could influence the expression of functional NIS, thereby reducing the efficacy of RAI therapy in advanced DTC. Genetic alternations (such as BRAF and the rearranged during transfection [RET]/papillary thyroid cancer [PTC] rearrangement) have been widely reported to be prominently responsible for the onset, progression, and dedifferentiation of PTC, mainly through activating the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling cascades. These genetic alternations have been suggested to associate with the reduced expression of iodide-handling genes in thyroid cancer, especially the NIS gene, disabling iodine uptake and causing resistance to RAI therapy. Recently, novel and promising approaches aiming at various targets have been attempted to restore the expression of these iodine-metabolizing genes and enhance iodine uptake through in vitro studies and studies of RAI-refractory (RAIR)-DTC patients. In this review, we discuss the regulation of NIS, known mechanisms of dedifferentiation including the MAPK and PI3K pathways, and the current status of redifferentiation therapy for RAIR-DTC patients.
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Expert consensus on computed tomography-assisted three-dimensional-printed coplanar template guidance for interstitial permanent radioactive 125I seed implantation therapy.
Wang, J, Chai, S, Wang, R, Zheng, G, Zhang, K, Huo, B, Huo, X, Jiang, Y, Ji, Z, Jiang, P, et al
Journal of cancer research and therapeutics. 2019;(7):1430-1434
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Abstract
Interstitial permanent radioactive seed implantation delivers a high local dose to tumors and sharply drops off at surrounding normal tissues. Radioactive seeds implanted via ultrasound or computed tomography (CT) guidance are minimally invasive and facilitate quick recovery. Transrectal ultrasound-guided 125I seed implantation assisted by a transperineal plane template is standard for early-stage prostate carcinoma, with a highly consistent target volume dose distribution. The postplan dose evaluation is consistent with the preplan evaluation. Until now, there was no workflow for seed implantation elsewhere in the body, and it was difficult to effectively preplan for seed implantation because of patients' position changes, organ movement, and bone structure interference. Along with three-dimensional (3D) printing techniques and seed implantation planning systems for brachytherapy, coplanar and X Y axis coordinate templates were created, referred to as 3D-printed coplanar templates (3D-PCT). 125I seed implantation under CT guidance with 3D-PCT assistance has been very successful in some carcinomas. Preplanning was very consistent with postplanning of the gross tumor volume. All needles are kept parallel for 3D-PCT, with no coplanar needle rearrangement. No standard workflow for 3D-PCT-assisted seed implantation exists at present. The consensus topics for CT-assisted guidance compared to 3D-PCT-assisted guidance for seed implantation are as follows: Indications for seed implantation, preplanning, definition of radiation doses and dosimetry evaluation, 3D-PCT workflow, radiation protection, and quality of staff. Despite current data supporting 125I seed implantation for some solid carcinomas, there is a need for prospectively-randomized multicenter clinical trials to gather strong evidence for using 125I seed implantation in other solid carcinomas.