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1.
Does Radioactive Iodine Therapy for Hyperthyroidism Cause Cancer?
Kim, BW
The Journal of clinical endocrinology and metabolism. 2022;(2):e448-e457
Abstract
Radioactive iodine has been considered a safe and effective therapeutic option for hyperthyroidism secondary to Graves disease and autonomously functioning thyroid nodules since the mid-20th century. The question of whether I-131 at the doses used for hyperthyroidism might increase the risk of cancer has been investigated in a number of observational cohort studies over the years, with the preponderance of evidence being reassuring as to its safety. In particular, the 1998 Cooperative Thyrotoxicosis Therapy Follow-up Study (CTTFUS) has been widely cited as compelling evidence that I-131 is safe in hyperthyroidism therapy with respect to carcinogenesis. However, in 2019, a study by Kitahara and colleagues re-analyzed the CTTFUS cohort, extending the follow-up time and applying a novel dosimetric model for estimating tissue absorbed doses of radiation. This new analysis concluded that radioactive iodine was associated with an increased risk for mortality from overall cancer, breast cancer, and non-breast solid cancers. Reaction to this study was vociferous and particularly negative in the nuclear medicine literature. This mini-review was inspired by the 2019 CTTFUS controversy, and it is intended to provide the necessary context for clinicians to provide nuanced advice to their patients on the subject. To that end, the pre-2019 literature is surveyed, the 2019 CTTFUS study and a 2020 follow-up are discussed, and lessons from the literature and critical commentaries are considered.
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2.
131I-metaiodobenzylguanidine and peptide receptor radionuclide therapy in pheochromocytoma and paraganglioma.
Jungels, C, Karfis, I
Current opinion in oncology. 2021;(1):33-39
Abstract
PURPOSE OF REVIEW Pheochromocytomas and paragangliomas are rare tumors arising, respectively, from the adrenal medulla and extra-adrenal sympathetic or parasympathetic paraganglia. The main therapeutic objectives in case of metastatic disease are the reduction of tumor burden and the control of symptoms resulting from excessive catecholamine secretion. Treatment choices constitute not only a wait and see attitude, locoregional approaches, chemotherapy regiments but also radiopharmaceutical agents, and they should be discussed in a specialized multidisciplinary board. This review will briefly discuss the radiopharmaceutical modalities in patients with pheochromocytomas and paragangliomas (I-MIBG and PRRT). RECENT FINDINGS I-MIBG (Azedra) has received FDA approval for patients with iobenguane-scan-positive, unresectable, locally advanced or metastatic pheochromocytomas and paragangliomas who require systemic anticancer therapy, whereas peptide receptor radionuclide therapy using radiolabelled somatostatin analogues is currently performed in compassionate use, with very promising results. No prospective head-to-head comparison between the modalities has been conducted to date. SUMMARY Promising results have been reported for both radiopharmaceutical agents, mostly in the setting of retrospective series. No prospective head-to-head comparison between the modalities is yet available.
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3.
Kinase-Inhibitors in Iodine-Refractory Differentiated Thyroid Cancer-Focus on Occurrence, Mechanisms, and Management of Treatment-Related Hypertension.
Kaae, AC, Kreissl, MC, Krüger, M, Infanger, M, Grimm, D, Wehland, M
International journal of molecular sciences. 2021;(22)
Abstract
Differentiated thyroid cancer (DTC) usually has a good prognosis when treated conventionally with thyroidectomy, radioactive iodine (RAI) and thyroid-stimulating hormone suppression, but some tumors develop a resistance to RAI therapy, requiring alternative treatments. Sorafenib, lenvatinib and cabozantinib are multikinase inhibitors (MKIs) approved for the treatment of RAI-refractory DTC. The drugs have been shown to improve progression-free survival (PFS) and overall survival (OS) via the inhibition of different receptor tyrosine kinases (RTKs) that are involved in tumorigenesis and angiogenesis. Both sorafenib and lenvatinib have been approved irrespective of the line of therapy for the treatment of RAI-refractory DTC, whereas cabozantinib has only been approved as a second-line treatment. Adverse effects (AEs) such as hypertension are often seen with MKI treatment, but are generally well manageable. In this review, current clinical studies will be discussed, and the toxicity and safety of sorafenib, lenvatinib and cabozantinib treatment will be evaluated, with a focus on AE hypertension and its treatment options. In short, treatment-emergent hypertension (TE-HTN) occurs with all three drugs, but is usually well manageable and leads only to a few dose modifications or even discontinuations. This is emphasized by the fact that lenvatinib is widely considered the first-line drug of choice, despite its higher rate of TE-HTN.
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4.
Neuroendocrine Tumor Theranostics: An Update and Emerging Applications in Clinical Practice.
Sheikhbahaei, S, Sadaghiani, MS, Rowe, SP, Solnes, LB
AJR. American journal of roentgenology. 2021;(2):495-506
Abstract
OBJECTIVE. Theranostics have shown great promise for delivering precision medicine, particularly in neuroendocrine tumors (NETs). The clinical applications of radiolabeled somatostatin analogues in imaging and radionuclide therapy have been rapidly increasing over the past 2 decades and are currently integrated into the management guidelines of NETs. This article summarizes the available literature on different somatostatin receptor-targeting radiopharmaceuticals with theranostic potential in NETs, pheochromocytomas, and paragangliomas. We discuss the clinical application, administration, and toxicity of recent FDA-approved radionuclide therapies, including 177Lu-DOTATATE in advanced gastroenteropancreatic NETs and 131I-MIBG in advanced paragangliomas and pheochromocytomas. CONCLUSION. Several studies support the safety and clinical efficacy of peptide receptor radionuclide therapies in disease control and quality-of-life improvement in patients with NETs and report potential benefits of combined radionuclide treatment approaches. The utility and pitfalls of functional imaging in therapy response assessment and surveillance of NETs remain to be established.
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5.
High-Specific-Activity-131I-MIBG versus 177Lu-DOTATATE Targeted Radionuclide Therapy for Metastatic Pheochromocytoma and Paraganglioma.
Jha, A, Taïeb, D, Carrasquillo, JA, Pryma, DA, Patel, M, Millo, C, de Herder, WW, Del Rivero, J, Crona, J, Shulkin, BL, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2021;(11):2989-2995
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Abstract
Targeted radionuclide therapies (TRT) using 131I-metaiodobenzylguanidine (131I-MIBG) and peptide receptor radionuclide therapy (177Lu or 90Y) represent several of the therapeutic options in the management of metastatic/inoperable pheochromocytoma/paraganglioma. Recently, high-specific-activity-131I-MIBG therapy was approved by the FDA and both 177Lu-DOTATATE and 131I-MIBG therapy were recommended by the National Comprehensive Cancer Network guidelines for the treatment of metastatic pheochromocytoma/paraganglioma. However, a clinical dilemma often arises in the selection of TRT, especially when a patient can be treated with either type of therapy based on eligibility by MIBG and somatostatin receptor imaging. To address this problem, we assembled a group of international experts, including oncologists, endocrinologists, and nuclear medicine physicians, with substantial experience in treating neuroendocrine tumors with TRTs to develop consensus and provide expert recommendations and perspectives on how to select between these two therapeutic options for metastatic/inoperable pheochromocytoma/paraganglioma. This article aims to summarize the survival outcomes of the available TRTs; discuss personalized treatment strategies based on functional imaging scans; address practical issues, including regulatory approvals; and compare toxicities and risk factors across treatments. Furthermore, it discusses the emerging TRTs.
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6.
Current approach to surgical management of hyperthyroidism.
Barczyński, M
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.... 2021;(2):124-131
Abstract
Hyperthyroidism is a set of disorders that involve excess synthesis and secretion of thyroid hormones by the thyroid gland, which leads to thyrotoxicosis. The most common forms of hyperthyroidism include diffuse toxic goiter (Graves' disease), toxic multinodular goiter (Plummer disease), and a solitary toxic adenoma. The most reliable screening measure of thyroid function is the thyroid-stimulating hormone (TSH) level. Options for treatment of hyperthyroidism include: antithyroid drugs, radioactive iodine therapy (the preferred treatment of hyperthyroidism among US thyroid specialists), or thyroidectomy. Massive thyroid enlargement with compressive symptoms, a suspicious nodule, Graves' orbitopathy, and patient preference are indications for surgical treatment of thyrotoxicosis. This paper reviews the current literature and controversies on the surgical approach to the management of hyperthyroidism.
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7.
Dosimetry study of three-dimensional print template for 125I implantation therapy.
Chen, E, Zhang, Y, Zhang, H, Jia, C, Liang, Y, Wang, J
Radiation oncology (London, England). 2021;(1):115
Abstract
BACKGROUND 125I seed implantation has been found to show good therapeutic effects on tumors. Recent studies showed that three-dimensional (3D) print template-assisted 125I seed implantation can optimize radiation dose distribution. This study aimed to compare the dose distribution differences in 125I seed implantation among 3D print noncoplanar template- (3DPNCT), 3D print coplanar template- (3DPCT) assisted implantation and traditional free-hand implantation. METHODS We systematically searched the PubMed, EMbase, Cochrane Library, Wan Fang Med Online, China National Knowledge Infrastructure (CNKI) from the earliest to November 2020 without time or language restrictions. And the references of primary literature were also searched. The outcome measures were dosimetry and operation time. This meta-analysis was carried out using Stata 12.0. RESULTS A total of 16 original articles were selected for inclusion. The differences of D90, D100, V90, and V100 values pre- and post-implantation with traditional free-hand implantation showed statistically significant (p < 0.05). The differences of D90, D100, V100, V150, V200, and D2cc of organs at risk (OAR) values pre- and post-implantation with 3D print template showed no statistically significant (p > 0.05). Compared with traditional free-hand implantation without any templates, 3D print template could improve postoperative D90 (Standard mean difference, SMD = 0.67, 95% confidence interval (CI) = 0.35 to 0.98, p < 0.001), D100 (SMD = 0.82, 95%CI = 0.40 to 1.23, p < 0.001), V90 (SMD = 1.48, 95%CI = 0.95 to 2.00, p < 0.001), V100 (SMD = 1.41, 95%CI = 0.96 to 1.86, p < 0.001), and reduce operation time (SMD = - 0.93, 95%CI = - 1.34 to - 0.51, p < 0.001). In three studies, both 3DPNCT and 3DPCT plans were designed for all patients. The prescribed dose and seed activity were same. Pooled analysis of D90, D100, V100, D2cc of OAR, number of seeds and number of needles showed no significant differences between 3DPNCT and 3DPCT groups (p > 0.05). However, in 3DPNCT group, V150 and V200 were increased (SMD = 0.35, 0.49; 95%CI = 0.04 to 0.67, 0.02 to 0.96; p = 0.028, 0.043); the number of through bone needles was reduced (SMD = - 1.03, 95%CI = - 1.43 to - 0.64, p < 0.001). CONCLUSIONS Compared with traditional free-hand implantation, 3D print template-assisted 125I seeds implantation can optimize dose distribution and reduce the implantation time at the same time. Compared with 3D print coplanar template, 3D print noncoplanar template can increase the volume of high dose within tumor target and is more safer in the respect of puncture route.
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8.
Novel Therapeutics in Radioactive Iodine-Resistant Thyroid Cancer.
Fullmer, T, Cabanillas, ME, Zafereo, M
Frontiers in endocrinology. 2021;:720723
Abstract
Iodine-resistant cancers account for the vast majority of thyroid related mortality and, until recently, there were limited therapeutic options. However, over the last decade our understanding of the molecular foundation of thyroid function and carcinogenesis has driven the development of many novel therapeutics. These include FDA approved tyrosine kinase inhibitors and small molecular inhibitors of VEGFR, BRAF, MEK, NTRK and RET, which collectively have significantly changed the prognostic outlook for this patient population. Some therapeutics can re-sensitize de-differentiated cancers to iodine, allowing for radioactive iodine treatment and improved disease control. Remarkably, there is now an FDA approved treatment for BRAF-mutated patients with anaplastic thyroid cancer, previously considered invariably and rapidly fatal. The treatment landscape for iodine-resistant thyroid cancer is changing rapidly with many new targets, therapeutics, clinical trials, and approved treatments. We provide an up-to-date review of novel therapeutic options in the treatment of iodine-resistant thyroid cancer.
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9.
Graves' orbitopathy: a multidisciplinary approach.
Limone, PP, Mellano, M, Ruo Redda, MG, Macera, A, Ferrero, V, Sellari Franceschini, S, Deandrea, M
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.... 2021;(2):157-171
Abstract
Orbitopathy is the main extra thyroidal manifestation of Graves' disease. It is a very challenging condition, which requires a cooperation between many specialists (endocrinologists, ophthalmologists, radiologists, radiotherapeutic, orbital surgeons) for an optimal clinical management. An accurate diagnostic assessment is required, in order to plan an adequate treatment of Graves' orbitopathy. Medical therapy, radiotherapy or surgery may be necessary to control the disease. In this review, the authors analyze the various therapeutic strategies, as well the more recent therapies based on pharmacologic immunomodulation.
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10.
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.