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1.
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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2.
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.
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The effect of radioiodine treatment on the diseased thyroid gland.
Riley, AS, McKenzie, GAG, Green, V, Schettino, G, England, RJA, Greenman, J
International journal of radiation biology. 2019;(12):1718-1727
Abstract
Purpose: Radioiodine (I131) therapy is the treatment mainstay for several benign and malignant thyroid disorders, however I131 is known to cause DNA damage and liberation of thyroidal self-antigens inducing secondary immunoreactivity. The exact mechanisms underpinning cellular death and subsequent induction of autoimmune thyroid disease following I131 treatment have not yet been fully elucidated. This manuscript aims to review the literature concerning the effects of I131 on the thyroid gland.Conclusion: The effects of I131 on malignant thyroid cells appears to depend on absorbed dose with the literature demonstrating a clear initial delay in the triggering of apoptosis in response to I131-mediated cellular damage. Some studies also observed necrotic cellular death following high-dose I131 treatment. Liberation of thyroidal self-antigen following I131 treatment helps to explain phenomena such as the subsequent induction of autoimmune thyroid disease. The clinical utility of cytokines and autoantibodies for prognostication of hypothyroidism and treatment failure following I131 remains uncertain and further appropriately-powered studies are required to clarify their role. The potential role of other cell death mechanisms activated after treatment with I131 should also be explored in order to fully delineate the thyroidal response.
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Managing the adverse events associated with lenvatinib therapy in radioiodine-refractory differentiated thyroid cancer.
Cabanillas, ME, Takahashi, S
Seminars in oncology. 2019;(1):57-64
Abstract
Lenvatinib is a multikinase inhibitor of vascular endothelial growth factor (VEGF) receptors 1-3, fibroblast growth factor receptors 1-4, RET, KIT, and platelet-derived growth factor receptor-α. Lenvatinib is approved as a monotherapy for the treatment of radioiodine-refractory differentiated thyroid cancer and in combination with everolimus for the second-line treatment of advanced renal cell carcinoma. Lenvatinib is also under investigation for the treatment of several malignancies including unresectable hepatocellular carcinoma. Although lenvatinib is associated with favorable efficacy, it is associated with adverse events (AEs) that the clinician will have to closely monitor for and proactively manage. Most of these AEs are known class effects of VEGF-targeted therapies, including hypertension, diarrhea, fatigue or asthenia, decreased appetite, and weight loss. This review summarizes the safety profile of lenvatinib and offers guidance for the management of both frequent and rare AEs. We discuss the potential mechanisms underlying these AEs and present practical recommendations for managing toxicities. The development of treatment plans that include prophylactic and therapeutic strategies for the management of lenvatinib-associated AEs has the potential to improve patient quality of life, optimize adherence, minimize the need for dose reductions, treatment interruptions, or discontinuations, and maximize patient outcomes.
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Radioiodine therapy of advanced differentiated thyroid cancer: clinical considerations and multidisciplinary approach.
Giovanella, L, Scappaticcio, L
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.... 2019;(3):229-234
Abstract
Differentiated thyroid cancer (DTC) accounts for 95% of all thyroid cancers and is generally an indolent tumor, treated effectively with surgery, radioactive iodine, and thyroid-stimulating hormone suppressive therapy. However, 5-10% of patients have advanced disease, with aerodigestive tract invasion, distant metastases, or radioiodine refractory disease, with poor prognosis. This review focuses on the approaches for treating advanced DTC, including management of gross extra-thyroidal extension, recurrent loco-regional or distant metastatic disease, the role of external beam radiation therapy and systemic treatment. Locally ablative treatment modalities, including surgery, radiation therapy, and thermal ablation are evolving and can be used in selected patients. In recent years, new therapeutic agents with molecular targets have become available and two multi-kinase inhibitors, sorafenib and lenvatinib, have been licensed for iodine refractory DTC showing an advantage in terms of progression-free survival, although an impact on overall survival has not been proven yet and remarkable side-effects emerged. Management of advanced thyroid cancer can be challenging but a multidisciplinary approach can significantly improve outcomes for this patient population.
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The medical treatment of radioiodine-refractory differentiated thyroid cancers in 2019. A TUTHYREF® network review.
de la Fouchardiere, C, Alghuzlan, A, Bardet, S, Borget, I, Borson Chazot, F, Do Cao, C, Godbert, Y, Leenhardt, L, Zerdoud, S, Leboulleux, S
Bulletin du cancer. 2019;(9):812-819
Abstract
Patients with radioiodine-refractory (RAIR) differentiated thyroid carcinoma (DTC) represent a challenging subgroup of DTC because they are at higher risk of cancer-related death. Multidisciplinary discussions can assess the role and the nature of local treatments, but also determine the optimal timing for first-line antiangiogenic therapy as some of these patients can be followed for several months or years without any treatment. In this review, we will examine the definition of RAIR-DTC, the different treatment options and finally some of the most recent cancer research breakthroughs for RAIR-DTC.
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8.
Interpretation of adverse reactions and complications in Chinese expert consensus of Iodine-125 brachytherapy for pancreatic cancer.
Li, Q, Liang, Y, Zhao, Y, Gai, B
Journal of cancer research and therapeutics. 2019;(4):751-754
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Abstract
Owing to the location of the pancreas and its complex anatomical relationship, it is difficult to perform radioactive Iodine-125 seed implantation in patients with pancreatic cancer as it can cause surgical side effects and further complications. To standardize the procedure of radioactive Iodine-125 seed implantation in the treatment of pancreatic cancer and reduce the occurrence of adverse reactions and complications during and after operation, the Chinese Medical Doctor Association of Radioactive Seed Implantation Technology Expert Committee, Committee of Minimally Invasive Therapy in Oncology, Chinese Anti-Cancer Association, and the Radioactive Seed Therapy Branch organized and helped establish an expert consensus in China regarding radioactive Iodine-125 seed implantation in the treatment of pancreatic cancer. This article aims at interpreting the adverse reactions and complications after the implantation of radioactive seeds.
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Physics aspects of setting up a multicenter clinical trial involving internal dosimetry of radioiodine treatment of differentiated thyroid cancer.
Taprogge, J, Leek, F, Flux, GD
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.... 2019;(3):271-277
Abstract
The field of molecular radiotherapy is expanding rapidly, with the advent of many new radiotherapeutics for the treatment of common as well as for rare cancers. Treatment outcome is dependent on the absorbed doses delivered to target volumes and to healthy organs-at-risk, which are shown to vary widely from fixed administrations of activity. There have been significant developments in quantitative imaging and internal dosimetry in recent years, although clinical implementation of these methods has been slow in comparison with external beam radiotherapy, partly due to there being relatively few patients treated at single centers. Multicenter clinical trials are therefore essential to acquire the data required to ensure best practice and to develop the personalized treatment planning that this area is well suited to, due to the unrivalled opportunity to image the therapeutic drug in vivo. Initial preparation for such trials requires a significant effort in terms of resources and trial design. Imaging systems in participating centers must be characterized and set up for quantitative imaging to allow for collation of data. Data transfer for centralized processing is usually necessary but is hindered in some cases by data protection regulations and local logistics. Recent multicenter clinical trials involving radioiodine therapy have begun to establish the procedures necessary for quantitative SPECT imaging in a multicenter setting using standard and anthropomorphic phantoms. The establishment of national and international multicenter imaging and dosimetry networks will provide frameworks to develop and harmonize best practice with existing therapeutic procedures and to ensure rapid and optimized clinical implementation of new radiotherapeutics across all centers of excellence that offer molecular radiotherapy. This will promote networks and collaborations that can provide a sound basis for further developments and will ensure that nuclear medicine maintains a key role in future developments.
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Medical Therapy of Patients Contaminated with Radioactive Cesium or Iodine.
Aaseth, J, Nurchi, VM, Andersen, O
Biomolecules. 2019;(12)
Abstract
Follow-up studies after the Chernobyl and Fukushima accidents have shown that 137Cs and 131I made up the major amount of harmful contaminants in the atmospheric dispersion and fallout. Other potential sources for such radionuclide exposure may be terrorist attacks, e.g., via contamination of drinking water reservoirs. A primary purpose of radionuclide mobilization is to minimize the radiation dose. Rapid initiation of treatment of poisoned patients is imperative after a contaminating event. Internal contamination with radioactive material can expose patients to prolonged radiation, thus leading to short- and long-term clinical consequences. After the patient's emergency conditions are addressed, the treating physicians and assisting experts should assess the amount of radioactive material that has been internalized. This evaluation should include estimation of the radiation dose that is delivered and the specific radionuclides inside the body. These complex assessments warrant the reliance on a multidisciplinary approach that incorporates regional experts in radiation medicine and emergencies. Regional hospitals should have elaborated strategies for the handling of radiation emergencies. If radioactive cesium is a significant pollutant, Prussian blue is the approved antidote for internal detoxification. Upon risks of radioiodine exposure, prophylactic or immediate treatment with potassium iodide tablets is recommended. Chelators developed from calcium salts have been studied for gastrointestinal trapping and enhanced mobilization after strontium exposure.