Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iodine-131 (I-131) has been used for the ablation of residual thyroid remnants and cancer cells in well-differentiated thyroid cancers. It has also been used for metastatic well-differentiated thyroid cancers, especially lung and bone metastases. For small lung metastases, I-131 treatment has curative potential, particularly in young patients. Suppression of the thyroid stimulating hormone is also important for prolonging the survival of thyroid cancer patients. Strontium-89 (Sr-89) chloride has a mechanism similar to calcium, and it has been used for the treatment of bone metastases, especially osteoblastic metastases. It has been reported to have analgesic effects in an average of 76% of cases, and it is more effective if used in the early bone metastatic phase. Ibritumomab tiuxetan (Zevalin) is an anti-CD20 mouse monoclonal antibody labeled with Yttrium-90 (Y-90). It is used for treatment-resistant low grade or follicular B-cell non-Hodgkin's lymphomas and mantle lymphomas. Recently, radium-223 (Ra-223) has been used for bone metastases from castration resistant prostate cancers, and in a phase III trial, it has been proven to prolong survival of these patients. Cancer therapy using unsealed radioisotopes has been thought to be promising because it exhibits more targeted therapy than external beam irradiation. Therefore, if many more ideal targeting agents are developed in the future, this treatment might be used more commonly. As many agents such as I-131, Sr-89, and Ra-223 are available for treating bone metastasis, the combined use of other treatments such as high precision radiotherapy, bisphosphonates, hormonal agents, and molecular targeted agents should be investigated.
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PMID:[Cancer therapy using unsealed radioisotopes-the present and future]. 2559 49

Cabozantinib is an oral once-daily multitarget tyrosine kinase inhibitor of MET, VEGFR2, RET, acting against KIT, AXL, FLT3 and Tie-2. Cabozantinib has shown anti-cancer effects in preclinical and clinical models of cancers derived from both epithelial and mesenchymal origins [prostate cancer, non small lung cancer, medullary thyroid cancer (MTC) and differentiated thyroid cancer (DTC), renal cell carcinoma, etc.]. In a Phase III clinical study, cabozantinib improved PFS (11.2 months versus 4.0 months in the placebo group) of patients with MTC (independently of age, bone metastases, RET status and prior treatment). Cabozantinib was approved in 2012 by FDA for metastatic MTC and in 2013 by EMA. Cabozantinib has been also evaluated in metastatic DTC patients, because they have activation on tyrosine kinases, including MET, VEGFR2 and RET, suggesting the possible use of cabozantinib in metastatic DTC. Actually, two Phase II trials of cabozantinib in DTC patients resistant to RAI are ongoing. To increase the antineoplastic effect of cabozantinib, and to overcome the occurrence of drug resistance, combination studies with other anticancer agents are ongoing. In conclusion, cabozantinib has shown to exert an important therapeutic effect in patients with MTC improving PFS. In DTC patients, cabozantinib has shown promising results.
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PMID:Cabozantinib in Thyroid Cancer. 2615 49

Follicular thyroid carcinoma (FTC) is the second most common type of thyroid cancer after papillary carcinoma. Based on the extent of invasion, it has been classified into minimally and widely invasive subtypes. The minimally invasive type usually grows slowly and is clinically indolent but in rare cases has an aggressive behavior with distant metastases. The lungs and bones are the most common sites of metastasis. The literature mentions very few cases of scalp metastases. We report an unusual case of minimally invasive FTC with multiple scalp and bone metastases as the initial presenting complaint. In conclusion, awareness of the histopathological characteristics and variations in the metastatic behavior of thyroid carcinomas can help us overcome the difficulty in the diagnosis of such lesions.
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PMID:Cutaneous and bone metastasis of follicular thyroid carcinoma: a case report. 2616 17

Objective. To present a complicated case of differentiated thyroid carcinoma (DTC) with metastases to the skull that was evident on I-131 whole body scan (WBS) but negative on other imaging modalities in a low risk patient. Methods. We will discuss clinical course, imaging, pathological findings, and treatment of the patient with skull metastasis from DTC. Pertinent literature on imaging and pathology findings as well as radioactive iodine (RAI) treatment impact on quality of life and survival in patients with bone metastases from DTC will be reviewed. Results. The patient is a 37-year-old woman with a diagnosis of DTC who had focal areas of increased uptake in the head on WBS with no correlative findings on CT and MRI. Initially, false positive findings were suspected since patient had a low risk for developing metastases. However, the persistent findings on post-RAI treatment WBS, following two courses of treatment, were highly concerning for metastatic bone disease. WBC performed 6 months following the second RAI treatment revealed resolution of the findings. Conclusions. False positive findings in WBS are frequent and may be due to contamination, perspiration, or folliculitis of the scalp as well as benign lesions such as meningioma, hematoma, cavernous angioma, and metallic sutures. However, metastatic disease should always be considered even if the patient has low risk of distant metastatic disease and correlative images do not support the diagnosis. RAI therapy appears to improve the survival rates and quality of life of thyroid cancer patients with bone metastases based on retrospective studies.
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PMID:Unexpected Bone Metastases from Thyroid Cancer. 2623 12

Iodine-positive bone metastases (BMs) are often resistant after initial radioiodine therapy applying the standard-activity approach. A comprehensive lesion-based response study for BMs has not, to our knowledge, yet been performed. In this study, pretherapy and follow-up 124I PET/CT data on BMs from differentiated thyroid cancer patients were retrospectively analyzed to assess the relationship between absorbed dose (AD) of radiation and response after initial radioiodine treatment.
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PMID:124I PET Assessment of Response of Bone Metastases to Initial Radioiodine Treatment of Differentiated Thyroid Cancer. 2719 62

Bone metastases is a well described event in the natural history of thyroid cancers and has the potential to severely impact the quality of life by causing pain, fractures and spinal cord compression. Follicular thyroid carcinomas have a greater propensity for distal metastasis than papillary and anaplastic thyroid carcinomas. The most common sites of skeletal metastasis among thyroid cancer patients are femur followed by humerus, pelvis, radius, and scapula. Clavicle metastasis at initial presentation is exceedingly rare. Although many studies have examined the various prognostic factors for patients with bony metastases from thyroid cancers, very few have actually evaluated the effects of surgical management. We present an unusual case of metastatic papillary carcinoma thyroid presenting with clavicle metastasis and review the role of surgical management of bone metastases. Clavicular resection as a part of the management of metastatic papillary carcinoma thyroid has, to the best of our knowledge never been reported before.
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PMID:Clavicle metastasis from carcinoma thyroid- an atypical skeletal event and a management dilemma. 2721 76

Thyroid cancer is usually, relatively hypofunctional; most patients with thyroid cancer are clinically euthyroid. The combination of thyroid cancer and thyrotoxicosis is not common. We herein, report a case of follicular thyroid cancer with hyperfunctioning metastasis in a 43-year-old woman who presented with thyrotoxicosis, a cold right thyroid nodule, and low I-131 uptake at the thyroid bed. An additional total body scan with I-131 revealed a large radioiodine avid osteolytic bone metastasis with soft tissue masses and liver metastasis. The patient received treatment with total thyroidectomy, methimazole, and I-131 at a cumulative dose of 600 mCi along with recombinant human thyroid-stimulating hormone before the first I-131 treatment and palliative radiation. The patient had normal liver function test and experienced a mild degree of bone marrow suppression after I-131. At the 2-year follow-up, the patient was still alive with the progression of bone metastases but was doing well with less severe thyrotoxicosis, good ambulation, and an Eastern Cooperative Oncology Group performance status of 2. Clinicians should be aware of the unusual concurrent presentation of thyrotoxicosis and thyroid cancer, a differential diagnosis in patients with thyrotoxicosis and low or normal radioiodine uptake over the neck and also potential pitfalls during radionuclide treatment.
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PMID:A case report of hyperfunctioning metastatic thyroid cancer and rare I-131 avid liver metastasis. 2738 94

Molecular imaging using radiopharmaceuticals has a clear role in visualising the presence and extent of tumour at diagnosis and monitoring response to therapy. Such imaging provides prognostic and predictive information relevant to management, e.g. by quantifying active tumour mass using positron emission tomography/computed tomography (PET/CT). As these techniques require only pharmacologically inactive doses, age and potential frailty are generally not important. However, this may be different for therapy involving radionuclides because the radiation can impact normal bodily function (e.g. myelosuppression). Since the introduction of Iodine-131 as a targeted therapy in thyroid cancer, several radiopharmaceuticals have been widely used. These include antibodies and peptides targeting specific epitopes on cancer cells. Among therapeutic bone seeking agents, radium-223 (223Ra) stands out as it results in survival gains in patients with castration-resistant prostate cancer and symptomatic bone metastases. The therapeutic use of radiopharmaceuticals in elderly cancer patients specifically has received little attention. In elderly prostate cancer patients, there may be advantages in radionuclides' ease of use and relative lack of toxicity compared with cytotoxic and cytostatic drugs. When using radionuclide therapies, close coordination between oncology and nuclear medicine is needed to ensure safe and effective use. Bone marrow reserve has to be considered. As most radiopharmaceuticals are cleared renally, dose adjustment may be required in the elderly. However, compared with younger patients there is less, if any, concern about adverse long-term radiation effects such as radiation-induced second cancers. Issues regarding the safety of medical staff, care givers and the wider environment can be managed by current precautions.
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PMID:Radiopharmaceuticals in the elderly cancer patient: Practical considerations, with a focus on prostate cancer therapy: A position paper from the International Society of Geriatric Oncology Task Force. 2839 Oct 26

Little was written in the stars above the city of Tabriz in Iran on March 15, 1938 indicating that a newborn citizen would immigrate to America and become a master of modern mo-lecular imaging with a sharp focus on 18F-FDG PET to the benefit of millions of people around the world. Nonetheless, that's what happened. A gifted boy who lost his farther early and grew up with his uneducated mother and two siblings in humble circumstances to become a premium student, nationally no. 1 in mathematics while in school, and later a medical doctor before he decided in 1966 to seek his fortune in the US. Here he started education in internal medicine, hematology and oncology, albeit found this unsatisfactory due to tradition and rote learning. He turned to radiology and nuclear medicine in a search for new knowledge and better methods to benefit patients and society, an attitude he had been taught from early childhood. The very same attitude has been the beacon for Alavi's activities throughout his professional life, instead of money, power and social status. He married into a highly academic environment. His wife, Jane Bradley Alavi, was a specialist in hematology and oncology and is still his life partner. They never had children, so their many students and the numerous medical doctors, physicists and other academics they coached became their family. While Jane Alavi retired some years ago, Abass Alavi continued his professional career and has no plans of retirement when he turns 80 on March 15, 2018 after 46 years in nuclear medicine at the University of Pennsylvania and with an admirable network of pupils and colleagues across all five continents. On the contrary, Alavi has probably never been busier, his scientific work goes on, his multinational scientific "family" steadily increases all over the world as does the appli-cation of PET in the shape of PET/CT or PET/MRI. Alavi's contributions to the scientific literature has more than doubled within the last decade making him one of the most cited researchers at the University of Pennsylvania with a production of more than 1,200 articles, a similar number of published abstracts and close to 58,000 citations according to Google Scholar, of which about 20,000 since 2012 when he was 74. This is just part of an amazing story. Having turned to nuclear medicine in 1971, Alavi entered into one of the World's most ingenious and productive medical research en-vironments comprising collaboration of experts in nuclear medicine (David Kuhl) and neurology (Martin Reivich) at Penn, and in physiology and pharmacology (Louis Sokoloff) at the NIH, all of whom contributed significantly to the development of PET. Focus was on cerebral research with beta-emitting 14C-labeled deoxyglucose for mapping regional cerebral glucose metabolism by means of autoradiography. Alavi became a junior member of this collaboration in which the idea of labeling deoxyglucose with a gamma-emitting isotope arose to allow in vivo examination of the normal and diseased human brain. They contacted Alfred Wolf at Brookhaven National Laboratory who had an interest in synthesizing positron-emitting compounds. He suggested labeling instead with 18F-FDG and in 1975 Wolf's group including Tatsuo Ido and Joanna Fowler succeeded in synthesizing 18F-FDG. In the meantime, investigators at Penn had developed high energy collimators for the Mark IV scanner to allow imaging with 18F-FDG, so in August 1976, two normal volunteers were the first to receive a dose of 18F-FDG for tomographic brain imaging showing concentration of 18F-FDG in the gray matter while in one volunteer a "whole-body" scan from the top of the scull to mid-thigh was also obtained. A year before, investigators at Washington University, i.e., Michel Ter-Pogossian in collaboration with Michael Phelps, Edward Hoffmann, and Nizar Mullani had developed what they termed a positron-emission transaxial tomograph for nuclear imaging, i.e. a machine which was the starting point of today's PET scanners. Alavi understood from the beginning the potential of PET and in particular 18F-FDG PET even if PET images at that time were blurry and difficult to interpret, a circum-stance which for a quarter of a century brought the method in poor standing in the minds of many. Alavi started as a brain researcher, but training in internal medicine, hematology, radiology and nuclear medicine broadened his scope and over the years there are few diseases and clinical specialties in which Alavi has not provided results obtained with molecular imaging. He was a pioneer in using iodine-123 in thyroid cancer, MIBG in pheochromocytoma, radiolabeled white blood cells in infection, and 99mTc for the detection of gastrointestinal bleeds, and together with his wife 18F-FDG PET for the demonstration of recurrent brain tumors. Thus, Alavi has contributed often very successfully by promoting new ideas and their implementation to achieve improved ways of examining a variety of medical disorders. Alavi has been accused of seeing 18F-FDG as the only useful PET tracer. In a way this is true. FDG became the dominant tracer and has remained so for over 40 years now. In his 2008 SNM Highlight Lecture, Henry N. Wagner, Jr. called FDG the "tracer molecule of the 20thth century". According to a recent forecast of the Global Nuclear Medicine Radioisotopes Market, the global 18F-FDG market is expected to grow from an estimated $1.233 billion in 2014 to $2.148 billion in 2019 and the vast majority of this growth is due to a continued increase in the use of 18F-FDG, indicating that this tracer may remain the tracer molecule of at least the first half of the 21st century. The world calls for more specific tracers than 18F-FDG, and like others Dr. Alavi has constantly been looking for these, but with time, it became apparent that our body holds few organ or disease specific targets, so that the concept of very specific disease-characterizing tracers is not as rosy as previously assumed. Thus, in cancer, genetic profiling has demonstrated that tumors are genetically often a mixture of cellular clones and that these are not necessarily also present in local, regional or remote metastases, meaning that ultra-specific PET tracers for cancer diagnosis and staging may be more a utopian vision than a realistic future possibility. This, together with inborn limitations of the PET technique has made Abass Alavi more prudent and hesitant toward reports of highly promising new PET tracers and an advocate of timely carefulness when using our limited financial resources. Teaching and education of talented young individuals is one of Alavi's main academic missions. Thus, with Gerald Mandell, MD, he established the Alavi-Mandell Award, presented for the first time at the SNM meeting in 1999 to a candidate selected from among all those in a given year who were trainees at the time their names appeared as first authors of papers in JNM. Together with his wife Jane, Alavi established the Bradley-Alavi Student Fellowship which was presented for the first time in 2001 and is given to the top students selected by the SNMMI Education and Research Foundation. Alavi himself is a recipient of multiple awards, including the Georg Charles de Hevesy Nuclear Pioneer Award (2004), the Benedict Cassen Prize for Research in Nuclear Medicine (2012), the Honorary Citizenship of his native town Tabriz (2015) and the Gold Medal of the National Institute for Medical Research Development, Tehran (2015). In addition, he has received the Honorary PhD Degree in Molecular Biology of the University of Shiraz (2007), and the Honorary Doctoral Degrees of the University of Bologna (2007), the University of the Sciences in Philadelphia (2008), the Medical University of Gdansk (2016), and the University of Southern Denmark (2016). Since January 2011, Alavi has been a frequent guest in the city of Odense, Denmark. Its University Hospital holds one of the biggest departments of nuclear medicine and PET in Northern Europe. From being behind, Denmark has become the country in the world with the highest relative number of PET/CT scanners and PET scans, i.e., an estimated 0.7 and 1000, respectively, per 100 000 inhabitants in 2017. At 17 consecutive interdisciplinary Abass Alavi Meetings in Odense, he has been inspirer and initiator of multi-disciplinary scientific projects that have resulted in more than 100 publications and as many scientific presentations. Abass Alavi personifies the polymath, a species rarely found today. He discusses and produces science in as diverse areas as brain, cardiovascular, and musculoskeletal diseases, inflammation, cancer and many more disorders that plague humanity, and he has a clear eye to make results clinically useful. Had the Noble Prize been awarded not only for single inventions but also for the cumulated contribution of an outstanding researcher to patients who suffer and mankind as a whole, Dr. Abass Alavi would be on top of the candidate list. What may such an experienced birthday-person foretell about the future? He would probably say that the gamma camera and SPET will be entirely substituted by PET, that skeletal metastases are bone marrow and not bone metastases and that all indirect methodologies for imaging of skeletal metastases, including bone scintigraphy and CT, will be replaced by PET imaging with 18F-FDG or more cancer specific tracers. Also that motion and partial volume correction will be satisfactorily dealt with to allow calculation of a global disease score representing the total burden of disease in the body, whether caused by cancer, atherosclerosis or other severe disorders, and that, thus, PET will take its lead position as the diagnostic imaging modality of the 21st century. It is hard to say how many of these predictions will come true while Dr. Alavi is still going strong. What is certain is that very few persons, if any, has contributed so significantly to the development and clinical implementation of PET imaging worldwide as have this 80 year old giant in modern nuclear and molecular medicine! Abass Alavi currently holds appointments as Professor and Director of Research Education in the Department of Radiology, Perelman School of Medicine, of the University of Pennsylvania and as Honorary Fellow of the International Society of Medical Olympicus Association in Greece.
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PMID:Abass Alavi: A giant in Nuclear Medicine turns 80 and is still going strong! 2955 Aug 53

Metastatic follicular thyroid carcinoma (FTC), unresectable or resistance to radioactive iodine, is associated with poor survival. It is believed that this kind of FTC is driven by mutated genes. However, what kind of changes of genome and underlying mechanisms are elusive. The aim of this article is to understand whether there are somatic mutations in circulating cell-free tumor DNA (cfDNA) in a FTC patient with lung and bone metastases. A 55-year-old woman was diagnosed with FTC with bone and lung metastases. Appropriate amounts of DNA were extracted from formalin-fixed, paraffin-embedded thyroid tumor, peripheral cell-free plasma, and peripheral blood leukocytes and then sequenced. The significance of DNA sequencing was evaluated. There were 13,519 common variants in both tissue DNA and cfDNA. Fifty-five somatic mutations were identified in tumor, with 5 of them nonsynonymous. Seventy-two somatic mutations were found in cfDNA, with 2 of them causing amino acid change. Sixteen common alterations existed in both samples, that is, 31.3% of all the tissue somatic mutations. This pilot study provided proof that cfDNA represents the genomic characteristics of FTC primary tissue DNA well, but also metastatic tumors. Further studies are needed to better prove the effectiveness of cfDNA in the field of thyroid cancer metastatic mechanism research and real-time monitoring.
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PMID:Case report: Whole exome sequencing of circulating cell-free tumor DNA in a follicular thyroid carcinoma patient with lung and bone metastases. 2962 11


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