Therapy Of Metastatic Thyroid Cancer Research Articles

[18F]TFB PET/CT misses intense [124I]iodine-avid metastases after redifferentiation therapy in metastatic thyroid cancer

BackgroundFluorine 18-labelled tetrafluoroborate ([18F]TFB) is a substrate for the sodium/iodide symporter. In thyroid cancer, [18F]TFB-PET/CT may be an alternative to iodine imaging to evaluate the extent of disease, eligibility for radioiodine treatment, and success of redifferentiation therapies. We report the results of a pilot study to determine tumor uptake of [18F]TFB and compare its properties to [124I]IodinePET/CT in patients with metastatic thyroid cancer.MethodsFive patients were included in a prospective study. All patients received PET/CT 1 h after injection of 356 ± 12 MBq [18F]TFB and were given 230 ± 9 MBq [124I]Iodine orally on the same day, followed by PET/CT after 48 h. Before redifferentiation therapy, patients underwent an additional baseline [124I]Iodine PET/CT. Cases were analyzed by two board-certified specialists. Detection rates and Spearman correlation for [18F]TFB and [124I]Iodine were calculated.ResultsThree patients had poorly differentiated thyroid cancer and received trametinib in a redifferentiation trial. Two patients had papillary thyroid cancer and did not receive redifferentiation therapy. Of the 33 lesions seen before/without redifferentiation therapy, 19 (58%) were visible on [18F]TFB and 30 (91%) on [124I]Iodine imaging. In the patients who underwent redifferentiation therapy, 48 lesions were newly seen on [124I]Iodine PET/CT with a median SUVmax of 3.3 (range, 0.4–285.0). All of these lesions were [18F]TFB-negative.Conclusion[18F]TFB failed to predict radioactive iodine uptake in patients with poorly differentiated thyroid cancer who underwent redifferentiation therapy with trametinib. It is unclear whether such discrepancies may also occur in other redifferentiation therapies or may even be encountered in redifferentiation-naïve thyroid cancer.Trial registration numberNCT03196518, registered on June 22, 2017.

Radiovirotherapy at twenty

Radiovirotherapy at twenty

Extending expressed RNA genomics from surgical decision making for cytologically indeterminate thyroid nodules to targeting therapies for metastatic thyroid cancer.

The Afirma Genomic Sequencing Classifier (GSC) is a rule‐out test for malignancy/noninvasive follicular thyroid neoplasms with papillary‐like nuclear features among patients with Bethesda category III/IV nodules, whereas the complimentary Xpression Atlas provides genomic insights from a curated panel of 511 genes among GSC suspicious and Bethesda category V/VI nodules. Together, they facilitate personalized treatment decisions based on genomic insights derived from the transcriptome of the biopsied target and extend the diagnostic and therapeutic reach of cytopathologists and fine‐needle aspiration biopsy sample collection.

A retrospective analysis of efficacy of systemic therapy in metastatic thyroid cancer

Objective: Thyroid cancer is the most common type of endocrinecancer. The current approaches in the systemic therapies ofmetastatic thyroid cancers are chemotherapy that is investigated inphase II clinical trials and tyrosine kinase inhibitors, investigatedin phase III clinical trials. The aim of this study was to evaluate theefficacy of systemic therapies in metastatic thyroid cancer patients.Materials and Methods: We investigated 57 patientsretrospectively, diagnosed with thyroid cancer who were referred toMaslak Acibadem Hospital Medical Oncology Department between2008-2015 and Umraniye Training and Research Hospital between2016-2018. They had received systemic treatment due to the refractoryprofile to radioiodine therapy and metastatic thyroid cancer.Results: Medical records of 57 patients with metastatic thyroidcancer, who were referred for systemic therapy were retrospectivelyanalysed. 52% (n:30) of the cases were women and 48% (n:27)were men, and the mean age was 57.11 years. All patients wasabove the age of 18. Of the patients, 59.8% (n:35) had welldifferentiated thyroid cancer, 29.8% (n:17) had medullary thyroidcancer, 5.3% (n:3) had anaplastic thyroid cancer, 3.5% (n:2) hadpoorly differentiated thyroid cancer and 1.8% (n:1) had medullarypapillarysynchronous cancer. When first line systemic therapywas evaluated for all 57 patients, progression free survival (PFS)was found 4.25 and 6.33 months for chemotherapy and sorafenib,respectively (P:0.035). All cases were evaluated retrospectivelyfor second line systemic therapy and PFS was 4.1 and 7.77 monthsfor chemotherapy and sorafenib, respectively (P<0.001).Conclusion: Tyrosine kinase inhibitors are used in the treatmentof radioactive iodine-refractory differentiated thyroid cancers andmedullary thyroid cancers. The effect of lenvatinib, sorafenib andvandetanib on progression-free survival in thyroid cancers is foundto be superior to systemic chemotherapy. It was concluded thatsorafenib is a systemic treatment option which can be preferred interms of efficacy and toxicity profile in radioactive iodine refractorywell-differentiated thyroid cancer especially in our country.

An In Vivo Mouse Model of Metastatic Human Thyroid Cancer

Mouse models of metastatic human cancers are important tools in preclinical studies for testing new systematic therapies and studying effectors of cancer metastasis. The major drawbacks of current mouse models for metastatic thyroid cancer are that they have low metastasis rates and do not allow in vivo tumor detection. Here, we report and characterize an in vivo detectable metastasis mouse model of human thyroid cancer using multiple thyroid cancer cell lines. Human anaplastic thyroid cancer cell lines 8505C, C-643, SW-1736, and THJ-16T; follicular thyroid cancer cell lines FTC-133, FTC-236, and FTC-238; and Hürthle cell carcinoma cell line XTC-1 were transfected with a linearized pGL4.51[luc2/CMV/Neo] vector or transduced with lentivirus containing Luc2-eGFP reporter genes. The stably transfected cells were injected intravenously into NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ mice. Tumors were detected with an in vivo imaging system-Xenogen IVIS. Vemurafenib, a BRAF inhibitor, was used to treat lung metastases generated from 8505C-Luc2 cells with a BRAF(V600E) mutation to test the accuracy of the model to evaluate response to therapy. Intravenous injection of as few as 30,000 8505C-Luc2 cells produced lung metastases in 100% of the injected mice, and many of these mice also developed bone metastases at a later stage of the disease. Similarly, metastatic tumors also developed in all mice injected with C-643-Luc2, THJ-16T-Luc2, FTC-133-Luc2, FTC-236-Luc2, FTC-238-Luc2, and XTC-1-Luc2 cells. The metastases were easily detectable in vivo, and tumor progression could be dynamically and accurately followed and correlated with the actual tumor burden. Furthermore, disease progression could be easily controlled by adjusting the number of injected cells. The in vivo treatment of 8505C xenograft lung metastases with vemurafenib dramatically reduced the growth and signal intensity with good correlation with actual tumor burden. Herein we report an in vivo detectable mouse model of metastatic human thyroid cancer that is reliable and reproducible. It will serve as a useful tool in the preclinical testing of alternative systematic therapies for metastatic thyroid cancer, and for functional studies of thyroid cancer tumor biology in vivo.

Five-Year Survival Is Similar in Thyroid Cancer Patients with Distant Metastases Prepared for Radioactive Iodine Therapy with either Thyroid Hormone Withdrawal or Recombinant Human TSH

Context:Elevated levels of TSH markedly enhance the effectiveness of radioiodine (RAI) therapy in metastatic thyroid cancer.Objective:The objective of the study was to compare short-term overall survival in thyroid cancer patients with RAI-avid distant metastases prepared for RAI therapy with either traditional thyroid hormone withdrawal (THW) or recombinant human TSH (rhTSH) stimulation.Design:This was a retrospective chart review.Setting:The study was conducted at a tertiary care comprehensive cancer center.Patients:Patients included 175 patients with RAI avid metastatic disease to lung and/or bone.Interventions:In 58 patients, all RAI treatments (remnant ablation and therapy of metastatic disease) were done with rhTSH stimulation. In 35 patients, all RAI treatments were done after THW. In 82 patients, THW was used for initial RAI treatment(s) with subsequent administered activities given after rhTSH stimulation.Main Outcome Measure:Overall survival was measured.Results:After a median follow-up of 5.5 yr, there were no significant differences in overall survival between patients prepared for RAI therapy with rhTSH alone, THW alone, or THW followed by rhTSH (Kaplan-Meier analysis,P = 0.80). In a multivariate analysis that included clinicopathological features and method of preparation (rhTSH or TWH), only age at diagnosis was an independent predictor of overall survival.Conclusions:Preparation for RAI therapy using either THW or rhTSH stimulation was associated with similar 5-yr overall survival rates in patients with RAI avid thyroid cancer metastases to lung or bone.

Hematologic Toxicity in Patients Treated with Sunitinib for Advanced Thyroid Cancer

Although thyroid carcinoma is more indolent than other solid tumors, distant metastatic disease due to differentiated thyroid carcinoma (DTC) and medullary thyroid carcinoma (MTC) is often refractory to treatment and thus a challenge for clinicians. New agents such as tyrosine kinases inhibitors have been introduced recently for therapy of metastatic thyroid cancer but they have toxic side effects as well as therapeutic benefits. The objective of this study was to determine the hematologic toxicities of sunitinib, a multiple receptor tyrosine kinases inhibitor, when used to treat progressive, advanced DTC and MTC. Six patients with DTC and four with MTC who were treated with sunitinib were retrospectively studied for short-term hematological toxicities related to red cell and platelet mass and the major leukocyte series. Before the start of sunitinib treatment, 5 of 10 patients (50%) received external beam radiation therapy and 6 of 10 (60%) had hematologic abnormalities. During sunitinib treatment, some grade of neutropenia was noted in 6 of 10 patients (60%), anemia in 1 of 10 (10%), thrombocytopenia in 7 of 10 (70%), and lymphocytopenia in 4 of 10 (40%). Monocytopenia was present in all 10 patients. Considering grades 3 and 4 hematologic toxicities, neutropenia was noted in 2 of 10 (20%), anemia in 1 of 10 (10%), and thrombocytopenia in 1 of 10 (10%). There was no grade 3 or 4 lymphocytopenia, but we noted a 52.4% (+/-17.47% standard deviation) decrease in monocyte counts. All patients had macrocytosis, despite normal circulating folate and cobalamin levels. In one patient with DTC, sunitinib had to be permanently discontinued because of hematological toxicity. Despite the fact that most patients with DTC had received large doses of radioiodine and some had received external beam radiation therapy, both of which have myelosuppressive potential, treatment with sunitinib was well tolerated in most patients with DTC as well as in the patients with MTC. These results are encouraging, but, as our series was small and did not evaluate efficacy, more extensive studies in DTC and MTC are needed to determine the possible roles of sunitinib in these very different tumors.

What role for recombinant human TSH in the treatment of metastatic thyroid cancer?

The introduction into clinical practice of recombinant human thyroid-stimulating hormone (rhTSH) has marked a turning point in the management of patients with differentiated thyroid cancer. RhTSH offers a safe and reliable alternative to thyroid hormone withdrawal by avoiding both the clinical consequences of hypothyroidism, with a positive impact on quality of life and work productivity, and the potential risk of cancer growth due to a long-lasting endogenous TSH stimulation. In the follow-up of thyroid cancer patients, rhTSH stimulated thyroglobulin is now routinely proposed as it has been shown to be as sensitive as endogenously stimulated thyroglobulin for the detection of residual and metastatic cancer [1]. More recently, the use of rhTSH has been approved for the preparation of adult low-risk patients for postsurgical radioiodine ablation of thyroid remnants with 3.7 GBq I [2]. Although the activity necessary to achieve a comparable rate of ablation is probably higher than that required under hypothyroidism [3, 4], the use of rhTSH is associated with a lower whole-body radiation exposure [5] and allows a shorter hospitalization length, which partially compensates for its cost [6]. The use of rhTSH in the treatment of metastatic thyroid cancer is much more controversial. Although rhTSH has not been formally approved so far for this indication, it has been used off-label since the 1990s to treat patients in which thyroid hormones could not be stopped [7]. This includes patients unable to raise an adequate endogenous TSH response, either because of hypopituitarism or continued production of thyroxine by a thyroid remnant or metastatic tumour, and patients in poor condition due to advanced disease. The results obtained in some patients are encouraging. One may raise the question whether a wider use of rhTSH can be advovated in the therapeutic setting. In our opinion, both clinical and biological data from the literature argue against a more liberal use of rhTSH for the therapy of metastatic thyroid cancer. First, tumour cells of thyroid cancer have a reduced expression of most thyroid-specific genes, including the TSH receptor and the Na/I symporter (NIS) gene [8]. Although the standard two injections protocol of rhTSH provides a high plasma TSH peak, roughly in the range 100–150 mIU/L 24 h after the second injection [9], the concentration increase is short-lived [10]. In order to improve the number of NIS and TSH receptors, and thus enhance the iodine-trapping ability of the cells, a high and prolonged period of TSH stimulation elevation is desirable [11]. Indeed, a I whole-body scan under hypothyroidism is more sensitive than the same scan after rhTSH administration [12]. It should be remembered that a posttherapeutic scan of good quality is an invaluable tool to discover unsuspected metastases and to assess the efficacy of repeated I treatment in metastatic patients [13]. Second, published experience shows that rhTSH stimulates the uptake of radioiodine in metastatic lesions [7]. However, prospective randomized studies comparing the relative efficacy of rhTSH-aided metastatic cancer treatEur J Nucl Med Mol Imaging (2009) 36:883–885 DOI 10.1007/s00259-008-1046-0

Follow-up study of thyroid cancer treated by unilateral lobectomy

c oNsr~~n4nLE uncertainty persists concerning what constitutes adequate surgical resection for differentiated carcinoma of the thyroid gland. The present discussion will be limited to the problem of surgery of the thyroid gland itself, when cancer is found grossly involving only one lobe. In recent years, the trend has been toward more extensive resection of the thyroid gland. With rare exceptions [l-3] genera1 agreement has come that anything less than total lobectomy is inadequate and not curative in this situation, because of the high incidence of residual cancer (20 per cent) found on completing the Iobectomy [4] or of stump recurrence [s;]. Beyond this point, authoritative opinion is divided among those who advocate only total lobectomy with or without resection of the isthmus [6,7], those who advocate total Iobectomy plus resection of some portion of the opposite lobe [4,8], and those who advocate total thyroidectomy [9-201. Support for use of the more extensive procedures has come from the observation of intragIandular spread or “muIticentric involvement” by cancer, reported after routine surgical pathologic examination as I I to 30 per cent involvement of the opposite lobe [8,9,12-r4,18,19,21,22]. Crile [7], however, takes the position that “the mere presence of isoIated microfoci of cancer in a lobe of the thyroid does not necessariIy mean that cancer will develop cIinicaIIy.” For the past twelve years at The University of Texas M. D. Anderson Hospital and Tumor Institute, we have been engaged in evaIuating the adequacy of these primary surgical procedures for carcinoma of the thyroid gIand. Prior to rgfo, at this institution, total lobectomy on the involved side, with or without neck dissection, was considered adequate therapy whenever there was no gross involvement of the opposite lobe. Later, when total thyroid gland resections were performed to facilitate radioiodine therapy of metastatic thyroid cancer, a significant incidence of cancer in the contraIatera1 Iobe was observed. This cast doubt on the adequacy of tota unilateral lobectomy as a curative procedure. As a result, a program for evaluating the problem was initiated whereby patients who had undergone previous “curative” lobectomy would either be submitted to prophyIactic resection of the remaining lobe or would be observed clinically on a long-term basis. A third group of patients would be treated by tota thyroidectomy as the initial surgical procedure or following previous thyroid biopsy or partial lobectomy. A corolIary project was undertaken to study the resected gland, whenever possible, by subseria1 whoIe organ sections in order to determine the mode of intraglandular dissemination and the true incidence of contralateral lobe involvement. Previous communications from this institution [g,23] have reported this dissemination to the opposite lobe in 30 per cent of glands examined by routine pathologic technics and in 84 per cent of glands submitted to subseria1 whole organ study. The present report concerns that group of patients with thyroid cancer whose initial surgical management was total lobectomy with or without neck dissection. This was then folIowed either by immediate prophylactic

Indication and contraindications for treatment of thyroid cancer with radioactive iodine.

Article1 July 1952INDICATIONS AND CONTRAINDICATIONS FOR TREATMENT OF THYROID CANCER WITH RADIOACTIVE IODINEWILLIAM H. BEIERWALTES, M.D.WILLIAM H. BEIERWALTES, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-37-1-23 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTen years have now elapsed since the first patient with carcinoma of the thyroid was treated with radioactive iodine.1More than 250 thyroid carcinoma patients have been treated since then with radioactive iodine, I131.2Review of the literature and our experience in treating 24 such patients have indicated certain criteria to be of definite value in the selection of patients for I131therapy. Lack of regard for these criteria has, in our hands, led to wasteful use of I131and rise of false hopes in the thyroid cancer patient. It is the purpose of this discussion, therefore, to review these...Bibliography1. FrantzLarsenJaretzki VKWGA: An evaluation of radioactive iodine therapy in metastatic thyroid cancer, J. Clin. Endocrinol. 10: 1084, 1950. CrossrefGoogle Scholar2. Brucer M: Internally administered isotopes for cancer therapy, Nucleonics 10: 47, 1952. Google Scholar3. RawsonMarinelliSkanseTrunnellFluharty RWLDBNJRG: The effect of total thyroidectomy on the function of metastatic thyroid cancer, J. Clin. Endocrinol. 8: 826, 1948. CrossrefGoogle Scholar4. RawsonRallPeacock RWJEW(a) : Limitations and indications in the treatment of cancer of the thyroid with radioactive iodine, J. Clin. Endocrinol. 11: 1128, 1951. (b) Dobyns, B. M., and Maloof, F.: The study and treatment of 119 cases of carcinoma of the thyroid with radioactive iodine, J. Clin. Endocrinol. 11: 1323, 1951. CrossrefGoogle Scholar5. Trunnell JB: The treatment of human thyroid disease with radioactive iodine, Tr. New York Acad. Sc. 11: 195, 1949. CrossrefMedlineGoogle Scholar6. KeatingHainesPowerWilliams FRSFMHMM: Radioiodine-accumulating function of human thyroid gland as diagnostic test in clinical medicine, J. Clin. Endocrinol. 10: 1425, 1950. CrossrefGoogle Scholar7. MeansLerman JHJ: The curves of thyroxine decay in myxedema and of iodine response in thyrotoxicosis: their similarity and its possible significance, Ann. Int. Med. 12: 811, 1938. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Ann Arbor, Michigan*Presented at the Thirty-third Annual Session of the American College of Physicians, Cleveland, Ohio, April 23, 1952.From the Department of Internal Medicine, University of Michigan Medical School. The radioactive iodine used in this investigation was supplied by the Oak Ridge National Laboratories, Oak Ridge, Tennessee, and was obtained under allocation from the United States Atomic Energy Commission. These studies were assisted by a grant from the Michigan Memorial Phoenix Project, University of Michigan. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited bySurgical Management of Well-Differentiated Thyroid Cancer Locally Invasive to the Respiratory TractThe treatment of thyroid carcinoma with radioactive iodineIsotope und SchilddrüseCancer of the ThyroidRadiojod in Diagnostik und Therapie der SchilddrüsenneoplasmenDie malignen SchilddrüsentumorenTherapie der Schilddrüse mit RadiojodKrankheiten der SchilddrüseRADIO‐ACTIVE IODINE (I 131 ) AND PROTEIN‐BOUND IODINE IN THYROID DISORDERS 1 July 1952Volume 37, Issue 1Page: 23-30KeywordsCancer treatmentThyroidThyroid carcinoma Issue Published: 1 July 1952 PDF downloadLoading ...

Radiation dosimetry in the treatment of functional thyroid carcinoma with I131.

Among the several factors involved in the therapy of metastatic thyroid cancer with massive doses of I131, the dose of radiation delivered to lesions and to normal tissues is of particular importance (1). At present, the tissue doses arising from the presence of radio-elements in the body cannot be measured directly in situ by ionization methods, but reasonable estimates can be obtained by indirect means. Although these estimates are less precise than those available to conventional radiation therapy, they provide, nevertheless, information which should be useful to the establishment of a rational administration of the isotope and to the correct interpretation of the patient's clinical response. The Tumor Dose It has been shown (2) that the beta radiation dose and the I131 concentration in tissue are related by the following formulae: In these expressions, Te is the effective half-life in days of I131 in the tissue under consideration, i.e., the half-life resulting from both radioactive decay and physiolo...

Factors Involved in the Experimental Therapy of Metastatic Thyroid Cancer with I131

The treatment of metastatic thyroid cancer by radioactive iodine presents features of interest and importance to investigators concerned with the control of cancer by systemic means. In terms of number of patients benefited, this subject does not 100m large in the general field of cancer since encouraging results have been obtained in only a very small percentage of cases of an already uncommon type of tumor. Nevertheless, the causes of its success and its limitations should be worthy of thorough study because arrest of the disease has been attained in the presence of odds insurmountable by other forms of treatment (8, 9) The character of these few but definite successes strongly supports the long held view that if means were found to localize radioe1ements in tumors, important progress would be made toward control of the disease. Efforts to localize radioe1ements in neoplastic cells have not been wanting in the past, but concentrations of practical value have not thus far been attained in cancer tissue per se. The premises upon which treatment of thyroid cancer by I13l is based are no exception to the rule, inasmuch as this therapy is possible only when cells of thyroid cancer share with the parent gland the pronounced avidity for the isotope. Under these conditions it is axiomatic to anticipate destruction of normal thyroid tissue in the process of tumor inactivation and to expect myxedema when good control of the disease is obtained. With this exception, and as in any other type of radiotherapeutic cancer treatment, the ultimate aim of the procedure is to achieve inactivation of the tumor with minimum damage to normal structures. Locally, radioactive iodine will suit this purpose on account of the limited range of the beta radiation emitted, but the therapist is faced from the outset with the necessity of reducing the radiation dose to body structures which may be spatially removed from the tumors, but are very much in the metabolic path of the iodine. The experience gained in the last decade in the treatment of hyperthyroidism with p3l or p30 cannot be utilized fully in the treatment of thyroid cancer. In the case of hyperthyroidism, remission of symptoms is sought by partial inactivation of the thyroid gland, whereas in the case of cancer, radical devitalization of extensive tumor masses is attempted under conditions of differential uptake which as a rule are not as favorable (2, 4, 6). Among tumors, only metastasizing struma approaches in magnitude and uniformity the avidity of the thyroid gland in Graves' disease. Other tumors, either primary or metastatic, which exhibit moderate preference for the isotope are those showing orderly cellular structure in follicular arrangement containing colloid-like material. Thus far only one example of thyroid carcinoma of high-grade malignancy has been reported to retain I131, and this was a solid alveolar adenocarcinoma.