Radioiodine refractory differentiated thyroid cancer

Jin, Yuchen; Nostrand, Douglas Van; Cheng, Le; Liu, Min; Chen, Libo

doi:10.1016/j.critrevonc.2018.03.012

Cited by 69 publications

(65 citation statements)

References 77 publications

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“…With minor modifications due to the limited number of cases and the aim of this particular study, RAIR categories were defined according to the US guidelines , Schlumberger recommendation , the Chinese guidelines, and a recent RAIR review as follows: (I) metastatic foci never showed 131 I concentration; (II) despite previous 131 I avidity, metastatic foci lost the ability to concentrate 131 I or 131 I avidity was observed in some but not other lesion(s); and (III) metastatic foci showed 131 I uptake, but the total administered dose exceeded 600 mCi and the lesions did not regress and were still not amenable to surgery.…”

Section: Methodsmentioning

confidence: 99%

“…If distant metastases or local recurrences occur, then the 10‐year survival is reduced to approximately 42% . In these scenarios, 131 I therapy, metastasectomy, external beam radiotherapy, molecular targeted therapy, redifferentiation therapy, gene therapy, and cancer immunotherapy are among the potential therapeutic options . Unfortunately, approximately two‐thirds of patients with recurrent disease will develop an 131 I refractory (radioactive iodine refractory, RAIR) state, which carries the poorest overall prognosis .…”

Section: Introductionmentioning

confidence: 99%

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TERT promoter mutation in primary papillary thyroid carcinoma lesions predicts absent or lower ¹³¹i uptake in metastases

et al. 2019

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Genetic mutations play important roles in not only development of papillary thyroid carcinoma (PTC) but also determination of its properties. The radioactive iodine refractory (RAIR) state is a harbinger of poor outcomes for PTC. We used various statistical models to investigate the significance of TERT promoter, BRAF, and RAS mutations in distinguishing the RAIR state and their associations with 131I uptake. Mutations were examined in primary lesions of 33 RAIR cases and 34 age‐ and sex‐matched 131I‐treated cases with disease‐free status. Thyrotropin‐stimulated thyroglobulin (sTg) change, 131I uptake ability, and RAIR categories were evaluated in the RAIR cases. The prevalence of TERT mutation in the RAIR group was 24.24% (8/33), which was significantly higher than that in the disease‐free group (0/34). BRAF mutation showed a similar high prevalence in both the RAIR group (69.70%) and disease‐free group (64.71%). Among the eight TERT mutation‐positive cases, six carried both TERT and BRAF mutations. RAS mutation was detected in only one disease‐free case and in two RAIR cases. Despite a significantly higher prevalence of TERT mutations in the RAIR group, only tumor size and N1b lymph node involvement were independently associated with RAIR status. In the RAIR group, all patients carrying a TERT mutation showed maximum or increased sTg. Multivariate analyses demonstrated that the TERT mutation was associated with decreased 131I uptake and the RAIR categories of absent or weaker 131I uptake. TERT mutation constitutes a novel genetic biomarker indicating absent or weaker 131I‐avid lesions in RAIR PTC patients. It is worth evaluating the TERT status in all DTC patients undergoing 131I therapy. © 2019 IUBMB Life, 2019

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TERT promoter mutation in primary papillary thyroid carcinoma lesions predicts absent or lower ¹³¹i uptake in metastases

et al. 2019

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“…RR-PTC represents a major therapeutic challenge in thyroid cancer medicine, which is mainly caused by BRAF V600E mutation that leads to the abnormal activation of MAPK pathway. 21,22 Recent evidences have indicated that oncogenic signalling controls several key processes of epigenetic gene regulation. 23 Increasing numbers of studies, including ours, have confirmed that tumour epigenetics-based therapeutics offer a new direction for differentiation therapy.…”

Section: Discussionmentioning

confidence: 99%

Combined tazemetostat and MAPKi enhances differentiation of papillary thyroid cancer cells harbouring BRAF^V600E by synergistically decreasing global trimethylation of H3K27

Cheng

et al. 2020

J Cellular Molecular Medi

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Clinical efficacy of differentiation therapy with mitogen‐activated protein kinase inhibitors (MAPKi) for lethal radioiodine‐refractory papillary thyroid cancer (RR‐PTC) urgently needs to be improved and the aberrant trimethylation of histone H3 lysine 27 (H3K27) plays a vital role in BRAFV600E‐MAPK‐induced cancer dedifferentiation and drug resistance. Therefore, dual inhibition of MAPK and histone methyltransferase (EZH2) may produce more favourable treatment effects. In this study, BRAFV600E‐mutant (BCPAP and K1) and BRAF‐wild‐type (TPC‐1) PTC cells were treated with MAPKi (dabrafenib or selumetinib) or EZH2 inhibitor (tazemetostat), or in combination, and the expression of iodine‐metabolizing genes, radioiodine uptake, and toxicity were tested. We found that tazemetostat alone slightly increased iodine‐metabolizing gene expression and promoted radioiodine uptake and toxicity, irrespective of the BRAF status. However, MAPKi induced these effects preferentially in BRAFV600E mutant cells, which was robustly strengthened by tazemetostat incorporation. Mechanically, MAPKi‐induced decrease of trimethylation of H3K27 was evidently intensified by tazemetostat in BRAFV600E‐mutant cells. In conclusion, tazemetostat combined with MAPKi enhances differentiation of PTC cells harbouring BRAFV600E through synergistically decreasing global trimethylation of H3K27, representing a novel differentiation strategy.

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“…Prognoses in most DTC patients are excellent, with 10-year overall survival rates for PTC patients exceeding 90% (4). Among patients with metastatic DTC, one third showed CNS involvement in addition to the more common metastatic sites (lungs and skeleton); however, in only 1 to 3% of such patients, the CNS was the first metastatic site (5,6). Patients with CNS metastases from DTCs are typically older and with more advanced disease (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Intramedullary Spinal Cord Metastasis as the Presenting Feature of Papillary Thyroid Carcinoma

Yoel

Joshua

Shoukrun

et al. 2019

AACE Clinical Case Reports

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Objective:The objective of this report is to present an unusual case of intramedullary spinal cord metastasis (ISCM) as the presenting feature of papillary thyroid carcinoma (PTC).Methods: The presented case includes clinical, biochemical, and imaging findings as well as surgical and pathology reports. Treatment with radioactive iodine (RAI) and the response to this treatment are presented.Results: A 71-year-old woman was evaluated for debilitating low back pain and walking disability. Magnetic resonance imaging demonstrated an oval, lumbar, intramedullary mass with benign features and surgery was scheduled. On preoperative evaluation for the lumbar mass, a multinodular thyroid goiter (unfortunately overlooked previously) was noticed, causing severe narrowing of the trachea. Total thyroidectomy was performed with a pathology diagnosis of PTC. In a second operation, the lumbar lesion was removed and proved to represent meta-static PTC. External beam radiation was subsequently administered to the thyroid bed, lumbar spine, and other skeletal metastases, followed by 150 milliCurie of RAI. A post-treatment scan showed high uptake over the lumbar spine, and skeletal and lung lesions. Clinically, the patient restored her walking ability and back pain improved.Conclusion: ISCM rarely is the presenting feature of PTC. Our patient presented with back pain which is the typical, though non-specific symptom, of ISCM. She showed good clinical response to multimodal treatment which is in line with the few other differentiated thyroid cancer patients with ISCM reported in the literature. Prompt surgical resection, followed by external beam radiation and RAI, may improve neurological signs, alleviate pain, and improve quality of life. (AACE Clinical Case Rep. 2019;5:e271-e275) Abbreviations: CNS = central nervous system; DTC = differentiated thyroid carcinoma; FTC = follicular thyroid carcinoma; ISCM = intramedullary spinal cord metastasis; PTC = papillary thyroid carcinoma; RAI = radioactive iodine

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Radioiodine refractory differentiated thyroid cancer

Cited by 69 publications

References 77 publications

TERT promoter mutation in primary papillary thyroid carcinoma lesions predicts absent or lower ¹³¹i uptake in metastases

TERT promoter mutation in primary papillary thyroid carcinoma lesions predicts absent or lower ¹³¹i uptake in metastases

Combined tazemetostat and MAPKi enhances differentiation of papillary thyroid cancer cells harbouring BRAF^V600E by synergistically decreasing global trimethylation of H3K27

Intramedullary Spinal Cord Metastasis as the Presenting Feature of Papillary Thyroid Carcinoma

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Radioiodine refractory differentiated thyroid cancer

Cited by 69 publications

References 77 publications

TERT promoter mutation in primary papillary thyroid carcinoma lesions predicts absent or lower 131i uptake in metastases

TERT promoter mutation in primary papillary thyroid carcinoma lesions predicts absent or lower 131i uptake in metastases

Combined tazemetostat and MAPKi enhances differentiation of papillary thyroid cancer cells harbouring BRAFV600E by synergistically decreasing global trimethylation of H3K27

Intramedullary Spinal Cord Metastasis as the Presenting Feature of Papillary Thyroid Carcinoma

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TERT promoter mutation in primary papillary thyroid carcinoma lesions predicts absent or lower ¹³¹i uptake in metastases

TERT promoter mutation in primary papillary thyroid carcinoma lesions predicts absent or lower ¹³¹i uptake in metastases

Combined tazemetostat and MAPKi enhances differentiation of papillary thyroid cancer cells harbouring BRAF^V600E by synergistically decreasing global trimethylation of H3K27