Association of Thyrotropin Suppression With Survival Outcomes in Patients With Intermediate- and High-Risk Differentiated Thyroid Cancer

Kłubo-Gwieździńska, Joanna; Auh, Sungyoung; Gershengorn, Marvin C.; Daley, Brianna; Bikas, Athanasios; Burman, Kenneth D.; Wartofsky, Léonard; Urken, Mark L.; Dewey, Eliza H.; Smallridge, Robert C.; Chindriş, Ana Maria; Kebebew, Electron

doi:10.1001/jamanetworkopen.2018.7754

Cited by 26 publications

(18 citation statements)

References 31 publications

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“…Post-operative management of DTC involves administration of RAI [ 30 ], which has been shown to reduce both recurrence and death rates in DTC patients [ 31 ], and TSH suppression therapy, although data correlating TSH suppression with survival outcomes are equivocal [ 32 ]. Furthermore, in recent years, the new staging systems and prognostic tools suggested more conservative management of low- and intermediate-risk patients, indicating less extensive surgery and more use of RAI therapy [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

A multicenter, prospective study to observe the initial management of patients with differentiated thyroid cancer in China (DTCC study)

et al. 2021

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Background To assess the gaps between the initial management of patients with differentiated thyroid cancer (DTC) in real clinical practice and the recommendations of the 2012 Chinese DTC guidelines. Methods This multicenter, prospective study was conducted at nine tertiary hospitals across China. Eligible patients were those having intermediate or high-risk DTC after first-time thyroidectomy. During 1 year of follow-up, comprehensive medical records were collected and summarized using descriptive statistics. Results Of 2013 patients, 1874 (93.1%) underwent standard surgery according to the guidelines (including total lobectomy plus isthmusectomy and total/near total thyroidectomy), and 1993 (99.0%) underwent lymph node dissection; only 56 (2.8%) had postoperative complications. Overall, 982/2013 patients (48.8%) received radioactive iodine (RAI) therapy after thyroidectomy. Of all enrolled patients, 61.4% achieved the target serum thyroid-stimulating hormone level, with a median time to target of 234.0 days (95% CI: 222.0–252.0). At 1 year of follow-up, proportions of patients with excellent response, incomplete structural response, biochemical incomplete response, and indeterminate response were 34.6, 11.2, 6.6, and 47.5%, respectively; recurrence or metastasis occurred in 27 patients (1.3%). During the overall study period, 209 patients (10.4%) had at least one adverse event: 65.1% of cases were mild, 24.9% moderate, and 10.1% severe. Conclusions This was the first large-scale prospective study of how patients with DTC in China are treated in actual practice. Initial DTC management is generally safe and adheres to the 2012 Chinese guidelines but could be improved, and the level of guideline adherence did not produce the anticipated treatment response at 1 year of follow-up.

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Section: Discussionmentioning

confidence: 99%

A multicenter, prospective study to observe the initial management of patients with differentiated thyroid cancer in China (DTCC study)

et al. 2021

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“…Even in the studies that demonstrated the effect of TST, many of them failed to show any impact of TST on the patients with low-risk DTC [11,13]. One study has recently reported that TST showed a limited benefit on prognosis even in the indeterminate- or high-risk DTC patients [16]. Therefore, in the era of emphasizing importance of a risk-adapted approach and individualized treatment, it is not appropriate to perform TST uniformly to all patients with low-risk DTC.…”

Section: Discussionmentioning

confidence: 99%

Optimal Thyrotropin Suppression Therapy in Low-Risk Thyroid Cancer Patients after Lobectomy

Lee

Jeon

Kim

et al. 2019

JCM

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Background: This study aimed to identify the clinical results after thyrotropin suppression therapy (TST) cessation and evaluated clinical factors associated with successful TST cessation. Methods: Patients who underwent lobectomy due to low-risk papillary thyroid carcinoma (PTC) were included in this study. We compared clinical characteristics and outcomes between patients who succeeded to stop TST and failed to stop TST. Results: A total of 363 patients were included in the study. One hundred and ninety-three patients (53.2%, 193/363) succeeded to stop TST. The independent associated factors for successful TST cessation were the preoperative thyroid-stimulating hormone (TSH) level and the maintenance period of TST. Patients with low TSH level showed a higher success rate for levothyroxine (LT4) cessation than patients with high TSH level (1.79 ± 1.08 and 2.76 ± 1.82 mU/L, p < 0.001). Patients who failed to discontinue TST showed a longer maintenance period of TST than patients who succeeded to discontinue TST (54.09 ± 17.44 and 37.58 ± 17.68 months, p < 0.001). Conclusions: Preoperative TSH level and maintenance period of TST are important factors for successful cessation of TST. If TST cessation is planned for patients who are taking LT4 after lobectomy, a higher success rate of TST cessation is expected with low preoperative TSH level and early cessation of LT4.

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“…A recent review has concluded that TSH suppression in patients with intermediate-risk or high- risk differentiated thyroid cancers may be of limited benefit ( 34 ). It will be of interest and importance to determine whether this is a function of increased susceptibility of such tumors to T4-induction of radioresistance via integrin αvβ3.…”

Section: Thyrotropin (Tsh) Receptor and Integrin αVβ3mentioning

confidence: 99%

Actions of Thyroid Hormones on Thyroid Cancers

et al. 2021

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L-Thyroxine (T4) is the principal ligand of the thyroid hormone analogue receptor on the extracellular domain of integrin αvβ3. The integrin is overexpressed and activated in cancer cells, rapidly dividing endothelial cells, and platelets. The biologic result is that T4 at physiological concentration and without conversion to 3,3’,5-triiodo-L-thyronine (T3) may stimulate cancer cell proliferation and cancer-relevant angiogenesis and platelet coagulation. Pro-thrombotic activity of T4 on platelets is postulated to support cancer-linked blood clotting and to contribute to tumor cell metastasis. We examine some of these findings as they may relate to cancers of the thyroid. Differentiated thyroid cancer cells respond to physiological levels of T4 with increased proliferation. Thus, the possibility exists that in patients with differentiated thyroid carcinomas in whom T4 administration and consequent endogenous thyrotropin suppression have failed to arrest the disease, T4 treatment may be stimulating tumor cell proliferation. In vitro studies have shown that tetraiodothyroacetic acid (tetrac), a derivative of T4, acts via the integrin to block T4 support of thyroid cancer and other solid tumor cells. Actions of T4 and tetrac or chemically modified tetrac modulate gene expression in thyroid cancer cells. T4 induces radioresistance via induction of a conformational change in the integrin in various cancer cells, although not yet established in thyroid cancer cells. The thyroid hormone receptor on integrin αvβ3 mediates a number of actions of T4 on differentiated thyroid cancer cells that support the biology of the cancer. Additional studies are required to determine whether T4 acts on thyroid cancer cells.

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Association of Thyrotropin Suppression With Survival Outcomes in Patients With Intermediate- and High-Risk Differentiated Thyroid Cancer

Cited by 26 publications

References 31 publications

A multicenter, prospective study to observe the initial management of patients with differentiated thyroid cancer in China (DTCC study)

A multicenter, prospective study to observe the initial management of patients with differentiated thyroid cancer in China (DTCC study)

Optimal Thyrotropin Suppression Therapy in Low-Risk Thyroid Cancer Patients after Lobectomy

Actions of Thyroid Hormones on Thyroid Cancers

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