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Clinical Cancer Research : An Official... Jul 2023To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with...
PURPOSE
To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with a BRAF p.V600E mutation.
PATIENTS AND METHODS
A prospective phase II trial including patients with RECIST progression within 18 months and no lesion > 3 cm. Following a baseline recombinant human (rh)TSH-stimulated diagnostic whole-body scan (dc1-WBS), dabrafenib and trametinib were given for 42 days. A second rhTSH-stimulated dc WBS (dc2-WBS) was done at day 28 and 131I (5.5 GBq-150 mCi after rhTSH) was administered at day 35. Primary endpoint was the 6-month RECIST objective response rate. In case of partial response (PR) at 6 or 12 months, a second treatment course could be given. Among 24 enrolled patients, 21 were evaluable at 6 months.
RESULTS
Abnormal 131I uptake was present on 5%, 65%, and 95% of the dc1-WBS, dc2-WBS, and post-therapy scans, respectively. At 6 months, PR was achieved in 38%, stable disease in 52%, and progressive disease (PD) in 10%. Ten patients received a second treatment course: one complete response and 6 PRs were observed at 6 months. The median progression-free survival (PFS) was not reached. The 12- and 24-month PFS were 82% and 68%, respectively. One death due to PD occurred at 24 months. Adverse events (AE) occurred in 96% of the patients, with 10 grade 3-4 AEs in 7 patients.
CONCLUSIONS
Dabrafenib-trametinib is effective in BRAF p.V600E-mutated DTC patients for restoring 131I uptake with PR observed 6 months after 131I administration in 38% of the patients.
Topics: Humans; Thyroid Neoplasms; Iodine Radioisotopes; Proto-Oncogene Proteins B-raf; Thyrotropin Alfa; Prospective Studies; Pyridones; Pyrimidinones; Oximes; Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Mutation
PubMed: 37074727
DOI: 10.1158/1078-0432.CCR-23-0046 -
Renal Failure Dec 2023This cohort study was designed to explore whether roxadustat or erythropoietin could affect thyroid function in patients with renal anemia.
PURPOSE
This cohort study was designed to explore whether roxadustat or erythropoietin could affect thyroid function in patients with renal anemia.
METHODS
The study involved 110 patients with renal anemia. Thyroid profile and baseline investigations were carried out for each patient. The patients were divided into two groups: 60 patients taking erythropoietin served as the control group (rHuEPO group) and 50 patients using roxadustat served as the experimental group (roxadustat group).
RESULTS
The results indicated that there were no significant differences in serum total thyroxine (TT4), total triiodothyronine (TT3), free triiodothyronine (FT3), free thyroxine (FT4) or thyroid stimulating hormone (TSH) between the two groups at baseline. After treatment, TSH, FT3, and FT4 were significantly lower in the roxadustat group than in the rHuEPO group ( < 0.05). After adjusting for age, sex, dialysis modality, thyroid nodules and causes of kidney disease, Cox regression showed that roxadustat was an independent influencing factor on thyroid dysfunction (HR 3.37; 95% CI 1.94-5.87; < 0.001). After 12 months of follow-up, the incidence of thyroid dysfunction was higher in the roxadustat group than in the rHuEPO group (log-rank < 0.001).
CONCLUSION
Roxadustat may lead to a higher risk of thyroid dysfunction, including low TSH, FT3 and FT4, than rHuEPO in patients with renal anemia.
Topics: Humans; Triiodothyronine; Thyroxine; Thyroid Gland; Cohort Studies; Thyrotropin; Erythropoietin; Chronic Disease; Kidney Diseases; Epoetin Alfa; Anemia
PubMed: 37051660
DOI: 10.1080/0886022X.2023.2199093 -
Japanese Journal of Radiology Nov 2023Thyroid hormone withdrawal (THW) in preparation for radioactive iodine therapy (RIT) may lead to hyponatremia and hyperkalemia because hypothyroidism reduces the...
PURPOSE
Thyroid hormone withdrawal (THW) in preparation for radioactive iodine therapy (RIT) may lead to hyponatremia and hyperkalemia because hypothyroidism reduces the glomerular filtration rate. Using recombinant human thyrotropin (rhTSH) may avoid these changes; however, these two preparation methods have not been compared in the literature. The purpose of this study was to reveal whether THW and rhTSH as preparation methods for RIT affect serum electrolytes differently. We also evaluated clinical factors influencing the onset of hyponatremia and hyperkalemia during RIT.
MATERIALS AND METHODS
From April 2005 to December 2020, we analyzed 278 patients with thyroid cancer who received RIT. The patients were classified into two groups based on the preparation method, and renal function and serum electrolytes were compared between the groups. We also evaluated clinical factors that may affect overt hyponatremia (serum sodium level < 134 mmol/L) and hyperkalemia (serum potassium level ≥ 5.0 mmol/L).
RESULTS
Serum sodium and chloride levels in the THW group were significantly lower than those in the rhTSH group (p < 0.001 and p = 0.002, respectively). In contrast, the serum potassium level in the THW group was significantly higher than that in the rhTSH group (p = 0.008). As for clinical factors that may influence hyponatremia, age and estimated glomerular filtration rate (eGFR) were significantly associated with serum sodium level in the univariate analysis (p = 0.033 and p = 0.006, respectively). In the multivariate analysis, only age was significantly associated with serum sodium level (p = 0.030). Regarding hyperkalemia, distant metastases, the preparation method and eGFR were significantly associated with the serum potassium level in the univariate analysis (p = 0.005, p = 0.005 and p = 0.001, respectively). In the multivariate analysis, only eGFR was significantly associated with hyperkalemia (p = 0.019).
CONCLUSION
THW and rhTSH affect serum sodium and potassium levels differently. Renal function may be risk factors for hyperkalemia, whereas older age may be a risk factor for hyponatremia.
Topics: Humans; Thyroid Neoplasms; Thyrotropin Alfa; Iodine Radioisotopes; Hyperkalemia; Hyponatremia; Retrospective Studies; Thyrotropin; Potassium; Sodium; Electrolytes
PubMed: 37184818
DOI: 10.1007/s11604-023-01444-9 -
Endocrine Jul 2023To evaluate the predictive value of the rhTSH thyroglobulin stimulation test (rhTSH-Tg) compared to basal high-sensitive thyroglobulin (hs-Tg) under TSH suppressive...
PURPOSE
To evaluate the predictive value of the rhTSH thyroglobulin stimulation test (rhTSH-Tg) compared to basal high-sensitive thyroglobulin (hs-Tg) under TSH suppressive therapy at 12 months after the completion of initial treatment to predict the long-term response and Dynamic Risk Stratification (DRS) at the last follow-up visit in a long-term DTC cohort.
METHODS
Prospective study in 114 DTC patients (77.2% women, mean age 46.4 ± 14.1 years old, median/IQR evolution 6.7[3.1-8.0] years) from 2013 to 2020 undergoing total thyroidectomy and radioiodine ablation in whom hs-Tg and rhTSH-Tg was performed 12 months after completing initial treatment. Pearson correlation, receiving operating characteristics (ROC) and DRS at initial and last follow-up visit were analyzed.
RESULTS
hs-Tg and rhTSH-Tg show a strong positive linear correlation (r = 0.864, p < 0.001). The diagnostic performance of initial hs-Tg and rhTSH-Tg levels were evaluated via ROC-AUC as a predictor of excellent response (ER) in the last follow-up visit. Hs-Tg showed a better AUC (0.969, 95%CI = 0.941-0.997) than rhTSH-Tg (0.944, 95%IC = 0.905-0.984; p < 0.001). The hs-Tg and rhTSH-Tg cutoff point of highest sensitivity (S) and specificity (E) was 0.110 and 0.815 ng/dl, respectively. Hs-Tg showed a higher diagnostic accuracy than rhTSH-Tg (S = 100% vs 96.8%, E = 84.3% vs 84.3%, NPV = 100% vs 98.6%, PPV = 70.5% vs 69.7%; p < 0.05). The DRS based on initial hs-Tg showed better ability to predict ER (93.3% vs 86.7%) and biochemical incomplete response (53.3%vs13.3%) in the last follow-up visit compared to rhTSH-Tg.
CONCLUSIONS
Both initial hs-Th and rhTSH-Tg were good predictors of long-term ER. In patients with hs-Tg, the rhTSH-test did not provide relevant prognosis information. An ER after initial treatment was associated with a very high NPV at subsequent follow-up.
Topics: Adult; Female; Humans; Male; Middle Aged; Iodine Radioisotopes; Prospective Studies; Risk Assessment; Thyroglobulin; Thyroid Neoplasms; Thyroidectomy; Thyrotropin; Thyrotropin Alfa
PubMed: 36820996
DOI: 10.1007/s12020-023-03320-y