Correlation between remnant thyroid gland I-131 uptake and serum thyroglobulin levels: can we rely on I-131 whole body scans?

BACKGROUND: I-131 treatment (RAI) decision relies heavily on serum thyroglobulin (Tg) levels, as higher Tg levels are assumed to be correlated with higher I-131 uptake. Tg elevation, negative iodine scintigraphy (TENIS) definition is becoming more clinically relevant as alternative treatment methods are available. This study examined the correlation between Tg levels with I-131 uptake in remnant thyroid gland to evaluate the reliability of serum Tg levels in predicting I-131 uptake. METHODS: From March 2012 to July 2019, 281 papillary thyroid cancer patients treated with 150 mCi RAI were retrospectively enrolled. Early (2nd day) and Delayed (7th day) post-RAI whole-body scan (WBS) neck counts were correlated with clinical and pathologic findings. Patients with normal neck ultrasound and undetectable level of serum Tg (< 0.2 ng/mL) and thyroglobulin antibody (TgAb) (< 10 IU/mL) were defined as ablation success within 2 years after I-131 ablation. RESULTS: Thyroid gland weight, tumor size and thyroiditis were independent factors of preoperative serum Tg levels. Serum off-Tg levels correlated with Early and Delayed WBS neck counts, and thyroiditis pathology contributed to lower neck counts in both Early and Delayed WBSs. In multivariable analysis, Delayed WBS neck count, serum off-Tg and off-TgAb were significant factors for predicting ablation success. CONCLUSION: I-131 uptake and retention in remnant thyroid gland correlates with serum off-Tg levels, thyroiditis, and ablation success in thyroid cancer patients receiving high-dose I-131 therapy. Semi-quantitative I-131 analysis with Early and Delayed WBSs provides additional information in evaluating ablation success, with the potential application for metastasis treatment response evaluation.

Synergic chemoprevention with dietary carbohydrate restriction and supplementation of AMPK-activating phytochemicals: the role of SIRT1.

Calorie restriction or a low-carbohydrate diet (LCD) can increase life span in normal cells while inhibiting carcinogenesis. Various phytochemicals also have calorie restriction-mimetic anticancer properties. We investigated whether an isocaloric carbohydrate-restriction diet and AMP-activated protein kinase (AMPK)-activating phytochemicals induce synergic tumor suppression. We used a mixture of AMPK-activating phytochemical extracts including curcumin, quercetin, catechins, and resveratrol. Survival analysis was carried out in a B16F10 melanoma model fed a control diet (62.14% kcal carbohydrate, 24.65% kcal protein and 13.2% kcal fat), a control diet with multiple phytochemicals (MP), LCD (16.5, 55.2, and 28.3% kcal, respectively), LCD with multiple phytochemicals (LCDmp), a moderate-carbohydrate diet (MCD, 31.9, 62.4, and 5.7% kcal, respectively), or MCD with phytochemicals (MCDmp). Compared with the control group, MP, LCD, or MCD intervention did not produce survival benefit, but LCDmp (22.80±1.58 vs. 28.00±1.64 days, P=0.040) and MCDmp (23.80±1.08 vs. 30.13±2.29 days, P=0.008) increased the median survival time significantly. Suppression of the IGF-1R/PI3K/Akt/mTOR signaling, activation of the AMPK/SIRT1/LKB1pathway, and NF-κB suppression were the critical tumor-suppression mechanisms. In addition, SIRT1 suppressed proliferation of the B16F10 and A375SM cells under a low-glucose condition. Alterations in histone methylation within Pten and FoxO3a were observed after the MCDmp intervention. In the transgenic liver cancer model developed by hydrodynamic transfection of the HrasG12V and shp53, MCDmp and LCDmp interventions induced significant cancer-prevention effects. Microarray analysis showed that PPARα increased with decreased IL-6 and NF-κB within the hepatocytes after an MCDmp intervention. In conclusion, an isocaloric carbohydrate-restriction diet and natural AMPK-activating agents induce synergistic anticancer effects. SIRT1 acts as a tumor suppressor under a low-glucose condition.

Association Between Choroidal Thickness and Metabolic Activity on Positron Emission Tomography in Eyes With Choroidal Melanoma.

PURPOSE: To investigate the relationship between subfoveal choroidal thickness and metabolic activity in eyes with choroidal melanoma. DESIGN: Retrospective, interventional case series. METHODS: The medical records of 16 patients with unilateral choroidal melanoma who underwent ruthenium (Ru) 106 brachytherapy with adjuvant transpupillary thermotherapy and who had available pretreatment positron emission tomography-computed tomography (PET-CT) images were retrospectively reviewed. Subfoveal choroidal thickness was measured in tumor eyes and in unaffected fellow eyes using enhanced-depth imaging spectral-domain optical coherence tomography (EDI OCT). Tumor eyes were divided into 2 groups (metabolically active and inactive) based on PET-CT findings and subfoveal choroidal thickness was compared between groups. Additionally, choroidal thickness measurements were compared before and after treatment. RESULTS: Before treatment, mean choroidal thickness was 293.31 ± 46.80 µm in tumor eyes and 242.44 ± 65.37 µm in fellow eyes, a difference that was statistically significant (P = .003). Eyes with metabolically active tumors had a significantly thicker choroid (348.00 ± 17.32 µm) than eyes with metabolically inactive tumors (280.69 ± 42.04 µm, P = .019). In tumor eyes, mean choroidal thickness significantly decreased from pretreatment values to 253.56 ± 61.27 µm 6 months after treatment (P = .018). CONCLUSION: Eyes with choroidal melanoma had thicker choroids than unaffected fellow eyes. Increased choroidal thickness was more prominent in metabolically active tumors. Choroidal thickness significantly decreased in tumor eyes 6 months after treatment.

Regression of uveal melanoma after ru-106 brachytherapy and thermotherapy based on metabolic activity measured by positron emission tomography/computed tomography.

PURPOSE: To evaluate regression rates of uveal melanoma after combined Ru-106 plaque radiotherapy and thermotherapy according to metabolic activity measured by positron emission tomography/computed tomography imaging. METHODS: A retrospective medical chart review was conducted on 26 patients with uveal melanoma who underwent pretreatment whole-body positron emission tomography/computed tomography and received combined plaque radiotherapy and thermotherapy between 2006 and 2011. Tumors were classified as metabolically active and inactive based on the positron emission tomography/computed tomography imaging and compared with tumor height regression rates after treatment. RESULTS: Before treatment, the median tumor thickness was 8.8 mm for metabolically active tumors (7 eyes) and 5.0 mm for metabolically inactive tumors (19 eyes). The median tumor thicknesses with respect to the original thickness at 3, 6, and 12 months after treatment were 88%, 78%, and 64% for metabolically active tumors and 95%, 89%, and 81% for metabolically inactive tumors, respectively. The monthly tumor regression rates during the first 3 months (4.2% vs. 1.7%, P = 0.022) and the overall monthly tumor regression rates (3.0% vs. 1.5%, P = 0.041) were significantly higher for metabolically active tumors versus inactive tumors. Two patients with positive metabolic activity developed metastatic diseases 2 years after treatment, whereas no patient with negative metabolic activity developed metastatic disease during the study period. CONCLUSION: Positive metabolic activity of uveal melanoma based on the positron emission tomography/computed tomography was significantly associated with rapid initial tumor regression after combined plaque radiotherapy and thermotherapy, suggesting a prognostic value for this diagnostic approach.