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.

Tumor Glucose Metabolism and Its Heterogeneity on F-18 FDG PET/CT Provide Better Prognostication in Nonmetastatic Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma.

BACKGROUND: We aimed to evaluate the prognostic role of metabolic parameters on baseline F-18 fluorodeoxyglucose (FDG) PET/CT in patients with human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). METHODS: We retrospectively reviewed patients who were diagnosed with nonmetastatic HPV-related OPSCC using the 8th TNM staging system from 2010 to 2015 and underwent baseline F-18 FDG PET/CT. Tumor SUVmax to liver SUVmean ratio (SUVmax-TLR), metabolic tumor volume (MTV), tumor total lesion glycolysis to liver SUVmean ratio (TLG-TLR), and coefficient of variation (CV) of the primary tumor were measured. Patients were primarily treated with surgery or radiotherapy. Endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: Ninety consecutive patients (male, 72; female, 18) were enrolled. They were followed up for a median of 77.4 months (interquartile range, 48.4-106.4). Sixteen patients progressed, and 13 died. Multivariate analysis revealed that patients with advanced age, overall stage, and higher SUVmax-TLR or CV had poorer PFS and OS. CONCLUSION: Higher SUVmax-TLR and CV of the primary tumor on baseline F-18 FDG PET/CT were associated with poorer PFS and OS in patients with nonmetastatic HPV-related OPSCC. Further study is warranted to address the possible implications of F-18 FDG PET/CT on treatment de-intensification in these patients.

Association between PD-L1 expression and 18F-FDG uptake in ovarian cancer.

OBJECTIVE: Immunotherapy for programmed cell death 1 (PD-1) and its ligand, PD-L1, has been considered an effective treatment for ovarian cancer. 18F-labeled fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is a widely used noninvasive imaging tool for diagnosing several cancers. In this study, we investigated the association between PD-L1 expression and the maximum standardized uptake value (SUVmax) using 18F-FDG PET/CT. METHODS: We retrospectively analyzed clinical data of patients with ovarian cancer who underwent 18F-FDG PET/CT. Patients were categorized into two groups according to PD-L1 expression results. The relationship between clinicopathological characteristics of patients with ovarian cancer and PD-L1 expression was examined. RESULTS: SUVmax was significantly higher in PD-L1-positive tumors than in PD-L1-negative tumors (16.1 ± 5.2 and 12.7 ± 7.0, respectively; p = 0.026). There were no significant differences in age, histologic type, and tumor grade between the PD-L1-negative and PD-L1-positive groups. The receiver operating characteristic curve analysis demonstrated that the highest accuracy (61.8%) for predicting PD-L1 expression was obtained with an SUVmax cutoff value of 10.5. CONCLUSION: There was a significant correlation between 18F-FDG uptake and PD-L1 expression, suggesting a role of 18F-FDG PET/CT in selecting ovarian cancer candidates for anti-PD-L1 antibody therapy.

Prognostic value of metabolic tumor volume and total lesion glycolysis on preoperative 18F-FDG PET/CT in patients with localized primary gastrointestinal stromal tumors.

BACKGROUND: This study aimed to evaluate the prognostic value of pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with localized primary gastrointestinal stromal tumors (GISTs) and to compare the predictive values of 18F-FDG PET/CT parameters with those of clinicopathological prognostic factors. METHODS: Sixty-two localized GIST patients who underwent staging with 18F-FDG PET/CT from January 2007 to December 2013 before surgery were retrospectively enrolled. A volume of interest with a standardized uptake value (SUV) threshold of 2.5 was used to determine the metabolic tumor volume (MTV) and total lesion glycolysis (TLG). These metabolic indices, along with the maximum SUV (SUVmax), were analyzed to evaluate recurrence-free survival (RFS). Other significant clinical and pathologic indices were also retrospectively reviewed for RFS analysis. RESULTS: Patients were followed up for a median of 42.0 months (range, 5.6-111.5). During the follow-up period, 13 patients (21.0%) experienced disease recurrence. In univariate analysis, tumor size (> 5 cm), mitotic count (> 5/high-power field), modified National Institutes of Health (NIH) consensus criteria, adjuvant imatinib treatment, SUVmax (≥ 7.04), MTV (≥ 50.76 cm3), and TLG (≥ 228.79 g) were significant prognostic factors affecting RFS (p < 0.05). In multivariate analysis, only MTV (hazard ratio, 17.69; 95% confidence interval [CI], 2.03-154.17, p = 0.009) and TLG (hazard ratio, 20.48; 95% CI, 2.19-191.16, p = 0.008) were independent prognostic factors for RFS. The 5-year RFS rates were 96.4% and 96.6% in patients with a low MTV and TLG and 27.3% and 23.6% in patients with a high MTV and TLG, respectively (p < 0.001). CONCLUSION: MTV and TLG are independent prognostic factors for predicting recurrence in patients with localized primary GIST. Patients with a high MTV or TLG are at risk for poor prognosis and should be closely observed for disease recurrence.

Choroid Plexus as the Best Reference Region for Standardized Uptake Value Analysis on C11-Acetate PET/CT for Grading and Predicting Prognosis in Patients with Cerebral Gliomas.

PURPOSE: We aimed to compare different reference regions and select one with the most clinical relevance on C11-acetate (ACE) positron emission tomography/computed tomography (PET/CT) in patients with cerebral glioma. METHODS: We retrospectively reviewed 51 patients with cerebral glioma who underwent baseline ACE PET/CT at diagnosis. Other than the standardized uptake value (SUV) of the primary tumor, SUVs of the reference regions including the normal gray matter, white matter, choroid plexus, and cerebellum were measured. Then, the SUV ratio (SUVR = tumor SUVmax/reference region SUVmean) was calculated. The effect of patient age on the SUVmean of each reference was examined and the SUVRs of each reference region were compared between grades. age, sex, tumor size, histological grades, SUVR, and the presence of isocitrate dehydrogenase (IDH) mutation were included for survival analyses. RESULTS: Except for the cerebellum showing a mild negative correlation, we found no correlations between age and SUVmean using the gray matter, white matter, and choroid plexus (r = - 0.280, P = 0.047). Only the SUVR-choroid plexus was able to differentiate between the WHO grades (Grade II vs. III, P = 0.035; grade III vs. IV, P < 0.001; grade II vs. IV, P < 0.001). Multivariate Cox proportional hazards models found that the SUVR-choroid plexus and IDH mutation were statistically significant for predicting OS. CONCLUSION: Of the different reference regions used for grading cerebral gliomas, the choroid plexus was found to be the most optimal. In addition, the SUV ratio is useful to predict the overall survival in the model with the choroid plexus as a reference region.

Association of non-alcoholic steatohepatitis with subclinical myocardial dysfunction in non-cirrhotic patients.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular risk. Among categories of NAFLD, hepatic fibrosis is most likely to affect mortality. Myocardial function and its energy metabolism are tightly linked, which might be altered by an insulin resistant condition such as NAFLD. We investigated whether hepatic steatosis and fibrosis were associated with myocardial dysfunction relative to myocardial glucose uptake. METHODS: A total of 308 patients (190 without NAFLD, 118 with NAFLD) were studied in a tertiary care hospital. Myocardial glucose uptake was evaluated at fasted state using [18F]-fluorodeoxyglucose-positron emission tomography (18FDG-PET). Hepatic steatosis and fibrosis were assessed by transient liver elastography (Fibroscan®) with controlled attenuation parameter, which quantifies hepatic fat and by surrogate indices (fatty liver index and NAFLD fibrosis score). Cardiac structure and function were examined by echocardiogram. RESULTS: Compared to those without NAFLD, patients with NAFLD had alterations in cardiac remodeling, manifested by increased left ventricular mass index, left ventricular end-diastolic diameter, and left atrial volume index (all p <0.05). Hepatic steatosis was significantly associated with left ventricular filling pressure (E/e' ratio), which reflects diastolic dysfunction (p for trend <0.05). Those without NAFLD were more likely to have higher myocardial glucose uptake compared to those with NAFLD. Significant hepatic fibrosis was also correlated with diastolic dysfunction and impaired myocardial glucose uptake. Using multivariable linear regression, E/e' ratio was independently associated with hepatic fibrosis (standardized ß = 0.12 to 0.27; all p <0.05). Association between hepatic steatosis and E/e' ratio was also significant (standardized ß = 0.10 to 0.15; all p <0.05 excluding the model adjusted for adiposity). CONCLUSIONS: Hepatic steatosis and fibrosis are significantly associated with diastolic heart dysfunction. This association is linked with myocardial glucose uptake evaluated by 18FDG-PET. LAY SUMMARY: Non-alcoholic fatty liver disease is associated with an increased risk of cardiovascular disease. More severe forms of non-alcoholic fatty liver disease, where hepatic fibrosis occurs, are linked to increased mortality. In this study, we have shown that hepatic steatosis and fibrosis are associated with subclinical myocardial dysfunction. This association is linked to altered myocardial glucose uptake.

Correlation between KRAS mutation and 18F-FDG uptake in stage IV colorectal cancer.

PURPOSE: The purpose of this study is to evaluate the correlation between KRAS mutation, 18F-FDG uptake, and metastatic pattern in advanced stage colorectal cancer (CRC) patients. METHODS: Medical records of stage IV CRC patients who underwent 18F-FDG PET/CT for staging and KRAS mutation analysis were selected. On PET scans, a volume of interest (VOI) was drawn on the primary lesion. 18F-FDG indices (SUVmax, SUVmean, MTV, TLG) of the primary lesions were obtained and correlated with KRAS mutation of the primary lesion. Also, metastatic sites were recorded. Association between metastatic pattern and KRAS expression and FDG indices were analyzed. RESULTS: KRAS mutation was positive in 40 (43%) patients. Evaluation of FDG indices showed that higher SUVmax (14.0 vs. 11.2, p = 0.004), higher SUVmean (5.3 vs. 4.7, p = 0.005), and higher TLG (301.4 vs. 205.5, p = 0.023) were predictive of KRAS mutation compared to wild-type (WT) KRAS. Lung metastasis was more frequently involved in patients with KRAS mutation (50.0% vs. 22.6%, p = 0.006), and liver metastasis was more frequently involved in patients with WT KRAS (81.1% vs. 55.0%, p = 0.007). Multivariate analysis showed that  primary tumor location (OR 3.92, p = 0.07) and KRAS mutation (OR 2.45, p = 0.09) were significant factors in lung metastasis model. CONCLUSION: KRAS mutation patients had more frequent lung metastasis and had higher 18F-FDG uptake compared to WT KRAS in stage IV CRC.

A Comparison Study of Esophageal Findings on (18)F-FDG PET/CT and Esophagogastroduodenoscopy.

PURPOSE: The aim of this study was to compare the esophageal findings of 2-deoxy-2-[(18)F]fluoro-d-glucose positron emission tomography-computed tomography ((18)F-FDG PET/CT) and esophagogastroduodenoscopy (EGD). METHODS: We retrospectively reviewed (18)F-FDG PET/CT and EGD findings of 369 subjects who underwent medical examination between January 2014 and December 2014. The range and intensity of esophageal (18)F-FDG uptake were visually analyzed. The maximum standardized uptake value (SUVmax) of the esophagus and around the esophagogastric (EG) junction was measured. EGD results were provided by the gastroenterologist. We compared the esophageal findings obtained using (18)F-FDG PET/CT and EGD. RESULTS: There were typical linear FDG uptakes in (18)F-FDG PET/CT patients who underwent EGD the same day. In visual analysis of the range and intensity of the (18)F-FDG uptake, the patients who underwent (18)F-FDG PET/CT and EGD on the same day showed relatively diffuse and discernible (18)F-FDG uptake in the esophagus. Reflux esophagitis was diagnosed in 59 subjects, and 27 of these were classified as higher than Los Angeles classification A. With an increasing degree of reflux esophagitis observed on EGD, the SUVmax in the esophagus and around the EG junction was also increased. CONCLUSION: Our study showed that FDG uptake at the esophagus or the EG junction might be clinically significantly related to esophagitis. However, EGD performed before (18)F-FDG PET/CT on the same day may affect the esophageal (18)F-FDG uptake.

Visceral adiposity is associated with altered myocardial glucose uptake measured by (18)FDG-PET in 346 subjects with normal glucose tolerance, prediabetes, and type 2 diabetes.

BACKGROUND: The heart requires constant sources of energy mostly from free fatty acids (FFA) and glucose. The alteration in myocardial substrate metabolism occurs in the heart of diabetic patients, but its specific association with other metabolic variables remains unclear. We aimed to evaluate glucose uptake in hearts of subjects with normal glucose tolerance (NGT), prediabetes, and type 2 diabetes mellitus (T2DM) using [(18)F]-fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) in association with visceral and subcutaneous adiposity, and metabolic laboratory parameters. METHODS: A total of 346 individuals (NGT, n = 76; prediabetes, n = 208; T2DM, n = 62) in a health promotion center of a tertiary hospital were enrolled. The fasting myocardial glucose uptake, and visceral and subcutaneous fat areas were evaluated using (18)FDG-PET and abdominal computed tomography, respectively. RESULTS: Myocardial glucose uptake was significantly decreased in subjects with T2DM compared to the NGT or prediabetes groups (p for trend = 0.001). Multivariate linear regression analyses revealed that visceral fat area (ß = -0.22, p = 0.018), fasting FFA (ß = -0.39, p < 0.001), and uric acid levels (ß = -0.21, p = 0.007) were independent determinants of myocardial glucose uptake. Multiple logistic analyses demonstrated that decreased myocardial glucose uptake (OR 2.32; 95% CI 1.02-5.29, p = 0.045) and visceral fat area (OR 1.02, 95% CI 1.01-1.03, p = 0.018) were associated with T2DM. CONCLUSIONS: Our findings indicate visceral adiposity is strongly associated with the alteration of myocardial glucose uptake evaluated by (18)FDG-PET, and its association further relates to T2DM.

Risk Stratification of Thyroid Incidentalomas Found on PET/CT: The Value of Iodine Content on Noncontrast Computed Tomography.

BACKGROUND: The Hounsfield unit (HU) ratio of thyroid nodules was assessed compared to the contralateral thyroid lobe on noncontrast computed tomography (CT) to stratify further the risk of malignancy in thyroid incidentalomas found on 18F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/CT (PET/CT). METHODS: This retrospective analysis included 82 patients who had thyroid incidentalomas on PET/CT in 2011. On PET/CT, the maximal standardized uptake value ratios of the thyroid nodule compared to liver (T/BSUV) and the HU ratios of the thyroid nodule compared to contralateral thyroid lobe (T/BHU) were calculated. Diagnostic performances of the T/BSUV and T/BHU were compared. RESULTS: The area under the curve of T/BHU was higher than that of T/BSUV (0.941 vs. 0.689, p < 0.0001). The sensitivity, specificity, and accuracy of T/BHU were significantly higher than those of T/BSUV (100% vs. 77.8%, p = 0.0313; 80.0% vs. 60.0%, p = 0.0433; 86.6% vs. 65.9%, p = 0.0041, respectively). The risk of malignancy was much higher (71.1%) in nodules with a T/BHU cutoff value ≤0.68, whereas it was 0% in nodules with a T/BHU of >0.68. In this study, there were 18 nodules with nondiagnostic (n = 7) or atypia of undetermined significance or follicular lesion of undetermined significance cytologies (n = 11) after fine-needle aspiration biopsy (FNAB). When the T/BHU cutoff value was applied, three (60%) of the five nodules with a T/BHU of ≤0.68 were found to be papillary carcinomas. The remaining 13 nodules with a T/BHU of >0.68 were all benign with a risk of malignancy of 0%. CONCLUSIONS: T/BHU is a simple and effective parameter to stratify the risk of malignancy in thyroid incidentalomas found on PET/CT. This may be of clinical relevance in those nodules with nondiagnostic or undetermined significance cytologies upon FNAB in the scheme of current clinical practice.

Relationship Between 18F-FDG Uptake on PET and Recurrence Patterns After Curative Surgical Resection in Patients with Advanced Gastric Cancer.

UNLABELLED: This study evaluated the predictive value of 18F-FDG PET for distant metastasis-free survival and peritoneal recurrence-free survival as well as recurrence-free survival and overall survival after curative surgical resection in patients with advanced gastric cancer (AGC). METHODS: Two hundred seventy-nine patients with AGC who underwent preoperative 18F-FDG PET and subsequent curative surgical resection were included. The tumor-to-normal liver uptake ratio (TLR) of cancer lesions was measured, and the prognostic significance of TLR and tumor factors for distant metastasis-free survival, peritoneal recurrence-free survival, recurrence-free survival, and overall survival was assessed. RESULTS: The 5-y recurrence-free survival, peritoneal recurrence-free survival, distant metastasis-free survival, and overall survival rates were 46.9%, 68.5%, 76.0%, and 58.1%, respectively. Depth of tumor invasion, lymph node metastasis, lymphovascular invasion, and TLR were independent prognostic factors for both recurrence-free survival and overall survival (P<0.05). For distant metastasis-free survival, lymphovascular invasion and TLR were independent risk factors (P<0.05). In patients with a TLR of 2.0 or less, the 5-y distant metastasis-free survival rate was 95.5%; in patients with a TLR greater than 2.0, the 5-y distant metastasis-free survival rate was 68.8%. For peritoneal recurrence-free survival, TLR showed no statistical significance (P=0.7) whereas pT stage, lymph node metastasis, Lauren classification, and Bormann type were independent prognostic factors (P<0.05). CONCLUSION: 18F-FDG uptake of AGC is an independent prognostic factor for distant metastasis-free survival, recurrence-free survival, and overall survival. The possibility of distant metastasis during follow-up should be considered in patients with high 18F-FDG uptake.

Correlation Analysis and Prognostic Impact of (18)F-FDG PET and Excision Repair Cross-Complementation Group 1 (ERCC-1) Expression in Non-Small Cell Lung Cancer.

PURPOSE: The aim of this study was to determine the relationship between [(18)]-2-fluoro-2-deoxy-D-glucose (FDG) uptake and excision repair cross-complementation group 1 (ERCC-1) expression and to evaluate the prognostic effect of these two factors in resectable non-small cell lung cancer (NSCLC) patients. METHODS: We retrospectively reviewed 212 patients with resectable NSCLC who underwent FDG positron emission tomography/computed tomography (PET/CT) scan for cancer staging and ERCC-1 expression analysis between January 2008 to December 2011. All patients were then followed-up for survival analysis. Semiquantitative evaluation of ERCC-1 was performed with the H-scoring system and was correlated with maximum standardized uptake value (SUVmax) of NSCLC. Univariate and multivariate analyses were performed to evaluate for FDG uptake and ERCC-1 expression predicting overall survival. RESULTS: In 212 patients (139 male, median age 68 ± 9.11), 112 patients had ERCC-positive tumors and 100 patients had ERCC-negative tumors. There was no significant difference in SUVmax between ERCC-1-positive tumors (8.02 ± 5.40) and ERCC-1-negative tumors (7.57 ± 6.56, p = 0.584). All patients were followed-up for a median of 40.5 months (95 % confidence interval [CI], 38.5-42.2 months). Univariate analysis and multivariate analysis for all patients showed that both ERCC-1 expression (hazard ratio [HR], 2.78; 95 % CI, 1.20-6.47) and FDG uptake (HR, 4.50; 95 % CI, 2.07-9.77) independently predicted overall survival. CONCLUSIONS: We have found no statistical correlation between FDG uptake and ERCC-1 expression in NSCLC. However, both higher FDG uptake and positive ERCC-1 expression are independent predictive markers of prognosis, suggesting that both should be obtained during patient workup.

Prognostic significance of standardized uptake value on preoperative ¹8F-FDG PET/CT in patients with ampullary adenocarcinoma.

PURPOSE: The purpose of this study was to investigate the prognostic value of (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with ampullary adenocarcinoma (AAC) after curative surgical resection. METHODS: Fifty-two patients with AAC who had undergone (18)F-FDG PET/CT and subsequent curative resections were retrospectively enrolled. The maximum standardized uptake value (SUVmax) and tumor to background ratio (TBR) were measured on (18)F-FDG PET/CT in all patients. The prognostic significances of PET/CT parameters and clinicopathologic factors for recurrence-free survival (RFS) and overall survival (OS) were evaluated by univariate and multivariate analyses. RESULTS: Of the 52 patients, 19 (36.5%) experienced tumor recurrence during the follow-up period and 18 (35.8%) died. The 3-year RFS and OS were 62.3 and 61.5%, respectively. Preoperative CA19-9 level, tumor differentiation, presence of lymph node metastasis, SUVmax, and TBR were significant prognostic factors for both RFS and OS (p < 0.05) on univariate analyses, and patient age showed significance only for predicting RFS (p < 0.05). On multivariate analyses, SUVmax and TBR were independent prognostic factors for RFS, and tumor differentiation, SUVmax, and TBR were independent prognostic factors for OS. CONCLUSION: SUVmax and TBR on preoperative (18)F-FDG PET/CT are independent prognostic factors for predicting RFS and OS in patients with AAC; patients with high SUVmax (>4.80) or TBR (>1.75) had poor survival outcomes. The role of and indications for adjuvant therapy after curative resection of AAC are still unclear. (18)F-FDG uptake in the primary tumor could provide additive prognostic information for the decision-making process regarding adjuvant therapy.