Cumulative Metformin Use and Its Impact on Survival in Gastric Cancer Patients After Gastrectomy.

OBJECTIVE: The aim of this study was to evaluate the association between metformin and survival of gastric cancer (GC) patients. BACKGROUND: Metformin has recently received attention as a potential anticancer treatment. However, no study has shown the survival benefit of metformin for GC patients. METHODS: A total of 1974 GC patients who underwent curative gastrectomy were compared for survival according to groups; 132 diabetic patients treated with metformin, 194 diabetic patients without metformin, and 1648 non-diabetic patients. RESULTS: During the median follow-up period of 6.2 years (interquartile range, 4.7-7.8 years), 381 patients (19.3%) died, including 302 (15.3%) who died from GC. The non-diabetic patients had significantly better recurrence-free survival (RFS; P < 0.0001), cancer-specific survival (CSS; P = 0.006), and overall survival (OS; P < 0.0001). However, the diabetic patients treated with metformin had a significantly better prognosis than those who were not (OS: hazard ratio [HR] = 0.584, 95% confidence interval [CI], 0.369-0.926; CSS: HR = 0.57, 95% CI, 0.334-0.975; RFS: HR = 0.633, 95% CI, 0.410-0.977), and metformin treatment prolonged survival in diabetic patients to a rate comparable to that in non-diabetic patients. In multivariable analysis using the Cox proportional hazard model with time-dependent covariates, each cumulative 6 months of metformin use was significantly associated with a decreased risk of recurrence, cancer-specific mortality, and all-cause mortality (RFS: HR = 0.864, 95% CI, 0.797-0.937; CSS: HR = 0.865, 95% CI, 0.782-0.958; OS: HR 0.870, 95% CI, 0.801-0.945). CONCLUSIONS: The increased cumulative duration of metformin use decreased the recurrence, all-cause mortality, and cancer-specific mortality rates among GC patients with diabetes who underwent gastrectomy.

FDG-PET predicts outcomes of treated bone metastasis following palliative radiotherapy in patients with hepatocellular carcinoma.

AIMS: To determine the utility of FDG-PET in predicting long-term infield tumour control after RT in patients with metastatic hepatocellular carcinoma (HCC) to bone. METHODS: Among 223 patients with HCC skeletal metastases diagnosed, we reviewed 22 patients with 45 total sites treated with RT who had at least two FDG-PETs prior to and after RT. The median RT dose was 42 Gy (range, 22-48) with a median fraction of 3 Gy (range, 2-8). Helical tomotherapy was generally offered for lesions that received higher RT dose (36%). The intrahepatic control rate in all patients was 73% at the time of referral. The ratio of tumour SUV to blood-pool activity SUV (SUV-ratio) was calculated. The primary end-points were infield progression-free survival (infield-PFS) and infield event-free survival (infield-EFS; recurrent and intractable pain or skeletal-related events). RESULTS: Among 45 sites, 20 had tumour progression and 21 developed events in the previously treated area. A higher SUV-ratio before RT, SUV-ratio decline and higher radiation dose were independently and significantly correlated with better infield-PFS (both P<0.05). The tumours with a pre-RT SUV-ratio≥3.0 and SUV-ratio decline≥40% had significantly better infield-PFS and EFS than those with either a pre-RT SUV-ratio<3.0 or SUV-ratio decline<40% (both P<0.05). CONCLUSIONS: FDG-PET may help to predict outcomes of infield tumour control following palliative RT for treatment of HCC bone metastases. Tumours with low metabolic uptake before RT or with a minor decline in post-RT SUV-ratio showed poor long-term infield tumour control.

Evaluation of glymphatic system activity using diffusion tensor image analysis along the perivascular space and amyloid PET in older adults with objectively normal cognition: a preliminary study.

Objectives: Diffusion tensor image analysis along the perivascular space (DTI-ALPS) is a recently introduced method for the assessment of the glymphatic system without the need for contrast injection. The purpose of our study was to assess the glymphatic system in cognitively normal older adults with or without subjective cognitive decline (SCD) using DTI-ALPS, and correlating with amyloid PET. Design and participants: To evaluate the glymphatic system in cognitively normal older adults using DTI-ALPS, we built a prospective cohort including a total of 123 objectively cognitively normal older adults with or without SCD. The ALPS index was calculated from DTI MRI and was assessed by correlating it with standardized uptake value ratios (SUVRs) from amyloid PET and clinically relevant variables. The study subjects were also divided into amyloid "positive" and "negative" groups based on the result of amyloid PET, and the ALPS indices between those two groups were compared. Results: The ALPS index was not significantly different between the normal and SCD groups (P = 0.897). The mean ALPS index from the amyloid positive and amyloid negative group was 1.31 and 1.35, respectively, which showed no significant difference (P = 0.308). Among the SUVRs from variable cortices, that of the paracentral cortex was negatively correlated with the ALPS index (r = -0.218, P = 0.016). Multivariate linear regression revealed that older age (coefficient, -0.007) and higher SUVR from the paracentral cortex (coefficient, -0.101) were two independent variables with a significant association with a lower ALPS index (P = 0.015 and 0.045, respectively). Conclusion: DTI-ALPS may not be useful for evaluation of the glymphatic system in subjects with SCD. Older age was significantly associated with lower ALPS index. Greater amyloid deposition in the paracentral cortex was significantly associated with lower glymphatic activity in cognitively normal older adults. These results should be validated in future studies on the relationships between ALPS index and other fundamental compartments in glymphatic system, such as perivenous space and the meningeal lymphatic vessels.

Plasma amyloid-beta oligomer is related to subjective cognitive decline and brain amyloid status.

BACKGROUND: Subjective cognitive decline (SCD) is a target for Alzheimer's disease prediction. Plasma amyloid-beta oligomer (AßO), the pathogenic form of Aß in blood, has recently been proposed as a novel blood-based biomarker of AD prediction by representing brain Aß deposition. The relationship between plasma AßO, brain Aß deposition, and SCD in individuals with normal objective cognition has not been investigated. METHODS: In this cross-sectional study, we analyzed 126 participants with normal objective cognition. More SCD symptoms were expressed as higher scores of the Subjective Cognitive Decline Questionnaire (SCDQ) and Memory Age-associated Complaint Questionnaire (MACQ). The plasma AßO level of each participant was measured twice for validation and expressed as a concentration (ng/mL) and a ratio relative to the mean value of two internal standards. Brain Aß deposition was assessed by [18F] flutemetamol positron emission tomography (PET) and expressed as standard uptake value ratio (SUVR). Associations of SCDQ and MACQ with plasma AßO levels or SUVR were analyzed in multiple linear regression models. The association between plasma AßO level and flutemetamol PET positivity was assessed in logistic regression and receiver operative characteristic analyses. RESULTS: Overall, participants were 73.3 years old with female predominance (69.0%). After adjustment for confounders, high SCDQ and MACQ scores were associated with the high plasma AßO levels as both concentrations and ratios (ratios: standardized coefficient = 0.246 and p = 0.023 for SCDQ, standardized coefficient = 0.209 and p = 0.029 for MACQ; concentrations: standardized coefficient = 0.257 and p = 0.015 for SCDQ, standardized coefficient = 0.217 and p = 0.021 for MACQ). In contrast, SCDQ and MACQ were not significantly associated with SUVRs (p = 0.134 for SCDQ, p = 0.079 for MACQ). High plasma AßO levels were associated with flutemetamol PET (+) with an area under the curve of 0.694 (ratio) or 0.662 (concentration). Combined with APOE e4, plasma AßO presented area under the curves of 0.789 (ratio) and 0.783 (concentration). CONCLUSIONS: Our findings indicate that the high plasma AßO level could serve as a potential surrogate biomarker of severe SCD and the presence of brain Aß deposition in individuals with normal objective cognition.

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.

Characteristics of surgically transposed ovaries on 18F-FDG PET/CT among patients with cancer.

OBJECTIVE: Fertility preservation in women with cancer is important for improving their quality of life. Successful ovarian transposition protects the ovary from radiation and preserves ovarian endocrine function and fertility. With the increasing use of 18F-FDG PET/CT in gynecologic malignancies, the findings of transposed ovaries sometimes vary. This study aimed to characterize the 18F-FDG PET/CT findings of surgically transposed ovaries among a large number of patients with various medical conditions. METHODS: We retrospectively reviewed the medical records, including surgical history, and analyzed the findings of the transposed ovaries of patients who underwent ovarian transposition. Quantitative analysis was performed, and the maximum standardized uptake values (SUVs) were recorded. The Hounsfield unit (HU) and size (measured using the long diameter on the axial image) of the transposed ovary were evaluated. RESULTS: No significant change was found in the SUV of the transposed ovaries in relation to age and time after surgery. In two cases in which metastasis occurred in the transposed ovary, the lesions showed higher SUVs and HUs than did the other non-metastatic transposed ovaries. In several serial follow-up cases, varying 18F-FDG uptake was observed. CONCLUSION: The 18F-FDG uptake pattern of the transposed ovary did not differ from that of the normal ovary. Misinterpretation should be avoided by considering surgical records, presence of surgical clips, and patients' disease state. If there is a high uptake in the transposed ovary, it is necessary to check for soft tissue lesions and differentiate metastasis from the physiologic uptake.

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.

Splenic uptake on FDG PET/CT correlates with Kikuchi-Fujimoto disease severity.

Kikuchi-Fujimoto disease (KFD) is usually self-limiting, but prolonged systemic symptoms often result in frequent hospital visits, long admission durations, or missed workdays. We investigated the role of fluorine-18 fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in assessing KFD severity. We reviewed the records of 31 adult patients with pathologically confirmed KFD who underwent 18F-FDG PET/CT between November 2007 and April 2018 at a tertiary-care referral hospital. Disease severity was assessed using criteria based on clinical manifestations of advanced KFD. Systemic activated lymph nodes and severity of splenic activation were determined using semi-quantitative and volumetric PET/CT parameters. The median of the mean splenic standardized uptake value (SUVmean) was higher in patients with severe KFD than those with mild KFD (2.38 ± 1.18 vs. 1.79 ± 0.99, p = 0.058). Patients with severe KFD had more systemically activated volume and glycolytic activity than those with mild KFD (total lesion glycolysis: 473.5 ± 504.4 vs. 201.6 ± 363.5, p = 0.024). Multivariate logistic regression showed that myalgia (odds ratio [OR] 0.035; 95% confidence interval [CI] 0.001-0.792; p = 0.035), total lymph node SUVmax (cutoff 9.27; OR 24.734; 95% CI 1.323-462.407; p = 0.032), and spleen SUVmean (cutoff 1.79; OR 37.770; 95% CI 1.769-806.583; p = 0.020) were significantly associated with severe KFD. 18F-FDG PET/CT could be useful in assessing KFD severity.

Neural substrates for poststroke complex regional pain syndrome type I: a retrospective case-control study using voxel-based lesion symptom mapping analysis.

Poststroke complex regional pain syndrome (CRPS) is characterized by swelling, pain, and changes in the skin that appear on the affected wrist and hand. In this retrospective study, we analyzed the relationship between poststroke CRPS and the location of stroke lesion. From all patients admitted to our hospital from 2009 to 2019, we recruited 80 patients affected by their first unilateral stroke who met the inclusion/exclusion criteria. Thirty-eight patients diagnosed with CRPS after stroke were assigned to the experimental group according to the "Budapest criteria" adopted by the International Association for the Study of Pain, and 42 patients without CRPS were included as controls. Regions of interest were manually drawn on T1-weighted magnetic resonance images, and data were normalized to a standard brain template. In the poststroke CRPS group, the relationship between the location of brain lesion and pain severity was analyzed using Freedman-Lane multivariable regression adjusting for Medication Quantification Scale rating, which was the only parameter to show a statistically significant correlation with pain intensity. A threshold of P < 0.01 was considered statistically significant for all voxel-based lesion symptom mapping tests, corrected for multiple comparisons with 5000 permutations. Analyses using voxel-wise subtraction and Liebermeister statistics indicated that the corticospinal tract (CST) was associated with the development of poststroke CRPS. Statistically significant correlations were found between pain intensity and the CST and the adjacent lentiform nucleus. Our results suggest that the CST may be a relevant neural structure for development of poststroke CRPS and the intensity of pain caused by the syndrome.

Stepwise flowchart for decision making on sublobar resection through the estimation of spread through air space in early stage lung cancer1.

OBJECTIVES: The sensitivity for tumor spread through air space (STAS), an independent risk factor for locoregional recurrence after sublobar resection for lung cancer, has been relatively low in frozen sections. We aimed to determine predictors with high negative predictive value for the presence of STAS and to provide the flowchart in combination with these predictors for the decision-making for sublobar resection. MATERIALS AND METHODS: Between July 2015 and December 2017, 387 patients who underwent surgery for non-small cell lung cancer (NSCLC) with pathologic findings of the total masses measuring ≤ 2 cm were enrolled. The lesions were divided into two groups according to presence of STAS. We compared the preoperative characteristics, operative data, and developed a flowchart for STAS prediction using receiver operator characteristic curve analysis and multivariable logistic regression. RESULTS: The STAS-positive group (N = 111) had a significantly higher preoperative tumor size (1.70 [1.5] vs 1.50 [0.69], p < 0.001) and standardized uptake value tumor-to-liver (SUV T/L) ratio (1.40 [1.60] vs 0.60 [1.10], p < 0.001) and a significantly lower two-dimensional ground-glass opacity (GGO) percentage (35.86 [61.00] vs 78.14 [39.00], p < 0.001). Meanwhile, the STAS-negative group (N = 286) had higher lepidic predominance (41.6% vs. 1.8%, p < 0.001). We developed a flowchart for predicting STAS in combination with two-dimensional GGO percentage on computed tomography (CT), SUV T/L ratio on positron-emission CT, and lepidic predominant pattern. The sensitivity, specificity, and negative predictive value for STAS positivity were 79.3%, 68.5%, and 89.5%, respectively. CONCLUSIONS: The stepwise flowchart using two-dimensional GGO percentage on CT, maximum SUV, and lepidic predominance might be helpful in selecting patients with early NSCLC for sublobar resection.

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.

Pituitary 18F-FDG Uptake Correlates With Serum TSH Levels in Subjects With Diffuse Thyroid 18F-FDG Uptake.

PURPOSE: This study was to evaluate the relationship among FDG uptake in the pituitary gland (FDGp), FDG uptake in the thyroid gland (FDGt), and serum thyroid-stimulating hormone (TSH) levels in patients with diffuse FDGt incidentally noted on positron emission tomography/computed tomography (PET/CT). PATIENTS AND METHODS: We retrospectively reviewed FDG PET/CT scans of 2,945 subjects who underwent health screening. Of these, 44 subjects had diffuse FDGt and available thyroid function tests. FDGt and FDGp were correlated with serum TSH. FDGp in 44 paired control subjects without FDGt and 15 thyroid cancer patients undergoing thyroid hormone withdrawal were additionally measured, and compared with FDGp in the 44 subjects with FDGt divided into 3 groups according to serum TSH levels. RESULTS: In the 44 subjects, there was a strong correlation found between FDGp and TSH (P < 0.001, r = 0.618). As well, there were statistically significant differences in FDGp between the low, normal, and high TSH groups (P < 0.001). FDGp in the paired control subjects was not different from that in the normal TSH group (P = 0.384), and FDGp in the TSH-stimulated thyroid cancer patients was not different from that in the high TSH group (P = 0.463). CONCLUSION: We found a strong positive correlation between pituitary FDG uptake and serum TSH. Pituitary FDG uptake seems to hold an important clue to the functional status of the thyroid in subjects with diffuse thyroid FDG uptake. Furthermore, physiologic FDG uptake in the pituitary gland caused by hypothyroidism should not be confused with pathologic conditions such as macroadenoma or metastases.

(18)F-FDG PET as a single imaging modality in pediatric neuroblastoma: comparison with abdomen CT and bone scintigraphy.

OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) as a single imaging agent in neuroblastoma in comparison with other imaging modalities. METHODS: A total of 30 patients with pathologically proven neuroblastoma who underwent FDG PET for staging were enrolled. Diagnostic performance of FDG PET and abdomen CT was compared in detecting soft tissue lesions. FDG PET and bone scintigraphy (BS) were compared in bone metastases. Maximal standardized uptake value (SUVmax) of primary or recurrent lesions was calculated for quantitative analysis. RESULTS: Tumor FDG uptake was detected in 29 of 30 patients with primary neuroblastoma. On initial FDG PET, SUVmax of primary lesions were lower in early stage (I-II) than in late stage (III-IV) (3.03 vs. 5.45, respectively, p = 0.019). FDG PET was superior to CT scan in detecting distant lymph nodes (23 vs. 18 from 23 lymph nodes). FDG PET showed higher accuracy to identify bone metastases than BS both on patient-based analyses (100 vs. 94.4 % in sensitivity, 100 vs. 77.8 % in specificity), and on lesion-based analyses (FDG PET: 203 lesions, BS: 86 lesions). Sensitivity and specificity of FDG PET to detect recurrence were 87.5 % and 93.8, respectively. CONCLUSION: FDG PET was superior to CT in detecting distant LN metastasis and to BS in detecting skeletal metastasis in neuroblastoma. BS might be eliminated in the evaluation of neuroblastoma when FDG PET is performed.

The Role of (18) F-FDG PET/CT in Assessing Therapy Response in Cervix Cancer after Concurrent Chemoradiation Therapy.

PURPOSE: To determine whether persisting cervical fluorodeoxyglucose (FDG) uptake after concurrent chemoradiotherapy (CCRT) for cervical cancer can reflect residual malignancy. METHODS: F-FDG PET/CT was performed before and after CCRT in 136 patients with cervical cancer. The maximum and mean standardized uptake values (SUVmax and SUVmean) were recorded from PET/CT scans performed pre- and post-treatment. SUVs were correlated with treatment response after CCRT. Final treatment response was determined by MRI and further follow-up PET/CT. One hundred four of 136 patients underwent pelvic MRI, and 32 of 136 patients underwent further follow-up PET/CT. Patients were classified into two categories: patients with residual tumor or patients without residual tumor (complete responder). Pre- and post-treatment serum squamous cell carcinoma antigen (SCC) levels were also recorded for comparison. The optimal cutoff value of SUVmax for predicting residual cervical tumor was determined using receiver-operating characteristic (ROC) analysis. RESULTS: Of 136 patients, 124 showed complete response on further follow-up studies and 12 were confirmed to have residual tumor. The post-treatment SUVmax and pre-/post-treatment SUVmean of complete responders were significantly lower than those of patients with residual tumor: 2.5 ± 0.8 and 7.2 ± 4.2/1.9 ± 0.7 for complete responders and 5.7 ± 2.6 and 12.8 ± 6.9/3.7 ± 0.7 for patients with residual tumor (p < 0.05). The pre-treatment SUVmax and pre-/post-treatment serum SCC levels of the complete responders tended to be lower than those of patients with residual tumor, but this did not have statistical significance. Using ROC analysis, an optimal cutoff SUVmax of 4.0 on the post-treatment PET/CT yielded a sensitivity, specificity, positive predictive value, and negative predictive value of 92 %, 94 %, 61 %, and 99 %, respectively (p < 0.001). CONCLUSIONS: Persistent cervical FDG uptake in(18)F-FDG PET/CT after CCRT for cervical cancer may be caused by residual tumor or post-therapy inflammation. A higher cutoff SUVmax than conventional criteria for cervical cancer in post-CCRT PET/CT might help to detect residual tumor.

Prognostic Value of Metabolic Activity Measured by (18)F-FDG PET/CT in Patients with Advanced Endometrial Cancer.

PURPOSE: We evaluated the potential prognostic value of (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with stage IIIC/IV endometrial cancer. METHODS: Patients with stage IIIC/IV endometrial cancer who had undergone FDG PET/CT workup for staging were enrolled. Maximum standardized uptake values (SUVmax) measured from regions of interest (ROIs) of the primary tumor (SUVt) and lymph nodes (SUVn) were correlated with overall survival (OS). The SUVn was defined as the highest SUVmax of the metastatic lymph nodes. Survival probability was assessed using the Kaplan-Meier method. RESULTS: A total of 42 patients with a median age of 55.5 years (range 32-76 years) were included. Twenty-nine percent (n = 12) of patients were premenopausal and 71 % (n = 30) were postmenopausal. The average SUVt was 12.9 (range 1.8-36.5), and the average SUVn was 7.3 (range 2.0-22.5). Median follow-up time was 25.9 months (range 1-84 months). Using a SUVt of 9.5 as a cutoff value, two groups with different rates were determined (P = 0.026). In addition, patients with a low SUVn had significantly better OS than those with a high SUVn (P = 0.003). Patients in the International Federation of Obstetrics and Gynecology (FIGO) stage IV group with SUVt ≥ 9.5 or SUVn ≥ 7.3 showed a significantly longer OS than the other groups. CONCLUSIONS: FDG uptake of primary endometrial cancer and lymph nodes might be a prognostic factor in advanced endometrial cancer. More aggressive therapy could be considered in patients with stage IV endometrial cancer and high SUVt and/or high SUVn.

Correlation between (18)f-fluorodeoxyglucose uptake and epidermal growth factor receptor mutations in advanced lung cancer.

PURPOSE: Mutations in the epidermal growth factor receptor (EGFR) gene have been identified as potential targets for the treatment and prognostic factors for non-small cell lung cancer (NSCLC). We assessed the correlation between fluorodeoxyglucose (FDG) uptake and EGFR mutations, as well as their prognostic implications. METHODS: A total of 163 patients with pathologically confirmed NSCLC were enrolled (99 males and 64 females; median age, 60 years). All patients underwent FDG positron emission tomography before treatment, and genetic studies of EGFR mutations were performed. The maximum standardized uptake value (SUVmax) of the primary lung cancer was measured and normalized with regard to liver uptake. The SUVmax between the wild-type and EGFR mutant groups was compared. Survival was evaluated according to SUVmax and EGFR mutation status. RESULTS: EGFR mutations were found in 57 patients (60.8 %). The SUVmax tended to be higher in wild-type than mutant tumors, but was not significantly different (11.1 ± 5.7 vs. 9.8 ± 4.4, P = 0.103). The SUVmax was significantly lower in patients with an exon 19 mutation than in those with either an exon 21 mutation or wild type (P = 0.003 and 0.009, respectively). The EGFR mutation showed prolonged overall survival (OS) compared to wild-type tumors (P = 0.004). There was no significant difference in survival according to SUVmax. Both OS and progression-free survival of patients with a mutation in exon 19 were significant longer than in patients with wild-type tumors. CONCLUSION: In patients with NSCLC, a mutation in exon 19 was associated with a lower SUVmax and is a reliable predictor for good survival.

Using (18)F-FDG PET/CT to Detect an Occult Mesenchymal Tumor Causing Oncogenic Osteomalacia.

Oncogenic osteomalacia is a rare paraneoplastic syndrome characterized by renal phosphate excretion, hypophosphatemia, and osteomalacia. This syndrome is often caused by tumors of mesenchymal origin. Patients with oncogenic osteomalacia have abnormal bone mineralization, resulting in a high frequency of fractures. Tumor resection is the treatment of choice, as it will often correct the metabolic imbalance. Although oncogenic osteomalacia is a potentially curable disease, diagnosis is difficult and often delayed because of the small size and sporadic location of the tumor. Bone scintigraphy and radiography best characterize osteomalacia; magnetic resonance imaging findings are nonspecific. Here, we report a case of oncogenic osteomalacia secondary to a phosphaturic mesenchymal tumor that was successfully detected by (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT). This case illustrates the advantages of (18)F-FDG PET/CT in detecting the occult mesenchymal tumor that causes oncogenic osteomalacia.

Evaluation of Bone Metastasis from Hepatocellular Carcinoma Using (18)F-FDG PET/CT and (99m)Tc-HDP Bone Scintigraphy: Characteristics of Soft Tissue Formation.

PURPOSE: Bone metastasis from hepatocellular carcinoma (HCC) can present with soft tissue formation, resulting in oncologic emergency. Contrast-enhanced FDG PET/CT and bone scintigraphy were compared to evaluate characteristics of bone metastases with or without soft tissue formation from HCC. METHODS: Of 4,151 patients with HCC, 263 patients had bone metastases. Eighty-five patients with bone metastasis from HCC underwent contrast-enhanced FDG PET/CT. Fifty-four of the enrolled subjects had recent (99m)Tc-HDP bone scintigraphy available for comparison. Metastatic bone lesions were identified with visual inspection on FDG PET/CT, and maximum standardized uptake value (SUVmax) was used for the quantitative analysis. Confirmation of bone metastasis was based on histopathology, combined imaging modalities, or serial follow-up studies. RESULTS: Forty-seven patients (55%) presented with soft tissue formation, while the remaining 38 patients presented without soft tissue formation. Frequent sites of bone metastases from HCC were the spine (39%), pelvis (19%), and rib cage (14%). The soft-tissue-formation group had more frequent bone pain (77 vs. 37%, p < 0.0001), higher SUVmax (6.02 vs. 3.52, p < 0.007), and higher incidence of photon defect in bone scintigraphy (75 vs. 0%) compared to the non-soft-tissue-formation group. FDG PET/CT had higher detection rate for bone metastasis than bone scintigraphy both in lesion-based analysis (98 vs. 53%, p = 0.0015) and in patient-based analysis (100 vs. 80%, p < 0 .001). CONCLUSIONS: Bone metastasis from HCC showed a high incidence of soft tissue formation requiring emergency treatment. Although the characteristic findings for soft tissue formation such as photon defect in bone scintigraphy are helpful in detection, overall detectability of bone metastasis is higher in FDG PET/CT. Contrast-enhanced PET/CT will be useful in finding and delineating soft-tissue-forming bone metastasis from HCC.