Prognostic Value of Metabolic Tumor Volume on 11C-Methionine PET in Predicting Progression-Free Survival in High-Grade Glioma

Purpose

C-11 methionine (MET) PET is commonly used for diagnosing high-grade glioma (HGG). Recently, volumetric analysis has been widely applied to oncologic PET imaging. In this study, we investigated the prognostic value of metabolic tumor volume (MTV) on MET PET in HGG.

Methods

A total of 30 patients with anaplastic astrocytoma (n = 12) and glioblastoma multiforme (n = 18) who underwent MET PET before treatment (surgery followed by chemo-radiotherapy) were retrospectively enrolled. Maximal tumor-to-normal brain ratio (TNR_max, maximum tumor activity divided by mean of normal tissue) and MTV (volume of tumor tissue that shows uptake >1.3-fold of mean uptake in normal tissue) were measured on MET PET. Adult patients were classified into two subgroups according to Radiation Therapy Oncology Group Recursive Partitioning Analysis (RTOG RPA) classification. Prognostic values of TNR_max, MTV and clinicopathologic factors were evaluated with regard to progression-free survival (PFS).

Results

Median PFS of all patients was 7.9 months (range 1.0–53.8 months). In univariate analysis, MTV (cutoff 35 cm³) was a significant prognostic factor for PFS (P = 0.01), whereas TNR_max (cutoff 3.3) and RTOG RPA class were not (P = 0.80 and 0.61, respectively). Treatment of surgical resection exhibited a borderline significance (P = 0.06). In multivariate analysis, MTV was the only independent prognostic factor for PFS (P = 0.03).

Conclusion

MTV on MET PET is a significant and independent prognostic factor for PFS in HGG patients, whereas TNR_max is not. Thus, performing volumetric analysis of MET PET is recommended in HGG for better prognostication.     

Prognostic Significance of Volume-based Metabolic Parameters by 18F-FDG PET/CT in Gallbladder Carcinoma

Purpose

We investigated the prognostic values of volume-based metabolic parameters by ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) in gallbladder carcinoma patients and compared them with other prognostic parameters.

Materials and Methods

We enrolled 44 patients, who were initially diagnosed with gallbladder carcinoma and undergoing ¹⁸F-FDG PET/CT. Various metabolic volume-based PET parameters of primary tumors, including maximum and average standardized uptake values (SUV_max, SUV_avg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), were measured in gallbladder carcinoma patients using mediastinal blood pool activity as a threshold SUV for determining the tumor boundaries. Overall survival analysis was performed using the Kaplan-Meier method with PET parameters and other clinical variables. For determining independent prognostic factors, Cox proportional hazards regression analysis was performed.

Results

Of the 44 enrolled patients, cancer- or treatment-related death occurred in 30 (68.2 %). The mean clinical follow-up period was 22.2 ± 10.4 m (range, 0.6-35.9 m). Univariate analysis demonstrated that clinical or pathologic TNM stage (P < 0.001), treatment modality (P < 0.001), MTV (cutoff = 135 cm³, P = 0.001), and TLG (cutoff = 7,090, P < 0.05) were significant prognostic factors. In multivariate analysis, both clinical or pathologic TNM stage [hazard ratio (HR) = 2.019 (I vs II), 21.287 (I vs III), and 24.354 (I vs IV); P = 0.001) and TLG (HR = 2.930; P < 0.05) were independent prognostic factors for predicting overall survival.

Conclusions

In gallbladder cancer, TLG of the primary tumor, a volume-based metabolic parameter, is a significant independent prognostic factor for overall survival in conjunction with the clinical or pathological TNM stage.     

Prognostic Value of Metabolic Tumor Volume Measured by 18F-FDG PET/CT in Locally Advanced Head and Neck Squamous Cell Carcinomas Treated by Surgery

Purpose

We assessed the prognostic value of metabolic tumor volume (MTV) measured using¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) inpatients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Methods

We retrospectively reviewed 56 patients (51 men, five women; mean age 56.0 ± 8.8years) who had locally advanced HNSCC and underwent FDG PET/CT for initial evaluation. All patients had surgical resection and radiotherapy with or without concurrent chemotherapy. The peak standardized uptake value (SUV_peak) and MTV of the target lesion, including primary HNSCC andmetastatic cervical lymph nodes, were measured from FDG PET/CT images. We compared SUV_peak, MTV, and clinicopathologic variables such as age, Eastern Cooperative Oncology Group (ECOG) performance status, pN stage, pT stage, TNM stage, histologic grade and treatment modality to disease-free survival (DFS) and overall survival (OS).

Results

On the initial FDG PET/CT scans, the median SUV_peak was 7.8 (range, 1.8-19.0) and MTV was17.0 cm³ (range, 0.1-131.0 cm³). The estimated 2-year DFS and OS rates were 67.2% and 81.8%. The cutoff points of SUV_peak 6.2 and MTV 20.7 cm³ were the best discriminative values for predicting clinical outcome. MTV and ECOG performance status were significantly related to DFS and OS on univariate and multivariate analyses (p < 0.05).

Conclusion

The MTV obtained from initial FDG PET/CT scan is a significant prognostic factor for disease recurrence and mortality in locally advanced HNSCC treated with surgery and radiotherapy with or without chemotherapy.     

Prognostic Value of Volume-Based Metabolic Parameters Measured by 18F-FDG PET/CT of Pancreatic Neuroendocrine Tumors

Purpose

To date, the prognostic value of ¹⁸F-FDG PET/CT for patients with pancreatic neuroendocrine tumors (PNETs) has not been well characterized. We investigated the prognostic value of volumetric parameters using ¹⁸F-FDG PET/CT in this patient population.

Methods

We retrospectively reviewed 20 cases of pathologically proven PNET in patients who had undergone pre-therapeutic ¹⁸F-FDG PET/CT. PET parameters including maximum and average standardized uptake values (SUV_max, SUV_ave), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor were measured using a threshold SUV to determine the boundaries of the tumors. Univariate and multivariate survival analyses were performed with adjustments for PET parameters and other clinical values.

Results

The median clinical follow-up was 22.3 (range, 1.2–95.4) months. Cancer-related death occurred in 5 of 20 patients (25 %). Patients had clinical or pathological stages of I in seven patients, II in six patients, III in three patient, and IV in four patients. According to the WHO histological classification of subtypes, 3 patients exhibited well-differentiated PNETs, 13 patients had well-differentiated endocrine carcinomas, and 4 had poorly differentiatedendocrine carcinomas. Univariate analysis showed that tumor size (p = 0.028), AJCC stage (p = 0.009), T stage (p = 0.028), M stage (p = 0.029), treatment modality (p = 0.045), MTV (p = 0.003) and TLG (p = 0.027) were significant predictors of overall survival. On multivariate analysis, MTV (HR = 10.859, p = 0.031) was a significant independent predictor of overall survival along with the AJCC stage (HR = 11.556, p = 0.027).

Conclusion

In patients with PNETs, the MTV of the primary tumor as measured by ¹⁸F-FDG PET/CT along with the AJCC stage may be a significant independent prognostic factor for overall survival.     

Prognostic value of metabolic tumor burden on 18F-FDG PET in nonsurgical patients with non-small cell lung cancer

Purpose

The objective of this study was to assess the prognostic value of metabolic tumor burden on 2-deoxy-2-[¹⁸F]fluoro-D-glucose (¹⁸F-FDG) positron emission tomography (PET)/CT measured with metabolic tumor volume (MTV) and total lesion glycolysis (TLG), independent of Union Internationale Contra la Cancrum (UICC)/American Joint Committee on Cancer (AJCC) tumor, node, and metastasis (TNM) stage, in comparison with that of standardized uptake value (SUV) in nonsurgical patients with non-small cell lung cancer (NSCLC).

Methods

This study retrospectively reviewed 169 consecutive nonsurgical patients (78 men, 91 women, median age of 68?years) with newly diagnosed NSCLC who had pretreatment ¹⁸F-FDG PET/CT scans. The ¹⁸F-FDG PET/CT scans were performed in accordance with National Cancer Institute guidelines. The MTV of whole-body tumor (MTV_WB), of primary tumor (MTV_T), of nodal metastases (MTV_N), and of distant metastases (MTV_M); the TLG of whole-body tumor (TLG_WB), of primary tumor (TLG_T), of nodal metastases (TLG_N), and of distant metastases (TLG_M); the SUV_max of whole-body tumor (SUV_maxWB), of primary tumor (SUV_maxT), of nodal metastases (SUV_maxN), and of distant metastases (SUV_maxM) as well as the SUV_mean of whole-body tumor (SUV_meanWB), of primary tumor (SUV_meanT), of nodal metastases (SUV_meanN), and of distant metastases (SUV_meanM) were measured with the PETedge tool on a MIMvista workstation with manual adjustment. The median follow-up among survivors was 35?months from the PET/CT (range 2?C82?months). Statistical methods included Kaplan-Meier curves, Cox regression, and C-statistics.

Results

There were a total of 139 deaths during follow-up. Median overall survival (OS) was 10.9?months [95% confidence interval (CI) 9.0?C13.2?months]. The MTV was statistically associated with OS. The hazard ratios (HR) for 1 unit increase of ln(MTV_WB), ??(MTV_T), ??(MTV_N), and ??(MTV_M) before/after adjusting for stage were: 1.47/1.43 (p?p?p?p?=?0.007/0.043), respectively. TLG had statistically significant associations with OS with the HRs for 1 unit increase in ln(TLG_WB), ??(TLG_T), ??(TLG_N), and ??(TLG_M) before/after adjusting for stage being 1.36/1.33 (p?p?=?0.001/0.002), 1.05/1.04 (p?p?=?0.003/0.024), respectively. The ln(SUV_maxWB) and ??(SUV_maxN) were statistically associated with OS with the corresponding HRs for a 1 unit increase before/after adjusting for stage being 1.46/1.43 (p?=?0.013/0.024) and 1.22/1.16 (p?=?0.002/0.040). The ??(SUV_meanN) was statistically associated with OS before and after adjusting for stage with HRs for a 1 unit increase of 1.32 (p?p?=?0.015), respectively. The ??(SUV_meanM) and ??(SUV_maxM) were statistically associated with OS before adjusting for stage with HRs for a 1 unit increase of 1.26 (p?=?0.017) and 1.18 (p?=?0.007), respectively, but not after adjusting for stage (p?=?0.127 and 0.056). There was no statistically significant association between OS and ??(SUV_maxT), ln(SUV_meanWB), or ??(SUV_meanT). There was low interobserver variability among three radiologists with intraclass correlation coefficients (ICC) greater than 0.94 for SUV_maxWB, ln(MTV_WB), and ln(TLG_WB). Interobserver variability was higher for SUV_meanWB with an ICC of 0.806.

Conclusion

Baseline metabolic tumor burdens at the level of whole-body tumor, primary tumor, nodal metastasis, and distant metastasis as measured with MTV and TLG on FDG PET are prognostic measures independent of clinical stage with low inter-observer variability and may be used to further stratify nonsurgical patients with NSCLC. This study also suggests MTV and TLG are better prognostic measures than SUV_max and SUV_mean. These results will need to be validated in larger cohorts in a prospective study.     

Dual-time-point FDG PET/CT: Is It Useful for Lymph Node Staging in Patients with Non-Small-Cell Lung Cancer?

Purpose

Dual-time-point (DTP) FDG PET/CT has been shown to be useful for lymph node (LN) staging in patients with non-small-cell lung cancer (NSCLC). The aim of this study was to evaluate the LN staging ability of DTP FDG PET/CT in the predominant area of pulmonary tuberculosis.

Methods

Sixty-nine NSCLC patients underwent DTP PET/CT. Regions of interest were placed on each LN of each station, and the maximum SUVs were measured. Three variables were obtained: (1) the SUV on the early scan (SUV_early), (2) the SUV on the delayed scan (SUV_delayed), and (3) the retention index of the SUV (RI). Each patient had one final LN stage and three other LN stages according to the cutoff values of SUV_early, SUV_delayed, and RI.

Results

In the LN-based analysis, the area under the ROC curve of SUV_delayed (0.884) was significantly larger (P < 0.01) than those of SUV_early (0.868) and RI (0.717). Among the three variables, SUV_delayed was more accurate (P < 0.01) for detecting the mediastinal LN metastasis than SUV_early and RI. In the patient-based analysis, SUV_delayed had correctly determined LN stages in 55 of 69 patients (sensitivity, specificity, and accuracy = 88.7 %, 50.0 %, and 79.7 %), whereas SUV_early and RI correctly determined LN stages in 53 and 52 patients, respectively.

Conclusions

In this study, comparing the diagnostic efficacy of SUV_early, SUV_delayed, and RI for LN staging in patients with NSCLC, SUV_delayed was the most accurate variable for LN staging. DTP PET/CT could provide improved diagnostic accuracy for the LN staging of NSCLC.     

Usefulness of Combined Metabolic–Volumetric Indices of 18F-FDG PET/CT for the Early Prediction of Neoadjuvant Chemotherapy Outcomes in Breast Cancer

Purpose

The purpose of this study was to investigate the usefulness of metabolic-volumetric indices of ¹⁸F- fluorodeoxy-D-glucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) for the evaluation of neoadjuvant chemotherapy outcomes in breast cancer.

Methods

Twenty-four patients with locally advanced breast cancer were enrolled in the study. They underwent baseline ¹⁸F-FDG PET/CT scan and received four or six cycles of neoadjuvant chemotherapy, interim ¹⁸F-FDG PET/CT was done after second cycle of chemotherapy. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary lesions were calculated. Reduction rates of these parameters were obtained between baseline and interim ¹⁸F-FDG PET/CT. Chemotherapy outcomes were assessed using tumor size reduction rate and histological grading system (Miller and Payne system). Reduction rates of SUVmax, MTV, and TLG correlated with chemotherapy outcomes.

Results

MTV and TLG reduction rates showed significant correlation with tumor size reduction rate (R = 0.68, P = 0.0004; R = 0.62, P = 0.002, respectively). However, SUVmax reduction rate showed no significant correlation. MTV and TLG reduction rates were significantly higher in responders than nonresponders, as determined by Miller and Payne system (P < 0.0007, P < 0.002). However, SUVmax reduction rate showed no significant difference. On ROC analysis, the area under the MTV and TLG curves was 0.886, and that of SUVmax was 0.743. Sensitivity, specificity, positive predictive value, and negative predictive value to predict histopathologic response were the same for MTV and TLG, and the values were 100 %, 85.7 %, 83.3 %, and 100 %, respectively (at the reduction rate of 93.2 % for MTV, and 95.8 % for TLG).

Conclusion

Changes of metabolic–volumetric indices successfully reflected the neoadjuvant chemotherapy outcomes. MTV and TLG could be robust indices in discriminating pathologic responder as SUVmax, after neoadjuvant chemotherapy.     

Metabolic Tumor Volume Measured by F-18 FDG PET/CT can Further Stratify the Prognosis of Patients with Stage IV Non-Small Cell Lung Cancer

Purpose

This study aimed to further stratify prognostic factors in patients with stage IV non-small cell lung cancer (NSCLC) by measuring their metabolic tumor volume (MTV) using F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT).

Materials and Methods

The subjects of this retrospective study were 57 patients with stage IV NSCLC. MTV, total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) were measured on F-18 FDG PET/CT in both the primary lung lesion as well as metastatic lesions in torso. Optimal cutoff values of PET parameters were measured by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier survival curves were used for evaluation of progression-free survival (PFS). The univariate and multivariate Cox proportional hazards models were used to select the significant prognostic factors.

Results

Univariate analysis showed that both MTV and TLG of primary lung lesion (MTV-lung and TLG-lung) were significant factors for prediction of PFS (P < 0.001, P = 0.038, respectively). Patients showing lower values of MTV-lung and TLG-lung than the cutoff values had significantly longer mean PFS than those with higher values. Hazard ratios (95 % confidence interval) of MTV-lung and TLG-lung measured by univariate analysis were 6.4 (2.5–16.3) and 2.4 (1.0–5.5), respectively. Multivariate analysis revealed that MTV-lung was the only significant factor for prediction of prognosis. Hazard ratio was 13.5 (1.6–111.1, P = 0.016).

Conclusion

Patients with stage IV NSCLC could be further stratified into subgroups of significantly better and worse prognosis by MTV of primary lung lesion.     

The value of intratumoral heterogeneity of 18F-FDG uptake to differentiate between primary benign and malignant musculoskeletal tumours on PET/CT

Objective:

The cumulative standardized uptake value (SUV)–volume histogram (CSH) was reported to be a novel way to characterize heterogeneity in intratumoral tracer uptake. This study investigated the value of fluorine-18 fludeoxyglucose (¹⁸F-FDG) intratumoral heterogeneity in comparison with SUV to discriminate between primary benign and malignant musculoskeletal (MS) tumours.

Methods:

The subjects comprised 85 pathologically proven MS tumours. The area under the curve of CSH (AUC-CSH) was used as a heterogeneity index, with lower values corresponding with increased heterogeneity. As 22 tumours were indiscernible on ¹⁸F-FDG positron emission tomography, maximum standardized uptake value (SUV_max), mean standardized uptake value (SUV_mean) and AUC-CSH were obtained in 63 positive tumours. The Mann–Whitney U test and receiver operating characteristic (ROC) analysis were used for analyses.

Results:

The difference between benign (n = 35) and malignant tumours (n = 28) was significant in AUC-CSH (p = 0.004), but not in SUV_max (p = 0.168) and SUV_mean (p = 0.879). The sensitivity, specificity and accuracy for diagnosing malignancy were 61%, 66% and 64% for SUV_max (optical threshold value, >6.9), 54%, 60% and 57% for SUV_mean (optical threshold value, >3) and 61%, 86% and 75% for AUC-CSH (optical threshold value, ≤0.42), respectively. The area under the ROC curve was significantly higher in AUC-CSH (0.71) than SUV_max (0.60) (p = 0.018) and SUV_mean (0.51) (p = 0.005).

Conclusion:

The heterogeneity index, AUC-CSH, has a higher diagnostic accuracy than SUV analysis in differentiating between primary benign and malignant MS tumours, although it is not sufficiently high enough to obviate histological analysis.

Advances in knowledge:

AUC-CSH can assess the heterogeneity of ¹⁸F-FDG uptake in primary benign and malignant MS tumours, with significantly greater heterogeneity associated with malignant MS tumours. AUC-CSH is more diagnostically accurate than SUV analysis in differentiating between benign and malignant MS tumours.     

Differential Diagnosis of Borderline Ovarian Tumors from Stage I Malignant Ovarian Tumors using FDG PET/CT

Purpose

Borderline ovarian tumors (BOTs) are more common in young women of reproductive age, and exhibit a better prognosis than malignant ovarian tumors (MOTs). Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) were compared in their ability to differentiate BOTs from stage I MOTs.

Methods

Among 173 patients who had preoperative FDG PET/CT due to ovarian neoplasms between November 2006 and March 2009, there were 13 patients with BOTs or stage I MOTs. For differential diagnosis of the two tumors, cancer antigen-125 (CA-125) level, the longest diameter of tumors, metabolic indices including maximum standardized uptake value (SUV_max), and volumetric indices including metabolic tumor volume (MTV) were compared, respectively.

Results

The BOT group (n = 7) was comprised of five mucinous and two serous tumors, and the MOT group (n = 6) was comprised of three endometrioid, two clear cell and one mucinous tumors. Among the comparisons between two groups, SUV_max of the BOT group was significantly lower than that of the MOT group (2.9 ± 1.5 vs. 6.6 ± 2.9, p = 0.0223); otherwise, no significant difference was found in age, CA-125, diameter, or MTV. By receiver-operating characteristic curve analysis, SUV_max of 3.7 was the best cutoff value to differentiate BOTs from stage I MOTs, with a sensitivity of 83.3 % and specificity of 85.7, and the area under curve of 0.893 (p = 0.0001, 95 % CI: 0.601∼0.993).

Conclusions

We demonstrated that SUV_max could distinguish BOTs from stage I MOTs, with a high sensitivity and specificity. Metabolic indices determined by FDG PET/CT were more suitable than volumetric indices for differential diagnosis of the two tumors.     

Intratumoral Metabolic Heterogeneity for Prediction of Disease Progression After Concurrent Chemoradiotherapy in Patients with Inoperable Stage III Non-Small-Cell Lung Cancer

Purpose

We evaluated the value of variable ¹⁸F-FDG PET/CT parameters for the prediction of disease progression after concurrent chemoradiotherapy (CCRT) in patients with inoperable stage III non-small-cell lung cancer (NSCLC).

Methods

One hundred sixteen pretreatment FDG PET/CT scans of inoperable stage III NSCLC were retrospectively reviewed (stage IIIA: 51; stage IIIB: 65). The volume of interest was automatically drawn for each primary lung tumor, and PET parameters were assessed as follows: maximum standardized uptake value (SUV_max), metabolic tumor volume (MTV) using the boundaries presenting SUV intensity exceeding 3.0, and the area under the curve of the cumulative SUV-volume histograms (AUC-CSH), which is known to reflect the tumor heterogeneity. Progression-free survival (PFS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared with each PET and clinical parameters by univariate and multivariate survival analysis.

Results

In the ROC analysis, the optimal cutoff values of SUV_max, MTV (cm³), and AUC-CSH for prediction of PFS were determined as 21.5, 27.7, and 4,800, respectively. In univariate analysis, PFS was statistically significantly reduced in those with AUC-CSH < 4,800 (p = 0.004). In multivariate analysis, AUC-CSH and SUV_max were statistically significant independent prognostic factors (HR 3.35, 95 % CI 1.79–6.28, p < 0.001; HR 0.25, 95 % CI 0.09–0.70, p = 0.008, respectively). Multivariate analysis showed that AUC-CSH was the most significant independent prognostic factor for LRFS and DMFS (HR 3.27, 95 % CI 1.54–6.94, p = 0.002; HR 2.79, 95 % CI 1.42–5.50, p = 0.003).

Conclusions

Intratumoral metabolic heterogeneity of primary lung tumor in ¹⁸F-FDG PET/CT can predict disease progression after CCRT in inoperable stage III NSCLC.     

Hepatic FDG Uptake is not Associated with Hepatic Steatosis but with Visceral Fat Volume in Cancer Screening

Purpose

We aimed to evaluate the relation between visceral fat volume and fluorodeoxyglucose (FDG) uptake of the liver measured by maximum or mean standardized uptake value.

Methods

We retrospectively analyzed 96 consecutive records of positron emission tomography/computed tomography (PET/CT) performed for cancer screening between May 2011 and December 2011. Subjects were divided into 2 groups according to Hounsfield unit (HU) of the liver comparing with that of the spleen. The control group (20 women, 56 men) demonstrating HU of the liver equal or greater than that of the spleen included 76 patients, while the fatty liver group (2 women, 18 men) showing HU of the liver less than that of the spleen included 20 patients. We compared FDG uptake of the liver and visceral fat volume between two groups. We evaluated correlation of hepatic FDG uptake measured by maximum or mean standardized uptake value (SUV) with visceral fat volume and attenuation.

Results

The fatty liver disease group showed higher aspartate aminotransferase (AST)of (24.42 ± 7.22, p = 0.012), alanine aminotransferase (ALT) of (25.16 ± 11.68, p = 0.001), body mass index (BMI) of (24.58 ± 3.29, p = 0.021), and visceral fat volume (3063.53 ± 1561.43, p = 0.011) than the control group. There were no statistically significant differences of mean standardized uptake value of the liver (liver SUV_mean) (2.73 ± 0.19, p = 0.723), maximum standardized uptake value of the liver (liver SUV_max) (3.39 ± 0.53, p = 0.8248) and liver SUV_mean/spleen SUV_mean (1.13 ± 0.10, p = 0.081) between the two groups. Strong correlations were shown between liver SUV_mean and BMI (r = 0.609, p < 0.001) and between liver SUV_mean and visceral fat volume (r = 0.457, p < 0.001). Liver SUV_max was also strongly correlated with BMI (r = 0.622, p = 0.001) and visceral fat volume (r = 0.547, p < 0.001). There was no significant association of mean attenuation value of the liver (liver HU_mean) with liver SUV_mean (r = -0.003, p = 0.979) or liver SUV_max (r = -0.120, p = 0.244).

Conclusion

Hepatic FDG uptake quantified as SUV_mean or SUV_max is not correlated with hepatic steatosis but with visceral fat volume in cancer screening.     

Evaluation of Adrenal Masses in Lung Cancer Patients Using F-18 FDG PET/CT

Purpose

The aim of this study was to assess the diagnostic efficacy of PET/CT using various parameters for the characterization of adrenal nodules in lung cancer patients.

Methods

Sixty-one adrenal nodules in 51 lung cancer patients were evaluated. The final diagnosis was based on histology (n = 2) or imaging follow-up (n = 59, range of follow-up: 7–57 months, median 27 months). Each adrenal nodule was analyzed using four parameters of PET/CT: the maximum standardized uptake value (SUV_max), the adrenal nodule/liver ratio of the SUV (SUV ratio), Hounsfield units (HU) and size. The optimal cutoff of each parameter for the identification of metastatic nodule was determined by ROC analysis and then the diagnostic efficacy was compared among the parameters.

Results

Of the 61 adrenal nodules, 45 (73%) were considered metastasis. The optimal cutoff values of the parameters were SUV_max >2.7, SUV ratio >1.3, HU >18 and size >20 mm, respectively. The sensitivity, specificity and accuracy by SUV_max >2.7 were 88.9%, 87.5% and 88.5%, and those by SUV ratio >1.3 were 84.4%, 100% and 88.5%, respectively. The combination of SUV ratio >1.3 and HU >18 had sensitivity of 97.7%, specificity of 81.2% and accuracy of 93.4% to predict adrenal metastasis in patients with lung cancer.

Conclusion

SUV ratio from F-18 FDG PET/CT could identify the adrenal metastasis in lung cancer patients. The combination of SUV ratio and HU can improve the accuracy of differentiating benign and metastatic adrenal lesions in lung cancer patients.     

The Prognostic Value of the Metabolic Tumor Volume in FIGO stage IA to IIB Cervical Cancer for Tumor Recurrence: Measured by F-18 FDG PET/CT

Purpose

The purpose of this study was to evaluate the prognostic value of the metabolic tumor volume (MTV), in FIGO stage IA–IIB cervical cancer patients, measured by F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging.

Methods

Forty-five patients with invasive cervical cancer who underwent FDG-PET imaging were recruited. Metabolically active tumor regions were delineated on the pretreatment FDG-PET scans by encompassing regions equal to or greater than an standardized uptake value (SUV) of 40% of the peak tumor intensity. The relationship of the metabolic tumor volume (MTV) to the disease-free survival was analyzed. The MTV of the cervical cancer was compared with pathological and clinical prognostic factors, including lymph node metastasis, parametrial invasion, the depth of invasion, resection margins, tumor differentiation and FIGO stages.

Results

Cox proportional hazard regression analysis showed that the MTV was a significant independent predictor of recurrence of cervical cancer (p = 0.027). Patients with an MTV of >20 cm³ had a significantly reduced disease-free survival compared with patients with an MTV ≤ 20 cm³ (p = 0.029). The correlation of the MTV with traditional prognostic factors showed significantly higher values in patients that were lymph node (LN) metastasis positive (p = 0.028) and parametrial invasion positive (p = 0.022). The MTV significantly differed among the groups according to tumor differentiation (p = 0.0319) and FIGO stage (p = 0.001).

Conclusion

The MTV measured by FDG-PET was an independent prognostic factor for tumor recurrence in patients with stage IA–IIB cervical cancer. These findings must be confirmed by large population based prospective studies.     

Evaluation of Bone Metastasis from Hepatocellular Carcinoma Using 18F-FDG PET/CT and 99mTc-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 ^99mTc-HDP bone scintigraphy available for comparison. Metastatic bone lesions were identified with visual inspection on FDG PET/CT, and maximum standardized uptake value (SUV_max) 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 SUV_max (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.     

Usefulness of MRI-assisted metabolic volumetric parameters provided by simultaneous <Superscript>18</Superscript>F-fluorocholine PET/MRI for primary prostate cancer characterization

Purpose

The aim of this study was to determine the usefulness of MRI-assisted positron emission tomography (PET) parameters provided by simultaneous ¹⁸F-fluorocholine (FCH) PET/MRI for characterization of primary prostate cancer.

Methods

Thirty patients with localized prostate cancer (mean age 69.4?±?6.7 years) confirmed by biopsy were prospectively enrolled for simultaneous PET/MRI imaging. The patients underwent ¹⁸F-FCH PET/MRI 1 week before undergoing total prostatectomy. Multiple parameters of diffusion-weighted MRI [minimum and mean apparent diffusion coefficient (ADC_min and ADC_mean)], metabolic PET [maximum and mean standardized uptake value (SUV_max and SUV_mean)], and metabolic volumetric PET [metabolic tumor volume (MTV) and uptake volume product (UVP)] were compared with laboratory, pathologic, and immunohistochemical (IHC) features of the prostate cancer specimen. PET parameters were divided into two categories as follows: volume of interest (VOI) of prostate by SUV cutoff 2.5 (SUV_max, SUV_mean, MTV_SUV, and UVP_SUV) and MRI-assisted VOI of prostate cancer (SUV_maxMRI, SUV_meanMRI, MTV_MRI, and UVP_MRI).

Results

The rates of prostate cancer-positive cases identified by MRI alone, ¹⁸F-FCH PET alone, and ¹⁸F-FCH PET/MRI were 83.3, 80.0, and 93.3 %, respectively. Among the multiple PET/MRI parameters, MTV_MRI showed fair correlation with serum prostate-specific antigen (PSA; r?=?0.442, p?=?0.014) and highest correlation with tumor volume (r?=?0.953, p?<?0.001). UVP_MRI showed highest correlation with serum PSA (r?=?0.531, p?=?0.003), good correlation with tumor volume (r?=?0.908, p?<?0.001), and it was significantly associated with Gleason score (p?=?0.041). High MTV_MRI and UVP_MRI values were significant for perineural invasion, lymphatic invasion, extracapsular extension, seminal vesicle invasion, and positive B-cell lymphoma 2 (Bcl-2) expression (all p?<?0.05).

Conclusion

Simultaneous ¹⁸F-FCH PET/MRI demonstrated a better diagnostic value for localized prostate cancer detection than each individual modality. MRI-assisted metabolic volumetric PET parameters (MTV_MRI and UVP_MRI) provided more accurate characterization of prostate cancer than conventional PET and MRI parameters.

     

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

PurposeWe 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.MethodsWe 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 (SUV_R = tumor SUV_max/reference region SUV_mean) was calculated. The effect of patient age on the SUV_mean of each reference was examined and the SUV_Rs of each reference region were compared between grades. age, sex, tumor size, histological grades, SUV_R, and the presence of isocitrate dehydrogenase (IDH) mutation were included for survival analyses.ResultsExcept for the cerebellum showing a mild negative correlation, we found no correlations between age and SUV_mean using the gray matter, white matter, and choroid plexus (r = − 0.280, P = 0.047). Only the SUV_R-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.ConclusionOf 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.     

Prognostic Value of Volume-Based 18F-Fluorodeoxyglucose PET/CT Parameters in Patients with Clinically Node-Negative Oral Tongue Squamous Cell Carcinoma

Objective

To evaluate the prognostic value of volume-based metabolic parameters measured with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) in patients with clinically node-negative (cN0) oral tongue squamous cell carcinoma (OTSCC) as compared with other prognostic factors.

Materials and Methods

In this study, we included a total of 57 patients who had been diagnosed with cN0 tongue cancer by radiologic, ¹⁸F-FDG PET/CT, and physical examinations. The maximum standardized uptake value (SUV_max), average SUV (SUV_avg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for primary tumors were measured with ¹⁸F-FDG PET. The prognostic significances of these parameters and other clinical variables were assessed by Cox proportional hazards regression analysis.

Results

In the univariate analysis, pathological node (pN) stage, American Joint Committee on Cancer (AJCC) stage, SUV_max, SUV_avg, MTV, and TLG were significant predictors for survival. On a multivariate analysis, pN stage (hazard ratio = 10.555, p = 0.049), AJCC stage (hazard ratio = 13.220, p = 0.045), and MTV (hazard ratio = 2.698, p = 0.033) were significant prognostic factors in cN0 OTSCC patients. The patients with MTV ≥ 7.78 cm³ showed a worse prognosis than those with MTV < 7.78 cm³ (p = 0.037).

Conclusion

The MTV of primary tumor as a volumetric parameter of ¹⁸F-FDG PET, in addition to pN stage and AJCC stage, is an independent prognostic factor for survival in cN0 OTSCC.     

The Prognostic Value of 18F-FDG PET/CT for Early Recurrence in Operable Breast Cancer: Comparison with TNM Stage

Purpose

We evaluated whether the maximum standardized uptake values (SUV_max) of primary tumor from the initial staging by ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) of patients with breast cancer could identify patients at risk for early recurrence within 2 years, particularly in comparison to the American Joint Committee on Cancer (AJCC) stage.

Methods

We reviewed the staging ¹⁸F-FDG PET/CT images of patients with primary breast cancer and their medical records. The SUV_max of the primary tumor was measured. The presence or absence of FDG uptake in the axillary lymph node (ALN) was also assessed. The patient’s pathologic primary tumor stage (pT), pathologic regional lymph node stage (pN), stage grouping, age, estrogen receptor (ER) and progesterone receptor (PR) status, and neoadjuvant chemotherapy history were evaluated with the FDG uptake parameters for recurrence within 2 years following the end of first-line therapy.

Results

Recurrence within 2 years was present in 9.1 % (n = 40) out of the 441 patients assessed. The FDG uptake in ALN, pT, pN, stage grouping and neoadjuvant chemotherapy history were prognostic for early recurrence, while primary tumor SUV_max, age, and ER or PR status were not significant on logistic regression. On multivariate analysis, only the stage grouping (odds ratio 2.79; 95 % CI 1.73, 4.48; p < 0.0001) and neoadjuvant chemotherapy history (odds ratio 2.70; 95 % CI 1.22, 5.98; p = 0.0141) could identify patients at increased risk for recurrence within 2 years.

Conclusions

Primary tumor FDG uptake measured by SUV_max, and visual assessment of FDG uptake in the ALN in the initial staging PET/CT of patients with breast cancer may not have additional prognostic value compared with the AJCC stage grouping for early recurrence.     

Reproducibility of 18F-FDG PET uptake measurements in head and neck squamous cell carcinoma on both PET/CT and PET/MR

Objective:

To investigate reproducibility of fluorine-18 fludeoxyglucose (¹⁸F-FDG) uptake on ¹⁸F-FDG positron emission tomography (PET)/CT and ¹⁸F-FDG PET/MR scans in patients with head and neck squamous cell carcinoma (HNSCC).

Methods:

30 patients with HNSCC were included in this prospective study. The patients were scanned twice before radiotherapy treatment with both PET/CT and PET/MR. Patients were scanned on the same scanners, 3 days apart and according to the same protocol. Metabolic tumour activity was measured by the maximum and peak standardized uptake value (SUV_max and SUV_peak, respectively), and total lesion glycolysis from the metabolic tumour volume defined from ≥50% SUV_max. Bland–Altman analysis with limits of agreement, coefficient of variation (CV) from the two modalities were performed in order to test the reproducibility. Furthermore, CVs from SUV_max and SUV_peak were compared. The area under the curve from cumulative SUV–volume histograms were measured and tested for reproducibility of the distribution of ¹⁸F-FDG uptake.

Results:

24 patients had two pre-treatment PET/CT scans and 21 patients had two pre-treatment PET/MR scans available for further analyses. Mean difference for SUV_max, peak and mean was approximately 4% for PET/CT and 3% for PET/MR, with 95% limits of agreement less than ±20%. CV was small (5–7%) for both modalities. There was no significant difference in CVs between PET/CT and PET/MR (p = 0.31). SUV_max was not more reproducible than SUV_peak (p = 0.09).

Conclusion:

¹⁸F-FDG uptake in PET/CT and PET/MR is highly reproducible and we found no difference in reproducibility between PET/CT and PET/MR.

Advances in knowledge:

This is the first report to test reproducibility of PET/CT and PET/MR.Functional imaging with fluorine-18 fludeoxyglucose positron emission tomography combined with CT (¹⁸F-FDG PET/CT) has been shown to be useful for prognostication of head and neck squamous cell carcinoma (HNSCC),^1–3 and the use of ¹⁸F-FDG PET/CT has also been shown to reduce interobserver variability in target delineation for radiotherapy.^4,5 Furthermore, ¹⁸F-FDG PET/CT can identify regions of the tumour with a high risk of relapse, leading to the idea that ¹⁸F-FDG uptake might be a target for dose painting.^6,7 Finally, ¹⁸F-FDG PET/CT may be used in response evaluation.^8,9 Maximum standardized uptake value (SUV_max) has for many years been the main uptake measurement in prognostic studies for various malignancies. More recent studies have focused on demonstrating prognostic value of PET/CT-based volumetric parameters such as metabolic tumour volume (MTV) and total lesion glycolysis (TLG). MTV is the sum of the volume of voxels with standard uptake value (SUV) exceeding a certain threshold value in a tumour, and TLG is calculated by multiplying MTV and the mean standardized uptake value (SUV_mean) of the MTV. These volume-based PET parameters have increasingly gained interest and have been reported to be significant prognostic factors for various malignancies including HNSCC.^{10–13 18}F-FDG PET/CT is currently not routinely recommended as a diagnostic tool in HNSCC except in very specific situations,¹⁴ but reproducibility of the ¹⁸F-FDG signal is a prerequisite for a more widespread use of ¹⁸F-FDG PET for the above-mentioned indications. Yet, only a few studies of the reproducibility of ¹⁸F-FDG PET/CT exist^8,15–21 and none of these studies includes patients with HNSCC.MRI is gaining acceptance as an imaging modality for oncology as it offers superior soft-tissue contrast compared with CT alone, and it has been suggested that information from PET/CT and MR is complementary in head and neck cancer.²² The introduction of the integrated PET/MR scanner offers a unique opportunity to combine the high soft-tissue contrast of MR with the functional imaging from PET within a single imaging session. PET/MR is still in its infancy, but the combined modality imaging is potentially useful in the management of patients with HNSCC.^22–28 However, the same criteria of reproducibility as with PET/CT should be upheld by this new modality. The purpose of this prospective test–retest study is to assess the reproducibility of both ¹⁸F-FDG PET/CT and ¹⁸F-FDG PET/MR in a homogenous cohort of patients with HNSCC.