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There have been previous studies conducted to predict postoperative lung function with pulmonary function tests (PFTs). Computing tomography (CT) can quantitatively measure small airway walls' thickness, lung volume, pulmonary vessel volume, and emphysema area, which reflect the severity of respiratory diseases. These measurements are considered imaging biomarkers. This study aimed to predict postoperative lung function with imaging biomarkers. A retrospective analysis of 79 patients with lung cancer who had undergone lung surgery was completed. Postoperative lung function measured by forced expiratory volume in one second (FEV1) was defined as an outcome. Preoperative clinico-pathological parameters and imaging biomarkers representing airway walls' thickness, severity of emphysema, total lung volume, and pulmonary vessel volume were measured quantitatively in chest CT by an automated segmentation software, AVIEW COPD. Pi1 was defined as the first percentile along the histogram of lung attenuation that represents the degree of emphysema. Wafw was defined as the airway thickness, which was calculated by the full-width at half-maximum method. Logistic and linear regressions were used to assess these variables. If the actual postoperative FEV1 was higher than the postoperative FEV1 projected by a formula, the group was considered to be preserved. Among the 79 patients, 16 of the patients were grouped as a non-preserved group, and 63 of them were grouped as a preserved group. The patients in the preserved FEV1 group had a higher vessel volume than the non-preserved group. Pi1 and Wafw were independent predictors of postoperative lung function. Imaging biomarkers can be considered significant variables in predicting postoperative lung function in patients with lung cancer. [ABSTRACT FROM AUTHOR]

Background: The prognostic value of conducting 18F-FDG PET/CT imaging has yielded different results in patients with laryngeal cancer and hypopharyngeal cancer, but these results are controversial, and there is a lack of dedicated studies on each type of cancer. This study aimed to evaluate whether combining radiomic analysis of pre- and post-treatment 18F-FDG PET/CT imaging features and clinical parameters has additional prognostic value in patients with laryngeal cancer and hypopharyngeal cancer. Methods: From 2008 to 2016, data on patients diagnosed with cancer of the larynx and hypopharynx were retrospectively collected. The patients underwent pre- and post-treatment 18F-FDG PET/CT imaging. The values of ΔPre-Post PET were measured from the texture features. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to select the most predictive features to formulate a Rad-score for both progression-free survival (PFS) and overall survival (OS). Kaplan–Meier curve analysis and Cox regression were employed to assess PFS and OS. Then, the concordance index (C-index) and calibration plot were used to evaluate the performance of the radiomics nomogram. Results: Study data were collected for a total of 91 patients. The mean follow-up period was 71.5 mo. (8.4–147.3). The Rad-score was formulated based on the texture parameters and was significantly associated with both PFS (p = 0.024) and OS (p = 0.009). When predicting PFS, only the Rad-score demonstrated a significant association (HR 2.1509, 95% CI [1.100–4.207], p = 0.025). On the other hand, age (HR 1.116, 95% CI [1.041–1.197], p = 0.002) and Rad-score (HR 33.885, 95% CI [2.891–397.175], p = 0.005) exhibited associations with OS. The Rad-score value showed good discrimination when it was combined with clinical parameters in both PFS (C-index 0.802–0.889) and OS (C-index 0.860–0.958). The calibration plots also showed a good agreement between the observed and predicted survival probabilities. Conclusions: Combining clinical parameters with radiomics analysis of pre- and post-treatment 18F-FDG PET/CT parameters in patients with laryngeal cancer and hypopharyngeal cancer might have additional prognostic value. [ABSTRACT FROM AUTHOR]

In radiomics research, the issue of different instruments being used is significant. In this study, we compared three correction methods to reduce the batch effects in radiogenomic data from fluorodeoxyglucose (FDG) PET/CT images of lung cancer patients. Texture features of the FDG PET/CT images and genomic data were retrospectively obtained. The features were corrected with different methods: phantom correction, ComBat method, and Limma method. Batch effects were estimated using three analytic tools: principal component analysis (PCA), the k-nearest neighbor batch effect test (kBET), and the silhouette score. Finally, the associations of features and gene mutations were compared between each correction method. Although the kBET rejection rate and silhouette score were lower in the phantom-corrected data than in the uncorrected data, a PCA plot showed a similar variance. ComBat and Limma methods provided correction with low batch effects, and there was no significant difference in the results of the two methods. In ComBat- and Limma-corrected data, more texture features exhibited a significant association with the TP53 mutation than in those in the phantom-corrected data. This study suggests that correction with ComBat or Limma methods can be more effective or equally as effective as the phantom method in reducing batch effects. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the association between methionine (MET) metabolism and endocrine function of the pituitary gland in patients with suprasellar region tumor. Materials and methods: Twenty patients with intracranial germinoma were included in this study. Initial staging and all surveillance MET PET/CT scans and comparable serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and thyroid stimulating hormone (TSH) were analyzed. The patients were divided into two groups according to tumor location, with tumors in the suprasellar region (condition) or not (control). MET uptake of the pituitary gland (i.e., SUVR [standardized uptake value ratio]) and levels of FSH, LH, TSH were compared in the condition and control groups and in the before and after treatment phases of each group. Results: The SUVR in the control group was like that found in normal pituitary glands in previous studies, whereas the SUVR of the untreated condition group was high and that of treated condition group was low with significance compared to the control group. Serum levels of pituitary hormones in before and after treatment condition groups were significantly lower than those in the control group. The FSH and LH levels of curatively treated patients in the control group were positively correlated with SUVR with respective ß values of 3.71 and 0.98 (p <.001). The TSH level of the treated condition group was negatively correlated with SUVR (ß = -1.02, p <.001). Conclusion: This study is the first known investigation to examine the association between MET metabolism and endocrine function of the pituitary gland, and it confirmed that MET metabolism reflects endocrine function. A future study validating the result of correlation analysis is warranted. [ABSTRACT FROM AUTHOR]

Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (FDG) is widely used for management of nasopharyngeal carcinoma (NPC). Combining the radiomic features of pre- and post-treatment FDG PET images may improve tumor characterization and prognostic predication. We investigated prognostic value of radiomic features from pre- and post-radiotherapy FDG PET images in patients with NPC. Quantitative radiomic features of primary tumors were extracted from the FDG PET images of 145 NPC patients and the delta values were also calculated. The study population was divided randomly into two groups, the training and test sets (7:3). A random survival forest (RSF) model was adopted to perform analyses of progression-free survival (PFS) and overall survival (OS). There were 37 (25.5%) cases of recurrence and 16 (11.0%) cases of death during a median follow-up period of 54.5 months. Both RSF models with clinical variables and radiomic PET features for PFS and OS showed comparable predictive performance to RSF models with clinical variables and conventional PET parameters. Tumoral radiomic features of pre- and post-treatment FDG PET and the corresponding delta values may predict PFS and OS in patients with NPC. [ABSTRACT FROM AUTHOR]

Background: This study investigated the prognostic value of axillary lymph node (ALN) heterogeneity texture features through 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with locally advanced breast cancer (LABC). Methods: We retrospectively analyzed 158 LABC patients with FDG-avid, pathology-proven, metastatic ALN who underwent neoadjuvant chemotherapy (NAC) and curative surgery. Tumor and ALN texture parameters were extracted from pretreatment 18F-FDG PET/CT using Chang-Gung Image Texture Analysis software. The least absolute shrinkage and selection operator regression was performed to select the most significant predictive texture parameters. The predictive impact of texture parameters was evaluated for both progression-free survival and pathologic NAC response. Results: The median follow-up period of 36.8 months and progression of disease (PD) was observed in 36 patients. In the univariate analysis, ALN textures (minimum standardized uptake value (SUV) (p = 0.026), SUV skewness (p = 0.038), SUV bias-corrected Kurtosis (p = 0.034), total lesion glycolysis (p = 0.011)), tumor textures (low-intensity size zone emphasis (p = 0.045), minimum SUV (p = 0.047), and homogeneity (p = 0.041)) were significant texture predictors. On the Cox regression analysis, ALN SUV skewness was an independent texture predictor of PD (p = 0.016, hazard ratio 2.3, 95% confidence interval 1.16–4.58). Conclusions: ALN texture feature from pretreatment 18F-FDG PET/CT is useful for the prediction of LABC progression. [ABSTRACT FROM AUTHOR]

Simple Summary: Although texture parameters of F-18 fluorodeoxyglucose positron emission tomography/computed tomography images were known to associate tumor biology and clinical features, the types and implications of parameters are too various and complicated. To overcome the limitation of texture parameter, we attempted to produce a new simplified parameter from texture parameters of F-18 fluorodeoxyglucose positron emission tomography/computed tomography images in lung cancer patients using pseudotime analysis. Pseudotime analysis is a recently developed method to explore changes in cell or tissue characteristics based on transcriptomic expression. It is the first study to apply pseudotime analysis into radiomics dataset other than transcriptomics data. Herein, we demonstrated that pseudotime can be successfully estimated from texture parameters. In the aspect of prognostic prediction, pseudotime was an independent prognostic factor for overall survival in contrast to conventional parameters such as metabolic tumor volume and total lesion glycolysis. This study showed possibility of integrating various texture parameters into single parameter which reflects disease progression status. Pseudotime, as a concrete value of disease progression, is expected to be used in clinical field to evaluate disease and predict prognosis. Texture analysis provides image parameters from F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). Although some parameters are associated with tumor biology and clinical features, the types and implications of these parameters are complicated. We applied pseudotime analysis, which has recently been used to estimate changes in individual sample characteristics, to texture parameters from FDG PET/CT images of locally advanced non-small-cell lung cancer (NSCLC) patients undergoing neoadjuvant concurrent chemoradiation therapy (CCRT) followed by surgery. Our subjects were 303 NSCLC patients who underwent pretherapeutic FDG PET/CT and tri-modality therapy. Texture parameters of the primary tumor were calculated from FDG PET/CT images acquired before neoadjuvant CCRT. Pseudotime analysis was performed using the PhenoPath tool. Clinicopathologic features including survival data were collected and survival analysis was performed to compare the prognostic significances of pseudotime parameters with those of conventional PET parameters. Pseudotime was successfully estimated from texture parameters. Normalized co-occurrence homogeneity, normalized co-occurrence inverse difference moment, and black–white symmetry showed positive correlations with pseudotime, short run emphasis, normalized co-occurrence dissimilarity, and short zone emphasis negative correlation. The maximum standardized uptake value (SUV) and mean SUV were not associated with overall survival. Pseudotime, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) showed significant associations with overall survival. In contrast to MTV and TLG, pseudotime was an independent prognostic factor for overall survival. Various metabolic texture parameters can be integrated into a single parameter using pseudotime analysis. Pseudotime of the primary tumor, estimated from FDG PET/CT images, better predicts overall survival in locally advanced NSCLC patients treated with tri-modality therapy than conventional PET parameters. [ABSTRACT FROM AUTHOR]

Simple Summary: The pathological complete response (pCR) after neoadjuvant chemoradiotherapy (CCRT) is an independent prognostic factor for progression-free and overall survival in non-small cell lung cancer (NSCLC). 18F-FDG PET/CT has been performed for initial staging work-up, treatment response, and follow-up in patients with NSCLC. Machine learning (ML) as an empirical data science has become relevant to nuclear medicine. We investigated the predictive performance of 18F-FDG PET/CT using an ML model to assess the treatment response to neoadjuvant CCRT in patients with stage III NSCLC, and compared the performance of the ML model predictions to predictions from conventional PET parameters and from physicians. The predictions from the ML model using radiomic features of 18F-FDG PET/CT provided better accuracy than predictions from conventional PET parameters and from physicians for the neoadjuvant CCRT response of stage III non-small cell lung cancer. We investigated predictions from 18F-FDG PET/CT using machine learning (ML) to assess the neoadjuvant CCRT response of patients with stage III non-small cell lung cancer (NSCLC) and compared them with predictions from conventional PET parameters and from physicians. A retrospective study was conducted of 430 patients. They underwent 18F-FDG PET/CT before initial treatment and after neoadjuvant CCRT followed by curative surgery. We analyzed texture features from segmented tumors and reviewed the pathologic response. The ML model employed a random forest and was used to classify the binary outcome of the pathological complete response (pCR). The predictive accuracy of the ML model for the pCR was 93.4%. The accuracy of predicting pCR using the conventional PET parameters was up to 70.9%, and the accuracy of the physicians' assessment was 80.5%. The accuracy of the prediction from the ML model was significantly higher than those derived from conventional PET parameters and provided by physicians (p < 0.05). The ML model is useful for predicting pCR after neoadjuvant CCRT, which showed a higher predictive accuracy than those achieved from conventional PET parameters and from physicians. [ABSTRACT FROM AUTHOR]

Neuroinflammation involves activation of glial cells in the brain, and activated microglia play a particularly important role in neurodegenerative diseases such as Alzheimer's disease (AD). In this study, we developed 5-cyano-N-(4-(4-(2-[18F]fluoroethyl)piperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide ([18F]1) for PET imaging of colony-stimulating factor 1 receptor (CSF1R), an emerging target for neuroinflammation imaging. Non-radioactive ligand 1 exhibited binding affinity comparable to that of a known CSF1R inhibitor, 5-cyano-N-(4-(4-methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide (CPPC). Therefore, we synthesized radioligand [18F]1 by radiofluorination of chlorine-substituted precursor 7 in 13–15% decay-corrected radiochemical yield. Dynamic PET/CT images showed higher uptake in the lipopolysaccharide (LPS)-treated mouse brain than in control mouse brain. Ex vivo biodistribution study conducted at 45 min after radioligand injection showed that the brain uptake in LPS mice increased by 78% compared to that of control mice and was inhibited by 22% in LPS mice pretreated with CPPC, indicating specificity of [18F]1 for CSF1R. A metabolism study demonstrated that the radioligand underwent little metabolism in the mouse brain. Taken together, these results suggest that [18F]1 may hold promise as a radioligand for CSF1R imaging. [ABSTRACT FROM AUTHOR]

Introduction: The prognostic value of F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in hepatocellular carcinoma (HCC) was established in previous reports. However, there is no evidence suggesting the prognostic value of transcriptomes associated with tumor FDG uptake in HCC. It was aimed to elucidate metabolic genes and functions associated with FDG uptake, followed by assessment of those prognostic value. Methods: Sixty HCC patients with Edmondson–Steiner grade II were included. FDG PET/CT scans were performed before any treatment. RNA sequencing data were obtained from tumor and normal liver tissue. Associations between each metabolism-associated gene and tumor FDG uptake were investigated by Pearson correlation analyses. A novel score between glucose and lipid metabolism-associated gene expression was calculated. In The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset, the prognostic power of selected metabolism-associated genes and a novel score was evaluated for external validation. Results: Nine genes related to glycolysis and the HIF-1 signaling pathway showed positive correlations with tumor FDG uptake; 21 genes related to fatty acid metabolism and the PPAR signaling pathway demonstrated negative correlations. Seven potential biomarker genes, PFKFB4 , ALDOA , EGLN3 , EHHADH , GAPDH , HMGCS2 , and ENO2 were identified. A metabolic gene expression balance score according to the dominance between glucose and lipid metabolism demonstrated good prognostic value in HCC. Conclusions: The transcriptomic evidence of this study strongly supports the prognostic power of FDG PET/CT and indicates the potential usefulness of FDG PET/CT imaging biomarkers to select appropriate patients for metabolism-targeted therapy in HCC. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the role of positron emission tomography/computed tomography (PET/CT) in predicting pathologic complete response (pCR) and identify relevant prognostic factors from clinico-imaging-pathologic features of locally advanced esophageal squamous cell carcinoma (eSCC) patients undergoing trimodality therapy. Methods: We evaluated 275 patients with eSCCs of T3-T4aN0M0 and T1-T4aN1-N3M0 who received trimodality therapy. We correlated volume-based PET/CT parameters before and after concurrent chemoradiation therapy with pCR after surgery, clinico-imaging-pathologic features, and patient survival. Results: pCR occurred in 75 (27.3%) of 275 patients, of whom 61 (80.9%) showed 5-year survival. Pre-total lesion glycolysis (pre-TLG, OR = 0.318, 95% CI 0.169 to 0.600), post-metabolic tumor volume (post-MTV, OR = 0.572, 95% CI 0.327 to 0.999), and % decrease of average standardized uptake value (% SUVavg decrease, OR = 2.976, 95% CI = 1.608 to 5.507) were significant predictors for pCR. Among them, best predictor for pCR was pre-TLG with best cutoff value of 205.67 and with AUC value of 0.591. Performance status (HR = 5.171, 95% CI 1.737 to 15.397), pathologic tumor size (HR = 1.645, 95% CI 1.351 to 2.002), pathologic N status (N1, HR = 1.572, 95% CI 1.010 to 2.446; N2, HR = 3.088, 95% CI 1.845 to 5.166), and post-metabolic tumor volume (HR = 1.506, 95% CI 1.033 to 2.195) were significant predictors of overall survival. Conclusion: Pre-TLG, post-MTV, and % SUVavg decrease are predictive of pCR. Additionally, several clinico-imaging-pathologic factors are significant survival predictors in locally advanced eSCC patients undergoing trimodality therapy. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to find the best machine learning (ML) model using 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for evaluating metastatic mediastinal lymph nodes (MedLNs) in non-small cell lung cancer, and compare the diagnostic results with those of nuclear medicine physicians. Methods: A total of 1329 MedLNs were reviewed. Boosted decision tree, logistic regression, support vector machine, neural network, and decision forest models were compared. The diagnostic performance of the best ML model was compared with that of physicians. The ML method was divided into ML with quantitative variables only (MLq) and adding clinical information (MLc). We performed an analysis based on the 18F-FDG-avidity of the MedLNs. Results: The boosted decision tree model obtained higher sensitivity and negative predictive values but lower specificity and positive predictive values than the physicians. There was no significant difference between the accuracy of the physicians and MLq (79.8% vs. 76.8%, p = 0.067). The accuracy of MLc was significantly higher than that of the physicians (81.0% vs. 76.8%, p = 0.009). In MedLNs with low 18F-FDG-avidity, ML had significantly higher accuracy than the physicians (70.0% vs. 63.3%, p = 0.018). Conclusion: Although there was no significant difference in accuracy between the MLq and physicians, the diagnostic performance of MLc was better than that of MLq or of the physicians. The ML method appeared to be useful for evaluating low metabolic MedLNs. Therefore, adding clinical information to the quantitative variables from 18F-FDG PET/CT can improve the diagnostic results of ML. Key Points: • Machine learning using two-class boosted decision tree model revealed the highest value of area under curve, and it showed higher sensitivity and negative predictive values but lower specificity and positive predictive values than nuclear medicine physicians. • The diagnostic results from machine learning method after adding clinical information to the quantitative variables improved accuracy significantly than nuclear medicine physicians. • Machine learning could improve the diagnostic significance of metastatic mediastinal lymph nodes, especially in mediastinal lymph nodes with low 18F-FDG-avidity. [ABSTRACT FROM AUTHOR]

This study aimed to assess the role of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG-PET/CT) in the differential diagnosis of pericardial disease. The diagnosis is often troublesome because pericardial fluid analysis or biopsy does not always provide answers. 18FDG-PET/CT can visualize both inflammation and malignancy and offers a whole-body assessment. Patients who visited the Pericardial Disease Clinic of Samsung Medical Center with an 18FDG-PET/CT order code were extracted. Exclusion criteria were as follows: (1) the purpose of the differential diagnosis was not pericardial disease; (2) the patient had a known advanced-stage malignancy; (3) the patient already have confirmative diagnosis using a serology, pericardial effusion analysis or biopsy. The analysis included 107 patients. The most common final diagnosis was idiopathic (n = 46, 43.0%), followed by tuberculosis (n = 30, 28.0%) and neoplastic (n = 11, 10.3%). A maximum standardized uptake value (SUVmax) ≥ 5 typically indicates tuberculosis or neoplastic pericarditis except in just one case of autoimmune pericarditis); especially all of the SUVmax scores ≥ 10 had tuberculosis. The diagnostic yield of pericardial biopsy was very low (10.2%). Interestingly, all of the pericardium with an SUVmax < 4.4 had nondiagnostic results. In contrast, targeted biopsies based on 18FDG uptake demonstrated a higher diagnostic yield (38.7%) than pericardium. The sensitivity of 18FDG-PET/CT was 63.6%. The specificity was 71.9%. The positive predictive value was 20.6%. The negative predictive value 94.5%, and the accuracy was 71.0% for excluding malignancy based upon the FDG uptake patterns. It is possible to explore the differential diagnosis in some patients with difficult pericardiocentesis or pericardial biopsy in a noninvasive manner using on the SUVmax or uptake patterns. In addition, the biopsy strategy depending on 18FDG uptake is helpful to achieve biopsy more safely and with a higher yield. 18FDG-PET may enhance the diagnostic efficacy in patients with pericardial disease. [ABSTRACT FROM AUTHOR]

We aimed to report patients' survival after surgical resection of eSCC and to ascertain the clinical, imaging, and pathological factors related to patient prognosis. This retrospective study included 435 patients with eSCC of max) on positron emission tomography (PET)/computed tomography (CT) of the primary tumor was significantly correlated with tumor length, nodal metastasis, and pathologic T stage in a positive linear fashion. In the multivariate analysis, higher SUVmax on PET/CT was a negative prognostic factor for both disease-free survival (DFS) and overall survival (OS). Contrarily, the presence of nodal metastasis was a prognostic factor only for DFS, and pathologic T stage only for OS. By applying SUVmax cut-off, both DFS and OS were significantly different among three groups when divided by cut-off values (A: SUVmax ≤ 3.05, B: SUVmax 3.06 - 5.64, C: SUVmax ≥ 5.65). In patients with a surgically resectable eSCC, measuring the SUVmax of the primary tumor during PET/CT can help predict patient survival. Additionally, PET/CT renders triage criterion for endoscopic submucosal dissection (ESD; T1a cancer and SUVmax, ≤3.05). [ABSTRACT FROM AUTHOR]

Introduction: The maximum standardized uptake value (SUVmax) in 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) may be of prognostic significance for patients with malignant pleural mesothelioma (MPM). This retrospective study aimed to investigate the prognostic value of the SUVmax in patients with MPM. Materials and methods: Medical records were retrospectively reviewed for the patients who were diagnosed with histopathologically proven MPM between 2009 and 2018 at Samsung Medical Center. For each patient, SUVmax was calculated for the primary lesion on PET/CT. To determine optimal cutoff values for predicting mortality, receiver operating characteristic curves were used. Results: Among the 54 study patients, 34 (63.0%) had epithelioid subtype, 13 (24.1%) had sarcomatoid or biphasic subtype, and 7 (13.0%) had mesothelioma, not otherwise specified (NOS). The median overall survival (OS) was 8.7 months, and the median SUVmax was 9.9. The median values of SUVmax were 5.5 in patients with epithelioid subtype, 11.7 in those with sarcomatoid/biphasic subtype, and 13.3 in those with NOS subtype (P = 0.003). The optimal cutoff values of SUVmax to predict mortality were 10.1 in all patients, and 8.5 in patients with epithelioid subtype. In multivariate analysis, SUVmax was significantly associated with overall survival in all patients (P = 0.003) and in patients with epithelioid subtype (P = 0.012), but not in those with non-epithelioid subtype. Conclusions: SUVmax in PET/CT is an independent prognostic factor in patients with MPM, especially those with epithelioid subtype. The histologic subtype of MPM should be considered when evaluating the prognostic significance of SUVmax. [ABSTRACT FROM AUTHOR]

Purpose: The prognostic value of pretreatment 18F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG PET/CT) was assessed in patients with combined hepatocellular-cholangiocarcinoma (cHCC-CC). Methods: A total of 46 patients with cHCC-CC who underwent FDG PET/CT before treatment were retrospectively analysed. Tumour FDG avidity was measured in terms of the tumour-to-normal liver standardized uptake value ratio (TLR) of the primary tumour on FDG PET/CT. The prognostic significance of TLR using the median value of 3.4 as the cut-off value and other clinical variables was assessed using Cox proportional hazards regression models. Differences in progression-free survival (PFS) and overall survival (OS) in relation to TLR were examined by the Kaplan-Meier method. Results: During a median follow-up period of 29 months, 29 patients (63.0%) showed tumour recurrence or progression, and 25 patients (54.4%) died from cancer. Higher TLRs (>3.4) were associated with larger tumour size (p = 0.007) and higher tumour stage (p = 0.030). In a univariable analysis, TLR, tumour stage and CEA were significant prognostic predictors. In a multivariable analysis, TLR was an independent predictor of PFS (HR 5.19, 95% CI 1.80–15.01; p = 0.002) and OS (HR 3.95, 95% CI 1.27–12.24; p = 0.017). Patients with a higher TLR showed significantly worse PFS (2-year survival rate 17.8% vs. 62.9%; p = 0.001) and OS (2-year survival rate, 39.1% vs. 77.3%; p = 0.001) than those with a lower TLR. Conclusion: Pretreatment TLR of the primary tumour measured on FDG PET/CT is an independent predictor of survival in patients with cHCC-CC. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to establish a risk-stratification model integrating posttreatment metabolic response using the Deauville score and the pretreatment National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) in nodal PTCLs.Methods: We retrospectively analysed 326 patients with newly diagnosed nodal PTCLs between January 2005 and June 2016 and both baseline and posttreatment PET/CT data. The final model was validated using an independent prospective cohort of 79 patients.Results: Posttreatment Deauville score (1/2, 3, and 4/5) and the NCCN-IPI (low, low-intermediate, high-intermediate, and high) were independently associated with progression-free survival: for the Deauville score, the hazard ratios (HRs) were 1.00 vs. 2.16 (95% CI 1.47-3.18) vs. 7.86 (5.66-10.92), P < 0.001; and for the NCCN-IPI, the HRs were 1.00 vs. 2.31 (95% CI 1.20-4.41) vs. 4.42 (2.36-8.26) vs. 7.09 (3.57-14.06), P < 0.001. Based on these results, we developed a simplified three-group risk model comprising a low-risk group (low or low-intermediate NCCN-IPI with a posttreatment Deauville score of 1 or 2, or low NCCN-IPI with a Deauville score of 3), a high-risk group (high or high-intermediate NCCN-IPI with a Deauville score of 1/2 or 3, or low-intermediate NCCN-IPI with a Deauville score of 3), and a treatment failure group (Deauville score 4 or 5). This model was significantly associated with progression-free survival (5-year, 70.3%, 31.4%, and 4.7%; P < 0.001) and overall survival (5-year, 82.1%, 45.5%, and 14.7%; P < 0.001). Similar associations were also observed in the independent validation cohort.Conclusion: The risk-stratification model integrating posttreatment Deauville score and pretreatment NCCN-IPI is a powerful tool for predicting treatment failure in patients with nodal PTCLs. [ABSTRACT FROM AUTHOR]

We assessed the association between nonalcoholic fatty liver disease (NAFLD) and carotid artery inflammation measured by 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography. Participants were 755 consecutive otherwise healthy adult males who underwent a general health screening program. Carotid FDG uptake, represented as maximum target-to-background ratio, was increased with mild (n = 237; 1.61 ± 0.14; P = .033) and moderate NAFLD (n = 145; 1.63 ± 0.16; P = .005) compared with controls (n = 373; 1.58 ± 0.15). In patients aged >50 years, moderate NAFLD was the only independent risk factor for high carotid FDG uptake (odds ratio, 2.12; 95% confidence interval, 1.10-4.07; P = .001). Apparently healthy adult males with NAFLD have elevated carotid FDG uptake as well as increased carotid intima–media thickness, suggesting that they may be at an increased risk of having inflammatory atherosclerotic plaques in the carotid arteries. [ABSTRACT FROM PUBLISHER]

Phenformin (phenethylbiguanide; an anti-diabetic agent) plus oxamate [lactate dehydrogenase (LDH) inhibitor] was tested as a potential anti-cancer therapeutic combination. In in vitro studies, phenformin was more potent than metformin, another biguanide, recently recognized to have anti-cancer effects, in promoting cancer cell death in the range of 25 times to 15 million times in various cancer cell lines. The anti-cancer effect of phenformin was related to complex I inhibition in the mitochondria and subsequent overproduction of reactive oxygen species (ROS). Addition of oxamate inhibited LDH activity and lactate production by cells, which is a major side effect of biguanides, and induced more rapid cancer cell death by decreasing ATP production and accelerating ROS production. Phenformin plus oxamate was more effective than phenformin combined with LDH knockdown. In a syngeneic mouse model, phenformin with oxamate increased tumor apoptosis, reduced tumor size and 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography compared to control. We conclude that phenformin is more cytotoxic towards cancer cells than metformin. Furthermore, phenformin and oxamate have synergistic anti-cancer effects through simultaneous inhibition of complex I in the mitochondria and LDH in the cytosol, respectively. [ABSTRACT FROM AUTHOR]

Simple Summary: Thymic epithelial tumors have variable prognoses that depend on histological subtype, and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) currently plays an important part in oncology images. Thus, we prosecuted a retrospective review of data from 83 patients with thymic epithelial tumors who underwent pretreatment 18F-FDG PET/CT and investigated the prognostic significance along with WHO classification, Masaoka stage, and volumetric 18F-PET parameters. Masaoka stage, histologic type, treatment modality, maximum standardized uptake values (SUVmax), average standardized uptake values (SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were significant prognostic factors for time-to-progression on univariate survival analysis. On multivariate analysis, SUVavg and Masaoka stage were important independent prognostic factors for progression-free survival in thymic epithelial tumors. Background: Imaging tumor FDG avidity could complement prognostic implication in thymic epithelial tumors. We thus investigated the prognostic value of volume-based 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT parameters in thymic epithelial tumors with other clinical prognostic factors. Methods: This is a retrospective study that included 83 patients who were diagnosed with thymic epithelial tumors and underwent pretreatment 18F-FDG PET/CT. PET parameters, including maximum and average standardized uptake values (SUVmax, SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), were measured with a threshold of SUV 2.5. Univariate and multivariate analysis of PET parameters and clinicopathologic variables for time-to-progression was performed by using a Cox proportional hazard regression model. Results: There were 21 low-risk thymomas (25.3%), 27 high-risk thymomas (32.5%), and 35 thymic carcinomas (42.2%). Recurrence or disease progression occurred in 24 patients (28.9%). On univariate analysis, Masaoka stage (p < 0.001); histologic types (p = 0.009); treatment modality (p = 0.001); and SUVmax, SUVavg, MTV, and TLG (all p < 0.001) were significant prognostic factors. SUVavg (p < 0.001) and Masaoka stage (p = 0.001) were independent prognostic factors on multivariate analysis. Conclusion: SUVavg and Masaoka stage are independent prognostic factors in thymic epithelial tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study we explored the predictive ability of radiomics in non-small cell lung cancer patients, and reported the complementary role of radiomics in predicting the treatment response of the lymph nodes. Radiomics analysis is a cutting-edge technology for the noninvasive assessment of tumor biology, which converts medical images into mineable high-dimensional data. Our method is cost-effective with no need for additional studies, and moreover, we used an easily reproducible study method that can be applicable in further studies using radiomics in oncology. Although a substantial decrease in 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) uptake on positron emission tomography-computed tomography (PET-CT) indicates a promising metabolic response to treatment, predicting the pathologic status of lymph nodes (LN) remains challenging. We investigated the potential of a CT radiomics approach to predict the pathologic complete response of LNs showing residual uptake after neoadjuvant concurrent chemoradiotherapy (NeoCCRT) in patients with non-small cell lung cancer (NSCLC). Two hundred and thirty-seven patients who underwent NeoCCRT for stage IIIa NSCLC were included. Two hundred fifty-two CT radiomics features were extracted from LNs showing remaining positive FDG uptake upon restaging PET-CT. A multivariable logistic regression analysis of radiomics features and clinicopathologic characteristics was used to develop a prediction model. Of the 237 patients, 135 patients (185 nodes) met our inclusion criteria. Eighty-seven LNs were proven to be malignant (47.0%, 87/185). Upon multivariable analysis, metastatic LNs were significantly prevalent in females and patients with adenocarcinoma (odds ratio (OR) = 2.02, 95% confidence interval (CI) = 0.88–4.62 and OR = 0.39, 95% CI = 0.19–0.77 each). Metastatic LNs also had a larger maximal 3D diameter and higher cluster tendency (OR = 9.92, 95% CI = 3.15–31.17 and OR = 2.36, 95% CI = 1.22–4.55 each). The predictive model for metastasis showed a discrimination performance with an area under the receiver operating characteristic curve of 0.728 (95% CI = 0.654–0.801, p value < 0.001). The radiomics approach allows for the noninvasive detection of metastases in LNs with residual FDG uptake after the treatment of NSCLC patients. [ABSTRACT FROM AUTHOR]

We investigated the relationship between tumor 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) scans and thymidylate synthase (TS) expression. In addition, we evaluated the value of FDG uptake in predicting treatment response and prognosis when combined with TS expression in patients with advanced non-small cell lung cancer (NSCLC). We measured the maximum standard uptake value, metabolic tumor volume, and total lesion glycolysis (TLG) of tumor lesions on pretreatment scan in 234 patients (age: 60.1 ± 9.4 years; males: 56.4%) with stage IV non-squamous NSCLC who were enrolled in the prospective phase II clinical trial. We investigated the correlation of the parameters with TS expression and the predictive values of the parameters compared with other clinical factors. Among these parameters, TLG was the most relevant parameter that had a significant correlation with TS expression (ρ = 0.192, P = 0.008). A multivariable Cox proportional-hazards model revealed that high TLG was a significant independent predictor for treatment response (hazard ratio [HR]: 2.05; P = 0.027), progression-free survival (HR: 1.39; P = 0.043), and overall survival (HR: 1.65; P = 0.035) with other factors. In patients with advanced non-squamous NSCLC, tumor TLG on pretreatment PET/CT scan has predictive and prognostic value. [ABSTRACT FROM AUTHOR]

Background: The purpose of this prospective study was to evaluate the role of 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for assessing treatment response in patients with pulmonary multidrug-resistant tuberculosis (MDR-TB). Methods: The study subjects were four patients diagnosed with pulmonary MDR-TB who underwent MDR-TB treatment and serial 18F-FDG PET/CT at baseline and 6 and 12 months after treatment. The highest lung maximum standardized uptake value (SUVmax), average SUVmean (average of all hypermetabolic parenchymal lesions), total metabolic lung volume (TMLV, sum of metabolic volumes from the hypermetabolic parenchymal lesions), and total lung glycolysis (TLG, sum of lesion glycolysis from the hypermetabolic parenchymal lesions) were determined as representative quantitative PET parameters for each patient. Results: All patients except one had negative sputum culture conversion after one month of treatment and achieved successful treatment outcomes. Baseline TMLV and TLG PET parameters were much higher in the single patient with treatment failure than in the remaining three patients with treatment success. No other PET parameters at baseline or follow-up were associated with the treatment results. Conclusions: Pretreatment volume-based 18F-FDG PET/CT lung parameters were associated with the final therapeutic response in patients with pulmonary MDR-TB. Our preliminary results warrant a larger study. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prognostic role of metabolic response by the use of serial sets of positron emission tomography/computed tomography (PET/CT) in patients with cervical cancer who were treated with concurrent chemoradiation therapy (CCRT). Methods and Materials: A total of 60 patients who were treated with CCRT between February 2009 and December 2010 were analyzed. Three sequential PET/CT images were acquired for each patient: pre-CCRT, during-CCRT at 4 weeks of CCRT, and 1 month post-CCRT PET/CT. Metabolic responses were assessed qualitatively. The percentage changes in the maximum values of standardized uptake value (ΔSUVmax%) from the PET/CT images acquired pre-CCRT and during-CCRT were calculated. Receiver operating characteristic (ROC) curve analysis was performed to evaluate whether ΔSUVmax% could predict complete response (CR) on the post-CCRT PET/CT and to identify the best cutoff value. Prognostic factors of progression-free survival (PFS) were analyzed. Results: During-CCRT PET/CT showed that 8 patients (13%) had CR, and the other 52 patients (87%) had partial response (PR). On the post-CCRT PET/CT, 43 patients (73%) had CR, 12 patients (20%) had PR, and 4 patients (7%) had progressive disease. The average SUVmax in primary tumors was 16.3 (range, 6.4-53.0) on the pre-CCRT PET/CT images and 5.3 (range, 0-19.4) on the during-CCRT PET/CT images. According to ROC curve analysis, ΔSUVmax% could predict CR response on post-CCRT PET/CT (P<.001, cutoff value of 59.7%). In all patients, the PFS rate was 71.9% at 2 years. Multivariate analysis showed that ΔSUVmax% ≥60% (P=.045) and CR response on the post-CCRT PET/CT (P=.012) were statistically significant predictors of PFS. Conclusion: Metabolic responses on the during-CCRT images at 4 weeks of treatment and 1-month post-CCRT PET/CT images may predict treatment outcomes in patients with cervical cancer. ΔSUVmax% ≥60% at 4 weeks of CCRT may predict CR response on 1-month post-CCRT PET/CT and also PFS. [Copyright &y& Elsevier]

Purpose: To evaluate the impact of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on changes in treatment plan and target definition for preoperative radiotherapy in patients with rectal cancer.Methods: Embase, PubMed, and Cochrane Library were searched up to November 2020 for all studies investigating the role of preoperative FDG PET in patients who underwent neoadjuvant radiotherapy before curative-intent surgery. The proportion of patients whose treatment plan (curative vs. palliative intent) or target definition was changed after FDG PET was analyzed. A random-effects model was used for pooled analysis. The change in target definition was compared between conventional radiological imaging-based target volume [gross tumor volume (GTV) or planning target volume (PTV)] and PET-based target volume (GTV or PTV) using the standardized mean difference (SMD) and 95% confidence interval (CI).Results: A total of 336 patients from twelve studies were included. In eight studies, PET changed either the treatment intent or target definition in 24.8% of patients (95% CI 15.1% to 37.9%, I2 = 69%). In ten studies, the PET-based GTV was lower than the conventional imaging-based target volume (SMD -7.0, 95% CI -1.39 to -0.01). However, there was no significant difference between conventional imaging-based and PET-based PTV (SMD -0.07, 95% CI -0.75 to 0.62). In six studies evaluating the initial staging based on PET, the initial staging (nodal or metastasis status) was changed in 53 of 229 patients (23.1%). Newly detected or additional distant metastases were identified in 22 patients (9.6%) after FDG PET.Conclusion: The use of FDG PET influences radiotherapy planning in a fourth of patients with rectal cancer. FDG PET can provide additive information for accurate tumor delineation, although PET-based PTV did not significantly change. These findings suggest that FDG PET may be beneficial to patients with rectal cancer before establishing a radiotherapy plan. [ABSTRACT FROM AUTHOR]