Detection of individual brain tau deposition in Alzheimer's disease based on latent feature-enhanced generative adversarial network.

OBJECTIVE: The conventional methods for interpreting tau PET imaging in Alzheimer's disease (AD), including visual assessment and semi-quantitative analysis of fixed hallmark regions, are insensitive to detect individual small lesions because of the spatiotemporal neuropathology's heterogeneity. In this study, we proposed a latent feature-enhanced generative adversarial network model for the automatic extraction of individual brain tau deposition regions. METHODS: The latent feature-enhanced generative adversarial network we propose can learn the distribution characteristics of tau PET images of cognitively normal individuals and output the abnormal distribution regions of patients. This model was trained and validated using 1131 tau PET images from multiple centres (with distinct races, i.e., Caucasian and Mongoloid) with different tau PET ligands. The overall quality of synthetic imaging was evaluated using structural similarity (SSIM), peak signal to noise ratio (PSNR), and mean square error (MSE). The model was compared to the fixed templates method for diagnosing and predicting AD. RESULTS: The reconstructed images archived good quality, with SSIM = 0.967 ± 0.008, PSNR = 31.377 ± 3.633, and MSE = 0.0011 ± 0.0007 in the independent test set. The model showed higher classification accuracy (AUC = 0.843, 95 % CI = 0.796-0.890) and stronger correlation with clinical scales (r = 0.508, P < 0.0001). The model also achieved superior predictive performance in the survival analysis of cognitive decline, with a higher hazard ratio: 3.662, P < 0.001. INTERPRETATION: The LFGAN4Tau model presents a promising new approach for more accurate detection of individualized tau deposition. Its robustness across tracers and races makes it a potentially reliable diagnostic tool for AD in practice.

Early prediction of endocrine responsiveness in ER+/HER2-negative metastatic breast cancer (MBC): pilot study with 18F-fluoroestradiol (18F-FES) CT/PET.

BACKGROUND: 18F-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) is considered an accurate diagnostic tool to determine whole-body endocrine responsiveness. In the endocrine therapy (ET)-FES trial, we evaluated 18F-FES PET/CT as a predictive tool in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). PATIENTS AND METHODS: Eligible patients underwent an 18F-FES PET/CT at baseline. Patients with standardized uptake value (SUV) ≥ 2 received single-agent ET until progressive disease; patients with SUV < 2 were randomized to single-agent ET (arm A) or chemotherapy (ChT) (arm B). The primary objective was to compare the activity of first-line ET versus ChT in patients with 18F-FES SUV < 2. RESULTS: Overall, 147 patients were enrolled; 117 presented with 18F-FES SUV ≥ 2 and received ET; 30 patients with SUV < 2 were randomized to ET or ChT. After a median follow-up of 62.4 months, 104 patients (73.2%) had disease progression and 53 died (37.3%). Median progression-free survival (PFS) was 12.4 months [95% confidence interval (CI) 3.1-59.6 months] in patients with SUV < 2 randomized to arm A versus 23.0 months (95% CI 7.7-30.0 months) in arm B, [hazard (HR) = 0.71, 95% CI 0.3-1.7 months]; median PFS was 18.0 months (95% CI 11.2-23.1 months) in patients with SUV ≥ 2 treated with ET. Median overall survival (OS) was 28.2 months (95% CI 14.2 months-not estimable) in patients with SUV < 2 randomized to ET (arm A) versus 52.8 months (95% CI 16.2 months-not estimable) in arm B (ChT). Median OS was not reached in patients with SUV ≥ 2. 60-month OS rate was 41.6% (95% CI 10.4% to 71.1%) in arm A, 42.0% (95% CI 14.0% to 68.2%) in arm B, and 59.6% (95% CI 48.6% to 69.0%) in patients with SUV ≥ 2. In patients with SUV ≥ 2, 60-month OS rate was 72.6% if treated with aromatase inhibitors (AIs) versus 40.6% in case of fulvestrant or tamoxifen (P < 0.005). CONCLUSIONS: The ET-FES trial demonstrated that ER+/HER2- MBC patients are a heterogeneous population, with different levels of endocrine responsiveness based on 18F-FES CT/PET SUV.

Prognostic Factors among Patients with Resected Non-Adenocarcinoma of the Lung.

INTRODUCTION: Few studies have investigated the prognostic factors for non-adenocarcinoma of the lung. We retrospectively evaluated the prognostic factors on the basis of histological type of non-adenocarcinoma of the lung treated by pulmonary resection. METHODS: We enrolled 266 patients with non-adenocarcinoma of the lung in this retrospective study: 196 with squamous cell carcinoma (SCC) and 70 with non-SCC. RESULTS: Relapse-free survival (RFS) did not differ significantly between SCC and non-SCC patients (p = 0.33). For SCC patients, RFS differed significantly between patients who underwent wedge resection and non-wedge resection (p < 0.01) and between patients with Clavien-Dindo grade ≥3a and 0-2 postoperative complications (p < 0.01). For non-SCC patients, RFS rates were significantly different in the groups divided at neutrophil-to-lymphocyte ratio = 2.40 (p = 0.02), maximum standardized uptake value (SUVmax) = 8.39 (p < 0.01), between patients with pathological stage (pStage) 0-I and with pStage more than II (p < 0.01). For SCC patients, male sex (p = 0.04), wedge resection (p = 0.01), and Clavien-Dindo grade ≥3a (p = 0.02) were significant factors for RFS in multivariate analysis. For non-SCC patients, neutrophil-to-lymphocyte ratio >2.40 (p < 0.01), SUVmax >8.39 (p = 0.01), and pStage ≥II (p = 0.03) were significant factors for RFS in multivariate analysis. CONCLUSION: RFS did not differ significantly differently between SCC and non-SCC patients. It is necessary to perform more than segmentectomy and to avoid severe postoperative complications for SCC patients. SUVmax might be an adaptation criterion of adjuvant chemotherapy for patients with non-adenocarcinoma and non-SCC of the lung.

[18F]FDG-PET/CT-based risk stratification in women with locally advanced uterine cervical cancer.

BACKGROUND: [18F]FDG-PET/CT is used for staging and treatment planning in patients with locally advanced cervical cancer (LACC). We studied if a PET-based prediction model could provide additional risk stratification beyond International Federation of Gynaecology and Obstetrics (FIGO) staging in our population with LACC to aid treatment decision making. METHODS: In total, 183 patients with LACC treated with chemoradiation between 2013 and 2018 were included. Patients were treated according to FIGO 2009 and retrospectively reclassified according to FIGO 2018 staging system. After validation of an existing PET-based prediction model, the predicted recurrent free survival (RFS), disease specific survival (DSS) and overall survival (OS) at 1, 3, and 5 years, based on metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax) and highest level of [18F]FDG-positive node was calculated. Then the observed survival was compared to the predicted survival. An area under the curve (AUC) close to or higher than 0.7 was considered adequate for accurate prediction. The Youden (J) index defined survival chance cutoff values for low and high risk groups. RESULTS: All AUC values for the comparison between predicted and observed outcomes were > 0.7 except for 5-year RFS and for 5-year OS which were close to 0.7 (0.684 and 0.650 respectively). Cutoff values for low and high risk survival chance were 0.44 for the 3-year RFS and 0.47 for the 5-year OS. The FIGO 2009 system could not differentiate between the risk profiles. After reclassification according to FIGO 2018, all patients with stage IIIC2 and IVB fell in the high risk and almost all patients with stages IB2-IIIB and IVA in the low risk group. In patients with stage IIIC1 disease the FIGO stage cannot discriminate between the risk profiles. CONCLUSIONS: Low and high risk patients with LACC can be identified with the PET-based prediction model. In particular patients with stage IIIC1 need additional risk stratification besides the FIGO 2018 staging. The Kidd model could be a useful tool to aid treatment decision making in these patients. Our results also support the choice of [18F]FDG-PET/CT imaging in patients with LACC.

Correlation between Prostate Cancer Positive Cores and 68Ga-PSMA Distribution in Prostate Gland.

INTRODUCTION: The purpose of our study was to evaluate reliability of 68Ga-labeled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA PET/CT) and identify appropriate SUVmax cutoff values in order to use for diagnosis, especially in patients remained clinically suspicious for prostate cancer (PCa). METHODS: Eighty-four patients applied 68Ga-PSMA PET/CT subsequent to transrectal ultrasound-guided prostate biopsy (TRUS-bx) involved in this study retrospectively. 68Ga-PSMA PET/CT imagings were analyzed by a nuclear medicine physician, and region of interests were drawn manually in prostate diagrams including 6 segments for each patient. These marked diagrams were analyzed with histopathology reports TRUS-bx. 504 segments were grouped with Gleason scoring system, and all groups were compared with mean SUVmax values. RESULTS: Mean SUVmax value of Gleason grade group 1 (GG1, n: 352 segments) was 6.6 (±4.6) and significantly lower than the other groups (p < 0.001). No significant difference was detected within GG2-5 groups (p > 0.05). According to receiver operating characteristic curve analysis, SUVmax cutoff values were 1.0 (AUC: 0.961) for tumor detection, yielding a sensitivity, specificity, positive predictive value, negative predictive value of 99.4%, 92.1%, 96.5%, 98%, respectively, and 4.2 (AUC: 0.853) for detection of clinically significant PCa with 88.8%, 62.4%, 84.5%, and 71%, respectively. Although tumor percentage of biopsy core and Gleason group were correlated with SUVmax uptake, but patient age was not. CONCLUSION: 68Ga-PSMA PET appears to be a reliable option for diagnosis and disease management in PCa and can be considered especially in discrimination of csPCa, and patients remained suspicious for disease.

[Construction and analysis of brain metabolic network in temporal lobe epilepsy patients based on 18F-FDG PET].

The establishment of brain metabolic network is based on 18fluoro-deoxyglucose positron emission computed tomography ( 18F-FDG PET) analysis, which reflect the brain functional network connectivity in normal physiological state or disease state. It is now applied to basic and clinical brain functional network research. In this paper, we constructed a metabolic network for the cerebral cortex firstly according to 18F-FDG PET image data from patients with temporal lobe epilepsy (TLE).Then, a statistical analysis to the network properties of patients with left or right TLE and controls was performed. It is shown that the connectivity of the brain metabolic network is weakened in patients with TLE, the topology of the network is changed and the transmission efficiency of the network is reduced, which means the brain metabolic network connectivity is extensively impaired in patients with TLE. It is confirmed that the brain metabolic network analysis based on 18F-FDG PET can provide a new perspective for the diagnose and therapy of epilepsy by utilizing PET images.

The trends and significance of SSTR PET/CT added to MRI in follow-up imaging of low-grade meningioma treated with fractionated proton therapy.

PURPOSE: Overexpression of the somatostatin receptor (SSTR) has led to adoption of SSTR PET/CT for diagnosis and radiotherapy planning in meningioma, but data on SSTR expression during follow-up remain scarce. We investigated PET/CT quantifiers of SSTR tracers in WHO grade I meningioma following fractionated proton beam therapy (PBT) compared to standard response assessment with MRI. METHODS: Twenty-two patients diagnosed with low-grade meningioma treated by PBT were included. Follow-up included clinical visits, MRI, and [68Ga]Ga-DOTATOC PET/CT scans. Radiologic tumor response, MRI and PET volume (VMRI and VPET), maximum and mean standardied uptake value (SUVmax/SUVmean), total lesion activity (TLA), and heterogeneity index (HI) were evaluated. RESULTS: Median follow-up was 35.3 months (range: 6.4-47.9). Nineteen patients (86.4%, p = 0.0009) showed a decrease of SUVmax between baseline and first follow-up PET/CT (median: -24%, range: -53% to +89%) and in 81.8% of all cases, the SUVmax, SUVmean, and TLA at last follow-up were eventually lower than at baseline (p = 0.0043). Ambiguous trends without significance between the timepoints analyzed were observed for VPET. HI increased between baseline and last follow-up in 75% of cases (p = 0.024). All patients remained radiologically and clinically stable. Median VMRI decreased by -9.3% (range 0-32.5%, p < 0.0001) between baseline and last follow-up. CONCLUSION: PET/CT in follow-up of irradiated meningioma showed an early trend towards decreased binding of SSTR-specific tracers following radiation and MRI demonstrated consistently stable or decreasing tumor volume. Translational research is needed to clarify the underlying biology of the subsequent increase in SSTR PET quantifiers.

The Utility of SUVmax as an Adaptation Criterion for Limited Resection in Stage IA Non-Small Cell Lung Cancer.

INTRODUCTION: Although the consolidation diameter of a tumor on computed tomography (CT) is an adaptation criterion for limited resection in early-stage non-small cell lung cancer (NSCLC), whether the maximum standardized uptake value (SUVmax) is also an adaptation criterion for limited resection has not been evaluated. METHODS: In total, 478 NSCLC patients with clinical stage IA disease were analyzed, among whom 383 were used to perform a sub-analysis. RESULTS: Multivariate analysis showed that consolidation diameter (odds ratio [OR]: 3.05, p = 0.01), SUVmax (OR: 10.74, p = 0.02), and lymphatic invasion (OR: 10.34, p < 0.01) were risk factors for lymph node metastasis in clinical stage IA NSCLC patients. Furthermore, age (OR: 2.98, p = 0.03), SUVmax (OR: 13.07, p = 0.02), and lymphatic invasion (OR: 5.88, p = 0.02) were risk factors for lymph node metastasis in clinical stage IA lung adenocarcinoma patients according to multivariate analysis. CONCLUSION: Consolidation diameter of a tumor on CT, SUVmax, and lymphatic invasion are risk factors for lymph node metastasis. However, SUVmax was a risk factor for lymph node metastasis rather than consolidation diameter on CT in lung adenocarcinoma patients. These results suggest that for early-stage lung adenocarcinoma patients, SUVmax is more important for deciding the indication of limited resection than consolidation diameter of the tumor on CT.

Utility of serum ketone levels for assessment of myocardial glucose suppression for 18F-fluorodeoxyglucose PET in patients referred for evaluation of endocarditis.

BACKGROUND: 18F-FDG PET/CT is used to diagnose cardiac sarcoidosis and endocarditis. It requires myocardial glucose utilization (MGU) suppression to avoid false positives, which occur in up to 20% of patients. Serum beta-hydroxybutyrate (BHB) levels may help identify incomplete suppression of MGU. We determined the optimal timing and diagnostic thresholds to identify incomplete suppression of MGU. METHODS AND RESULTS: We retrospectively identified 114 patients referred for 18F-FDG PET/CT for endocarditis, wherein myocardial uptake outside of paravalvular regions is not related to pathology and can be confidently ascribed as being due to inadequate suppression of MGU. Patients followed a high-fat, low-carbohydrate diet and received heparin. Serum BHB, insulin, glucose and hemoglobin A1c were measured. Maximum standardized uptake value (SUVmax) of left ventricle (LV) and mean SUV (SUVmean) in LV blood pool (LVBP) was measured. Logistic regression and area under the receiver-operating characteristic analyses were used to quantify the relationship between biomarkers and MGU suppression. A threshold of BHB ≥ 0.35 mmol·L-1 to detect suppression resulted in sensitivity of 88% and specificity of 61%. A threshold of BHB ≥ 0.95 mmol·L-1 resulted in sensitivity of 45% and specificity of 100%. AUC was 0.87. BHB measured ~ 4 hours prior to 18F-FDG injection performed similarly to or better than later timepoints. CONCLUSIONS: Serum BHB levels are useful for assessing suppression of MGU and could simplify interpretation of 18F-FDG PET/CT inflammation studies.

Prognostic Impact of Cancer Inflammation Prognostic Index for Non-small Cell Lung Cancer.

PURPOSE: Cancer-inflammation prognostic index (CIPI) is calculated by multiplying the concentration of carcinoembryonic antigen by neutrophil-to-lymphocyte ratio. CIPI has been reported as a prognostic factor for colorectal cancer. Although carcinoembryonic antigen and neutrophil-to-lymphocyte ratio have been reported as prognostic factors for non-small cell lung cancer (NSCLC), it has not been investigated whether CIPI is a useful marker. METHODS: We analyzed the prognostic factors, including CIPI, in 700 NSCLC patients treated by pulmonary resection. We also analyzed a subgroup of 482 patients with pathological stage I NSCLC. RESULT: CIPI > 14.59 (P < 0.01), maximum standardized uptake value (SUVmax) > 5.35 (P < 0.01), lymphatic invasion (P = 0.01), and pathological stage (P < 0.01) were significant factors for relapse-free survival (RFS) in multivariate analysis. SUVmax > 5.35 (P < 0.01) and pathological stage (P < 0.01) were revealed as significant factors for overall survival in the multivariate analysis. In the subanalysis, CIPI > 14.88 (P = 0.01) and SUVmax > 5.07 (P < 0.01) were significant factors for RFS of pathological stage I NSCLC in multivariate analysis. CONCLUSION: CIPI was a significant factor for RFS in NSCLC patients treated surgically, even in those with pathological stage I disease. SUVmax was also a significant factor for RFS and overall survival in NSCLC patients treated surgically, and for RFS in patients with pathological stage I NSCLC. TRIAL REGISTRATION: The Institutional Review Board of Kanazawa Medical University approved the protocol of this retrospective study (Approval Number: I392), and written informed consent was obtained from all patients.

A novel classification model based on cerebral 18F-FDG uptake pattern facilitates the diagnosis of acute/subacute seropositive autoimmune encephalitis.

PURPOSE: To explore the intrinsic alteration of cerebral 18F-FDG metabolism in acute/subacute seropositive autoimmune encephalitis (AE) and to propose a universal classification model based on 18F-FDG metabolic patterns to predict AE. METHODS: Cerebral 18F-FDG PET images of 42 acute/subacute seropositive AE patients and 45 healthy controls (HCs) were compared using voxelwise and region of interest (ROI)-based schemes. The mean standardized uptake value ratios (SUVRs) of 59 subregions according to a modified Automated Anatomical Labeling (AAL) atlas were compared using a t-test. Subjects were randomly divided into a training set (70%) and a testing set (30%). Logistic regression models were built based on the SUVRs and the models were evaluated by determining their predictive value in the training and testing sets. RESULTS: The 18F-FDG uptake pattern in the AE group was characterized by increased SUVRs in the brainstem, cerebellum, basal ganglia, and temporal lobe, and decreased SUVRs in the occipital, and frontal regions with voxelwise analysis (false discovery rate [FDR] p<0.05). Utilizing ROI-based analysis, we identified 15 subareas that exhibited statistically significant changes in SUVRs among AE patients compared to HC (FDR p<0.05). Further, a logistic regression model incorporating SUVRs from the calcarine cortex, putamen, supramarginal gyrus, cerebelum_10, and hippocampus successfully enhanced the positive predictive value from 0.76 to 0.86 when compared to visual assessments. This model also demonstrated potent predictive ability, with AUC values of 0.94 and 0.91 observed for the training and testing sets, respectively. CONCLUSIONS: During the acute/subacute stages of seropositive AE, alterations in SUVRs appear to be concentrated within physiologically significant regions, ultimately defining the general cerebral metabolic pattern. By incorporating these key regions into a new classification model, we have improved the overall diagnostic efficiency of AE.

Diagnostic value of 18F-PSMA-1007 PET/CT combined with prostate specific antigen derived indicators in gray area prostate cancer. / 18F-PSMA-1007 PET/CTè”åˆå‰åˆ—è ºç‰¹å¼‚æ€§æŠ—åŽŸè¡ç”ŸæŒ‡æ ‡å¯¹ç°åŒºå‰åˆ—è ºç™Œçš„è¯Šæ–­ä»·å€¼.

OBJECTIVES: The incidence of prostate cancer is increasing every year, and precision diagnosis and treatment can help reduce unnecessary prostate punctures for prostate cancer patients in the gray area. This study aims to investigate the diagnostic value of 18F-prostate specific membrane antigen (PSMA) imaging combined with prostate specific antigen (PSA)-derived indicators for gray zone prostate cancer. METHODS: A total of 107 patients who underwent 18F-PSMA PET/CT imaging for suspicious prostate cancer with tPSA of 4 to 10 µg/L (PSA gray zone) in a hospital were retrospectively included, and were divided into a prostate cancer group and a non-prostate cancer group based on pathological findings. Patients underwent PSA testing, 18F-PSMA, and abdominal ultrasound, and age, tPSA, fPSA, f/tPSA, prostate volume, PSA density (PSAD), maximum standardized uptake value (SUVmax), and molecular imaging prostate specific membrane antigen (miPSMA) score were compared between the 2 groups. Multivariate logistic regression was used to analyze the influencing factors the diagnosis of gray zone prostate cancer. Receiver operating characteristic (ROC) curves were constructed to evaluate the efficacy of PSAD and SUVmax alone and in combination in diagnosing gray zone prostate cancer. RESULTS: The volume of the prostate cancer group [42.00(34.00, 58.00) cm3 vs 49.00(41.27, 60.41) cm3] was smaller than that of the non-prostate cancer group (Z=-2.376, P=0.017), and the PSAD [(0.18±0.06) µg/(L·cm3) vs 0.15±0.05 µg/(L·cm3)] and SUVmax [18.63(8.03, 28.57) vs 9.33(5.90, 13.52)] were higher than those in the non-prostate cancer group (both P<0.05). The percentage of miPSMA score ≥2 in the prostate cancer group was higher than that in the non-prostate cancer group (χ2=40.987, P<0.001). PSAD (OR=22.154, 95% CI 1.430 to 873.751, P=0.042) and SUVmax (OR=1.301, 95% CI 1.034 to 1.678, P=0.009) were independent influential factors for the diagnosis of prostate cancer in the gray zone. The optimal cut-off values of PSAD and SUVmax were 0.22 µg/(L·cm3) and 8.02, respectively, and the AUCs for the diagnosis of prostate cancer in the gray zone alone and in combination were 0.628 (95% CI 0.530 to 0.720, P<0.05) and 0.806 (95% CI 0.718 to 0.876, P<0.05), 0.847 (95% CI 0.765 to 0.910, P<0.05), with sensitivities of 41.03%, 76.92%, and 74.36% and specificities of 79.41%, 89.71%, and 92.65%, respectively. CONCLUSIONS: PSAD and SUVmax are increased in patients with gray zone prostate cancer, and the combination of PSAD and SUVmax is of high value in diagnosing gray zone prostate cancer.

Trimodality therapy for locally advanced esophageal squamous cell carcinoma: the role of volume-based PET/CT in patient management and prognostication.

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.

Prognostic impact of the tumor volume doubling time in clinical T1 non-small cell lung cancer with solid radiological findings.

BACKGROUND: The purpose of this study was to investigate better radiological prognostic factors in clinical T1 pure-solid non-small cell lung cancer (NSCLC). METHODS: This study enrolled 284 patients with clinical T1 solid NSCLC who underwent anatomical lung resection. The Cox proportional hazard model was used to evaluate the prognostic impact of tumor volume doubling time (VDT) at disease-free survival (DFS) and cancer-specific survival (CSS). RESULTS: The median VDT was 347 days. Age (hazard ratio (HR) = 1.04; 95% confidence interval (CI), 1.01-1.07) and standardized uptake value max (SUVmax) (>6.0) (HR = 2.61; 95% CI, 1.52-4.66) were identified as significantly independent worse prognostic factors for DFS in a multivariable analysis without VDT. Furthermore, a multivariable analysis without SUVmax identified age (HR = 1.06; 95% CI, 1.03-1.09), CEA (>5.0 ng/ml) (HR = 2.34; 95% CI, 1.30-4.02), tumor diameter on CT (>2.0 cm) (HR = 1.91; 95% CI, 1.18-3.13), and VDT (HR = 4.03; 95% CI, 2.41-6.93) as significantly independent worse prognostic factors for DFS. CONCLUSIONS: The VDT value could be a useful prognostic factor in clinical T1 solid NSCLC.

Prediction of local tumor control and recurrence-free survival in patients with pancreatic cancer undergoing curative resection after neoadjuvant chemoradiotherapy.

BACKGROUND AND OBJECTIVES: There is little data on the correlation between the reduction in fluorodeoxyglucose positron emission tomography (FDG-PET) radioactive accumulation and carbohydrate antigen 19-9 (CA19-9) levels with pathological tumor responses (PTRs) and prognosis after neoadjuvant chemoradiotherapy (NACRT) for patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: This study was a retrospective analysis of prospectively collected data from 102 patients with resectable (R-) and borderline resectable (BR-) PDAC who received NACRT, followed by curative resection. Data were prospectively collected and compared between the responders and nonresponders to NACRT. RESULTS: Patients with 60% or more reduction in maximum standardized uptake value (SUVmax) on FDG-PET, with 75% or more reduction in CA19-9 levels, or with 50%-100% of tumor cells destroyed due to NACRT had significantly better recurrence-free survival (RFS) than each of the nonresponders (p = 0.028, <0.001, and 0.022, respectively). The reduction rates of SUVmax and CA19-9 levels were correlated with PTR. The combined evaluation of these biomarkers reflected RFS. CONCLUSIONS: Reduction rates of FDG uptake and CA19-9 levels were preoperative predictors of pathological response to NACRT. These biomarkers of local response had prognostic value in R-PDAC and BR-PDAC. The combined evaluation of these biomarkers allowed for reliable prediction of RFS after surgery.

The clinical consequences of functional adrenal uptake in the absence of cross-sectional mass on FDG-PET/CT in oncology patients.

PURPOSE: Oncology patients undergoing positron emission tomography/computed tomography (PET/CT) occasionally show discrete adrenal [18F]-fluorodeoxyglucose (FDG) uptake without an associated nodule on CT, leaving the clinician uncertain about the need to proceed with biopsy or surgical referral. This study aimed to identify the prevalence of this radiological finding and to evaluate the effectiveness of FDG uptake values in risk stratification for adrenal metastasis. METHODS: From 2014 to 2015, oncology patients who underwent FDG-PET/CT and demonstrated elevated FDG uptake in the adrenal gland without discrete nodularity on cross-sectional imaging were included in a retrospective cohort analysis. Clinical records and FDG-PET/CT scans were reviewed for clinicopathological data, follow-up data, SUVmax (highest SUV of either adrenal gland), and SUVratio (SUVmax/background liver uptake). A receiver operating characteristic analysis was conducted to evaluate the associations between SUV values and the progression to adrenal metastasis. RESULTS: Of 3040 oncology patients who underwent FDG-PET/CT scans, 92 (3.0%) showed elevated adrenal uptake without associated mass. From the final study cohort of 66 patients with comprehensive follow-up data, 5 patients (7.6%) developed evidence of adrenal metastasis. At SUVmax < 3.25 (AUC = 0.757) and SUVratio < 1.27 (AUC = 0.907), 34.8% and 60.6% of patients could be excluded with 100% negative predictive value, respectively. CONCLUSIONS: Thresholds of SUVmax and SUVratio identified a significant proportion of patients who did not develop adrenal metastasis. In oncology patients who demonstrate increased adrenal FDG uptake without a discrete lesion on FDG-PET/CT, quantitative uptake values may be useful in selecting those not at risk of developing adrenal metastatic disease.

Motion-compensated FDG PET/CT for oesophageal cancer.

PURPOSE: Respiratory-induced motion of oesophageal tumours and lymph nodes can influence positron-emission tomography/computed tomography (PET/CT). The aim was to compare standard three-dimensional (3D) and motion-compensated PET/CT regarding standardized uptake value (SUV), metabolic tumour volume (MTV) and detection of lymph node metastases. METHODS: This prospective observational study (NCT02424864) included 37 newly diagnosed oesophageal cancer patients. Diagnostic PET/CT was reconstructed in 3D and motion-compensated PET/CT. MTVs of the primary tumour were calculated using an automated region-growing algorithm with SUV thresholds of 2.5 (MTV2.5) and ≥ 50% of SUVmax (MTV50%). Blinded for reconstruction method, a nuclear medicine physician assessed all lymph nodes showing 18F­fluorodeoxyglucose uptake for their degree of suspicion. RESULTS: The mean (95% CI) SUVmax of the primary tumour was 13.1 (10.6-15.5) versus 13.0 (10.4-15.6) for 3D and motion-compensated PET/CT, respectively. MTVs were also similar between the two techniques. Bland-Altman analysis showed mean differences between both measurements (95% limits of agreement) of 0.08 (-3.60-3.75), -0.26 (-2.34-1.82), 4.66 (-29.61-38.92) cm3 and -0.95 (-19.9-18.0) cm3 for tumour SUVmax, lymph node SUVmax, MTV2.5 and MTV50%, respectively. Lymph nodes were classified as highly suspicious (30/34 nodes), suspicious (20/22) and dubious (66/59) for metastases on 3D/motion-compensated PET/CT. No additional lymph node metastases were found on motion-compensated PET/CT. SUVmax of the most intense lymph nodes was similar for both scans: mean (95% CI) 6.6 (4.3-8.8) and 6.8 (4.5-9.1) for 3D and motion-compensated, respectively. CONCLUSION: SUVmax of the primary oesophageal tumour and lymph nodes was comparable on 3D and motion-compensated PET/CT. The use of motion-compensated PET/CT did not improve lymph node detection.

Significance of initial, interim and end-of-therapy 18F-FDG PET/CT for predicting transformation risk in follicular lymphoma.

BACKGROUND: Histological transformation (HT) of follicular lymphoma to a more aggressive lymphoma is a serious event affecting patients' outcomes. To date, no strong clinical HT predictors present at diagnosis have yet been identified. The fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) is highlighted as a non-invasive diagnostic tool for the detection of HT, but its ability to predict HT at early stage of disease has not been clear. Therefore, this study investigated the predictive values of the pre-transformation standardized uptake value (SUVmax) for the risk of transformation in FL. METHODS: This retrospective study involved 219 patients with FL between June 2008 and October 2019 who had undergone 18F-FDG PET/CT scan. One hundred and thirty-two, 64, and 78 patients underwent PET at baseline (PETbaseline), interim (PETinterim) and end-of-induction therapy (PETend), respectively. Qualitative assessment was performed using the 5-point Deauville scale. Statistical analysis was done using Cox regression models, receiver operating characteristic (ROC) analysis, and Kaplan-Meir survival curves. RESULTS: Of the 219 patients included, 128 had low-grade FL (grade 1-2) and 91 had high-grade FL (grade 3a). HT eventually occurred in 30 patients. The median time to HT was 13.6 months. Among clinical indicators, advance pathological grade was shown as the most significant predictor of HT (HR = 4.561, 95% CI 1.604-12.965). We further assessed the relationship between PET and HT risk in FL. Univariate Cox regression determined that SUVbaseline and SUVend were significant predictors for HT, while neither SUVinterim nor qualitative assessment of Deauville score has predictive value for HT. Due to the noticeable impact of high pathological grade on the HT risk, we conducted the subgroup analysis in patients with low/high pathological grade, and found SUVbaseline could still predict HT risk in both low-grade and high-grade subgroups. Multivariate analysis adjusted by FLIPI2 score showed the SUVbaseline (HR 1.065, 95% CI 1.020-1.111) and SUVend (HR 1.261, 95% CI 1.076-1.478) remained as significant predictors independently of the FLIPI2 score. According to the cut-off determined from the ROC analysis, increased SUVbaseline with a cutoff value of 14.3 and higher SUVend with a cutoff value of 7.3 were highly predictive of a shorter time to HT. CONCLUSIONS: In follicular lymphoma, quantitative assessment used SUVmax at the pre-treatment and end-of-treatment PET/CT scan may be helpful for early screen out patients at high risk of transformation and guide treatment decisions.

A convolutional neural network for fully automated blood SUV determination to facilitate SUR computation in oncological FDG-PET.

PURPOSE: The standardized uptake value (SUV) is widely used for quantitative evaluation in oncological FDG-PET but has well-known shortcomings as a measure of the tumor's glucose consumption. The standard uptake ratio (SUR) of tumor SUV and arterial blood SUV (BSUV) possesses an increased prognostic value but requires image-based BSUV determination, typically in the aortic lumen. However, accurate manual ROI delineation requires care and imposes an additional workload, which makes the SUR approach less attractive for clinical routine. The goal of the present work was the development of a fully automated method for BSUV determination in whole-body PET/CT. METHODS: Automatic delineation of the aortic lumen was performed with a convolutional neural network (CNN), using the U-Net architecture. A total of 946 FDG PET/CT scans from several sites were used for network training (N = 366) and testing (N = 580). For all scans, the aortic lumen was manually delineated, avoiding areas affected by motion-induced attenuation artifacts or potential spillover from adjacent FDG-avid regions. Performance of the network was assessed using the fractional deviations of automatically and manually derived BSUVs in the test data. RESULTS: The trained U-Net yields BSUVs in close agreement with those obtained from manual delineation. Comparison of manually and automatically derived BSUVs shows excellent concordance: the mean relative BSUV difference was (mean ± SD) = (- 0.5 ± 2.2)% with a 95% confidence interval of [- 5.1,3.8]% and a total range of [- 10.0, 12.0]%. For four test cases, the derived ROIs were unusable (< 1 ml). CONCLUSION: CNNs are capable of performing robust automatic image-based BSUV determination. Integrating automatic BSUV derivation into PET data processing workflows will significantly facilitate SUR computation without increasing the workload in the clinical setting.

Noninvasive evaluation of tumor immune microenvironment in patients with clear cell renal cell carcinoma using metabolic parameter from preoperative 2-[18F]FDG PET/CT.

PURPOSE: Nowadays, it is necessary to explore effective biomarkers associated with tumor immune microenvironment (TIME) noninvasively. Here, we investigated whether the metabolic parameter from preoperative 2-[18F]FDG PET/CT could provide information related to TIME in patients with clear cell renal cell carcinoma (ccRCC). METHODS: Ninety patients with newly diagnosed ccRCC who underwent 2-[18F]FDG PET/CT prior to surgery were retrospectively reviewed. The immunological features included tumor-infiltrating lymphocytes (TILs) density, programmed death-ligand 1 (PD-L1) expression, and tumor immune microenvironment types (TIMTs). TIMTs were classified as TIMT I (positive PD-L1 and high TILs), TIMT II (negative PD-L1 and low TILs), TIMT III (positive PD-L1 and low TILs), and TIMT IV (negative PD-L1 and high TILs). The relationship between maximum standardized uptake value (SUVmax) in the primary lesion from 2-[18F]FDG PET/CT and immunological features was analyzed. Cox proportional hazards analyses were performed to identify the prognostic factors for disease-free survival (DFS) after nephrectomy. RESULTS: Tumors with high TILs infiltration showed remarkable correlation with elevated SUVmax and aggressive clinicopathological characteristics, such as high World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade. PD-L1 expression on tumor cells was positively associated with WHO/ISUP grade and negatively correlated with body mass index (BMI). However, no correlation was observed between SUVmax and PD-L1 expression, regardless of its spatial tissue distribution. SUVmax of TIMT I and IV was higher than that of TIMT II, but there was remarkable difference merely between TIMT II and IV. In multivariate analysis, SUVmax (P = 0.022, HR 3.120, 95% CI 1.175-8.284) and WHO/ISUP grade (P = 0.046, HR 2.613, 95% CI 1.017-6.710) were the significant prognostic factors for DFS. Six cases (16.2%) with normal SUVmax showed disease progression, while 25 cases (71.4%) with elevated SUVmax experienced disease progression. Conversely, the immunological features held no prognostic value. CONCLUSIONS: Our findings demonstrated that 2-[18F]FDG PET/CT could provide metabolic information of TIME for ccRCC patients and develop image-guided therapeutic strategies accordingly. Patients with elevated preoperative SUVmax should be seriously considered, and perioperative immunotherapy might be beneficial for them.