Impact of Metabolic Activity in Hepatocellular Carcinoma: Association With Immune Status and Vascular Formation.
ABSTRACT: We evaluated the prognostic value of fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in hepatocellular carcinoma (HCC). Their association with programmed death ligand 1 (PD-L1) expression and vascular formation was further investigated. In this retrospective study, using a database of 418 patients who had undergone 18F-FDG PET/CT before hepatic resection for HCC, immunohistochemical staining of PD-L1, clusters of differentiation (CD) 8, CD68, and CD34 was performed. Patients with a high maximum standardized uptake value (SUVmax) on 18F-FDG PET/CT showed a significantly worse recurrence-free survival (RFS) (hazard ratio [HR]: 1.500; 95% confidence interval [CI]: 1.088-2.069; P = 0.0133) and overall survival (OS) (HR: 2.259; 95% CI: 1.276-4.000; P = 0.0052) than patients with a low SUVmax. Logistic regression analysis showed that a high SUVmax in HCC was significantly associated with PD-L1-positive expression (odds ratio: 4.407; 95% CI: 2.265-8.575; P < 0.0001). SUVmax values of HCC were associated with intratumoral CD8-positive T-cell counts (P = 0.0044) and CD68-positive macrophage counts (P = 0.0061). Stratification based on SUVmax, PD-L1 expression, and the vessels that encapsulate tumor clusters (VETC) status was also significantly associated with RFS and OS. SUVmax, VETC, and PDL1 expression were independently predictive of survival on multivariable analysis. Conclusion: Our large cohort study showed that a high SUVmax on 18F-FDG PET/CT is associated with a poor clinical outcome and PD-L1 expression in patients with HCC. Additionally, stratification of patients based on the combination of SUVmax, PD-L1 expression, and the VETC status predicts poor clinical outcome.
Project description:Programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) have been identified as novel targets of immunotherapy of lung cancer. In present study, we evaluated the metabolic characteristics of lung cancer by using <sup>18</sup> F-fluorodeoxyglucose positron emission tomography/computed tomography (<sup>18</sup> F-FDG PET/CT) with regard to PD-L1 protein expression. PD-L1 protein expression was evaluated by immunohistochemistry with the antibody clone SP142 in 579 surgically resected primary lung cancer patients. Cases with less than 5% tumor membrane staining were considered negative. We examined the association between the frequency of PD-L1 protein expression and the maximum standardized uptake value (SUVmax) in preoperative <sup>18</sup> F-FDG PET/CT. The cut-off values for SUVmax were determined by receiver operating characteristic curve analyses. The SUVmax was significantly higher in nonsmall cell lung cancer (NSCLC) patients with PD-L1 protein expression compared with those without PD-L1 protein expression (P < 0.0001). However, there was no correlation between SUVmax and PD-L1 protein expression in patients with neuroendocrine tumors (P = 0.6545). Multivariate analysis revealed that smoking, the presence of pleural invasion, and high SUVmax were independent predictors of PD-L1 positivity. PD-L1-expressing NSCLC had a high glucose metabolism. The SUVmax in preoperative <sup>18</sup> F-FDG PET/CT was a predictor of PD-L1 protein expression in patients with NSCLC.
Project description:Purpose:This study aimed to evaluate the role of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in expression of tumor programmed death ligand-1 (PD-L1) expression and prognostic significance of 18F-FDG PET/CT at different PD-L1 status in patients with lung adenocarcinoma. Patients and Methods:Seventy-three patients with primary lung adenocarcinoma who received 18F-FDG PET/CT before treatment were retrospectively included in this study. Expression of tumor PD-L1, programmed death-1 (PD-1) and glucose metabolic parameters were evaluated. Results:Tumor PD-L1 expression was positively correlated with maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), hexokinase II (HK-II) and glucose transporter 1 (GLUT-1) (P<0.0001 for all). SUVmax was a unique independent predictor of tumor PD-L1 expression, with an optimal cut-off value of 9.5. For all the patients, tumor stage (P<0.001) and SUVmax (P=0.009) were independent prognostic indicators of disease-free survival (DFS)/progression-free survival (PFS) while carcino-embryonic antigen (CEA) (P=0.003), Ki67 (P=0.042), PD-L1 (P=0.048) and TLG (P=0.004) were independent prognostic indicators of overall survival (OS). Tumor stage (P=0.004) and SUVmax (P=0.022) were independent prognostic indicators of DFS/PFS while TLG (P=0.012) and CEA (P=0.045) were independent prognostic indicators of OS in the PD-L1-positive group. In the PD-L1-negative group, tumor stage (P=0.002) and CEA (P=0.006) were unique independent prognostic indicators of DFS/PFS and OS, respectively. Conclusion:18F-FDG PET/CT may potentially predict tumor PD-L1 expression and play a role in predicting prognosis of PD-L1/PD-1 immunotherapy in lung adenocarcinoma.
Project description:Body mass index (BMI) is well known to be associated with poor prognosis in several cancers. The relationship between BMI and the long-term outcomes of patients with intrahepatic cholangiocarcinoma (ICC) is incompletely understood. This study investigated the relationships of BMI with clinicopathological characteristics and patient outcomes, focusing on metabolic activity and immune status. The relationship between BMI and the maximum standardized uptake value (SUVmax) on fluorine-18 fluorodeoxyglucose (<sup>18</sup>F-FDG) positron emission tomography/computed tomography (PET/CT) was analyzed. In addition, immunohistochemistry was performed for programmed cell death-ligand 1 (PD-L1), cluster of differentiation 8 (CD8), and forkhead box protein P3 (Foxp3). Seventy-four patients with ICC were classified into normal weight (BMI?<?25.0 kg/m<sup>2</sup>, n?=?48) and obesity groups (BMI???25.0 kg/m<sup>2</sup>, n?=?26), respectively. Serum carbohydrate antigen 19-9 levels were higher in the obesity group than in the normal weight group. Tumor size and the intrahepatic metastasis rate were significantly larger in the obesity group. Patients in the obesity group had significantly worse prognoses than those in the normal weight group. Moreover, BMI displayed a positive correlation with SUVmax on <sup>18</sup>F-FDG PET/CT (n?=?46, r?=?0.5152). Patients with high <sup>18</sup>F-FDG uptake had a significantly higher rate of PD-L1 expression, lower CD8?+?tumor-infiltrating lymphocyte (TIL) counts, and higher Foxp3?+?TIL counts. The elevated BMI might predict the outcomes of patients with ICC. Obesity might be associated with ICC progression, possibly through alterations in metabolic activity and the immune status.
Project description:The relationship between the local immune status and cancer metabolism regarding 18 F-FDG and 18 F-FAMT uptake in esophageal squamous cell carcinoma (ESCC) remains unknown. The present study examined the correlations between tumor immune status, clinicopathological factors, and positron emission tomography (PET) tracer uptake in ESCC. Forty-one ESCC patients who underwent 18 F-FDG PET and 18 F-FAMT PET before surgery were enrolled in the study. Immunohistochemistry was conducted for programmed death 1 (PD-1), CD8, Ki-67, CD34, GLUT1 (18 F-FDG transporter) and LAT1 (18 F-FAMT transporter). ESCC specimens with high tumoral PD-L1 and high CD8-positive lymphocytes were considered to have "hot tumor immune status." High PD-L1 expression (53.7%) was significantly associated with tumor/lymphatic/venous invasion (P = 0.028, 0.032 and 0.018), stage (P = 0.041), CD8-positive lymphocytes (P < 0.001), GLUT1 (P < 0.001), LAT1 expression (P = 0.006), Ki-67 labelling index (P = 0.009) and CD34-positive vessel counts (P < 0.001). SUVmax of 18 F-FDG was significantly higher in high PD-L1 cases than in low PD-L1 cases (P = 0.009). SUVmax of 18 F-FAMT was significantly higher in high PD-L1 (P < 0.001), high CD8 (P = 0.012) and hot tumor groups (P = 0.028) than in other groups. High SUVmax of 18 F-FAMT (?4.15) was identified as the only predictor of hot tumor immune status. High PET tracer uptake was significantly associated with cancer aggressiveness and hot tumor immune status in ESCC. PET imaging may be an effective tool to predict tumor immune status in ESCC with respect to immune checkpoint inhibitor sensitivity.
Project description:<b>Objective:</b> The purpose of this study was to explore the value of <sup>18</sup>F-FDG PET/CT in monitoring the disease activity and predicting the prognosis of the Adult-onset Still's disease (AOSD). <b>Methods:</b> We retrospectively analyzed the electronic medical records of 45 AOSD patients who underwent <sup>18</sup>F-FDG PET/CT in the Second Xiangya Hospital. PET/CT imaging and clinical information were retrospectively reviewed and analyzed. <sup>18</sup>F-FDG uptake was assessed by measuring standard uptake value (SUV) in the spleen, liver, bone marrow, and lymph nodes. The spleen-to-liver ratio of the SUVmax (SLRmax) and SUVmean (SLRmean), the bone-to-liver ratio of the SUVmax (BLRmax), and SUVmean (BLRmean), and the lymph nodes-to-liver ratio of the SUVmax (LyLRmax) were calculated. Clinical and laboratory information were collected and evaluated for association with metabolic parameters of <sup>18</sup>F-FDG PET/CT. The influencing factors for recurrence within 1 year were analyzed to determine whether <sup>18</sup>F-FDG PET/CT can predict the prognosis of AOSD patients. <b>Results:</b> Elevated <sup>18</sup>F-FDG uptake could be observed in bone marrow, spleen, and lymph nodes of AOSD patients. Correlation analysis between <sup>18</sup>F-FDG uptake of organs and laboratory examinations showed that SLRmean positively correlated with LDH, AST, ferritin, and the systemic score (<i>r</i> = 0.572, 0.353, 0.586, and 0.424, <i>P</i> < 0.05). The SLRmean had the highest correlation with ferritin (<i>r</i> = 0586, <i>P</i> < 0.001). All metabolic parameters in spleen, including SUVmax, SUVmean, SLRmax, and SLRmean, are positively correlated with LDH level (<i>r</i> = 0.405, 0.539, 0.481, and 0.572, <i>P</i> < 0.05). Bone marrow SUVmax, BLRmax, and BLRmean were correlated with C-reactive protein (CRP) level (<i>r</i> = 0.395, 0.437, and 0.469, <i>P</i> < 0.05). Analysis of the influencing factors of recurrence within 1 year showed that the spleen SUVmax, spleen SUVmean, SLRmax, SLRmean, ferritin, and the systemic score of the recurrence group was significantly higher than the non-recurrence group (<i>P</i> < 0.05). The SLRmean cutoff of 1.66 with a sensitivity of 72.7% and specificity of 80.0% had the highest performance in predicting recurrence. <b>Conclusion:</b> The glucose metabolism of the liver, spleen, and bone marrow of AOSD patients were correlated with laboratory inflammatory indicators and system score, suggesting that <sup>18</sup>F-FDG PET/CT could be applied to evaluate disease activity. Moreover, spleen <sup>18</sup>F-FDG uptake may be a potential biomarker for predicting clinical prognosis of AOSD patients.
Project description:<h4>Purpose</h4>FAPI ligands (fibroblast activation protein inhibitor), a novel class of radiotracers for PET/CT imaging, demonstrated in previous studies rapid and high tumor uptake. The purpose of this study is the head-to-head intra-individual comparison of <sup>68</sup>Ga-FAPI versus standard-of-care <sup>18</sup>F-FDG in PET/CT in organ biodistribution and tumor uptake in patients with various cancers.<h4>Material and methods</h4>This international retrospective multicenter analysis included PET/CT data from 71 patients from 6 centers who underwent both <sup>68</sup>Ga-FAPI and <sup>18</sup>F-FDG PET/CT within a median time interval of 10 days (range 1-89 days). Volumes of interest (VOIs) were manually drawn in normal organs and tumor lesions to quantify tracer uptake by SUVmax and SUVmean. Furthermore, tumor-to-background ratios (TBR) were generated (SUVmax tumor/ SUVmax organ).<h4>Results</h4>A total of 71 patients were studied of, which 28 were female and 43 male (median age 60). In 41 of 71 patients, the primary tumor was present. Forty-three of 71 patients exhibited 162 metastatic lesions. <sup>68</sup>Ga-FAPI uptake in primary tumors and metastases was comparable to <sup>18</sup>F-FDG in most cases. The SUVmax was significantly lower for <sup>68</sup>Ga-FAPI than <sup>18</sup>F-FDG in background tissues such as the brain, oral mucosa, myocardium, blood pool, liver, pancreas, and colon. Thus, <sup>68</sup>Ga-FAPI TBRs were significantly higher than <sup>18</sup>F-FDG TBRs in some sites, including liver and bone metastases.<h4>Conclusion</h4>Quantitative tumor uptake is comparable between <sup>68</sup>Ga-FAPI and <sup>18</sup>F-FDG, but lower background uptake in most normal organs results in equal or higher TBRs for <sup>68</sup>Ga-FAPI. Thus, <sup>68</sup>Ga-FAPI PET/CT may yield improved diagnostic information in various cancers and especially in tumor locations with high physiological <sup>18</sup>F-FDG uptake.
Project description:<h4>Purpose</h4>Tumor microenvironment immune types (TMITs) are closely related to the efficacy of immunotherapy. We aimed to assess the predictive ability of <sup>18</sup>F-fluorodeoxyglucose positron emission tomography/computed tomography (<sup>18</sup>F-FDG PET/CT)-based radiomics of TMITs in treatment-naive patients with non-small cell lung cancer (NSCLC).<h4>Methods</h4>A retrospective analysis was performed in 103 patients with NSCLC who underwent <sup>18</sup>F-FDG PET/CT scans. The patients were randomly assigned into a training set (n = 71) and a validation set (n = 32). Tumor specimens were analyzed by immunohistochemistry for the expression of programmed death-ligand 1 (PD-L1), programmed death-1 (PD-1), and CD8+ tumor-infiltrating lymphocytes (TILs) and categorized into four TMITs according to their expression of PD-L1 and CD8+ TILs. LIFEx package was used to extract radiomic features. The optimal features were selected using the least absolute shrinkage and selection operator (LASSO) algorithm, and a radiomics signature score (rad-score) was developed. We constructed a combined model based on the clinical variables and radiomics signature and compared the predictive performance of models using receiver operating characteristic (ROC) curves.<h4>Results</h4>Four radiomic features (GLRLM_LRHGE, GLZLM_SZE, SUVmax, NGLDM_Contrast) were selected to build the rad-score. The rad-score showed a significant ability to discriminate between TMITs in both sets (<i>p</i> < 0.001, <i>p</i> < 0.019), with an area under the ROC curve (AUC) of 0.800 [95% CI (0.688-0.885)] in the training set and that of 0.794 [95% CI (0.615-0.916)] in the validation set, while the AUC values of clinical variables were 0.738 and 0.699, respectively. When clinical variables and radiomics signature were combined, the complex model showed better performance in predicting TMIT-I tumors, with the AUC values increased to 0.838 [95% CI (0.731-0.914)] in the training set and 0.811 [95% CI (0.634-0.927)] in the validation set.<h4>Conclusion</h4>The FDG-PET/CT-based radiomic features showed good performance in predicting TMIT-I tumors in NSCLC, providing a promising approach for the choice of immunotherapy in a clinical setting.
Project description:<h4>Background</h4>This study aimed to investigate the correlation between miRNA-216b expression in patients with non-small cell lung cancer (NSCLC) and <sup>18</sup>F-fluorodeoxyglucose (FDG) uptake by PET/CT and to explore the clinical application value of 18F-FDG PET/CT in miRNA-216b based on therapy for NSCLC.<h4>Methods</h4>Eighty patients with NSCLC and 40 healthy subjects were enrolled in our study. The SUVmax of the lesion area by PET/CT imaging was calculated. SUVmax represented the highest concentration of 18F-FDG in the lesion. The expression of miRNA-216b in the plasma and fiber bronchoscopic puncture of NSCLC patients was detected by RT qPCR. Then Pearson correlation analysis was used to analyze the correlation between miRNA-216b expression and 18F-FDG uptake in patients with different types of NSCLC.<h4>Results</h4>Compared with healthy subjects, SUVmax of early adenocarcinoma and advanced adenocarcinoma were increased. Compared with healthy subjects, SUVmax of early squamous and advanced squamous were increased. And the SUVmax content of advanced adenocarcinoma and squamous cell carcinoma was higher than that of early adenocarcinoma and squamous cell carcinoma. Compared with healthy subjects, the expression of miRNA-216b in the plasma of patients with early and advanced adenocarcinoma was reduced, and the expression of miRNA-216b in the plasma of patients with early and advanced squamous cell carcinoma was reduced. Compared with adjacent tissues, the expression of miRNA-216b in early adenocarcinoma tissues and advanced adenocarcinoma tissues was reduced, and the expression in early squamous cell carcinoma and advanced squamous cell carcinoma was reduced. Pearson correlation analysis showed a negative correlation between SUVmax and miRNA-216b (plasma and tissue) in patients with four types of NSCLC.<h4>Conclusion</h4>miRNA-216b expression was negatively correlated with <sup>18</sup>F-FDG uptake in NSCLC. miRNA-216b could be used for the classification and staging of non-small cell lung cancer. <sup>18</sup>F-FDG PET/CT may be used to evaluate the therapeutic response in application of miRNA-216b-based cancer treatment.
Project description:<h4>Purpose</h4><sup>68</sup>Ga-FAPI (fibroblast activation protein inhibitor) is a novel and highly promising radiotracer for PET/CT imaging. The aim of this retrospective analysis is to explore the potential of FAPI-PET/CT in gynecological malignancies. We assessed biodistribution, tumor uptake, and the influence of pre- or postmenopausal status on tracer accumulation in hormone-sensitive organs. Furthermore, a comparison with the current standard oncological tracer <sup>18</sup>F-FDG was performed in selected cases.<h4>Patients and methods</h4>A total of 31 patients (median age 59.5) from two centers with several gynecological tumors (breast cancer; ovarian cancer; cervical cancer; endometrial cancer; leiomyosarcoma of the uterus; tubal cancer) underwent <sup>68</sup>Ga-FAPI-PET/CT. Out of 31 patients, 10 received an additional <sup>18</sup>F-FDG scan within a median time interval of 12.5 days (range 1-76). Tracer uptake was quantified by standardized uptake values (SUV)max and (SUV)mean, and tumor-to-background ratio (TBR) was calculated (SUVmax tumor/ SUVmean organ). Moreover, a second cohort of 167 female patients with different malignancies was analyzed regarding their FAPI uptake in normal hormone-responsive organs: endometrium (n = 128), ovary (n = 64), and breast (n = 147). These patients were categorized by age as premenopausal (<35 years; n = 12), postmenopausal (>65 years; n = 68), and unknown menstrual status (35-65 years; n = 87), followed by an analysis of FAPI uptake of the pre- and postmenopausal group.<h4>Results</h4>In 8 out of 31 patients, the primary tumor was present, and all 31 patients showed lesions suspicious for metastasis (n = 81) demonstrating a high mean SUVmax in both the primary (SUVmax 11.6) and metastatic lesions (SUVmax 9.7). TBR was significantly higher in <sup>68</sup>Ga-FAPI compared to <sup>18</sup>F-FDG for distant metastases (13.0 vs. 5.7; p = 0.047) and by trend for regional lymph node metastases (31.9 vs 27.3; p = 0.6). Biodistribution of <sup>68</sup>Ga-FAPI-PET/CT presented significantly lower uptake or no significant differences in 15 out of 16 organs, compared to <sup>18</sup>F-FDG-PET/CT. The highest uptake of all primary lesions was obtained in endometrial carcinomas (mean SUVmax 18.4), followed by cervical carcinomas (mean SUVmax 15.22). In the second cohort, uptake in premenopausal patients differed significantly from postmenopausal patients in endometrium (11.7 vs 3.9; p < 0.0001) and breast (1.8 vs 1.0; p = 0.004), whereas no significant difference concerning ovaries (2.8 vs 1.6; p = 0.141) was observed.<h4>Conclusion</h4>Due to high tracer uptake resulting in sharp contrasts in primary and metastatic lesions and higher TBRs than <sup>18</sup>F-FDG-PET/CT, <sup>68</sup>Ga-FAPI-PET/CT presents a promising imaging method for staging and follow-up of gynecological tumors. The presence or absence of the menstrual cycle seems to correlate with FAPI accumulation in the normal endometrium and breast. This first investigation of FAP ligands in gynecological tumor entities supports clinical application and further research in this field.
Project description:<b>Objective:</b> To elucidate the <sup>18</sup>F-fluorodeoxyglucose (FDG) PET/CT characteristics and its prognostic value in the patients with anti-melanoma differentiation associated protein 5 antibody positive (anti-MDA5+) dermatomyositis (DM). <b>Methods:</b> This retrospective cross-sectional study included 26 patients with anti-MDA5+ DM and 43 patients with anti-MDA5 negative (anti-MDA5-) idiopathic inflammatory myopathy (IIM) who were examined by <sup>18</sup>F-FDG PET/CT from January 1, 2017 to December 31, 2020. The maximum standardized uptake value (SUVmax) of multiple organs and other clinical characteristics of the patients were measured and analyzed. <b>Results:</b> Compared with the anti-MDA5- group, the patients in the anti-MDA5+ group showed higher bilateral lung SUVmax (<i>p</i> = 0.029), higher SUVmax of spleen (<i>p</i> = 0.011), and bone marrow (<i>p</i> = 0.048). Significant correlations between the spleen SUVmax and serum ferritin levels (<i>r</i> = 0.398, <i>p</i> < 0.001), erythrocyte sedimentation rate (ESR) (<i>r</i> = 0.274, <i>p</i> = 0.023), platelet count (<i>r</i> = -0.265, <i>p</i>= 0.028), myositis disease activity assessment score (<i>r</i> = 0.332, <i>p</i> = 0.005), bone marrow SUVmax (<i>r</i> = 0.564, <i>p</i> < 0.001), and bilateral lung SUVmax (<i>r</i> = 0.393, <i>p</i> < 0.001) were observed. <b>Conclusion:</b> <sup>18</sup>F-FDG PET/CT was found valuable in quantifying the pulmonary focal inflammation and potentially unveil the distinctive characteristics and pathophysiological mechanisms in the patients with anti-MDA5+ DM.