SUVmax Group Research Articles

Negative-predictive value of SUVmax for Ascertaining the efficacy of osimertinib in EGFR mutation-positive non-small cell lung cancer

BackgroundFluorine-18 2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) is routinely used to stage non-small cell lung cancer (NSCLC). However, whether 18F-FDG accumulation in primary tumors affects the efficacy of osimertinib in patients with epidermal growth factor receptor (EGFR) mutation-positive NSCLC remains unclear. MethodsWe retrospectively investigated 74 patients with advanced or postoperative recurrent EGFR mutation-positive NSCLC who underwent 18F-FDG PET/CT and were treated with osimertinib as first-line therapy between September 2018 and March 2023 at Kumamoto University Hospital. The maximum standardized uptake value (SUVmax) of each primary tumor was measured, and the patients were divided into two groups according to the median SUVmax. The effects of SUVmax on progression-free survival (PFS) and overall survival (OS) were assessed using a multivariate Cox proportional hazards model. ResultsThe median SUVmax was 8.2 (interquartile range: 5.5–11.4). The median PFS in the high SUVmax group (≥8.2) was significantly shorter than that in the low SUVmax group (<8.2). The respective median PFSs were 11.2 months (95% confidence interval [CI]: 3.1–19.3 months) vs. 22.9 months (95% CI: 12.4–33.4 months) (P = 0.015), although the OS values did not differ significantly. Multivariate analysis showed that a high SUVmax was an independent negative predictive factor for PFS in patients treated with osimertinib (hazard ratio, 2.25; 95% CI: 1.15–4.39, P = 0.017). ConclusionsHigh primary-lesion SUVmax in patients with EGFR mutation-positive NSCLC correlated with shorter PFS with first-line osimertinib therapy, suggesting that SUVmax is a useful predictive marker for the antitumor efficacy of osimertinib.

Prognostic Significance of 18F-FDG PET/CT and Tumor Metabolic Changes in Patients With Pancreatic Ductal Adenocarcinoma.

18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is reportedly associated with the malignant potential of cancer. This study aimed to evaluate the association between FDG accumulation and tumor metabolism in pancreatic ductal adenocarcinoma (PDAC). A prognostic analysis of data from 131 patients with PDAC who underwent FDG-PET/CT before curative-intent pancreatic surgery was performed. Capillary electrophoresis-mass spectrometry (CE-MS) was used to analyze the metabolome of tumor and non-neoplastic pancreas from 80 patients. These patients were divided into two groups: low SUVmax group (SUVmax <6.09) and high SUVmax group (SUVmax ≥6.09). Carbohydrate antigen 19-9 (CA19-9), maximum standardized uptake value (SUVmax) of PET, N stage, and postoperative chemotherapy were identified as significant prognostic factors by univariate analysis. SUVmax emerged as an independent prognostic factor for overall survival [hazard ratio (HR)=1.88, p<0.05] and disease-free survival (HR=2.01, p<0.05) in multivariate analysis. Metabolic analyses confirmed that 43 metabolites significantly differed depending on the accumulation of SUV in tumors. Metabolites involved in the removal of reactive oxygen species (e.g., hypotaurine, glutathione, Met), treatment resistance (UDP-N-acetylglucosamine), and proliferation (e.g., choline, leucine, isoleucine) were increased in the high SUVmax group. FDG accumulation is an important independent prognostic factor reflecting tumor activity associated with metabolic changes in cancer cells.

Towards a fast PET/MRI protocol for breast cancer imaging: maintaining diagnostic confidence while reducing PET and MRI acquisition times

ObjectivesTo investigate the diagnostic feasibility of a shortened breast PET/MRI protocol in breast cancer patients.MethodsAltogether 90 women with newly diagnosed T1tumor-staged (T1ts) and T2tumor-staged (T2ts) breast cancer were included in this retrospective study. All underwent a dedicated comprehensive breast [18F]FDG-PET/MRI. List-mode PET data were retrospectively reconstructed with 20, 15, 10, and 5 min for each patient to simulate the effect of reduced PET acquisition times. The SUVmax/mean of all malign breast lesions was measured. Furthermore, breast PET data reconstructions were analyzed regarding image quality, lesion detectability, signal-to-noise ratio (SNR), and image noise (IN). The simultaneously acquired comprehensive MRI protocol was then shortened by retrospectively removing sequences from the protocol. Differences in malignant breast lesion detectability between the original and the fast breast MRI protocol were evaluated lesion-based. The 20-min PET reconstructions and the original MRI protocol served as reference.ResultsIn all PET reconstructions, 127 congruent breast lesions could be detected. Group comparison and T1ts vs. T2ts subgroup comparison revealed no significant difference of subjective image quality between 20, 15, 10, and 5 min acquisition times. SNR of qualitative image evaluation revealed no significant difference between different PET acquisition times. A slight but significant increase of IN with decreasing PET acquisition times could be detected. Lesion SUVmax group comparison between all PET acquisition times revealed no significant differences. Lesion-based evaluation revealed no significant difference in breast lesion detectability between original and fast breast MRI protocols.ConclusionsBreast [18F]FDG-PET/MRI protocols can be shortened from 20 to below 10 min without losing essential diagnostic information.Key Points• A highly accurate breast cancer evaluation is possible by the shortened breast [18F]FDG-PET/MRI examination protocol.• Significant time saving at breast [18F]FDG-PET/MRI protocol could increase patient satisfaction and patient throughput for breast cancer patients at PET/MRI.

Heterogeneity derived from 18 F-FDG PET/CT predicts immunotherapy outcome for metastatic triple-negative breast cancer patients.

BackgroundRecently, immunotherapy has been used to treat metastatic triple‐negative breast cancer (mTNBC). Basic research has indicated a relation between tumor heterogeneity and the immune response. Tumor heterogeneity derived from 18F‐FDG PET/CT is a potential predictor of chemotherapy results; however, few studies have focused on immunotherapy. This study aims to develop a convenient and efficient measurement of tumor heterogeneity for the prediction of immunotherapy in mTNBC patients.MethodsWe enrolled mTNBC patients who received immunotherapy (PD‐1/PD‐L1 antibody) plus chemotherapy as first‐line treatment and underwent 18F‐FDG PET/CT scans before treatment. We defined a novel index representing tumor heterogeneity calculated from the standard uptake value (SUV) as IATH and IETH. Optimal cutoffs were determined using time‐dependent receiver operator characteristics (ROC) analysis.ResultsA total of 32 patients were enrolled and analyzed in this trial. A significantly longer median PFS was observed in the low SUVmax group than in the high SUVmax group (9.4 vs. 5.8 months, HR = 0.3, 95% CI 0.1–0.9, p = 0.025). The median PFS of low‐IATH patients was significantly longer than that of high‐IATH patients (HR = 0.3, 95% CI 0.1–0.8, p = 0.022). Similarly, patients with low IETH had significantly longer PFS than patients with high IETH (9.4 vs. 4.9 months, HR = 0.3, 95% CI 0.1–0.7, p = 0.01). Multivariate analysis demonstrated IETH as an independent predictor of PFS.ConclusionsThis study proposed a novel method to assess intratumor and intertumor heterogeneity among metastatic breast cancer patients and determined that baseline IETH derived from 18F‐FDG PET/CT could represent a simple and promising predictor for first‐line immunotherapy among mTNBC patients.

Abstract P2-12-23: Changes in 18F-FDG-PET uptake after the first course of DTX reflect response to preoperative chemotherapy and prognosis in breast cancer

Abstract [Purpose] It is important to make early decisions about treatment changes in treatment-resistant groups. The aim of this study is to extract non-responders among preoperative chemotherapy using 18F-fluorodeoxyglucose positron-emission tomography (18F-FDG PET) in primary breast cancer. We hypothesized that early evaluation of FDG PET after the first course of docetaxel (DTX) would predict treatment resistant group by the relationship between changes on FDG accumulation and tumor diameter on magnetic resonance imaging (MRI). [Patients and Methods] Thirty-seven of 41 patients were evaluated. Clinical stage was T1-4, N0-3, and M0 between August 2007 and December 2010. Four courses of DTX were administered followed by 4 courses of fluorouracil/epirubicin/cyclophosphamide (FEC) followed by surgery. FDG-PET evaluation was performed by the maximum standardized uptake value (SUVmax). FDG-PET scans were performed at baseline, at 15 days after the first course of DTX (C1D15), and at 15 days after 4 courses of DTX (C4D15). Tumor reduction rate was measured on MRI at baseline and at C4D15 according to Response Evaluation Criteria in Solid Tumors (RECIST). ROC analysis was performed by between SUVmax of C1D15 and MRI of C4D15. Changes of SUVmax C1D15 were divided into high and low group by ROC analysis. Core needle biopsy (CNB) was performed to evaluate the treatment effect pathologically after 4 courses of DTX (C4CNB). The pathological treatment effect of surgical specimens after 4 courses of FEC (C4FEC) was also examined. The difference in progression-free survival (PFS) rate or overall survival (OS) rate between the low and high SUVmax of C1D15 change rate was calculated using Kaplan-Meier survival curves and compared by log-rank test. The protocol of the study was approved by the Ethics Committee of the Gunma Prefectural Cancer Center (ECGPCC), and all patients gave their written informed consent before enrollment (No. 19011). The observational study was also approved by ECGPCC (No. 30087). [Results] There were ER+HER2-:17, ER+HER2+:4, ER-HER2-:11, and ER-HER2+:5 cases. SUVmax change rate C1D15 correlated with the SUVmax change rate C4D15 and tumor shrinkage rate on MRI C4D15 in univariate (SUVmax C4D15: γ=.567, p&amp;lt;.001, MRI C4D15: γ=.748, p&amp;lt;.001) and in multivariate analysis (SUVmax C4D15: γ=414, p=.002, MRI C4D15: γ=.616, p&amp;lt;.001). The SUVmax change rate C1D15 correlated with pathological effect of C4CNB (γ=.392, p=.032) and of surgical specimen C4FEC (γ=.440, p=.006) in univariate analysis. From ROC analysis based on SUVmax C1D15 and MRI C4D15 (AUC=.924, 95% CI: .828-1.000, p&amp;lt;.001), the SUVmax C1D15 were divided into two groups with high and low SUVmax changes. The mean SUVmax in the low group (&amp;lt;30%) (n=15) was 15.8% (±9.7). The mean SUVmax in the high group (≥30%) (n=22) was 50.8% (±11.7). The mean of MRI change rate of C4D15 was 20.4% (±5.4) in the low SUVmax change group and 69.2% (±5.8) in the high SUVmax change group, showing a significant difference between the two groups (p&amp;lt;.001). The low SUVmax change group showed shorter PFS than the high SUVmax group (median 80.9 vs 93.7 months, p=.050), but there was no difference in OS (p=.719). [Conclusion] Changes less than 30% of 18F-FDG uptake after the first course of DTX may reflect the treatment resistance and poor prognosis in primary breast cancer. Citation Format: Tomoko Hirakata, Yasuhiro Yanagita, Tomomi Fujisawa, Teruhiko Kinoshita, Hiroyuki Horikoshi, Nariyuki Oya, Tsukasa Akiyoshi, Misa Iijima, Takeshi Miyamoto, Keiko Yanai, Hiroshi Matsumoto, Kenichi Inoue, Rie Horii, Takaaki Fujii, Ken Shirabe. Changes in 18F-FDG-PET uptake after the first course of DTX reflect response to preoperative chemotherapy and prognosis in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-23.

Preoperative Body Composition Combined with Tumor Metabolism Analysis by PET/CT Is Associated with Disease-Free Survival in Patients with NSCLC.

Objective To evaluate the relationship between preoperative primary tumor metabolism and body composition in patients with NSCLC and analyze their effects on DFS. Method A retrospective study was conducted on 154 patients with NSCLC. All patients were scanned by baseline 18F-FDG PET/CT. SUVmax (maximum standard uptake value) of primary tumor, liver SUVmean (mean standard uptake value), and spleen SUVmean were measured by AW workstation. The skeletal muscle area (SMA), skeletal muscle mass index (SMI), skeletal muscle radiation density (SMD), visceral fat area (VFA), visceral adipose tissue index (VATI), and skeletal muscle visceral fat ratio (SVR) were measured by ImageJ software. Kaplan–Meier survival analysis was used to evaluate the impact of the above parameters on DFS. Results Compared with the low SUVmax group of primary tumors, the mean values of SMA, VFA, and VATI in the high SUVmax group were significantly higher. In addition, there were obvious differences in histopathological type, pathological differentiation, AJCC stage, and T stage between the two groups. Univariate analysis of DFS showed that VFA, VATI, pathological differentiation, tumor SUVmax, AJCC stage, tumor T stage, and N stage all affected the DFS of patients except for the parameters reflecting skeletal muscle content. Multivariate regression analysis showed that only VFA and SUVmax were associated with DFS. Kaplan–Meier survival analysis showed that high SUVmax, low VFA, high T stage, and high N stage were related to the decrease of DFS. Conclusion：Preoperative 18F-FDG PET/CT could comprehensively evaluate the primary tumor SUVmax, skeletal muscle, and visceral fat in patients with NSCLC. The combination of primary tumor SUVmax and visceral fat area can well evaluate the prognosis of patients with NSCLC.

Clinical Significance of 18F-fluorodeoxyglucose and Glucose Transporter 1 mRNA in Clear Cell Renal Cell Carcinoma.

18F-fluorodeoxyglucose (FDG) uptake measurement on positron emission tomography/computed tomography (PET/CT) is difficult in renal tumors because of the nearby renal parenchyma and urinary tract, which excrete FDG. We carefully examined the maximum standardized uptake value (SUVmax) on FDG-PET/CT and investigated the relationship between major glucose transporters in the kidney and clear cell renal cell carcinoma (ccRCC) progression. Forty-five patients with ccRCC underwent FDG-PET/CT for staging and nephrectomy. Glucose transporter mRNA expression was examined in the removed kidney. SUVmax was increased in high-stage and high-grade tumors. Glucose transporter 1 (GLUT1) mRNA expression was higher in tumor tissues, in contrast to other glucose transporters. SUVmax was not correlated with GLUT1 mRNA expression. Kaplan-Meier analysis showed reduced overall and recurrence-free survival in the high SUVmax group. Primary ccRCC lesions show a high SUVmax and GLUT1 mRNA over-expression. SUVmax increases with tumor upstaging and upgrading.

Variation of Tumor Volume During Moderate Hypo-Fractionated Stereotactic Body Radiation Therapy for Lung Cancer.

AimTo investigate the variation of tumor volume during moderate hypo-fractionated stereotactic body radiation therapy (SBRT).Patients and MethodsTwenty patients, who received SBRT at our institution, were included in the analysis. A prescribed dose was 56 Gy at iso-center in seven fractions. Tumor volumes before and during SBRT were calculated. In order to investigate factors affecting the variation of tumor volume in RT 2 (after first irradiation) and RT 7 (after last irradiation), various parameters were verified by the Mann-Whitney U test.ResultsWith regard to the low maximum standardized uptake values (SUVmax) group, transient increase of tumor volume was found in RT 2, and tumor volume reduction was hardly found in RT 7. With regard to the high SUVmax group, a transient increase was not found, and a definite reduction was found in the treatment course.ConclusionAccurate prediction of tumor volume variation is required for more accurate treatment, such as adaptive radiation therapy.

Support Vector Machine Parameter Optimization for Positron Emission Tomography Images for Estimation of Recurrent Laryngeal Nerve Injury with Thyroid Nodules

This study aimed to explore positron emission tomography-computed tomography (PET-CT) images based on support vector machine (SVM) algorithm for the classification of thyroid nodules (TN) and its evaluation value in postoperative injury rate (PPIR) of recurrent laryngeal nerve (RLN). The parameters of the SVM algorithm were optimized using the particle swarm optimization (PSO) algorithm. A total of 58 patients who were diagnosed with TN by PET/CT at a hospital were divided into a group with benign nodules (group B, 25 cases) and a group with malignant nodules (group M, 33 cases). The characteristics of the PET-CT images and difference in the max standardized uptake value (SUVmax) of PET-CT were analyzed. The PPIR of RLN was calculated. It was found that when the number of iterations was 19, the fitness and the classification accuracy of the SVM algorithm was 98.3% and 91.1%, respectively. When SUVmax = 4.56, its sensitivity and specificity were 81.33% and 76.18%, respectively. The SUVmax of group B was much lower ( P &lt; 0.01 ). It indicated that the established method could realize higher classification accuracy on TN and was of great significance in the evaluation of the PPIR of RLN.

Implications of Standardized Uptake Values of Oral Squamous Cell Carcinoma in PET-CT on Prognosis, Tumor Characteristics and Mitochondrial DNA Heteroplasmy.

Simple SummaryIn this study, we evaluated the prognostic value of the positron emission tomography–computed tomography (PET-CT) imaging technique in patients with newly diagnosed oral squamous cell carcinomas. PET-CT is routinely used to detect and quantify metabolically active tissues such as tumors. By using receiver operating characteristic (ROC) analysis, we successfully determined an optimal cut-off value for patient stratification in order to predict clinical outcome in this population. Furthermore, other clinical variables and their impact on clinical outcome as well as PET-CT values were evaluated. We show that, based on the determined optimal cut-off value, PET-CT is a reliable and independent predictor for clinical outcome, even in a fully adjusted model. Finally, we analyzed mitochondrial DNA to evaluate if potentially deleterious mutations might be a potential cause of metabolic changes, leading to differences in PET-CT values and consequently, clinical outcome.Under aerobic conditions, some cancers switch to glycolysis to cover their energy requirements. Taking advantage of this process, functional imaging techniques such as PET-CT can be used to detect and assess tumorous tissues. The aim of this study was to investigate standardized uptake values and mitochondrial DNA mutations in oral squamous cell carcinoma. A cohort of 57 patients underwent 18[F]FDG-PET-CT and standardized uptake values were collected. In 15 patients, data on mitochondrial DNA mutations of the tumor were available. Kaplan–Meier curves were calculated, and correlation analyses as well as univariate Cox proportional hazard models were performed. Using ROC analysis to determine a statistical threshold for SUVmax in PET investigations, a cut-off value was determined at 9.765 MB/mL. Survival analysis for SUVmax in these groups showed a Hazard Ratio of 4 (95% CI 1.7–9) in the high SUVmax group with 5-year survival rates of 23.5% (p = 0.00042). For SUVmax and clinicopathological tumor features, significant correlations were found. A tendency towards higher mtDNA heteroplasmy levels in high SUVmax groups could be observed. We were able to confirm the prognostic value of SUVmax in OSCC, showing higher survival rates at lower SUVmax levels. Correlations between SUVmax and distinct tumor characteristics were highly significant, providing evidence that SUVmax may act as a reliable diagnostic parameter. Correlation analysis of mtDNA mutations suggests an influence on metabolic activity in OSCC.

Assessment of the prognostic value of interim fluorodeoxyglucose positron emission tomography/computed tomography in nasal-type extranodal natural killer/T-cell lymphoma.

The prognostic value of interim positron emission tomography/computed tomography (PET/CT) for nasal-type extranodal natural killer/T-cell lymphoma (ENKTL) is controversial. We evaluated the prognostic value of interim PET/CT in ENKTL patients to facilitate risk stratification and guide clinical treatment. Patients with ENKTL who received first-line chemotherapy based on L-asparaginase/pegaspargase with/without involved-field radiotherapy were recruited for this study. Pretreatment and interim PET/CT evaluations were performed. Interim PET/CT was evaluated via the maximum standardized uptake value (SUVmax) and the Deauville 5-point scale (DS); and the capacity to predict progression-free survival (PFS) and overall survival (OS) was evaluated. Receiver operating characteristic (ROC) curves were used to determine the optimal SUVmax cutoff. Fisher's exact test was used to analyze relationships between interim PET/CT results and clinical characteristics. Univariate and multivariate analyses were performed to examine the independent effects of interim PET/CT. The Cochran-Mantel-Haenszel test was used to assess the prognostic value of interim PET/CT at different timepoints. Overall, 129 ENKTL patients were enrolled. The optimal interim PET/CT SUVmax cut-off was 4.95. The median follow-up was 34 [2-90] months, in the low SUVmax group (≤4.95), the 2-year PFS and OS rates were 76.3% and 88.0%, respectively; in the high SUVmax group (>4.95), the PFS and OS rates were 15.6% and 44.5%, respectively. Likewise, for the DS 1-3 group, the PFS and OS rates were 78.9% and 91.2%, respectively; and in the DS 4 or 5 group, the rates of PFS and OS were 49.7% and 69.0%, respectively. In univariate analysis, interim PET/CT evaluation based on SUVmax and DS scores were both PFS and OS predictors. In multivariate analysis, SUVmax was independently significantly associated with PFS (P<0.001) and OS (P=0.002), and DS was independently significantly associated with PFS (P=0.004) but not OS (P=0.204). In the Cochran-Mantel-Haenszel testing, the SUVmax and DS were significantly associated with PFS and OS after adjustments for the interim PET/CT timing. Interim PET/CT was of prognostic value concerning ENKTL. The SUVmax is an independent prognostic indicator of PFS and OS, while the DS is an independent prognostic indicator of PFS but not OS. The SUVmax is of greater prognostic value than DS.

Physiological FDG uptake in growth plate on pediatric PET.

18F-Fluorodeoxyglucose (FDG) uptake in children is different from that in adults. Physiological accumulation is known to occur in growth plates, but the pattern of distribution has not been fully investigated. Our aim was to evaluate the metabolic activity of growth plates according to age and location. We retrospectively evaluated 89 PET/CT scans in 63 pediatric patients (male : female=25 : 38, range, 0-18 years). Patients were classified into four age groups (Group A: 0-2 years, Group B: 3-9 years, Group C: 10-14 years and Group D: 15-18 years). The maximum standardized uptake value (SUVmax) of the proximal and distal growth plates of the humerus, the forearm bones and the femur were measured. The SUVmax of each site and each age group were compared and statistically analyzed. We also examined the correlations between age and SUVmax. As for the comparison of SUVmax in each location, the SUVmax was significantly higher in the distal femur than those in the other sites (p< 0.01). SUVmax in the distal humerus and the proximal forearm bones were significantly lower than those in the other sites (p< 0.01). In the distal femur, there was large variation in SUVmax, while in the distal humerus and the proximal forearm bones, there was small variation. As for the comparison of SUVmax in each age group, the SUVmax in group D tended to be lower than those in the other groups, but in the distal femur, there was no significant difference among each age group. Our data indicate that FDG uptake in growth plates varies depending on the site and age with remarkable uptake especially in the distal femur.

Physiologic colonic uptake of 18F-FDG on PET/CT is associated with clinical response and gut microbiome composition in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICI) represent the backbone treatment for advanced non-small cell lung cancer (NSCLC). Emerging data suggest that increased gut microbiome diversity is associated with favorable response to ICI and that antibiotic-induced dysbiosis is associated with deleterious outcomes. 18F-FDG physiologic colonic uptake on PET/CT increases following treatment with antibiotics (ATB) and could act as a surrogate marker for microbiome composition and predict prognosis. The aim of this study was to determine if 18F-FDG physiologic colonic uptake prior to ICI initiation correlates with gut microbiome profiling and clinical outcomes in patients with advanced NSCLC. Seventy-one patients with advanced NSCLC who underwent a PET/CT prior to ICI were identified. Blinded colonic contouring was performed for each colon segment and patients were stratified according to the median of the average colon SUVmax as well as for each segment in low vs. high SUVmax groups. Response rate, progression-free survival (PFS), and overall survival (OS) were compared in the low vs. high SUVmax groups. Gut microbiome composition was analyzed for 23 patients using metagenomics sequencing. The high colon SUVmax group had a higher proportion of non-responders (p = 0.033) and significantly shorter PFS (4.1 vs. 11.3months, HR 1.94, 95% CI 1.11-3.41, p = 0.005). High caecum SUVmax correlated with numerically shorter OS (10.8 vs. 27.6months, HR 1.85, 95% CI 0.97-3.53, p = 0.058). Metagenomics sequencing revealed distinctive microbiome populations in each group. Patients with low caecum SUVmax had higher microbiome diversity (p = 0.046) and were enriched with Bifidobacteriaceae, Lachnospiraceae, and Bacteroidaceae. Lower colon physiologic 18F-FDG uptake on PET/CT prior to ICI initiation was associated with better clinical outcomes and higher gut microbiome diversity in patients with advanced NSCLC. Here, we propose that 18F-FDG physiologic colonic uptake on PET/CT could serve as a potential novel marker of gut microbiome composition and may predict clinical outcomes in this population.

Comparing prognostic factors of Glut-1 expression and maximum standardized uptake value by FDG-PET in patients with resectable pancreatic cancer

BackgroundThis study aimed to assess the prognostic values of preoperative maximum standardized uptake value (SUVmax) of primary pancreatic tumors and Glut-1 expression in patients with resectable pancreatic ductal adenocarcinoma (R-PDAC), and to investigate whether Glut-1 expression is more effective than SUVmax in predicting survival in patients with R-PDAC. MethodsWe investigated 101 R-PDAC patients who underwent pancreatectomy for pancreatic cancer treatment. SUVmax analyzed through 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT), and Glut-1 expression, were assessed for predicting the prognosis of patients with R-PDAC. ResultsIn patients with R-PDAC, the high SUVmax group (≥4.25) had significantly shorter overall survival (OS) and disease-free survival (DFS) than the low SUVmax group (＜4.25). Surprisingly, Glut-1 expression was not significantly correlated with SUVmax. Moreover, the high Glut-1 expression group, which was related to higher levels of CA 19–9, had significantly shorter OS and DFS than the low Glut-1 expression group. Furthermore, among the high SUVmax group, OS and DFS were significantly shorter in the high Glut-1 expression group. Multivariate analyses revealed that Glut-1 overexpression was an independent prognostic factor in patients with R-PDAC. Glut-1 knockdown also induced cell cycle arrest in PDAC cells in vitro. ConclusionsThe study determined that Glut-1 overexpression is a more powerful prognostic factor than SUVmax for predicting OS and higher risk of recurrence in R-PDAC patients. Glut-1 overexpression is also more likely to be associated with malignant activity in PDAC patients.

18F-FDG PET-CT在评估局部晚期非小细胞肺癌预后中的应用

Objective To explore the value of 18F-FDG PET-CT in evaluating the prognosis of locally advanced non-small cell lung cancer (NSCLC) patients. Methods The clinical characteristics and 18F-FDG PET-CT parameters of 138 locally advanced NSCLC patients from 2013 to 2016 in Suzhou Municipal Hospital and People′s Hospital of Suzhou New District were analyzed retrospectively. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured. Area under the curve (AUC) of SUVmax, MTV and TLG were calculated to determine optimal cut-off value for patients grouping, with receiver-operating characteristic curve (ROC) analysis. Progression-free survival (PFS) and overall survival (OS) were assessed by Kaplan-Meier method and the survival difference between the two groups was estimated by log-rank test. Multivariate survival analysis was performed by Cox proportional hazard model. Results According to ROC analysis, SUVmax (AUC=0.716, cut-off value was 11.8, P<0.001) had a better predictive value for OS, whereas the predictive values of MTV (AUC=0.580, P=0.101) and TLG (AUC=0.635, P=0.005) were less. There was no significant correlation between SUVmax and patients′ age (χ2=1.222, P=0.269), gender (χ2=0.029, P=0.865), TNM stage (χ2=0.073, P=0.787), pathologic subtype (χ2=0.541, P=0.462), smoking (χ2=0.266, P=0.606), differentiation (χ2=0.285, P=0.593) or tumor location (χ2=0.509, P=0.476). The 1-year, 2-year and 3-year OS rates of low SUVmax group (n=59) were 93.2%, 67.0% and 15.6% respectively, and those of high SUVmax group (n=79) were 77.2%, 25.0% and 5.62% respectively. The OS rate of low SUVmax group was higher than that of high SUVmax group (χ2=19.153, P<0.001). The 1-year and 2-year PFS rates of low SUVmax group were 79.3% and 56.9% respectively, and those of high SUVmax group were 46.2%, 13.0% respectively. The PFS rate of low SUVmax group was higher than that of high SUVmax group (χ2=25.945, P<0.001). Single factor analysis showed that differentiation (HR=1.839, 95%CI: 1.161-2.913, P=0.017), SUVmax (HR=0.357, 95%CI: 0.231-0.550, P<0.001), MTV (HR=0.470, 95%CI: 0.270-0.819, P=0.001) and TLG (HR= 0.508, 95%CI: 0.327-0.789, P=0.002) were independent influencing factors of OS. The degree of differentiation (HR=1.909, 95%CI: 1.167-3.123, P=0.018) and SUVmax (HR=0.250, 95%CI: 0.160-0.410, P<0.001) were the independent influencing factors of PFS. Multivariate analysis showed that only SUVmax was an independent influencing factor of OS (HR=2.189, 95%CI: 1.222-3.189, P=0.008)and PFS (HR=4.412, 95%CI: 2.318-8.398, P<0.001). Conclusion PET-CT SUVmax of primary tumor is significantly correlated with OS and PFS of patients. It has important guiding value for prognosis judgment and treatment plan selection of patients with locally advanced NSCLC. Key words: Carcinoma, non-small-cell lung; 18F-FDG PET-CT; Prognosis

Reappraisal of Prognostic Impact of Tumor SUVmax by 18F-FDG-PET/CT in Intrahepatic Cholangiocarcinoma.

We previously reported that tumor standardized uptake value (SUVmax) by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) was a potential predictor in patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC). However, the prognostic value of SUVmax in the era of multidisciplinary strategy has remained unclear. The aim of this study was to reappraise the prognostic value of tumor SUVmax in patients undergoing surgery for ICC. Data from 82 consecutive ICC patients, who underwent 18F-FDG-PET/CT and subsequent surgery between 2006 and 2017, were retrieved from a prospectively maintained institutional database. Adjuvant strategy was administrated during this study period in our center. Tumor SUVmax was associated with tumor size (p = 0.002) and tumor number (p = 0.005), but not associated with T and N stage classified by American Joint Committee on Cancer-classification system, and other tumor factors. According to the tumor SUVmax cut-off values of 8.0 based on the minimum p value approach, actuarial 5-year overall survival (OS) rates in patients undergoing upfront surgery for ICC were significantly stratified at 54.7% versus 26.0% (low vs. high tumor SUVmax group, p = 0.008). The actuarial 3-year disease-free survival (DFS) rates were also significantly stratified at 41.0% versus 18.3% (p < 0.001). Multivariate Cox regression analyses revealed that tumor SUVmax retained its significance on OS (p = 0.039) as well as DFS (p < 0.001). Even in the era of multidisciplinary strategy, high tumor SUVmax still represents poor prognosis in patients undergoing surgery for ICC. These patients, therefore, would probably be required more effective strategies.

Significance of 18F-Fluorodeoxyglucose (FDG) Uptake in Response to Chemoradiotherapy for Pancreatic Cancer.

A metabolic shift to glycolysis is reportedly involved in radioresistance. We examined whether pretreatment 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), which can detect enhanced glucose uptake, was able to predict the therapeutic response to chemoradiotherapy (CRT) in patients with pancreatic cancer (PC). Of 125 PC patients (75 unresectable and 50 borderline resectable), 37 and 26 underwent induction chemotherapy before CRT and surgical resection after CRT, respectively. FDG-PET was performed at three different institutions. Of the 88 patients who underwent upfront CRT, 31 (35%), 34 (39%), and 23 (26%) showed a partial response (PR), stable disease, and progressive disease, respectively. The tumor PR rate was an independent factor associated with longer overall survival (OS) on multivariate analysis. We evaluated the optimal cut-off of maximum standardized uptake values (SUVmax) at initial diagnosis to detect the tumor PR rate at the three institutions separately. The SUVmax was independently associated with tumor response rate on multivariate analysis. In the low SUVmax group, induction chemotherapy had no significant impact on OS. In contrast, induction chemotherapy was significantly associated with longer OS in the high SUVmax group. FDG-PET SUVmax was significantly associated with the therapeutic response to CRT in PC patients. Moreover, induction chemotherapy may improve the prognosis of patients with a high SUVmax tumor.

Use of 18F-FDG-PET/CT for Retroperitoneal/Intra-Abdominal Soft Tissue Sarcomas.

Rationale To assess the diagnostic value of 18F-FDG-PET/CT for different retroperitoneal soft tissue sarcomas (STS) and other similar tumors. To analyze the predictive value of 18F-FDG-PET/CT for histological grade and main prognostic factors. Methods 195 patients with 44 different diseases have been included. Relationship between SUVmax, Clinical, pathological, and prognostic information has been analyzed. Results Malignant tumors do not show higher SUVmax than benign ones (P=0.443). We divided all 44 different diseases into two groups; SUVmax of group 1 is significantly higher than group 2 (P ≤ 0.001). The ROC curve suggests 4.35 is the cutoff value to distinguish groups 1 and 2 (sensitivity = 0.789; specificity = 0.736). SUVmax correlates with Ki-67 index, mitotic count, vascular resection, histological grade, and recurrent STS without considering pathological diagnosis (P=0.001, P=0.012, P=0.002, P ≤ 0.001, and P=0.037, resp.). Conclusion 18F-FDG-PET/CT cannot simply distinguish malignant and benign tumors in retroperitoneal/intra-abdominal cavity; however, the SUVmax of malignant tumors, inflammatory pseudotumor, and PPGL group is higher than the SUVmax of benign tumors, lymph node metastasis, hematoma, and low malignant STS group. Guidance of “SUVmax location” may be helpful for biopsy and pathology dissection.

Evaluation of radiosensitivity enhancement by irisquinone with 18F-FETNIM microPET/CT imaging in breast cancer bearing nude mice

Objective To investigate the effect of irisquinone (IR) on the radiosensitization of MDA-MB-231 breast cancer in nude mice using 18F-fluoroerythronitroimidazole (18F-FETNIM) microPET/CT. Methods Thirty-two nude mice bearing MDA-MB-231 breast cancer were divided into 4 groups by random number table method (n=8 for each group): group A was treated with radiotherapy alone, group B was treated with radiotherapy and IR, group C was treated with IR alone, and group D was fed with distilled water. 18F-FETNIM microPET/CT images were obtained to monitor the maximum standardized uptake value (SUVmax) of tumor before radiotherapy and 24 h after radiotherapy. The mice were sacrificed and tumor tissues were removed for HE staining. The expression of hypoxia inducible factor-1α (HIF-1α) was detected by immunohistochemical (IHC) method. Data were analyzed by paired t test, one-way analysis of variance, the least significant different t test and Pearson correlation analysis. Results There was no significant difference in SUVmax among the 4 groups before radiotherapy (1.429±0.090, 1.430±0.076, 1.445±0.071, 1.432±0.074; F=0.072, P>0.05). At 24 h after radiotherapy, the SUVmax of group A and B decreased significantly (1.075±0.098, 0.890±0.076; t values: 12.888, 33.217, both P<0.05), and there was significant difference between group B and group A (t=4.197, P<0.05). However, the SUVmax of group C and D increased significantly (1.617±0.090, 1.644±0.063; t values: -11.009, -16.061, both P<0.05). Pathological results showed that tumor cells in group A and B were reduced. IHC results showed that the expression of HIF-1α was lower in group B than others ((26.75±7.19)%; F=46.745, t values: 2.898-9.743, all P<0.05). The expression of HIF-1α was positively correlated with SUVmax (r=0.89, P<0.05). Conclusion 18F-FETNIM microPET/CT could evaluate the radiosensitization effect of IR on MDA-MB-231 breast cancer in nude mice. Key words: Breast neoplasms; Radiation-sensitizing agents; Radiotherapy; Positron-emission tomography; Tomography, X-ray computed; Nitroimidazoles

Abstract P5-02-01: Predictive value of TILs in evaluation of 18F-FDG-PET in breast cancer

Abstract Background: Several recent clinical studies have evaluated the prognostic and predictive importance of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC). 18F-Fluorodeoxyglucose positron-emission (FDG-PET) CT was found to be effective for monitoring cancer cell viability of tissues and tumors, and it is used to evaluate the glucose metabolic rates of such tissues because most neoplasms have high glycolytic rates. FDG-uptake is also influenced by many factors, including inflammatory cells. In the present study, we investigated the relationship in evaluation of FDG-PET and degrees of TILs. Patients and Methods: Invasive carcinoma tissues of 100 breast cancer patients were examined. All patients underwent surgery. None of the patients had received preoperative chemotherapy. The proportional grades of stromal (Str)-TILs in surgical specimens were determined as follows: low (0-10%), intermediate (20-40%) and high (50-90%) grade, using the criteria of the International Working Group for TILs 2014 in breast cancer, using an immunohistochemical (IHC) method. The evaluation of PET was determined as follows, using standardized uptake value max (SUV max): low (&amp;lt;5) and high (&amp;gt;5). Estrogen receptor (ER), progesterone receptor (PgR), HER2, Ki67, and nuclear glade were also measured by IHC. Results: Among the 100 patients, range of age was 36 to 86 (mean 58) years. Twenty-seven patients were pre-menopausal, seventy-one were postmenopausal, and two were unknown. Invasive ductal carcinoma was diagnosed in 97 (97%) of the patients, invasive lobular carcinoma was diagnosed in 2 (2%), and others was 1 (1%).We divided the cases into three groups based on the degrees of TILs, low (57%), Intermediate (33%) and high (10%). We divided the cases into three based on the degrees SUV max, low (78%) and high (22%). High TILs group significantly showed higher SUV max than that of lower SUV max group (P=0.009). High TILs group had statistically higher rates of ER negative (P=0.001), PgR negative (P=0.002), HER2 positive (P=0.007), and nuclear grade 3 (P=0.013) than those of low TILs group. Conclusion: The proportional grades of stromal (Str)-TILs were associated with the degrees of SUV max in primary breast tumor in FDG-PET. High FDG uptake is predictive of poor prognosis and aggressive features in patients with breast cancer. From our findings, the evaluation of TILs is to be useful for predicting a better prognosis or therapeutic effect in cases with high FDG-uptake which indicate higher risk of recurrent disease. Citation Format: Hirakata T, Takaaki F, Kurozumi S, Katayama C, Yajima R, Obayashi S, Nakazawa Y, Tokuda N, Yanai K, Honda C, Kuwano H. Predictive value of TILs in evaluation of 18F-FDG-PET in breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-02-01.