Correlation Study of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Pathological Subtypes of Invasive Lung Adenocarcinoma and Prognosis.
ABSTRACT: Purpose: To investigate the correlation between 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) metabolic parameters and clinicopathological factors in pathological subtypes of invasive lung adenocarcinoma and prognosis. Patients and Methods: Metabolic parameters and clinicopathological factors from 176 consecutive patients with invasive lung adenocarcinoma between August 2008 and August 2016 who underwent 18F-FDG PET/CT examination were retrospectively analyzed. Invasive lung adenocarcinoma was divided into five pathological subtypes:lepidic predominant adenocarcinoma (LPA), acinar predominant adenocarcinoma (APA), papillary predominant adenocarcinoma (PPA), solid predominant adenocarcinoma (SPA), and micropapillary predominant adenocarcinoma (MPA). The differences in metabolic parameters [maximal standard uptake value (SUVmax), mean standard uptake value (SUVmean), total lesion glycolysis (TLG), and metabolic tumor volume (MTV)] and tumor diameter for different pathological subtypes were analyzed. Patients were divided into two groups according to their prognosis: good prognosis group (LPA, APA, PPA) and poor prognosis group (SPA, MPA). Logistic regression was used to filter predictors and construct a predictive model, and areas under the receiver operating curve (AUC) were calculated. Cox regression analysis was performed on prognostic factors. Results: 82 (46.6%) females and 94 (53.4%) males of patients with invasive lung adenocarcinoma were enrolled in this study. Metabolic parameters and tumor diameter of different pathological subtype had statistically significant (P < 0.05). The predictive model constructed using independent predictors (Distant metastasis, Ki-67, and SUVmax) had good classification performance for both groups. The AUC for SUVmax was 0.694 and combined with clinicopathological factors were 0.745. Cox regression analysis revealed that Stage, TTF-1, MTV, and pathological subtype were independent risk factors for patient prognosis. The hazard ratio (HR) of the poor prognosis group was 1.948 (95% CI 1.042-3.641) times the good prognosis group. The mean survival times of good and poor prognosis group were 50.2621 (95% CI 47.818-52.706) and 35.8214 (95% CI 27.483-44.159) months, respectively, while the median survival time was 47.00 (95% CI 45.000-50.000) and 31.50 (95% CI 23.000-49.000) months, respectively. Conclusion: PET/CT metabolic parameters combined with clinicopathological factors had good classification performance for the different pathological subtypes, which may provide a reference for treatment strategies and prognosis evaluation of patients.
Project description:BACKGROUND:To evaluate the clinicopathological and prognostic significance of the percentage change between maximum standardized uptake value (SUVmax) at 60?min (SUVmax1) and SUVmax at 120?min (SUVmax2) (?SUVmax%) using dual time point 18F-fluorodeoxyglucose emission tomography/computed tomography (18F-FDG PET/CT) in breast cancer. METHODS:Four hundred and sixty-four patients with primary breast cancer underwent 18F-FDG PET/CT for preoperative staging. ?SUVmax% was defined as (SUVmax2?-?SUVmax1) / SUVmax1?×?100. We explored the optimal cutoff value of SUVmax parameters (SUVmax1 and ?SUVmax%) referring to the event of relapse by using receiver operator characteristic curves. The clinicopathological and prognostic significances of the SUVmax1 and ?SUVmax% were analyzed by Cox's univariate and multivariate analyses. RESULTS:The optimal cutoff values of SUVmax1 and ?SUVmax% were 3.4 and 12.5, respectively. Relapse-free survival (RFS) curves were significantly different between high and low SUVmax1 groups (P?=?0.0003) and also between high and low ?SUVmax% groups (P?=?0.0151). In Cox multivariate analysis for RFS, SUVmax1 was an independent prognostic factor (P?=?0.0267) but ?SUVmax% was not (P?=?0.152). There was a weak correlation between SUVmax1 and ?SUVmax% (P?<?0.0001, R2?=?0.166). On combining SUVmax1 and ?SUVmax%, the subgroups of high SUVmax1 and high ?SUVmax% showed significantly worse prognosis than the other groups in terms of RFS (P?=?0.0002). CONCLUSION:Dual time point 18F-FDG PET/CT evaluation can be a useful method for predicting relapse in patients with breast cancer. The combination of SUVmax1 and ?SUVmax% was able to identify subgroups with worse prognosis more accurately than SUVmax1 alone.
Project description:Background According to the current pathological classification, lung adenocarcinoma includes histological subtypes with significantly different prognoses, which may require specific surgical approaches. The aim of the study was to assess the role of CT and PET parameters in stratifying patients with stage I adenocarcinoma according to prognosis. Patients and methods Fifty-eight patients with pathological stage I lung adenocarcinoma who underwent surgical treatment were retrospectively reviewed. Adenocarcinoma in situ and minimally-invasive adenocarcinoma were grouped as non-invasive adenocarcinoma. Other histotypes were referred as invasive adenocarcinoma. CT scan assessed parameters were: ground glass opacity (GGO) ratio, tumour disappearance rate (TDR) and consolidation diameter. The prognostic role of the following PET parameters was also assessed: standardized uptake value (SUV) max, SUVindex (SUVmax to liver SUVratio), metabolic tumour volume (MTV), total lesion glycolysis (TLG). Results Seven patients had a non-invasive adenocarcinoma and 51 an invasive adenocarcinoma. Five-year disease-free survival (DFS) and cancer-specific survival (CSS) for non-invasive and invasive adenocarcinoma were 100% and 100%, 70% and 91%, respectively. Univariate analysis showed a significant difference in SUVmax, SUVindex, GGO ratio and TDR ratio values between non-invasive and invasive adenocarcinoma groups. Optimal SUVmax, SUVindex, GGO ratio and TDR cut-off ratios to predict invasive tumours were 2.6, 0.9, 40% and 56%, respectively. TLG, SUVmax, SUVindex significantly correlated with cancer specific survival. Conclusions CT and PET scan parameters may differentiate between non-invasive and invasive stage I adenocarcinomas. If these data are confirmed in larger series, surgical strategy may be selected on the basis of preoperative imaging.
Project description:Background:The pro-tumoral action of the cluster of differentiation 147 (CD147), which is associated with the chemotherapy resistance of lung adenocarcinoma, is partly due to accelerated tumor cell glycolysis. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) metabolic parameters included maximal standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG), which are non-invasive markers of the glucose metabolism of tumor cells in vivo. This study aimed to clarify the correlation between PET metabolic parameters and CD147 expression, and to evaluate the prognostic value of CD147 expression in resectable lung adenocarcinoma patients. Methods:A total of 89 lung adenocarcinoma chemotherapy-naive patients who underwent 18F-fluorodeoxyglucose positron emission tomography and computerized tomography scan before pulmonary surgery were retrospectively analyzed. The PET metabolic parameters were calculated by 18F-FDG PET imaging, and CD147 expression was analyzed by immunohistochemistry. SUVmax, SUVmean, MTV, and TLG compared for their performance in predicting the expression of CD147 were illustrated with statistical analysis. All patients were then followed-up for survival analysis. Results:The SUVmax was significantly correlated with the CD147 expression and was the primary predictor for the CD147 expression of lung adenocarcinoma. A cut-off value of the SUVmax, 9.77 allowed 85.1% sensitivity and 64.3% specificity for predicting the CD147 positive lung adenocarcinoma. CD147 expression was correlated with tumor differentiation and metastasis. Univariate survival analysis showed that CD147 expression was significantly associated with a shorter overall survival (OS) time. Multivariate analysis revealed that CD147 was an independent prognostic factor of lung adenocarcinoma patients. Conclusion:The SUVmax of a primary tumor measured with 18F-FDG PET may be a simple and non-invasive marker for predicting CD147 expression in lung adenocarcinoma. CD147 is an independent prognostic factor related to OS of postoperative lung adenocarcinoma patients.
Project description:BACKGROUND:Although 18F- FDG PET/CT is validated in baseline workup of esophageal cancer to detect distant metastases, it remains underused in assessing local staging and biology of the primary tumor. This study aimed to evaluate the association between 18F- FDG PET/CT-derived parameters of esophageal cancer, and its clinico-pathological features and prognosis. METHODS:All patients (n =?86) with esophageal adenocarcinoma or squamous cell cancer operated between 2005 and 2014 were analyzed. Linear regression was used to identify clinico-pathologic features of esophageal cancer associated with the tumor's maximal Standardized Uptake Value (SUVmax), Total Lesion Glycolysis (TLG) and Metabolic Tumor Volume (MTV). ROC curve analysis was performed to precise the optimal cutoff of each variable associated with a locally advanced (cT3/4) status, long-term survival and recurrence. Kaplan Meier curves and Cox regression were used for survival analyses. RESULTS:High baseline SUVmax was associated with cT3/4 status and middle-third tumor location, TLG with a cT3/4 and cN+ status, whereas MTV only with active smoking. A cT3/4 status was significantly predicted by a SUVmax >?8.25?g/mL (p <?0.001), TLG?>?41.7 (p <?0.001) and MTV?>?10.70?cm3 (p <?0.01) whereas a SUVmax >?12.7?g/mL was associated with an early tumor recurrence and a poor disease-free survival (median 13 versus 56?months, p =?0.030), particularly in squamous cell cancer. CONCLUSIONS:Baseline 18F- FDG PET/CT has a high predictive value of preoperative cT stage, as its parameters SUVmax, TLG and MTV can predict a locally advanced tumor with high accuracy. A SUVmax >?12.7?g/mL may herald early tumor recurrence and poor disease-free survival.
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:Background:We aim at investigating the correlation between skip N2 metastases (SN2) and SUVmax, long diameter of tumor mass after 18F-FDG PET/CT, and pathological Ki67 expression in patients with non-small-cell lung cancer (NSCLC). Methods and Results:We retrospectively analyzed the factors that might affect the pathogenesis of SN2 in these patients. The clinical SN2 symptoms in patients with squamous carcinoma or adenocarcinoma were investigated. The work curve was utilized to analyze the optimal cutoff value for the SUVmax and long diameter of tumor. Multivariate analysis revealed that high expression of Ki67 was a risk factor for mediastinal SN2 (OR = 1.042, 95% CI: 1.009-1.076). Subgroup analysis indicated that the SUVmax of the non-SN2 group was significantly higher than that of the SN2 group in patients with squamous carcinoma (16.3 ± 6.0 vs. 10.7 ± 5.6, P = 0.026). In the patients with adenocarcinoma, the long diameter of tumor in the SN2 group was significantly longer than that of the non-SN2 group (43.8 ± 16.3?mm vs. 30.1 ± 13.8?mm, P = 0.032). The Ki67 expression in the SN2 group was significantly higher than that of the non-SN2 group (51.7 ± 24.0 vs. 30.0 ± 19.2, P = 0.028). Conclusions:The differences of clinical features of the patients in the SN2 group and non-SN2 group in the NSCLC patients were associated with the pathological subtypes, which were featured by lower SUVmax in the SN2 of the squamous carcinoma, and longer diameter of SN2 in the adenocarcinoma patients.
Project description:It remains unclear whether the accumulation of 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) before the initiation of anti-programmed death-1 (PD-1) antibody can predict the outcome after its treatment. The aim of this study is to retrospectively examine the prognostic significance of 18F-FDG uptake as a predictive marker of anti-PD-1 antibody. Eighty-five patients with previously treated non-small cell lung cancer (NSCLC) who underwent 18F-FDG-positron emission tomography (PET) just before administration of nivolumab or pembrolizumab monotherapy were eligible in our study, and metabolic tumor volume (MTV), total lesion glycolysis (TLG) and the maximum of standardized under value (SUVmax) on 18F-FDG uptake were assessed. Objective response rate, median progression-free survival and median overall survival were 36.6%, 161 days and 716 days, respectively. The frequency of any immune-related adverse events was significantly higher in patients with low 18F-FDG uptake on PET than in those with high uptake. By multivariate analysis, the tumor metabolic activity by TLG and MTV was identified as an independent prognostic factor for predicting outcome after anti-PD-1 antibody therapy, but not SUVmax, predominantly in patients with adenocarcinoma. Metabolic tumor indices as TLG and MTV on 18F-FDG uptake could predict the prognosis after anti-PD-1 antibodies in patients with previously treated NSCLC.
Project description:Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, while lung ADC exhibits significant glucose independence. Clinically, elevated GLUT1-mediated glycolysis in lung SqCC strongly correlates with high 18F-FDG uptake and poor prognosis. This previously undescribed metabolic heterogeneity of NSCLC subtypes implicates significant potential for the development of diagnostic, prognostic and targeted therapeutic strategies for lung SqCC, a cancer for which existing therapeutic options are clinically insufficient.
Project description:There is a lack of markers for predicting favorable outcomes after pembrolizumab therapy in patients with non-small cell lung cancer (NSCLC) with programmed death ligand-1 (PD-L1) expression???50%. This retrospective study examined the prognostic significance of 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) uptake as a predictive marker of first-line pembrolizumab. Forty-eight patients with previously untreated NSCLC and PD-L1 expression levels???50% who underwent 18F-FDG-positron emission tomography (PET) just before administration of pembrolizumab monotherapy were eligible and underwent assessment of metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum of standardized uptake value (SUVmax) on 18F-FDG uptake. The objective response rate, median progression-free survival, and median overall survival were 51.1%, 7.1 months, and 18.6 months, respectively. In univariate survival analyses, high MTV was barely a significant prognostic predictor and was confirmed as an independent factor linked to worse outcomes in multivariate analysis, predominantly in patients with a histological diagnosis of adenocarcinoma. A high MTV was significantly associated with distant metastases (especially bone metastasis), C-reactive protein (CRP) level, and PD-L1 expression???75%. Metabolic tumor activity assessed as MTV from 18F-FDG uptake predicted the prognosis after first-line pembrolizumab treatment in patients with NSCLC and PD-L1 expression???50%, especially for adenocarcinoma.
Project description:18F-fluorodeoxyglucose positron emission tomography (FDG-PET) can reveal the metabolic activity of malignant tumors. Recent advances gained from molecular studies suggest that tumor biology can be a good predictor of prognosis in breast cancer. We compared the ability of maximum standardized uptake values (SUVmax) derived by FDG-PET with tumor burden in predicting tumor recurrence for patients with breast cancer.496 patients with breast cancer who underwent preoperative FDG-PET between April 2004 and May 2009 were retrospectively identified. SUVmax was obtained by FDG-PET, and the cutoff point was defined using a time-dependent receiver operating characteristic curve for recurrence-free survival (RFS). The primary endpoint was RFS.In multivariate analysis for RFS, SUVmax carried independent prognostic significance (hazard ratio, 2.39; 95% confidence interval, 1.20 to 4.76; P = 0.012). When the patients were classified into four groups according to the combined factors of tumor size (?2 cm versus >2 cm) and SUVmax (<4 versus ?4), RFS differed significantly (P < 0.001). Similarly, SUVmax had prognostic value in combination with nodal status (negative versus positive) or stage (I versus II and III) (P < 0.001 and P = 0.001, respectively). In hormone receptor-positive disease, SUVmax remained a significant prognostic factor for RFS based on multivariate analysis.Our results highlight the prognostic value of FDG-PET in prediction of tumor relapse for patients with breast cancer. Particularly in patients with hormone receptor-positive disease, the tumor metabolic information provided by FDG-PET is more significantly correlated with prognosis than tumor burden.