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1.  Maximum standard uptake value of 18F-fluorodeoxyglucose positron emission tomography is a prognostic factor for progression-free survival of newly diagnosed patients with diffuse large B cell lymphoma 
Annals of Hematology  2012;92(2):239-244.
The treatment of patients with diffuse large B cell lymphoma (DLBCL) would be greatly facilitated with a rapid method for determining prognosis that can be performed more easily and earlier than cytological or specific pathological examinations. It has been suggested that newly diagnosed patients with DLBCL who have low maximum standard uptake value (SUVmax) on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) are more likely to be successfully treated and remain in remission compared with patients with high SUVmax, but this concept has been poorly studied. We retrospectively analyzed 50 patients with de novo DLBCL to evaluate the relationship between the SUVmax and disease progression. For patients with low SUVmax (n = 10) and high SUVmax (n = 40) (P = 0.255), respectively, the 3-year overall survival rates were 90 and 72 %, and the progression-free survival (PFS) rates were 90 and 39 % (P = 0.012). By multivariate analysis, the revised International Prognostics Index (R-IPI) and SUVmax at diagnosis were shown to predict longer PFS. The 3-year PFS for patients with low SUVmax classified into the good prognosis group by R-IPI was 100 vs. 62 % for those with high SUVmax (P = 0.161), and patients with low SUVmax classified into the poor prognosis group by R-IPI was 80 vs. 18 % for those with high SUVmax (P = 0.050). We conclude that the SUVmax on FDG-PET for newly diagnosed patients with DLBCL is an important predictor of disease progression, especially for patients with poor prognosis by R-IPI.
PMCID: PMC3542423  PMID: 23079891
SUVmax; FDG-PET; Diffuse large B cell lymphoma; Progression; Revised IPI
2.  Adding Maximum Standard Uptake Value of Primary Lesion and Lymph Nodes in 18F-Fluorodeoxyglucose PET Helps Predict Distant Metastasis in Patients with Nasopharyngeal Carcinoma 
PLoS ONE  2014;9(7):e103153.
To find out the most valuable parameter of 18F-Fluorodeoxyglucose positron emission tomography for predicting distant metastasis in nasopharyngeal carcinoma.
From June 2007 through December 2010, 43 non-metastatic NPC patients who underwent 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) before radical Intensity-Modulated Radiation Therapy were enrolled and reviewed retrospectively. PET parameters including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glucose (TLG) of both primary tumor and cervical lymph nodes were calculated. Total SUVmax were recorded as the sum of SUVmax of primary tumor and cervical lymph nodes. Total SUVmean, Total MTV and Total TLG were calculated in the same way as Total SUVmax.
The median follow-up was 32 months (range, 23–68 months). Distant metastasis was the main pattern of treatment failure. Univariate analysis showed higher SUVmax, SUVmean, MTV, and TLG of primary tumor, Total SUVmax, Total MTV, Total TLG, and stage T3-4 were factors predicting for significantly poorer distant metastasis-free survival (p = 0.042, p = 0.008, p = 0.023, p = 0.023, p = 0.024, p = 0.033, p = 0.016, p = 0.015). In multivariate analysis, Total SUVmax was the independent predictive factor for distant metastasis (p = 0.046). Spearman Rank correlation analysis showed mediate to strong correlationship between Total SUVmax and SUVmax-T, and between Total SUVmax and SUVmax-N(Spearman coefficient:0.568 and 0.834;p = 0.000 and p = 0.000).
Preliminary results indicated that Total SUVmax was an independently predictive factor for distant metastasis in patients of nasopharyngeal carcinoma treated with Intensity-Modulated Radiation Therapy.
PMCID: PMC4113368  PMID: 25068373
3.  Revisiting the prognostic value of preoperative 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) in early-stage (I & II) non-small cell lung cancers (NSCLC) 
The aims were to determine if the maximum standardized uptake value (SUVmax) of the primary tumor as determined by preoperative 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) is an independent predictor of overall survival and to assess its prognostic value after stratification according to pathological staging.
A retrospective clinicopathologic review of 363 patients who had a preoperative 18F-FDG PET done before undergoing attempted curative resection for early-stage (I & II) non-small cell lung cancer (NSCLC) was performed. Patients who had received any adjuvant or neoadjuvant chemotherapy or radiation therapy were excluded. The primary outcome measure was duration of overall survival. Receiver-operating characteristic (ROC) curves were plotted to find out the optimal cutoff values of SUVmax yielding the maximal sensitivity plus specificity for predicting the overall survival. Survival curves stratified by median SUVmax and optimal cutoff SUVmax were estimated by the Kaplan-Meier method and statistical differences were assessed using the log-rank test. Multivariate proportional hazards (Cox) regression analyses were applied to test the SUVmax’s independency of other prognostic factors for the prediction of overall survival.
The median duration of follow-up was 981 days (2.7 years). The median SUVmax was 5.9 for all subjects, 4.5 for stage IA, 8.4 for stage IB, and 10.9 for stage IIB. The optimal cutoff SUVmax was 8.2 for all subjects. No optimal cutoff could be established for specific stages. In univariate analyses, each doubling of SUVmax [i.e., each log (base 2) unit increase in SUVmax] was associated with a 1.28-fold [95% confidence interval (CI): 1.03–1.59, p = 0.029] increase in hazard of death. Univariate analyses did not show any significant difference in survival by SUVmax when data were stratified according to pathological stage (p = 0.119, p = 0.818, and p = 0.882 for stages IA, IB, and IIB, respectively). Multivariate analyses demonstrated that SUVmax was not an independent predictor of overall survival (p > 0.05).
Each doubling of SUVmax as determined by preoperative PET is associated with a 1.28-fold increase in hazard of death in early-stage (I & II) NSCLC. Preoperative SUVmax is not an independent predictor of overall survival.
PMCID: PMC2844956  PMID: 19915840
18F-FDG PET; Non-small cell lung cancer; Prognosis; Survival; SUV
4.  Prognostic value of interim 18F-FDG PET/CT in diffuse large B-cell lymphoma 
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. The prognostic factor currently used is not accurate enough to predict the outcomes of patients with DLBCL. The prognostic significance of interim PET/CT in DLBCL remains controversial. The aim of this study is to determine the predictive value of interim 18F-FDG PET/CT after first-line treatment in patients with DLBCL.
Thirty-two patients with DLBCL underwent baseline, interim and post-treatment 18F-FDG PET/CT scans. Imaging results were analyzed for the survival of patients via software SPSS 13.0, retrospectively.
Thirty-one of the 32 patients were treated with R-CHOP regimen, and interim 18F-FDG PET/CT of 24 patients was performed after 2 cycles of treatment. After a median follow-up period of 16.7 months, the 2-year progression-free survival (PFS) rates were significantly different between the groups above and below SUVmax cut-off value of 2.5 (P=0.039). No significant differences were found in the 2-year PFS rates if SUVmax cut-off values were set as 2.0 and 3.0, respectively (P=0.360; P=0.113).
Interim PET/CT could predict the prognosis of DLBCL patients with the SUVmax cut-off value of 2.5, but more clinical data should be concluded to confirm this conclusion.
Key Words
Fludeoxyglucose F18; lymphoma; large cell; diffuse; prognosis; standard utility value
PMCID: PMC3555293  PMID: 23372347
5.  Difference in prognostic values of maximal standardized uptake value on fluorodeoxyglucose-positron emission tomography and cyclooxygenase-2 expression between lung adenocarcinoma and squamous cell carcinoma 
The maximal standardized uptake value (SUVmax) on fluorodeoxyglucose-positron emission tomography (FDG-PET) for primary tumors is correlated with clinicopathological and prognostic factors in patients with non-small cell lung cancer. However, previous investigations have discussed the role of SUVmax without distinguishing among the histological subtypes of lung cancer. Herein, we investigated the correlations among the SUVmax on FDG-PET, clinicopathological or prognostic factors, and the expression of tumor angiogenic biomarkers according to histological subtypes.
We conducted a retrospective review of data from 52 patients with invasive adenocarcinoma (ADC) and 32 patients with squamous cell carcinoma (SQC) measuring less than 3 cm in diameter. Immunohistochemical staining for cyclooxygenase-2 (Cox-2), Ki-67, and vascular endothelial growth factor, which might influence cancer progression, was performed and the correlations between the expressions of these biomarkers and the SUVmax were evaluated.
Among ADC patients, a statistically significant correlation was observed between the SUVmax and the major clinicopathological factors; among SQC patients, however, no statistically significant association was observed. The disease-free survival (DFS) period of the ADC patients with a high SUVmax was significantly poorer than that of the patients with a low SUVmax, but the DFS of the SQC patients with a high SUVmax was not significantly poorer. In a multivariate analysis, the pathological stage and the SUVmax were independent prognostic factors of the DFS among the ADC patients. Among the SQC patients, however, only Cox-2 expression was an independent prognostic factor of DFS.
Some clear differences in prognostic values of the SUVmax on FDG-PET and Cox-2 expression exist between patients with ADC and those with SQC. Based on these relationships between the SUVmax and clinicopathological or biological factors that influence cancer progression, the importance of the SUVmax appears to be quite different for patients with ADC and those with SQC.
PMCID: PMC4254182  PMID: 25392182
Non-small cell lung cancer; FDG-PET; SUV; Cox-2
6.  Prediction of pathologic prognostic factors in patients with lung adenocarcinomas: comparison of thin-section computed tomography and positron emission tomography/computed tomography 
Cancer Imaging  2014;14(1):3.
The ratio of the maximum diameter of consolidation to the maximum tumor diameter (C/T ratio) on thin-section computed tomography (TSCT) and the maximum standardized uptake value (SUVmax) on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) are often used as preoperative independent variables to evaluate the invasiveness of lung adenocarcinoma. We investigated the associations between these independent variables and pathologic invasiveness in pulmonary adenocarcinomas.
We selected patients with peripheral lung adenocarcinomas, definitively diagnosed by surgical resection, with diameters of ≤ 30 mm over a 4-year period ending in December 2010. The association between 3 independent variables (tumor size, SUVmax, and C/T ratio) and pathologic prognostic factors was evaluated using logistic analysis.
We evaluated a total of 163 primary lung adenocarcinomas in 148 patients (93 males and 55 females; age range: 34 to 84 years). Using multivariate logistic regression analysis, SUVmax and the C/T ratio were significantly associated with tumor invasiveness (odds ratio [OR] = 1.227; p = 0.025 and OR = 1.019; p = 0.008, respectively). Tumor size was not associated with invasiveness (OR = 1.003; p = 0.925). For solid type adenocarcinomas, only SUVmax was significantly associated with invasiveness (OR = 1.558; p = 0.003). For subsolid type adenocarcinomas, only the C/T ratio was significantly associated with invasiveness (OR = 1.030; p = 0.009).
Both the C/T ratio and the SUVmax are significantly correlated with pathologic invasiveness in patients with small lung adenocarcinomas, while there was a difference between the 2 evaluations. Solid type adenocarcinomas with SUVmax values of ≥ 4.4 and subsolid type adenocarcinomas with C/T ratio ≥ 53% were so highly invasive.
PMCID: PMC4212530  PMID: 25609076
Lung neoplasms; Adenocarcinoma; Computed tomography; Positron emission tomography; Fluorodeoxyglucose; Prognostic factor
7.  Primary Tumor Standardized Uptake Value Measured on F18-Fluorodeoxyglucose Positron Emission Tomography Is of Prediction Value for Survival and Local Control in Non–Small-Cell Lung Cancer Receiving Radiotherapy 
Journal of Thoracic Oncology  2014;9(6):834-842.
The 2-[18F]-Fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) has become an imaging tool for clinical assessment of tumor, node, metastasis in non–small-cell lung cancer (NSCLC). Primary tumor maximum standardized uptake value (SUVmax) on 18F-FDG PET/CT before and after radiation therapy (RT) has been studied as a potential prognostic factor for NSCLC patients receiving radiotherapy. However, the sample sizes of most studies were small, and the results of the prediction value of SUVmax remained undetermined, which lead us to perform a meta-analysis to improve the precision in estimating its effect.
We performed a meta-analysis of published literature for primary tumor SUVmax-based biomarkers of the outcome of NSCLC receiving radiotherapy. The required data for estimation of individual hazard ratios (HRs) to compare patients with a low and a high SUVmax were extracted from each publication. A combined HR was calculated by Stata statistical software (Version 11). All of the results were verified by two persons to ensure its accuracy.
Thirteen studies were finally included into this meta-analysis; data are available in 13 studies for pre-RT primary tumor SUVmax and in five studies for post-RT. For overall survival, the combined HR estimate was 1.05 (95% confidence interval [CI], 1.02–1.08) and 1.32 (95% CI, 1.15–1.51) for pre-RT SUVmax and post-RT SUVmax, respectively; 1.26 (95% CI, 1.05–1.52) and 2.01 (95% CI, 1.16–3.46) for local control (LC). In stereotactic body radiotherapy (SBRT) group, HR for LC was 1.11 (95% CI, 1.06–1.18) and 2.19 (95% CI, 1.34–3.60) for pre-SBRT SUVmax and post-SBRT SUVmax, respectively.
Both pre-RT and post-RT primary tumor SUVmax can predict the outcome of patients with NSCLC treated with radiotherapy. Patients with high levels of pre-RT SUVmax seemed to have poorer overall survival and LC.
PMCID: PMC4219540  PMID: 24787963
Primary tumor maximum standardized uptake value; Prognosis; Non–small-cell lung cancer; Meta-analysis; Radiotherapy
8.  Impact of maximum Standardized Uptake Value (SUVmax) evaluated by 18-Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT) on survival for patients with advanced renal cell carcinoma: a preliminary report 
BMC Cancer  2010;10:667.
In this era of molecular targeting therapy when various systematic treatments can be selected, prognostic biomarkers are required for the purpose of risk-directed therapy selection. Numerous reports of various malignancies have revealed that 18-Fluoro-2-deoxy-D-glucose (18F-FDG) accumulation, as evaluated by positron emission tomography, can be used to predict the prognosis of patients. The purpose of this study was to evaluate the impact of the maximum standardized uptake value (SUVmax) from 18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) on survival for patients with advanced renal cell carcinoma (RCC).
A total of 26 patients with advanced or metastatic RCC were enrolled in this study. The FDG uptake of all RCC lesions diagnosed by conventional CT was evaluated by 18F-FDG PET/CT. The impact of SUVmax on patient survival was analyzed prospectively.
FDG uptake was detected in 230 of 243 lesions (94.7%) excluding lung or liver metastases with diameters of less than 1 cm. The SUVmax of 26 patients ranged between 1.4 and 16.6 (mean 8.8 ± 4.0). The patients with RCC tumors showing high SUVmax demonstrated poor prognosis (P = 0.005 hazard ratio 1.326, 95% CI 1.089-1.614). The survival between patients with SUVmax equal to the mean of SUVmax, 8.8 or more and patients with SUVmax less than 8.8 were statistically different (P = 0.0012). This is the first report to evaluate the impact of SUVmax on advanced RCC patient survival. However, the number of patients and the follow-up period were still not extensive enough to settle this important question conclusively.
The survival of patients with advanced RCC can be predicted by evaluating their SUVmax using 18F-FDG-PET/CT. 18F-FDG-PET/CT has potency as an "imaging biomarker" to provide helpful information for the clinical decision-making.
PMCID: PMC3016292  PMID: 21129184
9.  Prognostic Value of Primary Tumor Uptake on F-18 FDG PET/CT in Patients with Invasive Ductal Breast Cancer 
To determine the prognostic implications of pretreatment F-18 FDG PET/CT in patients with invasive ductal breast cancer (IDC), we evaluated the relationship between FDG uptake of the primary tumor and known prognostic parameters of breast cancer. Prognostic significance of tumoral FDG uptake for the prediction of progression-free survival (PFS) was also assessed.
Materials and Methods
Fifty-five female patients with IDC who underwent pretreatment F-18 FDG PET/CT were enrolled. The maximum standardized uptake value of the primary tumor (pSUVmax) was compared with clinicopathological parameters including tumor size, grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor2 (HER2), axillary lymph node (LN) metastasis, and stage. The prognostic value of pSUVmax for PFS was assessed using the Kaplan-Meier method.
A high pSUVmax was significantly related to a higher stage of tumor size (P < 0.05), grade (P < 0.001), and stage (P < 0.001). pSUVmax was significantly higher in ER-negative tumors (P < 0.001), PR-negative tumors (P < 0.001), and positive LN metastasis (P < 0.01), but not different according to HER2 status. pSUVmax was significantly higher in patients with progression compared to patients who were disease-free (10.6 ± 5.1 vs. 4.7 ± 3.5, P < 0.001). A receiver-operating characteristic curve demonstrated a pSUVmax of 6.6 to be the optimal cutoff for predicting PFS (sensitivity; 86.7%, specificity; 82.5%). The patients with a high pSUVmax (more than 6.6) had significantly shorter PFS compared to patients with a low pSUVmax (P < 0.0001).
pSUVmax on pretreatment F-18 FDG PET/CT could be used as a good surrogate marker for the prediction of progression in patients with IDC.
PMCID: PMC4043019  PMID: 24899990
F-18 FDG PET/CT; Invasive ductal breast cancer; SUVmax; Prognosis
10.  Baseline 18F-FDG PET/CT Parameters as Imaging Biomarkers of Overall Survival in Castrate-Resistant Metastatic Prostate Cancer 
The aim of this prospective investigation was to assess the association of parameters derived from baseline 18F-FDG PET/CT with overall survival (OS) in men with castrate-resistant metastatic prostate cancer.
Eighty-seven men with castrate-resistant metastatic prostate cancer underwent 18F-FDG PET/CT and were followed prospectively for OS. Median follow-up in patients who were alive was 22.2 mo (range, 1.6–62.5 mo). OS was defined as the time between the PET/CT imaging or the start of chemotherapy, whichever was later, and death, with patients who were alive censored at the last follow-up date. PET parameters included maximum standardized uptake value (SUVmax) of the most active lesion, sum of SUVmax, and average SUVmax of all metabolically active lesions, after subtraction of patient-specific background-liver average SUV. Comparison of OS was based on univariate and multivariable Cox regression analyses of continuous PET parameters adjusted for standard clinical parameters (age, serum prostate-specific antigen level, alkaline phosphatase, use of pain medication, prior chemotherapy, and Gleason score at initial diagnosis). Survival curves based on Kaplan–Meier estimates are presented.
Among the 87 patients, 61 were dead at the time of last follow-up. Median OS was 16.5 mo (95% confidence interval [CI], 12.1–23.4 mo), and the OS probability at 24 mo was 39% ± 6%. For the univariate analysis, the hazard ratios associated with each unit increase were 1.01 (95% CI, 1.006–1.02) for sum of SUVmax (P = 0.002), 1.11 (95% CI, 1.03–1.18) for maximum SUVmax (P = 0.010), and 1.13 (95% CI, 0.99–1.30) for average SUVmax (P = 0.095). For the multivariable analysis adjusting for relevant clinical parameters, the continuous parameter sum of SUVmax remained significant (P = 0.053), with a hazard ratio of 1.01 (95% CI, 1.001–1.02). When sum of SUVmax was grouped into quartile ranges, there was poorer survival probability for the patients in the fourth-quartile range than for those in the first-quartile range, with a univariate hazard ratio of 3.8 (95% CI, 1.8–7.9).
Sum of SUVmax derived from 18F-FDG PET/CT contributes independent prognostic information on OS in men with castrate-resistant metastatic prostate cancer, and this information may be useful in assessing the comparative effectiveness of various conventional and emerging treatment strategies.
PMCID: PMC3783857  PMID: 23785174
18F-FDG; prostate; cancer; castrate-resistant; survival
11.  Prediction of outcome with FDG-PET in definitive chemoradiotherapy for esophageal cancer 
Journal of Radiation Research  2013;54(5):890-898.
The purpose of this study was to assess the efficacy of 18F-fluoro-2-deoxy-glucose uptake positron emission tomography (FDG-PET) for the prediction of outcome in definitive chemoradiotherapy (CRT) for esophageal cancer. We enrolled 56 patients with esophageal cancer treated with definitive CRT and examined by FDG-PET before treatment. We examined the correlation of the maximum standardized uptake value (SUVmax) in FDG-PET of the primary tumor with overall survival (OS), progression-free survival (PFS), local control (LC) and response of the primary tumor. After definitive CRT, 30 patients had a clinical complete response (CR), making the CR rate 54%. For all 56 patients, the 2-year OS rate, PFS rate and LC rates were 64%, 38% and 51%, respectively. We divided the patients into two groups according to SUVmax: SUVmax < 10 (low-SUV) and ≥10 (high-SUV). The 2-year OS rates in the low- and high-SUV groups were 100% and 41%, the PFS rates were 73% and 19%, the LC rates were 71% and 39%, and the CR rates were 100% and 32%, respectively. A univariate analysis revealed significant differences between the low- and high-SUV group in OS, PFS, LC and response (P = 0.0005, 0.0002, 0.048, and <0.0001, respectively). SUVmax and T stage were significantly associated with OS, PFS, LC and response. A multivariate analysis showed significant differences between the SUVmax <10 and ≥10 groups in overall survival and response (P < 0.05). Our result suggests that the SUVmax in FDG-PET of the primary tumor before treatment may have prognostic value for esophageal cancer.
PMCID: PMC3766293  PMID: 23520267
FDG-PET; esophageal cancer; chemoradiotherapy; SUVmax
12.  Prognostic significance of SUVmax and serum carbohydrate antigen 19-9 in pancreatic cancer 
AIM: To investigate the prognostic significance of pretreatment standardized maximum uptake value (SUVmax) and serum carbohydrate antigen (CA)19-9 in pancreatic cancer.
METHODS: From January 2007 to October 2011, 80 consecutive patients with pancreatic cancer who received positron emission/computed tomography before any treatment were enrolled in this study. The pretreatment SUVmax and CA19-9 level of the primary pancreatic tumor were obtained and compared with clinicopathological and prognostic factors. Student’s t test for unpaired data was used to analyze the differences between two groups. Univariate analysis and Cox proportional hazards regression were used to examine the independent effects of each significant variable. Survival was analyzed by the Kaplan-Meier method.
RESULTS: There was a significant correlation between both the SUVmax and serum CA19-9 of pancreatic cancer and R0 surgical resection (P = 0.043 and P = 0.007). Lymph node metastasis was associated with SUVmax (P = 0.017), but not serum CA19-9 (P = 0.172). On the contrary, the tumor stage was significantly related to serum CA19-9 (P = 0.035), but not SUVmax (P = 0.110). The univariate analysis showed that survival time was significantly related to tumor stage (P < 0.001), lymph node metastasis (P = 0.043), R0 surgical resection (P < 0.001), serum CA19-9 (P = 0.001), SUVmax (P < 0.001) and SUVmax plus CA19-9 (P = 0.002). Multivariate analysis clearly showed that only tumor stage (hazard ratio = 0.452; P = 0.020) was an independent prognostic factor for overall survival in pancreatic cancer. Higher SUVmax or CA19-9 showed worse prognosis. We found that high serum CA19-9 plus SUVmax was the most significant variable.
CONCLUSION: Higher pretreatment SUVmax and serum CA19-9 indicates poor prognosis. SUVmax plus serum CA19-9 is the most significant variable in predicting survival.
PMCID: PMC4024797  PMID: 24914348
Pancreatic cancer; Maximum standardized uptake value; Carbohydrate antigen 19-9; Prognostic factors
13.  Prognostic Value of FDG PET Imaging in Patients with Laryngeal Cancer 
PLoS ONE  2014;9(5):e96999.
Background and Purpose
To investigate the prognostic value of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with laryngeal cancer.
Materials and Methods
The study included 51 patients of whom 30 underwent definitive radiotherapy with or without chemotherapy and 21 underwent radical surgery with or without adjuvant chemoradiation therapy. FDG uptake by both the primary lesion and the neck node was measured using the maximum standardized uptake value (SUVmax). The effects of clinicopathological factors including primary tumor SUVmax and nodal SUVmax on progression-free survival, local control, nodal progression-free survival, and distant metastasis-free survival were evaluated using the log-rank test and Cox method.
The median duration of follow-up was 48.6 months (range 8 to 82.1 months). Univariate analysis showed that nodal SUVmax, N status, and tumor TNM stage were significantly associated with recurrence, whereas primary tumor SUVmax, age, treatment strategy and T status were not. Multivariate analysis demonstrated that only the nodal SUVmax was a significantly unfavorable factor for progression-free survival (p = 0.029, hazard ratio 0.54, 95% CI 0.38-0.87) and nodal progression-free survival (p = 0.023, hazard ratio 0.51, 95% CI 0.34-0.81). ROC curve analysis and log-rank test showed that patients with a high nodal SUVmax (≧4) had a significantly lower progression-free survival rate than those with a low SUVmax (<4; p<0.0001).
The pretreatment SUVmax of nodal disease in patients with laryngeal cancer is prognostic for recurrence.
PMCID: PMC4018388  PMID: 24818750
14.  Tumor Burden Assessed by the Maximum Standardized Uptake Value and Greatest Diameter on FDG-PET Predicts Prognosis in Untreated Diffuse Large B-cell Lymphoma 
It is uncertain whether the tumor burden as assessed using FDG-PET has prognostic significance in newly diagnosed diffuse large B-cell lymphoma (DLBCL). The authors undertook this study to determine whether a parameter that reflects both FDG uptake magnitude and the greatest tumor diameter is a prognostic indicator in DLBCL.
Materials and Methods
Forty-two DLBCL patients (age, 57.4 ± 15.5 years; male/female = 25/17; stage I/II/III/IV=5/17/10/10) who underwent FDG-PET before chemotherapy were enrolled. A lesion with the highest maximum standardized uptake value (MaxSUV) on the PET image was selected, and size-incorporated MaxSUV (SIMaxSUV) of mass was calculated as MaxSUV × greatest diameter (mm) on the transaxial PET image. Median follow-up duration was 20.0 months.
Twelve (28.6% = 12/42) patients experienced disease progression, and 10 (23.8% = 10/42) died during follow-up. Among six variables [Ann Arbor stage, %Ki-67 expression, International Prognostic Index (IPI), MaxSUV, greatest diameter, and SIMaxSUV] investigated, only SIMaxSUV was found to be a single determinant of progression-free and overall survivals by multivariate analyses (p < 0.05).
These results suggest that SIMaxSUV, a new FDG-PET parameter that incorporates FDG uptake magnitude and the greatest tumor diameter, may be a useful indicator of prognosis in untreated DLBCL.
PMCID: PMC4042962  PMID: 24899936
FDG-PET; Lymphoma; Prognosis; SUV; Size-incorporated maxSUV; Greatest diameter
15.  FDG-PET SUVmax Combined with IASLC/ATS/ERS Histologic Classification Improves the Prognostic Stratification of Patients with Stage I Lung Adenocarcinoma 
Annals of surgical oncology  2012;19(11):3598-3605.
We investigated the association between the newly proposed International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification and 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET), and whether the combination of these radiologic and pathologic factors can further prognostically stratify patients with stage I lung adenocarcinoma.
We retrospectively evaluated 222 patients with pathologic stage I lung adenocarcinoma who underwent FDG-PET scanning before undergoing surgical resection between 1999 and 2005. Patients were classified by histologic grade according to the IASLC/ATS/ERS classification (low, intermediate, or high grade) and by maximum standard uptake value (SUVmax) (low <3.0, high ≥3.0). The cumulative incidence of recurrence (CIR) was used to estimate recurrence probabilities.
Patients with high-grade histology had higher risk of recurrence (5-year CIR, 29 % [n = 25]) than those with intermediate-grade (13 % [n = 181]) or low-grade (11 % [n = 16]) histology (p = 0.046). High SUVmax was associated with high-grade histology (p < 0.001) and with increased risk of recurrence compared to low SUVmax (5-year CIR, 21 % [n = 113] vs. 8 % [n = 109]; p = 0.013). Among patients with intermediate-grade histology, those with high SUVmax had higher risk of recurrence than those with low SUVmax (5-year CIR, 19 % [n = 87] vs. 7 % [n = 94]; p = 0.033). SUVmax was associated with recurrence even after adjusting for pathologic stage (p = 0.037).
SUVmax on FDG-PET correlates with the IASLC/ATS/ERS classification and can be used to stratify patients with intermediate-grade histology, the predominant histologic subtype, into two prognostic subsets.
PMCID: PMC4049004  PMID: 22644511
16.  Modified Number of Extranodal Involved Sites as a Prognosticator in R-CHOP-Treated Patients with Disseminated Diffuse Large B-Cell Lymphoma 
Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (R-CHOP) has improved survival in patients with diffuse large B-cell lymphoma (DLBCL) and weakened the prognostic power of the international prognostic index (IPI). We evaluated the efficacy of the IPI and revised IPI (R-IPI) in patients with DLBCL who were treated with R-CHOP, focusing on extranodal site number (ENS) because extranodal involvement occurs frequently in Koreans.
A total of 126 R-CHOP-treated patients with stage III/IV DLBCL were analyzed. We performed a retrospective analysis of the clinicopathologic factors and verified the predictive power of the standard IPI and R-IPI. Various numbers of extranodal sites were analyzed for further stratification, and we set the extranodal site-modified IPI (E-IPI) as the IPI when the number of extranodal sites was stratified as < 3 vs. ≥ 3.
A univariate analysis showed that ENS was associated with complete response (CR, p = 0.04), event-free survival (EFS, p = 0.01), and overall survival (OS, p < 0.001) when the ENS cut-off was set at ≥ 3. A multivariate analysis revealed that an ENS ≥ 3 remained associated with EFS (p < 0.01; hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.29 to 5.26) and OS (p < 0.01; HR, 3.52; 95% CI, 1.68 to 7.35). The IPI was effective for determining prognosis in terms of OS (p = 0.04) but not EFS (p = 0.17). The R-IPI was effective in terms of both variables (p = 0.02 and 0.04, respectively), as was the E-IPI (p = 0.01 and 0.001, respectively).
An ENS < 3 vs. ≥ 3, rather than the original < 2 vs. ≥ 2, was the most significant prognostic factor for EFS and OS. All three indices were predictive, but only the E-IPI identified the high-risk group of R-CHOP-treated Korean patients with disseminated DLBCL.
PMCID: PMC2932944  PMID: 20830228
Prognosis; Lymphoma, large B-cell, diffuse; Rituximab; Extranodal
17.  18F-FDG PET/CT for Early Response Assessment in Diffuse Large B-Cell Lymphoma: Poor Predictive Value of International Harmonization Project Interpretation 
PET using 18F-FDG has prognostic value when performed at the completion of initial chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL). 18F-FDG PET may also be predictive of outcome when performed during the treatment course of DLBCL, but robust prospective studies and standardization of 18F-FDG PET interpretation in this setting are lacking.
In this prospective study, patients with advanced-stage DLBCL were treated with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, and 18F-FDG PET/CT was performed after cycle 2 or 3 and at the end of therapy. The 18F-FDG PET/CT scans were interpreted according to the International Harmonization Project for Response Criteria in Lymphoma, and the maximum standardized uptake value (SUV) of the most 18F-FDG–avid lesions was recorded.
Fifty patients were enrolled, and all underwent interim 18F-FDG PET/CT. At a median follow-up of 33.9 mo, the positive predictive value (PPV) of interim 18F-FDG PET/CT for relapse or progression was 42%, and the negative predictive value (NPV) was 77%. Interim 18F-FDG PET/CT was significantly associated with event-free survival (P = 0.017) and with progression-free survival (P = 0.04) but not with overall survival (P = 0.08). End-of-therapy 18F-FDG PET/CT had high PPV and NPV (71% and 80%, respectively) and was significantly associated with event-free survival, progression-free survival, and overall survival (P < 0.001). SUV measurements did not discriminate patients who relapsed or progressed from those who remained in remission.
When performed after 2 cycles of immunochemotherapy and interpreted according to International Harmonization Project criteria, early response assessment with PET/CT has a high NPV but low PPV in patients with advanced-stage DLBCL. Prospective trials are required to validate different criteria for the interpretation of interim 18F-FDG PET/CT and establish the role of interim 18F-FDG PET/CT in the management of patients with DLBCL.
PMCID: PMC4019941  PMID: 21321279
18F-FDG; PET; PET/CT; non-Hodgkin lymphoma; prognosis
18.  What parameters from 18F-FDG PET/CT are useful in evaluation of adrenal lesions? 
Prior studies have suggested that 18F-FDG PET/CT can help characterize adrenal lesions and differentiate adrenal metastases from benign lesions. The aim of this study was to assess the value of 18F-FDG PET/CT for the differentiation of malignant from benign adrenal lesions.
This retrospective study included 85 patients (47 men and 38 women, age 63.8 ± 10.8 years) who had undergone 18F-FDG PET/CT (60 min after injection 300 – 370 MBq 18F-FDG; Biograph 64 scanner) for evaluation of 102 nonsecreting adrenal masses. For semiquantitative analysis, the maximum standardized uptake value (SUVmax), adrenal to liver (T/L) SUVmax ratio, mean CT attenuation value and tumour diameter were measured in all lesions and compared with the pathological findings.
Malignant adrenal tumours (68 % of evaluated tumours) had a significantly higher mean SUVmax (13.0 ± 7.1 vs. 3.7 ± 3.0), a higher T/L SUVmax ratio (4.2 ± 2.6 vs. 1.0 ± 0.9), a higher CT attenuation value (31.9 ± 16. 7 HU vs. 0.2 ± 25.8 HU) and a greater diameter (43.6 ± 23.7 mm vs. 25.6 ± 13.3 mm) than benign lesions. The false-positive findings were tuberculosis and benign phaeochromocytoma. Based on ROC analysis, a T/L SUVmax ratio >1.53, an adrenal SUVmax >5.2, an attenuation value >24 HU and a tumour diameter >30 mm were chosen as the optimal cut-off values for differentiating malignant from benign tumours. The areas under the ROC curves for the selected cut-off values were 0.96, 0.96, 0.88 and 0.77, respectively. A multivariate logistic regression model revealed that the T/L SUVmax ratio was an independent prognostic factor for malignancy (p < 0.001); a CT attenuation value of >25 HU and a tumour diameter >30 mm had no additional individual importance in the diagnosis of malignancy.
Using a T/L SUVmax ratio >1.53 and an adrenal SUVmax >5.2 in 18F-FDG PET/CT led to high diagnostic sensitivity, specificity and negative predictive value for characterizing adrenal tumours. The diagnostic accuracies of the two parameters were comparable, but T/L SUVmax ratio was an independent predictor of malignancy.
PMCID: PMC4226932  PMID: 25027709
18F-FDG; PET/CT; Adrenal lesion
19.  Prediction of 2 years-survival in patients with stage I and II non-small cell lung cancer utilizing 18F-FDG PET/CT SUV quantification 
Radiology and Oncology  2013;47(3):219-223.
The purpose of the study was to evaluate the correlation between the maximum standardized uptake value (SUVmax), size of primary lung lesion, disease-free survival (DFS) and overall survival (OS) in patients with stage I and II non-small cell lung cancer (NSCLC) in 2 years follow-up.
Patients and methods.
Forty-nine patients with stage I–II NSCLC were included in this study. Pre-surgical 2-deoxy-2-[18F]fluoro-D-glucose positron-emission tomography (18F-FDG PET/CT) study was performed for all patients. The relationship between SUVmax, tumour size and clinical outcome was measured. The cut-off value for SUVmax and tumour size with the best prognostic significance, probability of DFS and the correlation between SUVmax and the response to therapy were calculated.
There was a statistically significant correlation between SUVmax and DFS (p = 0.029). The optimal cut-offs were 9.00 for SUVmax (p = 0.0013) and 30mm for tumour size (p = 0.0028). Patients with SUVmax > 9 and primary lesion size > 30 mm had an expected 2years-DFS of 37.5%, while this rose to 90% if the tumour was <30 mm and/or SUVmax was <9.
In stage I-II, SUVmax and tumour size might be helpful to identify the subgroup of patients with high chance for recurrence.
PMCID: PMC3794876  PMID: 24133385
2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography; non-small cell lung cancer; maximum standardized uptake value; disease-free survival; overall survival
20.  Standardized uptake value of 18F-fluorodeoxyglucose positron emission tomography for prediction of tumor recurrence in breast cancer beyond tumor burden 
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.
Electronic supplementary material
The online version of this article (doi:10.1186/s13058-014-0502-y) contains supplementary material, which is available to authorized users.
PMCID: PMC4308858  PMID: 25551703
21.  Oxidative stress and redox state-regulating enzymes have prognostic relevance in diffuse large B-cell lymphoma 
Oxidative stress and redox-regulating enzymes may have roles both in lymphomagenesis and resistance to lymphoma therapy. Previous studies from the pre-rituximab era suggest that antioxidant enzyme expression is related to prognosis in diffuse large B-cell lymphoma (DLBCL), although these results cannot be extrapolated to patient populations undergoing modern treatment modalities. In this study we assessed expression of the oxidative stress markers 8-hydroxydeoxyguanosine (8-OHdG) and nitrotyrosine and the antioxidant enzymes thioredoxin (Trx), manganese superoxide dismutase (MnSOD) and glutamate-cysteine ligase (GCL) via immunohistochemistry in 106 patients with DLBCL. All patients were treated with CHOP-like therapy combined with rituximab. Immunostaining results were correlated with progression-free survival, disease-specific survival and traditional prognostic factors of DLBCL.
Strong 8-OHdG immunostaining intensity was associated with extranodal involvement (p = 0.00002), a high International Prognostic Index (p = 0.002) and strong Trx (p = 0.011) and GCL (p = 0.0003) expression. Strong Trx staining intensity was associated with poor progression-free survival (p = 0.046) and poor disease-specific survival (p = 0.015). Strong GCL immunostaining intensity predicted poor progression-free survival (p = 0.049). Patients with either strong Trx or strong nitrotyrosine expression showed significantly poorer progression-free survival (p = 0.003) and disease-specific survival (p = 0.031) compared with the other patients.
The redox state-regulating enzymes GCL and Trx are promising markers in the evaluation of DLBCL prognosis in the era of modern immunochemotherapy.
PMCID: PMC3506993  PMID: 23210982
Antioxidant enzyme; Nitrotyrosine; Prognosis; Reactive oxygen species; Thioredoxin
22.  The Preoperative Maximum Standardized Uptake Value Measured by 18F-FDG PET/CT as an Independent Prognostic Factor of Overall Survival in Endometrial Cancer Patients 
BioMed Research International  2014;2014:234813.
Purpose. The aim of this study was to determine if the preoperative maximum standardized uptake value (SUVmax) measured by 18F-FDG PET/CT in the primary tumor has prognostic value in the group of patients with endometrial cancer. Patients, Materials, and Methods. A total of one hundred one consecutive endometrial cancer patients, age range 40–82 years (mean 62 years) and FIGO I–IV stage, who underwent 18-FDG-PET/CT within two weeks prior radical surgery, were enrolled to the study. The maximum SUV was measured and compared with the clinicopathologic features of surgical specimens. The relationship between SUVmax and overall survival was analyzed. Results. The mean preoperative SUVmax was 14.34; range (3.90–33.80) and was significantly lower for FIGO I than for higher stages (P = 0.0012), as well as for grade 1 than for grade 2 and 3 (P = 0.018), deep myometrial invasion (P = 0.0016) and for high risk group (P = 0.0004). The analysis of survival ROC curve revealed SUVmax cut-off value of 17.7 to predict high risk of recurrence. Endometrial cancer patients with SUVmax higher than 17.7 characterized by lower overall survival. Conclusion. The preoperative SUVmax measured by 18F-FDG PET/CT is considered as an important indicator reflecting tumor aggressiveness which may predict poor prognosis. High value of SUVmax would be useful for making noninvasive diagnoses and deciding the appropriate therapeutic strategy for patients with endometrial cancer.
PMCID: PMC3956283  PMID: 24719847
23.  Correlations Between Selected Tumor Markers and Fluorodeoxyglucose Maximal Standardized Uptake Values in Esophageal Cancer 
Esophageal cancer tumor biology is best assessed clinically by FDG-PET. Both FDG-PET SUVmax and selected tumor markers have been shown to correlate with stage, nodal disease, and survival in esophageal cancer. Interestingly, there is limited data examining the relationship between FDG-PET SUVmax and expression of these tumors markers in esophageal cancer. The purpose of this study was to determine the correlation of tumor markers with FDG-PET SUVmax in esophageal cancer.
FDG-PET SUVmax was calculated in 67 patients with esophageal cancer of which 59 (88%) had adenocarcinoma. Neoadjuvant radiotherapy and/or chemotherapy were administered to (28/67) 42% of patients. Esophageal tumor tissue and surrounding normal tissue was obtained and tissue microarrays were created. Immunohistochemical analysis was performed for 5 known esophageal cancer tumor markers (GLUT1, p53, cyclin D1, EGFR, and VEGF). Assessment of each tumor marker was made by two independent, blinded pathologists using common grading criteria of intensity and percentage of cells stained. A p-value < 0.05 was considered significant.
There were 55 men (82%) and 12 women (18%) with a median age of 63 years (range 40-83). Pathologic staging included stage I (N=29, 43%), stage II (N=19, 28%), stage III disease (N=18, 27%), and stage IV disease (N=1, 2%). PET SUVmax correlated with T stage (p=0.001). In patients undergoing surgery without induction therapy, increasing SUVmax values correlated with increased expression of GLUT1 transporter (p=0.01). There was no correlation between SUVmax and EGFR, cyclin D1, VEGF, or p53 expression in primary tumor.
FDG-PET SUVmax correlates with an increased expression of GLUT1 transporter in esophageal cancer specimens not subjected to induction therapy. No significant difference in tumor marker expression was noted between patients undergoing induction therapy or surgery alone except p53 expression decreased in primary tumors following induction therapy. Failure of SUVmax values to correlate with known prognostic esophageal cancer tumor markers suggests that FDG-PET may have limited clinical utility in assessing response to therapies targeting these markers.
PMCID: PMC2878130  PMID: 19136271
esophageal cancer; tumor markers; FDG-PET
24.  Relationship between pretreatment FDG-PET and diffusion-weighted MRI biomarkers in diffuse large B-cell lymphoma 
The purpose of this study was to determine the correlation between the 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) standardized uptake value (SUV) and the diffusion-weighted magnetic resonance imaging (MRI) apparent diffusion coefficient (ADC) in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Pretreatment FDG-PET and diffusion-weighted MRI of 21 patients with histologically proven DLBCL were prospectively analyzed. In each patient, maximum, mean and peak standardized uptake value (SUV) was measured in the lesion with visually highest FDG uptake and in the largest lesion. Mean ADC (ADCmean, calculated with b-values of 0 and 1000 s/mm2) was measured in the same lesions. Correlations between FDG-PET metrics (SUVmax, SUVmean, SUVpeak) and ADCmean were assessed using Pearson’s correlation coefficients. In the lesions with visually highest FDG uptake, no significant correlations were found between the SUVmax, SUVmean, SUVpeak and the ADCmean (P=0.498, P=0.609 and P=0.595, respectively). In the largest lesions, there were no significant correlations either between the SUVmax, SUVmean, SUVpeak and the ADCmean (P=0.992, P=0.843 and P=0.894, respectively). The results of this study indicate that the glycolytic rate as measured by FDG-PET and changes in water compartmentalization and water diffusion as measured by the ADC are independent biological phenomena in newly diagnosed DLBCL. Further studies are warranted to assess the complementary roles of these different imaging biomarkers in the evaluation and follow-up of DLBCL.
PMCID: PMC3999403  PMID: 24795837
FDG-PET; diffusion-weighted MRI; standardized uptake value; apparent diffusion coefficient; diffuse large B-cell lymphoma
25.  FDG-PET-based Prognostic Nomograms for Locally Advanced Cervical Cancer 
Gynecologic oncology  2012;127(1):136-140.
Patients with cervical cancer of the same clinical FIGO stage can have distinctly different outcomes. We previously found that several individual factors determined by positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG), including primary cervical tumor maximum standardized uptake value (SUVmax), cervical tumor volume, and highest level of lymph node (LN) involvement, provide prognostic information about patient outcome. For this study, we aimed to evaluate the combined prognostic value of these three factors assessed on pretreatment FDG-PET for recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS).
Patients and Methods:
The study included 482 cervical cancer patients, FIGO stage Ia2-IVa, treated with definitive radiation or chemoradiation therapy. All patients underwent FDG-PET or FDG-PET/CT at diagnosis, from which cervical tumor volume, LN status, and tumor SUVmax were recorded. Using these PET-based factors, prognostic nomograms based on Cox regression were created for RFS, DSS, and OS. The prediction accuracies of the nomograms were measured using the concordance index (c-statistic).
Fifty-seven percent of patients had FDG-avid lymph nodes on PET; the highest level of nodal involvement was pelvic in 186, para-aortic in 65, and supraclavicular in 26. The average cervix tumor SUVmax was 11.8 (range, 2.0–50.4). PET tumor volume ranged from 3.0 to 535.7 cm3 (average, 65.2 cm3). The median follow-up was 57.5 months for patients alive at the time of last follow-up. PET LN status had the greatest influence on outcome and SUVmax was the second most important factor for all 3 endpoints. The c-statistics for the 3 nomograms were 0.756 for RFS, 0.733 for DSS, and 0.649 for OS.
Pretreatment FDG-PET LN status, cervical tumor SUVmax, and PET tumor volume combined in a nomogram create good models for cervical cancer RFS, DSS, and OS.
PMCID: PMC3991305  PMID: 22735785
FDG-PET; lymph node; prognosis; cervix; nomogram

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