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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.  Role of FDG-PET/CT for monitoring soft tissue tumors 
Oncology Letters  2014;7(4):1243-1248.
The aim of the current study was to evaluate the limitations of 2-deoxy-2-F18-fluoro-D-glucose positron emission tomography combined with computed tomography (FDG-PET/CT) when monitoring soft tissue tumors. The diagnostic criteria of malignancy was defined as the tumor having a maximum standardized uptake value (SUVmax) ≥2.0 and a maximum diameter ≥5 cm as measured using FDG-PET/CT. One-hundred-and-thirteen patients, that were either included in the criteria or not, were compared. In addition, the values of SUVmax of the primary tumor and relapse in 12 patients were evaluated. The Kaplan-Meier analysis demonstrated that patients with tumors measuring ≥5 cm size and ≥2.0 SUVmax were associated with a worse survival rate. Among the 12 patients with relapse, statistical significances were detected in the tumor diameters, however, not in the SUVmax values. Thus, the criteria identified patients that were associated with a poor prognosis, and the SUVmax of distant metastases and local recurrences were identified to be significantly affected by tumor size.
PMCID: PMC3961202  PMID: 24660036
soft tissue tumor; 2-deoxy-2-F18-fluoro-D-glucose positron emission tomography; computed tomography; maximum standardized uptake value; prognosis; metastasis; recurrence
3.  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
4.  Baseline total lesion glycolysis measured with 18F-FDG PET/CT as a predictor of progression-free survival in diffuse large B-cell lymphoma: a pilot study 
This pilot study investigates the value of baseline total lesion glycolysis (TLG) in 18F-FDG PET/CT scans for prediction of progression-free survival (PFS) in patients with Diffuse Large B-Cell Lymphoma (DLBCL). We also evaluate the role of other quantitative parameters measured at baseline and interim PET/CT for prediction of PFS. A retrospective review (2003-2010) of patients with DLBCL who underwent 18F-FDG PET/CT before, after cycle two, and after completion of R-CHOP treatment, identified 84 patients. Twenty patients fulfilled the inclusion criteria. Standardized uptake values (SUVmax and SUVmean), total metabolic tumor volume (TMTV), and TLG were measured in baseline and interim PET/CT. Relationship between quantitative parameters and PFS was statistically analyzed using Log-rank test and univariate Cox-regression analysis. Of 20 patients (F/M: 7/13, range: 20-73 years), six patients (30%) developed recurrence after chemotherapy (mean follow-up: 51.35±17.05 months, range: 12-81 months). Results of statistical analysis showed TLG as the only discriminator of recurrence at baseline (cut-point: 704.77 g, HR: 11.21, CI: 1.29-97, P=0.02). Among the interim PET/CT parameters, SUVmean (cut -point: 2.07, HR: 6.31, CI: 1.25-31.61), SUVmax (cut-point: 2.3, HR: 6.31, CI: 1.25-31.61), and TLG (cut-point: 96.5 g, HR: 6.38, CI: 1.29 - 31.61) could all help predict PFS (P<0.05). Although not routinely reported, high baseline TLG may be a useful index to identify patients with DLBCL who are at increased risk for relapse after conventional R-CHOP. If confirmed in larger prospective studies, this may allow the selection of alternate therapeutic choices at the onset of treatment.
PMCID: PMC3627523  PMID: 23638338
Diffuse large B-cell lymphoma; 18F-FDG PET/CT; progression-free survival; quantitative parameters
5.  Correlations between Functional Imaging Markers Derived from PET/CT and Diffusion-Weighted MRI in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma 
PLoS ONE  2014;9(1):e84999.
To investigate the correlations between functional imaging markers derived from positron emission tomography/computed tomography (PET/CT) and diffusion-weighted magnetic resonance imaging (DWI) in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Further to compare the usefulness of these tumor markers in differentiating diagnosis of the two common types of Non-Hodgkin's lymphoma (NHL).
Materials and Methods
Thirty-four consecutive pre-therapy adult patients with proven NHL (23 DLBCL and 11 FL) underwent PET/CT and MRI examinations and laboratory tests. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and metabolic tumor burden (MTB) were determined from the PET/CT images. DWI was performed in addition to conventional MRI sequences using two b values (0 and 800 s/mm2). The minimum and mean apparent diffusion coefficient (ADCmin and ADCmean) were measured on the parametric ADC maps.
The SUVmax correlated inversely with the ADCmin (r = −0.35, p<0.05). The ADCmin, ADCmean, serum thymidine kinase (TK), Beta 2-microglobulin (B2m), lactate dehydrogenase (LD), and C-reactive protein (CRP) correlated with both whole-body MTV and whole-body MTB (p<0.05 or 0.01). The SUVmax, TK, LD, and CRP were significantly higher in the DLBCL group than in the FL group. Receiver operating characteristic curve analysis showed that they were reasonable predictors in differentiating DLBCL from FL.
The functional imaging markers determined from PET/CT and DWI are associated, and the SUVmax is superior to the ADCmin in differentiating DLBCL from FL. All the measured serum markers are associated with functional imaging markers. Serum LD, TK, and CRP are useful in differentiating DLBCL from FL.
PMCID: PMC3893149  PMID: 24454777
6.  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
7.  Prognostic Impact of [18F]Fluorothymidine and [18F]Fluoro-D-Glucose Baseline Uptakes in Patients with Lung Cancer Treated First-Line with Erlotinib 
PLoS ONE  2013;8(1):e53081.
3′-deoxy-3′-[18F]fluoro-L-thymidine (FLT) and 2′-deoxy-2′-[18F]fluoro-D-glucose (FDG) are used to visualize proliferative and metabolic activity of tumors. In this study we aimed at evaluating the prognostic value of FLT and FDG uptake measured by positron emission tomography (PET) in patients with metastatic non-small cell lung cancer (NSCLC) prior to systemic therapy with erlotinib. FLT and FDG maximum standardized uptake (SUVmax) values per patient were analyzed in 40 chemotherapy naive patients with advanced NSCLC (stage IV) before treatment with erlotinib. Prior therapy median SUVmax was 6.6 for FDG and 3.0 for FLT, respectively. In univariate analysis, patients with an FDG SUVmax <6.6 had a significantly better overall survival (16.3 months [95% confidence interval [CI] 7.1–25.4 months]) compared to patients with an FDG SUVmax ≥6.6 (3.1 months [95% CI 0.6–5.5 months]) (p<0.001, log rank). Similarly, low FLT uptake (SUVmax <3.0) was associated with significantly longer survival (10.3 months (0–23.3 months, 95% CI) compared to high FLT uptake (3.4 months (0–8.1 months, 95% CI) (p = 0.027). The independent prognostic value of baseline FDG uptake was demonstrated in multivariate analysis (p = 0.05, Cox regression). These data suggest that baseline SUVmax values for both FDG and FLT PET might be further developed as markers for prognostic stratification of patients in advanced NSCLC treated with tyrosine kinase inhibitors (TKI) directed against the epidermal growth factor receptor (EGFR).
Trial Registration, Identifier: NCT00568841
PMCID: PMC3537767  PMID: 23308140
8.  18 F-FDG PET-CT during chemo-radiotherapy in patients with non-small cell lung cancer: the early metabolic response correlates with the delivered radiation dose 
To evaluate the metabolic changes on 18 F-fluoro-2-deoxyglucose positron emission tomography integrated with computed tomography (18 F-FDG PET-CT) performed before, during and after concurrent chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC); to correlate the metabolic response with the delivered radiation dose and with the clinical outcome.
Twenty-five NSCLC patients candidates for concurrent chemo-radiotherapy underwent 18 F-FDG PET-CT before treatment (pre-RT PET-CT), during the third week (during-RT PET-CT) of chemo-radiotherapy, and 4 weeks from the end of chemo-radiotherapy (post-RT PET-CT). The parameters evaluated were: the maximum standardized uptake value (SUVmax) of the primary tumor, the SUVmax of the lymph nodes, and the Metabolic Tumor Volume (MTV).
SUVmax of the tumor and MTV significantly (p=0.0001, p=0.002, respectively) decreased earlier during the third week of chemo-radiotherapy, with a further reduction 4 weeks from the end of treatment (p<0.0000, p<0.0002, respectively). SUVmax of lymph nodes showed a trend towards a reduction during chemo-radiotherapy (p=0.06) and decreased significantly (p=0.0006) at the end of treatment. There was a significant correlation (r=0.53, p=0.001) between SUVmax of the tumor measured at during-RT PET-CT and the total dose of radiotherapy reached at the moment of the scan. Disease progression free survival was significantly (p=0.01) longer in patients with complete metabolic response measured at post-RT PET-CT.
In patients with locally advanced NSCLC, 18 F-FDG PET-CT performed during and after treatment allows early metabolic modifications to be detected, and for this SUVmax is the more sensitive parameter. Further studies are needed to investigate the correlation between the metabolic modifications during therapy and the clinical outcome in order to optimize the therapeutic strategy. Since the metabolic activity during chemo-radiotherapy correlates with the cumulative dose of fractionated radiotherapy delivered at the moment of the scan, special attention should be paid to methodological aspects, such as the radiation dose reached at the time of PET.
PMCID: PMC3410758  PMID: 22781363
18F-FDG PET-CT; NSCLC; Chemo-radiotherapy; Metabolic response
9.  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
10.  The effectiveness of dual-phase 18F-FDG PET/CT in the detection of epithelial ovarian carcinoma: a pilot study 
The aim of our study is to establish the potential role of dual-phase 18F-fluorodeoxyglucose positron emission tomography / computed tomography (FDG-PET/CT) in patients presenting ovarian masses with diffuse peritoneal infiltration for differentiating benign from malignant lesions.
Twenty patients (13 with ovarian cancers and 7 with benign lesions) were evaluated preoperatively by dual-phase 18F-FDG-PET/CT performed 1 h and 2 h after injection of 18F-FDG. The maximum standardized uptake value (SUVmax) for both time points SUVmax1 and SUVmax2 were determined, respectively, and the retention index (RI) was calculated by subtracting the SUVmax1 from the SUVmax2 and dividing by SUVmax1.
The areas under the receiver operating characteristic curves (AUCs) of SUVmax1 and SUVmax2 were 0.753 (P = 0.062, 95% confidence interval [CI] = 0.512–0.915) and 0.835 (P = 0.001, 95% CI = 0.604–0.961), respectively. The AUC of the RI was 0.901 (P < 0.001, 95% CI = 0.684–0.988). Using pairwise comparisons, the AUC of SUVmax2 was significantly higher than that of SUVmax1 (P = 0.032). The AUC of the RI was higher than those of SUVmax1 and SUVmax2, but the difference was not statistically significant.
Dual-phase 18F-FDG PET/CT might be considered when preoperative imaging is indeterminate. A larger-scaled, prospective study is needed to verify these results.
PMCID: PMC3922340  PMID: 24499648
Standardized uptake value; Ovarian cancer; Positron emission tomography; Retention index; Dual-phase
11.  Maximum standardized uptake value in 18F-fluoro-2-deoxyglucose positron emission tomography is associated with advanced tumor factors in esophageal cancer 
Molecular and Clinical Oncology  2014;2(2):313-321.
Positron emission tomography/computed tomography (PET/CT) with 18F-fluoro-2-deoxyglucose (FDG-PET/CT) has become established in cancer imaging, and derived maximum standardized uptake values (SUVmax) add functional information regarding cancer, including esophageal squamous cell carcinoma (ESCC). The aim of the present study was to determine the clinical significance and association of tumor progression using SUVmax derived from PET/CT images in patients with ESCC. In total, 101 patients with ESCC were assessed using FDG-PET/CT and the SUVmax was then compared with the clinical backgrounds and prognoses of the patients. Endoscopic ESCC biopsy specimens were obtained in order to analyze mRNA expression relative to tumor progression. The results showed that values for SUVmax were significantly higher in patients with tumor progression factors, particularly those with lymph node metastasis. Analysis of receiver operating characteristics curves revealed an optimum SUVmax cut-off value of 10.26 for node-positive disease. Patients with SUVmax ≥10.26 had gene alterations with epithelial-mesenchymal transition (EMT) and significantly worse overall survival (P=0.0012). A higher SUVmax in patients with ESCC was associated with lymph node metastasis and a poorer prognosis. Thus, the SUVmax may reflect the potential of EMT in patients with ESCC.
PMCID: PMC3917778  PMID: 24649354
esophageal squamous cell carcinoma; 18F-fluoro-2-deoxyglucose; positron emission tomography; maximum standardized uptake value; epithelial-mesenchymal transition
12.  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
13.  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
14.  Prognostic value of 18-fluorodeoxyglucose positron emission tomography-computed tomography in resectable colorectal cancer 
AIM: To assess the prognostic value of preoperative 18 fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) in patients with resectable colorectal cancer.
METHODS: One hundred sixty-three patients with resectable colorectal cancer who underwent FDG-PET/CT before surgery were included. Patient data including pathologic stage at presentation, histology, treatment, disease-free survival and the maximum standardized uptake value (SUVmax) of the primary tumor on FDG-PET/CT were retrospectively analyzed. Median follow up duration was 756 (range, 419-1355). The primary end point was disease-free survival.
RESULTS: Twenty-five of 163 patients (15.3%) had recurrences. The median SUVmax values of the recurrence and no-recurrence groups were 8.9 (range, 5-24) and 8.2 (range, 0-23, P = 0.998). Receiver operating characteristic (ROC) curve analysis showed no significant association between SUVmax and recurrence (area under the curve = 0.5, P = 0.998, 95% CI: 0.389-0.611). Because a statistically significant value was not found, SUVmax was dichotomized at its median of 8.6. The disease-free survival curve was analyzed using the median SUVmax (8.6) as the cut off. Univariate and multivariate analysis did not provide evidence that disease-free survival rates for the subgroups defined by the median SUVmax were significantly different (P = 0.52, P = 0.25).
CONCLUSION: Our study suggests that the high FDG uptake of primary mass in resectable colorectal cancer doesn’t have a significant relationship with tumor recurrence and disease-free survival.
PMCID: PMC3460334  PMID: 23049216
Positron-emission tomography; Colorectal neoplasms; Disease-free survival; Recurrence; Prognosis
15.  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
16.  Quantitative Assessment of Diffusion-Weighted MR Imaging in Patients with Primary Rectal Cancer: Correlation with FDG-PET/CT 
Molecular Imaging and Biology  2010;13(5):1020-1028.
The aim of the study was to assess correlations between parameters on diffusion-weighted imaging and 2-deoxy-2-[18F]fluoro-d-glucose–positron emission tomography/computed tomography (FDG-PET/CT) in rectal cancer.
Thirty-three consecutive patients with pathologically confirmed rectal adenocarcinoma were included in this study. Apparent diffusion coefficient (ADC) maps were generated to calculate ADCmean (average ADC), ADCmin (lowest ADC), tumor volume, and total diffusivity index (TDI). PET/CT exams were performed within 1 week of magnetic resonance imaging. Standardized uptake values (SUVs) were normalized to the injected FDG dose and body weight. SUVmax (maximum SUV), SUVmean (average SUV), tumor volume, and total lesion glycolysis (TLG) were calculated using a 50% threshold.
Significant negative correlations were found between ADCmin and SUVmax (r = −0.450, p = 0.009), and between ADCmean and SUVmean (r = −0.402, p = 0.020). A significant positive correlation was found between TDI and TLG (r = 0.634, p < 0.001).
The significant negative correlations between ADC and SUV suggest an association between tumor cellularity and metabolic activity in primary rectal adenocarcinoma.
PMCID: PMC3179585  PMID: 20872077
ADC; DWI; SUV; PET/CT; Primary rectal adenocarcinoma; TDI; TLG
17.  Risk Assessment Based on FDG-PET Imaging in Patients with Synovial Sarcoma 
Synovial sarcoma generally is associated with poor prognosis. With recent advances in molecular biology, it has become apparent not all synovial sarcomas share the same tumor biology. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is useful for risk assessment in several types of sarcomas. We therefore assessed the clinical value of 18F-FDG-PET-derived maximum standard uptake value (SUVmax) for predicting survival in patients with synovial sarcoma. 18F-FDG-PET was performed in 44 patients with synovial sarcoma before therapy and resection. SUVmax was calculated for each tumor and then evaluated for prognostic usefulness along with metastasis at presentation, tumor grade, histopathologic subtype, age, gender, postsurgical margins, anatomic location, and tumor size for overall survival and progression-free survival. SUVmax ranged from 1.2 to 13.0 (median, 4.35). Pretherapy tumor SUVmax predicted overall survival and progression-free survival. Patients presenting with a SUVmax greater than 4.35 had a decreased disease-free survival and were therefore at high risk for having local recurrences and metastatic disease.
Level of Evidence: Level I, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.
PMCID: PMC2674162  PMID: 19048352
18.  Testicular relapse of non-Hodgkin Lymphoma noted on FDG-PET 
Testicular relapse of leukemia and lymphoma is a well-recognized phenomenon, with testicular relapse of lymphoma being more common in the adult population and leukemia relapse being more common in the pediatric population. With the advent of F-18 fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in the evaluation of lymphoma it is possible to evaluate testicular uptake of FDG and to detect primary testicular lymphoma or testicular relapse on the FDG-PET examination. Testicular relapse of non-Hodgkin lymphoma (NHL) detected on FDG-PET has been reported previously. We report an additional case in which there was testicular activity at presentation, a response to therapy (orchiectomy not performed) and then testicular relapse followed by orchiectomy. We review the literature with regard to testicular recurrence and testicular uptake of FDG-PET. There have been studies that have examined normal standardized uptake value maximum (SUVmax) values in the testicle, with normal values ranging from 2.81 (30–39 years) to 2.18 (80–89 years), depending upon age. However, it should be noted that there could be considerable variability in SUVmax values depending upon the units used (e.g. normalized to lean body mass vs. body weight) and depending upon examination variables such as dietary conditions, muscle uptake or extravasation of FDG. Elevated activity or lateralizing activity should be viewed with suspicion, with etiologies including primary testicular tumor, primary or secondary testicular lymphoma and metastatic disease with other etiologies less likely.
PMCID: PMC3303329  PMID: 22470678
Non-Hodgkin’s Lymphoma; testicular lymphoma; PET/CT; PET
19.  Addition of rituximab to the CHOP regimen has no benefit in patients with primary extranodal diffuse large B-cell lymphoma 
The Korean Journal of Hematology  2011;46(2):103-110.
The addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy (R-CHOP) has significantly improved clinical outcomes for patients with diffuse large B-cell lymphoma (DLBCL). However, new predictors of patient response to R-CHOP have not been established. We aimed to evaluate the impact of R-CHOP compared with CHOP in patients with DLBCL and to establish clinical predictors of better outcomes in these patients.
We retrospectively identified 177 patients diagnosed with CD20-positive DLBCL and treated with CHOP (N=82) or R-CHOP (N=95). The response rate, event-free survival (EFS), and overall survival (OS) rates were compared between the 2 treatment groups. All patients were classified into primary extranodal lymphoma (PENL) or nodal lymphoma (NL) subgroups, and the clinical parameters of each subgroup were analyzed.
The overall response rate was higher in R-CHOP group (95% vs. 84%, P=0.07). The 3-year EFS rate was significantly higher in R-CHOP group (71% vs. 52%, P=0.013), but the OS rate was comparable between the 2 groups (79% vs. 69%, P=0.23). A significant survival benefit was seen with R-CHOP compared to CHOP therapy in NL patients (P=0.002 for EFS and 0.04 for OS). Multivariate analyses confirmed that R-CHOP therapy is an independent prognostic factor for EFS (hazard ratio of 0.32 [0.17-0.62], P=0.001) and OS (hazard ratio of 0.4 [0.18-0.87], P=0.02) in NL patients.
Patients in the PENL group did not benefit from R-CHOP chemotherapy.
PMCID: PMC3128890  PMID: 21747882
CHOP; Diffuse large B-cell lymphoma; Rituximab; Primary extranodal lymphoma
20.  The correlation of SUVmax with pathological characteristics of primary tumor and the value of Tumor/ Lymph node SUVmax ratio for predicting metastasis to lymph nodes in resected NSCLC patients 
We aimed to investigate the correlation of maximum standardized uptake value (SUVmax) with pathological characteristics of primary tumor and to determine a Tumor/ Lymph node (T/LN) SUVmax ratio predicting metastasis to lymph nodes in NSCLC patients.
Eighty-one NSCLC patients who had PET/CT examination at initial staging and subsequently underwent surgical resection were retrospectively evaluated. There were 100 PET/CT positive mediastinal or hilar lymph node stations. Pathological characteristics of the tumor such as largest tumor diameter, tumor histology, differentiation, number of mitosis, degree of stromal inflammation, necrosis; etiology of PET/CT positive lymph node stations; SUVmax of primary tumor and positive lymph node stations were recorded. A T/LN SUVmax ratio was calculated for each lymph node station.
SUVmax of the primary tumor was positively correlated with the largest tumor diameter (p = 0.001, r = 0.374), number of mitosis (p < 0.001, r = 0.405), and postoperative pathological stage (p = 0.007, r = 0.298). Patients with squamous cell carcinoma had a statistically significant higher mean SUVmax, number of mitosis and advanced N stages compared to adenocarcinoma. The etiology of 100 PET/CT positive lymph node stations were metastasis in 14, anthracosis in 40, reactive in 39, granulomatous in 4, and silicosis in 3 patients. A T/LN SUVmax ratio of 5 or lower was suggestive for a malignant lymph node with a sensitivity of 92.8% and specificity of 47%.
SUVmax of a primary tumor is related to certain pathological characteristics, such as largest diameter, histology, and number of mitosis. A T/LN SUVmax ratio lower than 5 predicts the metastasis to lymph nodes with a high sensitivity.
PMCID: PMC3622559  PMID: 23557204
21.  Quantitative F18-Fluorodeoxyglucose Positron Emission Tomography Accurately Characterizes Peripheral Nerve Sheath Tumors as Malignant or Benign 
Cancer  2010;116(2):451-458.
Correct pretreatment classification is critical for optimizing diagnosis and treatment of patients with peripheral nerve sheath tumors (PNSTs). The aim of this study was to evaluate whether F18-fluorodeoxyglucose positron emission tomography (FDG PET) can differentiate malignant (MPNST) from benign PNSTs.
Thirty-four adult patients presenting with PNST who underwent a presurgical FDG PET/computed tomography (CT) scan between February 2005 and November 2008 were included in the study. Tumors were characterized histologically, by FDG maximum standardized uptake value (SUVmax [g/mL]), and by CT size (tumor maximal diameter [cm]). The accuracy of FDG PET for differentiating MPNSTs from benign PNSTs (neurofibroma and schwannoma) was evaluated by receiver operating characteristic (ROC) curve analysis.
SUVmax was measured in 34 patients with 40 tumors (MPNSTs: n = 17; neurofibromas: n = 9; schwannomas: n = 14). SUVmax was significantly higher in MPNST compared with benign PNST (12.0 ± 7.1 vs 3.4 ± 1.8; P < .001). An SUVmax cutoff point of ≥6.1 separated MPNSTs from BPSNTs with a sensitivity of 94% and a specificity of 91% (P < .001). By ROC curve analysis, SUVmax reliably differentiated between benign and malignant PNSTs (area under the ROC curve of 0.97). Interestingly, the difference between MPNSTs and schwannomas was less prominent than that between MPNSTs and neurofibromas.
Quantitative FDG PET imaging distinguished between MPNSTs and neurofibromas with high accuracy. In contrast, MPNSTs and schwannomas were less reliably distinguished. Given the difficulties in clinically evaluating PNST and in distinguishing benign PNST from MPNST, FDG PET imaging should be used for diagnostic intervention planning and for optimizing treatment strategies.
PMCID: PMC3188986  PMID: 19924789
positron emission tomography; computed tomography; malignant peripheral nerve sheath tumor; schwannoma; neurofibroma
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.  FDG-PET/CT as prognostic factor and surveillance tool for postoperative radiation recurrence in locally advanced head and neck cancer 
Radiation Oncology Journal  2011;29(4):243-251.
To evaluate the prognostic value of metabolic tumor volume (MTV) and maximum standardized uptake value (SUVmax) on initial positron emission tomography-computed tomography (PET-CT) and investigate the clinical value of SUVmax for early detection of locoregional recurrent disease after postoperative radiotherapy in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).
Materials and Methods
A total of 100 patients with locally advanced HNSCC received primary tumor excision and neck dissection followed by adjuvant radiotherapy with or without chemotherapy. The MTV and SUVmax were measured from primary sites and neck nodes. The prognostic value of MTV and SUVmax were assessed using initial staging PET/CT (study A). Follow-up PET/CT scan available after postoperative concurrent chemoradiotherapy or radiotherapy were evaluated for the SUVmax value and correlated with locoregional recurrence (study B). A receiver operating characteristic (ROC) curve analysis was used to define a threshold value of SUVmax with the highest accuracy for recurrent disease assessment.
High MTV (>41 mL) is negative prognostic factor for disease free survival (p = 0.041). Postradiation SUVmax was significantly correlated with locoregional recurrence (hazard ratio, 1.812; 95% confidence interval, 1.361 to 2.413; p < 0.001). A cut-off value of 5.38 from follow-up PET/CT was identified as having maximal accuracy for detecting locoregional recurrence by ROC analysis.
MTV at staging work-up was significantly associated with disease free survival. The SUVmax value from follow-up PET/CT showed high diagnostic accuracy for the detection of locoregional recurrence in postoperatively irradiated HNSCC.
PMCID: PMC3429909  PMID: 22984677
Head and neck squamous cell carcinoma; Metabolic tumor volume; Positron-emission tomography; Postoperative radiation therapy; Locoregional recurrence
24.  High-SUVmax on FDG-PET indicates pleomorphic subtype in epithelioid malignant pleural mesothelioma: Supportive evidence to reclassify pleomorphic as non-epithelioid histology 
We have recently proposed to reclassify the pleomorphic subtype of epithelioid malignant pleural mesothelioma (MPM) as non-epithelioid (biphasic/sarcomatoid) histology due to its similarly poor prognosis. We sought to investigate whether preoperative maximum standardized uptake value (SUVmax) on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) correlates with histologic subtype in MPM.
Clinical data was collected for 78 patients with MPM who underwent preoperative FDG-PET. We retrospectively classified the epithelioid tumors into five subtypes: trabecular, tubulopapillary, micropapillary, solid and pleomorphic. Tumors were categorized by SUVmax into two groups: low (<10.0) and high (≥10.0).
The median overall survival of epithelioid tumors with high-SUVmax (n=12) was significantly shorter (7.1 months) than that of epithelioid tumors with low-SUVmax (n=54, 18.9 months, p<0.001) and comparable to non-epithelioid tumors (n=12, 7.2 months). Epithelioid tumors with pleomorphic subtype (n=9) had marginally higher SUVmax (mean±SD: 10.6±5.9) than epithelioid non-pleomorphic subtype (n=57, 6.5±3.2, p=0.050), and were comparable to that of non-epithelioid tumors (n=12, 9.1±4.8). Among the epithelioid tumors with high-SUVmax (n=12), 50% (n=6) showed pleomorphic subtype. In contrast, among epithelioid tumors with low-SUVmax (n=54), 6% (n=3) showed epithelioid pleomorphic subtypes (p=0.001). A positive correlation between mitotic count and SUVmax was observed (r=0.30, p=0.010).
Pleomorphic subtype of epithelioid MPM showed higher SUVmax than epithelioid non-pleomorphic subtype and was similar to non-epithelioid histology. Preoperative SUVmax on FDG-PET in epithelioid MPM can indicate patients with pleomorphic subtype with poor prognosis, supporting their reclassification as non-epithelioid.
PMCID: PMC3691682  PMID: 22617244
Mesothelioma; Pleural neoplasm; Positron emission tomography; Pleomorphic
25.  18F-FDG PET Metabolic Parameters and MRI Perfusion and Diffusion Parameters in Hepatocellular Carcinoma: A Preliminary Study 
PLoS ONE  2013;8(8):e71571.
Glucose metabolism, perfusion, and water diffusion may have a relationship or affect each other in the same tumor. The understanding of their relationship could expand the knowledge of tumor characteristics and contribute to the field of oncologic imaging. The purpose of this study was to evaluate the relationships between metabolism, vasculature and cellularity of advanced hepatocellular carcinoma (HCC), using multimodality imaging such as 18F-FDG positron emission tomography (PET), dynamic contrast enhanced (DCE)-MRI, and diffusion weighted imaging(DWI).
Materials and Methods
Twenty-one patients with advanced HCC underwent 18F-FDG PET, DCE-MRI, and DWI before treatment. Maximum standard uptake values (SUVmax) from 18F-FDG-PET, variables of the volume transfer constant (Ktrans) from DCE-MRI and apparent diffusion coefficient (ADC) from DWI were obtained for the tumor and their relationships were examined by Spearman’s correlation analysis. The influence of portal vein thrombosis on SUVmax and variables of Ktrans and ADC was evaluated by Mann-Whitney test.
SUVmax showed significant negative correlation with Ktransmax (ρ = −0.622, p = 0.002). However, variables of ADC showed no relationship with variables of Ktrans or SUVmax (p>0.05). Whether portal vein thrombosis was present or not did not influence the SUV max and variables of ADC and Ktrans (p>0.05).
In this study, SUV was shown to be correlated with Ktrans in advanced HCCs; the higher the glucose metabolism a tumor had, the lower the perfusion it had, which might help in guiding target therapy.
PMCID: PMC3733842  PMID: 23940769

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