Seung Hyup Hyun

Metabolic Tumor Volume of [18F]-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Predicts Short-Term Outcome to Radiotherapy With or Without Chemotherapy in Pharyngeal Cancer

Purpose: This study aimed to investigate whether metabolic tumor volume (MTV) measured from [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) predicts short-term outcome to radiotherapy with or without chemotherapy and disease-free survival (DFS) in patients with pharyngeal cancers. Experimental Design: The MTVs of primary sites with or without neck nodes were measured in 82 patients. Short-term outcome was assessed using the treatment response evaluation by the Response Evaluation Criteria in Solid Tumors and recurrence events during follow-up (complete response/no recurrence or residual disease/recurrence). Results: A total of 64 patients had complete response/no recurrence as of the last follow-up. A cutoff of 40 mL for the MTV was the best discriminative value for predicting treatment response. By univariate analyses, patients with MTV >40 mL showed a significantly lower number of complete response/no recurrence than did patients with MTV ≤40 mL [68.2% versus 87.8%; hazard ratio (HR), 3.34; 95% confidence interval (95% CI), 1.09-10.08; P = 0.03], as is the same in tumor-node-metastasis stage (87.5% for I-II versus 90% for III versus 63.8% for IV; P = 0.02). However, MTV was only a significant predictor of short-term outcome by multivariate analyses (HR, 4.09; 95% CI, 1.02-16.43; P = 0.04). MTV >40 mL indicated a significantly worse DFS than MTV ≤40 mL (HR, 3.42; 95% CI, 1.04-11.26;P = 0.04). The standardized uptake value for the primary tumor did not show any correlation with treatment outcome or DFS. Conclusion: MTV has a potential value in predicting short-term outcome and DFS in patients with pharyngeal cancers. (Clin Cancer Res 2009;15(18):5861–8)

Volume-Based Parameters of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Improve Outcome Prediction in Early-Stage Non-Small Cell Lung Cancer After Surgical Resection.

Objective: To evaluate the prognostic significance and predictive performance of volume-based parameters of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in early-stage non–small cell lung cancer (NSCLC). Background: Although surgical resection remains the optimal treatment for early-stage NSCLC, approximately 40% of patients with stage I and 60% of patients with stage II NSCLC relapse and die within 5 years after curative resection. Therefore, identification of additional prognostic biomarkers is needed to develop risk-adapted treatment strategies. Methods: We retrospectively reviewed 529 consecutive patients with pathologically proven early-stage NSCLC who underwent preoperative 18F-FDG PET/CT. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for the primary tumors were measured. Overall survival (OS) and disease-free survival (DFS) were assessed by the Kaplan-Meier method. The prognostic significance of PET parameters and other clinicopathological variables was assessed by Cox proportional hazards regression analysis. To evaluate and compare the predictive performance of PET parameters, time-dependent receiver operating characteristic (ROC) curve analysis was used. Results: In the multivariate analyses, volume-based parameters of PET (MTV and TLG) that were analyzed as continuous variables were significantly associated with an increased risk of recurrence (P = 0.001 for MTV, P < 0.001 for TLG) and death (P = 0.009 for MTV, P = 0.007 for TLG), after adjusting for age, sex, histology, tumor stage, and type of surgery. SUVmax analyzed as a continuous variable was not a significant prognostic factor for both DFS (P = 0.056) and OS (P = 0.525). In the time-dependent ROC curve analysis, the volume-based parameter of PET showed better predictive performance than SUVmax (P < 0.001). Conclusions: The volume-based parameter of PET is an independent prognostic factor for survival in addition to pathological tumor-node-metastasis stage and a promising tool for better prediction of outcome in patients with early-stage NSCLC.

Prognostic significance of volume-based PET parameters in cancer patients.

Accurate prediction of cancer prognosis before the start of treatment is important since these predictions often affect the choice of treatment. Prognosis is usually based on anatomical staging and other clinical factors. However, the conventional system is not sufficient to accurately and reliably determine prognosis. Metabolic parameters measured by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) have the potential to provide valuable information regarding prognosis and treatment response evaluation in cancer patients. Among these parameters, volume-based PET parameters such as metabolic tumor volume and total lesion glycolysis are especially promising. However, the measurement of these parameters is significantly affected by the imaging methodology and specific image characteristics, and a standard method for these parameters has not been established. This review introduces volume-based PET parameters as potential prognostic indicators, and highlights methodological considerations for measurement, potential implications, and prospects for further studies.

Prognostic Value of Volume-Based 18 F-Fluorodeoxyglucose PET/CT Parameters in Patients with Clinically Node-Negative Oral Tongue Squamous Cell Carcinoma

Objective To evaluate the prognostic value of volume-based metabolic parameters measured with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in patients with clinically node-negative (cN0) oral tongue squamous cell carcinoma (OTSCC) as compared with other prognostic factors. Materials and Methods In this study, we included a total of 57 patients who had been diagnosed with cN0 tongue cancer by radiologic, 18F-FDG PET/CT, and physical examinations. The maximum standardized uptake value (SUVmax), average SUV (SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for primary tumors were measured with 18F-FDG PET. The prognostic significances of these parameters and other clinical variables were assessed by Cox proportional hazards regression analysis. Results In the univariate analysis, pathological node (pN) stage, American Joint Committee on Cancer (AJCC) stage, SUVmax, SUVavg, MTV, and TLG were significant predictors for survival. On a multivariate analysis, pN stage (hazard ratio = 10.555, p = 0.049), AJCC stage (hazard ratio = 13.220, p = 0.045), and MTV (hazard ratio = 2.698, p = 0.033) were significant prognostic factors in cN0 OTSCC patients. The patients with MTV ≥ 7.78 cm3 showed a worse prognosis than those with MTV < 7.78 cm3 (p = 0.037). Conclusion The MTV of primary tumor as a volumetric parameter of 18F-FDG PET, in addition to pN stage and AJCC stage, is an independent prognostic factor for survival in cN0 OTSCC.

Risk stratification on the basis of Deauville score on PET-CT and the presence of Epstein-Barr virus DNA after completion of primary treatment for extranodal natural killer/T-cell lymphoma, nasal type: a multicentre, retrospective analysis

BACKGROUND Assessment of tumour viability after treatment is essential for prediction of treatment failure in patients with extranodal natural killer/T-cell lymphoma (ENKTL). We aimed to assess the use of the post-treatment Deauville score on PET-CT and Epstein-Barr virus DNA as a predictor of residual tumour, to establish the risk of treatment failure in patients with newly diagnosed ENKTL. METHODS In a retrospective analysis of patient data we assessed the prognostic relevance of the Deauville score (five-point scale) on PET-CT and circulating Epstein-Barr virus DNA after completion of treatment in consecutive patients with ENKTL who met eligibility criteria (newly diagnosed and received non-anthracycline-based chemotherapy, concurrent chemoradiotherapy, or both together) diagnosed at the Samsung Medical Center in Seoul, South Korea. The primary aim was to assess the association between progression-free survival and risk stratification based on post-treatment Deauville score and Epstein-Barr virus DNA. With an independent cohort from two different hospitals (Hong Kong and Singapore), we validated the prognostic value of our risk model. FINDINGS We included 102 patients diagnosed with ENKTL between Jan 6, 2005, and Nov 18, 2013, in the study cohort, and 38 patients diagnosed with ENKTL between Jan 7, 2009, and June 27, 2013, in the validation cohort. In the study cohort after a median follow-up of 47·2 months (IQR 30·0-65·5), 45 (44%) patients had treatment failure and 33 (32%) had died. Post-treatment Deauville score and Epstein-Barr virus DNA positivity were independently associated with progression-free and overall survival in the multivariable analysis (for post-treatment Deauville score of 3-4, progression-free survival hazard ratio [HR] 3·607, 95% CI 1·772-7·341, univariable p<0·0001; for post-treatment Epstein-Barr virus DNA positivity, progression-free survival HR 3·595, 95% CI 1·598-8·089, univariable p<0·0001). We stratified patients into three groups based on risk of treatment failure: a low-risk group (post-treatment Epstein-Barr virus negativity and post-treatment Deauville score of 1-2), a high-risk group (post-treatment Epstein-Barr virus negativity with a Deauville score 3-4, or post-treatment Epstein-Barr virus positivity with a Deauville score 1-2), and treatment failure (Deauville score of 5 or post-treatment Epstein-Barr positivity with a Deauville of score 3-4). This risk model showed a significant association with progression-free survival (for low risk vs high risk, HR 7·761, 95% CI 2·592-23·233, p<0·0001; for low risk vs failure, HR 18·546, 95% CI 5·997-57·353, p<0·0001). The validation cohort showed the same associations (for low risk vs high risk, HR 22·909, 95% CI 2·850-184·162, p=0·003; for low risk vs failure, HR 50·652, 95% CI 6·114-419·610, p<0·0001). INTERPRETATION Post-treatment Deauville score on PET-CT scan and the presence of Epstein-Barr virus DNA can predict the risk of treatment failure in patients with ENKTL. Our results might be able to help guide clinical practice. FUNDING Samsung Biomedical Research Institute.

Potential value of radionuclide cisternography in diagnosis and management planning of spontaneous intracranial hypotension.

OBJECTIVES Spontaneous intracranial hypotension (SIH) is caused by spontaneous spinal cerebrospinal fluid (CSF) leaks. However, there is debate regarding clinical indication of radionuclide cisternography (RNC) for identification of the actual site of a CSF leak. We therefore investigated the potential value of RNC in SIH. PATIENTS AND METHODS RNC was performed on 30 patients with SIH. Patients were managed with conservative management only or epidural blood patches (EBPs) according to clinical conditions and RNC findings. RESULTS RNC revealed direct signs of spinal CSF leaks in 80% of patients. Of this group, complete resolution of headache was obtained in 12 (71%) of 17 patients who received EBP vs. 1 (14%) of 7 patients treated with conservative management only (p=0.02). Complete headache relief with conservative management only was seen in one (14%) patient with direct signs of spinal CSF leaks compared to five (83%) patients without direct signs (p=0.03). CONCLUSION RNC is useful for diagnosis and better management planning of SIH.

Volume-based Metabolic Tumor Response to Neoadjuvant Chemotherapy Is Associated with an Increased Risk of Recurrence in Breast Cancer

PURPOSE To evaluate the prognostic value of a volume-based metabolic tumor response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. MATERIALS AND METHODS This study was approved by the institutional review board, with waivers of informed consent. One hundred sixty-seven patients (mean age, 44 years; range, 22-68 years) with clinical stage II or III breast cancer who underwent fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography scans at baseline and after completion of neoadjuvant chemotherapy between July 2006 and June 2013 were selected. The association between the metabolic response parameters and the disease-free survival was assessed by using a Cox proportional hazards regression model and time-dependent receiver operating characteristic curve analysis. Metabolic response parameters included the maximum standardized uptake value (SUVmax), the total metabolic tumor volume (MTVtotal), and the relative decrease in SUVmax and MTVtotal. RESULTS In the Cox model, posttreatment SUVmax (P = .029) and MTVtotal (P = .028) and relative decreases in SUVmax (P = .032) and MTVtotal (P = .005) after neoadjuvant chemotherapy were significantly associated with disease-free survival after adjusting for pretreatment clinical stage, yp stage, and tumor subtype. In the time-dependent receiver operating characteristic curve analysis, MTVtotal after neoadjuvant chemotherapy had the highest association with outcome compared with the other parameters (P < .001). MTVtotal of up to 0.2 cm(3) after neoadjuvant chemotherapy was significantly associated with a favorable outcome in patients who did not achieve pathologic complete response after neoadjuvant chemotherapy. CONCLUSION The volume-based metabolic tumor response to neoadjuvant chemotherapy is associated with an increased risk of recurrence, regardless of tumor subtype and pathologic tumor response.

Association Between Nonalcoholic Fatty Liver Disease and Carotid Artery Inflammation Evaluated by 18F-Fluorodeoxyglucose Positron Emission Tomography:

We assessed the association between nonalcoholic fatty liver disease (NAFLD) and carotid artery inflammation measured by 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography. Participants were 755 consecutive otherwise healthy adult males who underwent a general health screening program. Carotid FDG uptake, represented as maximum target-to-background ratio, was increased with mild (n = 237; 1.61 ± 0.14; P = .033) and moderate NAFLD (n = 145; 1.63 ± 0.16; P = .005) compared with controls (n = 373; 1.58 ± 0.15). In patients aged >50 years, moderate NAFLD was the only independent risk factor for high carotid FDG uptake (odds ratio, 2.12; 95% confidence interval, 1.10-4.07; P = .001). Apparently healthy adult males with NAFLD have elevated carotid FDG uptake as well as increased carotid intima–media thickness, suggesting that they may be at an increased risk of having inflammatory atherosclerotic plaques in the carotid arteries.

Neovascularization Precedes Occlusion in Moyamoya Disease: Angiographic Findings in 172 Pediatric Patients

Background: Both basal collaterals (BC) and cortical microvascularization (CM) on angiography have been suggested as moyamoya disease (MMD)-specific findings; however, it is unknown whether the vascular network represents compensatory mechanisms for vascular occlusion or aberrant active neovascularization. Methods: We investigated the grade of antegrade MCA flow, the degree of BC, and the presence of CM on conventional angiography in relation to disease severity in pediatric MMD. CM was defined as enlarged and winding distal cortical arteries and categorized into anterior or posterior CM depending on their sources. Findings from basal and acetazolamide stress brain perfusion SPECT studies were also evaluated. Results: A total of 172 pediatric patients with MMD were enrolled in this study. As the severity of MMD increased, the grade of antegrade MCA flow gradually diminished. While the degree of BC peaked at Suzuki stage 3-4, CM was frequently observed at early MMD stages. About two-thirds of hemispheres with normal antegrade MCA flow on angiography and normal perfusion status on SPECT had anterior and/or posterior CM. Both anterior and posterior CM gradually decreased with the advancement of MMD. Conclusion: Our findings from a large cohort of angiographically confirmed pediatric MMD patients indicate that neovascularization may occur before significant hemodynamic impairment in MMD.

Utility of FDG PET/CT for Differential Diagnosis of Patients Clinically Suspected of IgG4-Related Disease.

Purpose We investigated the capacity of 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) to differentially diagnose immunoglobulin G4–related disease (IgG4-RD) in clinically suspected patients. Materials and Methods Subjects were 94 clinically suspected patients who had tissue IgG4 staining (n = 85) or serum IgG4 greater than 135 mg/dL (n = 9) and underwent FDG PET/CT within 40 days. Clinical, serologic, pathological, and PET/CT findings were analyzed. Binary logistic regression analysis was performed to assess the diagnostic performance of PET/CT. Results Final diagnosis was IgG4-RD in 28, malignancy in 29, IgG4-unrelated inflammation in 35, and undetermined cause in 2 subjects. Patients with IgG4-RD had lower maximum standardized uptake value (SUVmax) of FDG uptake in lesions (4.6 ± 1.7 vs 7.1 ± 5.0) and higher submandibular gland SUVmax (2.8 ± 1.0 vs 2.3 ± 0.6) and were more likely to have diffuse/heterogeneous uptake pattern (78.6% vs 54.8%). The relation between SUVmax of lesions and histopathological findings was weak. On binary logistic regression analysis, lesion SUVmax, submandibular gland SUVmax, and multiorgan involvement were significant predictors of IgG4-RD and provided an area under the receiver operating characteristics curve of 0.824. With optimum criteria, FDG PET/CT had a sensitivity of 85.7% and specificity of 66.1% for diagnosing IgG4-RD. Conclusions FDG PET/CT findings may have the capacity to potentially differentiate IgG4 RD from other diseases in clinically suspected patients.