Assessment of tumor response to definitive chemoradiotherapy and prognosis prediction in patients with esophageal cancer judged by PET response criteria in solid tumors: multicenter study in Japan.

OBJECTIVES: The aim of the study was to evaluate PET response criteria in solid tumors (PERCIST) to indicate therapeutic response to definitive chemoradiotherapy, as well as prediction of recurrence and death in patients with esophageal cancer. METHODS: Before and after recieving definitive chemoradiotherapy, 181 patients with esophageal cancer underwent fluorodeoxyglucose-PET/computed tomography (FDG-PET/CT). PERCIST, reduction rates of tumor uptake and volume of whole lesions, tumor node metastasis (TNM) staging regarding progression-free survival (PFS), and overall survival (OS) were analyzed using log-rank and Cox methods. RESULTS: Complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD) shown by PERCIST were seen in 42 (23.2%), 113 (62.4%), 14 (7.7%), and 12 (6.6%) patients, respectively. Progression developed in 137 (75.7%) patients and 101 (56.1%) patients died (median follow-up 16.9, range 3.2-124.9 months). Those who achieved CMR showed significantly longer PFS and OS as compared with patients who did not (PMR, SMD, and PMD) (both P < 0.0001). In univariate analysis, initial clinical T status (P = 0.0048), N status (P = 0.011), and TNM stage (P = 0.0006), PERCIST (P < 0.0001), and reduction rate of peak lean body mass standardized uptake value (P < 0.0001), of metabolic tumor volume (P < 0.0001), and of total lesion glycolysis (TLG) (P < 0.0001) were associated with significantly increased OS. Multivariate analysis confirmed PERCIST [hazard ratio (HR): 13.15, 95% confidence interval (CI), 4.54-55.8; P < 0.0001], and TLG reduction rate (HR: 2.21, 95% CI, 1.04-4.68; P = 0.040) as independent OS predictors. CONCLUSION: PERCIST is useful for evaluating therapeutic response to definitive chemoradiotherapy, and predicting progression and death in patients with esophageal cancer.

Semiquantitative Assessment of 18F-FDG Uptake in the Normal Skeleton: Comparison Between PET/CT and Time-of-Flight Simultaneous PET/MRI.

OBJECTIVE: Differences in the attenuation correction methods used in PET/CT scanners versus the newly introduced whole-body simultaneous PET/MRI reportedly result in differences in standardized uptake values (SUVs) in the normal skeleton. The aim of the study was to compare the semiquantitative FDG uptake in the normal skeleton using time-of-flight (TOF) PET/MRI versus PET/CT with and without TOF. SUBJECTS AND METHODS: Participants received a single FDG injection and underwent non-TOF and TOF PET/CT (n = 23) or non-TOF PET/CT and TOF PET/MRI (n = 50). Mean SUV (SUVmean) and maximum SUV (SUVmax) were measured from all PET scans for nine normal regions of the skeleton. Pearson correlation coefficients (r) were used to evaluate the SUVmax and SUVmean of normal skeleton between non-TOF and TOF PET/CT, as well as between non-TOF PET/CT and TOF PET/MRI. In addition, percentage differences in SUVmax and SUVmean of the normal skeleton between non-TOF and TOF PET/CT and between non-TOF PET/CT and TOF PET/MRI were evaluated. RESULTS: The SUVmax and SUVmean in the normal skeleton significantly increased between non-TOF and TOF PET/CT, but they significantly decreased between non-TOF PET/CT and TOF PET/MRI. The SUVmax and SUVmean in normal skeleton showed good correlation between non-TOF PET/CT and TOF PET/MRI (SUVmax, r = 0.88; SUVmean, r = 0.91) and showed a similar trend between non-TOF and TOF PET/CT (SUVmax, r = 0.88; SUVmean, r = 0.94). CONCLUSION: In the normal skeleton, SUVmax and SUVmean showed high correlations between PET/MRI and PET/CT. The MRI attenuation correction used in TOF PET/MRI provides reliable semiquantitative measurements in the normal skeleton.

Differentiation of Brain Tumor Recurrence from Post-Radiotherapy Necrosis with 11C-Methionine PET: Visual Assessment versus Quantitative Assessment.

PURPOSE: The aim of this multi-center study was to assess the diagnostic capability of visual assessment in L-methyl-11C-methionine positron emission tomography (MET-PET) for differentiating a recurrent brain tumor from radiation-induced necrosis after radiotherapy, and to compare it to the accuracy of quantitative analysis. METHODS: A total of 73 brain lesions (glioma: 31, brain metastasis: 42) in 70 patients who underwent MET-PET were included in this study. Visual analysis was performed by comparison of MET uptake in the brain lesion with MET uptake in one of four regions (around the lesion, contralateral frontal lobe, contralateral area, and contralateral cerebellar cortex). The concordance rate and logistic regression analysis were used to evaluate the diagnostic ability of visual assessment. Receiver-operating characteristic curve analysis was used to compare visual assessment with quantitative assessment based on the lesion-to-normal (L/N) ratio of MET uptake. RESULTS: Interobserver and intraobserver κ-values were highest at 0.657 and 0.714, respectively, when assessing MET uptake in the lesion compared to that in the contralateral cerebellar cortex. Logistic regression analysis showed that assessing MET uptake in the contralateral cerebellar cortex with brain metastasis was significantly related to the final result. The highest area under the receiver-operating characteristic curve (AUC) with visual assessment for brain metastasis was 0.85, showing no statistically significant difference with L/Nmax of the contralateral brain (AUC = 0.89) or with L/Nmean of the contralateral cerebellar cortex (AUC = 0.89), which were the areas that were the highest in the quantitative assessment. For evaluation of gliomas, no specific candidate was confirmed among the four areas used in visual assessment, and no significant difference was seen between visual assessment and quantitative assessment. CONCLUSION: The visual assessment showed no significant difference from quantitative assessment of MET-PET with a relevant cut-off value for the differentiation of recurrent brain tumors from radiation-induced necrosis.

Simultaneous whole-body time-of-flight 18F-FDG PET/MRI: a pilot study comparing SUVmax with PET/CT and assessment of MR image quality.

PURPOSE: The recent introduction of hybrid PET/MRI scanners in clinical practice has shown promising initial results for several clinical scenarios. However, the first generation of combined PET/MRI lacks time-of-flight (TOF) technology. Here we report the results of the first patients to be scanned on a completely novel fully integrated PET/MRI scanner with TOF. MATERIALS AND METHODS: We analyzed data from patients who underwent a clinically indicated F FDG PET/CT, followed by PET/MRI. Maximum standardized uptake values (SUVmax) were measured from F FDG PET/MRI and F FDG PET/CT for lesions, cerebellum, salivary glands, lungs, aortic arch, liver, spleen, skeletal muscle, and fat. Two experienced radiologists independently reviewed the MR data for image quality. RESULTS: Thirty-six patients (19 men, 17 women, mean [±standard deviation] age of 61 ± 14 years [range: 27-86 years]) with a total of 69 discrete lesions met the inclusion criteria. PET/CT images were acquired at a mean (±standard deviation) of 74 ± 14 minutes (range: 49-100 minutes) after injection of 10 ± 1 mCi (range: 8-12 mCi) of F FDG. PET/MRI scans started at 161 ± 29 minutes (range: 117 - 286 minutes) after the F FDG injection. All lesions identified on PET from PET/CT were also seen on PET from PET/MRI. The mean SUVmax values were higher from PET/MRI than PET/CT for all lesions. No degradation of MR image quality was observed. CONCLUSION: The data obtained so far using this investigational PET/MR system have shown that the TOF PET system is capable of excellent performance during simultaneous PET/MR with routine pulse sequences. MR imaging was not compromised. Comparison of the PET images from PET/CT and PET/MRI show no loss of image quality for the latter. These results support further investigation of this novel fully integrated TOF PET/MRI instrument.

Observer variation study of the assessment and diagnosis of incidental colonic FDG uptake.

PURPOSE: The aim of this study was to evaluate the interpretations of incidental colonic 18F-FDG uptake made by 10 experienced readers and to more clearly identify the pattern of suspicious colonic FDG uptake. The potential contributions of delayed FDG-PET scanning and of immune fecal occult blood testing (FOBT) in making a diagnosis were also analyzed. MATERIALS AND METHODS: Visual interpretations by 10 readers were made for 147 FDG uptake sites from 126 PET scans (cancer, 38 sites; adenoma, 43 sites; and no abnormality, 66 sites) with colonic FDG uptake. Assessments for the early FDG-PET images were (1) FDG uptake pattern, (2) FDG uptake degree, and (3) likelihood of malignancy. For the delayed images, the assessments were (1) change in the FDG uptake position, (2) change in FDG uptake degree, and (3) likelihood of malignancy. The results of FOBT were analyzed independently of the visual interpretations. RESULTS: Interobserver agreement (κ) was 0.501 for assessing FDG uptake patterns, while agreement on assessing changes in uptake degree and changes in uptake position between early and delayed imaging were low (κ = 0.213-0.229). Logistic regression analysis indicated that 'FDG uptake patterns' and 'FDG uptake degree' were significantly related to decide on the suspicion of malignancy (p < 0.001) and the final result (p < 0.001). "Small localized" and "large irregular localized" types had a high probability of a lesion regardless of either (1) FDG uptake degree or (2) variation in the uptake between the early and the delayed image. The delayed image decreased false-positive cases for some FDG uptake patterns, but it had little impact on distinguishing clearly between "cancer or adenoma" and "normal". The addition of FOBT had little impact on the diagnosis. CONCLUSION: There was highest agreement among readers with respect to the recognition of specified colonic FDG uptake patterns, and this pattern recognition had the most influence on the diagnosis. "Small localized" and "large irregular localized" types had a high probability of a lesion. The addition of delayed imaging and of FOBT results to the early imaging did not have much impact on the diagnosis.

Early assessment by FDG-PET/CT of patients with advanced renal cell carcinoma treated with tyrosine kinase inhibitors is predictive of disease course.

BACKGROUND: We reported previously that (18)F-2-fluoro-2-deoxyglucose positron emission tomography/ computed tomography (FDG PET/CT) had potential for evaluating early response to treatment by tyrosine kinase inhibitors (TKIs) in advanced renal cell carcinoma (RCC). This time we investigated the relation of the early assessment by FDG PET/CT to long-term prognosis with an expanded number of patients and period of observation. METHODS: Patients for whom TKI treatment for advanced RCC was planned were enrolled. FDG PET/CT was performed before TKI treatment and after one month of TKI treatment. The relations of the FDGPET/CT assessment to progression free survival (PFS) and overall survival (OS) were investigated. RESULTS: Thirty-five patients were enrolled (sunitinib 19 cases, sorafenib 16 cases). The patients with RCC showing high SUVmax in pretreatment FDG PET/CT demonstrated short PFS (P =0.024, hazard ratio 1.137, 95% CI 1.017-1.271) and short OS (P =0.004, hazard ratio 1.210 95% CI 1.062-1.379). Thirty patients (sunitinib 16 cases, sorafenib 14 cases) were evaluated again after 1 month. The PFS of the patients whose SUVmax decreased<20% was shorter than that of the patients whose SUVmax decreased<20% (P = 0.027, hazard ratio 3.043, 95% CI 1.134-8.167). The PFS of patients whose tumor diameter sum increased was shorter than that of the patient with tumors whose diameter sum did not (P =0.006, hazard ratio 4.555, 95% CI 1.543-13.448). The patients were classified into three response groups: good responder (diameter sum did not increase, and SUVmax decreased ≥ 20%), intermediate responder (diameter sum did not increase, and SUVmax decreased<20%), and poor responder (diameter sum increased, or one or more new lesions appeared). The median PFS of good, intermediate, and poor responders were 458 ± 146 days, 131 ± 9 days, and 88 ± 26 days (good vs. intermediate P = 0.0366, intermediate vs. poor P = 0.0097, log-rank test). Additionally the mean OSs were 999 ± 70 days, 469 ± 34 days, and 374 ± 125 days, respectively (good vs. intermediate P = 0.0385, intermediate vs. poor P = 0.0305, log-rank test). CONCLUSIONS: The evaluation of RCC response to TKI by tumor size and FDG uptake using FDG PET/CT after 1 month can predict PFS and OS.

A meta-analysis of (18)F-Fluoride positron emission tomography for assessment of metastatic bone tumor.

PURPOSE: The aim of this study was to assess the diagnostic performance of (18)F-Fluoride positron emission tomography (PET) or positron emission tomography/computed tomography (PET/CT) compared with bone scintigraphy (BS) planar or BS planar and single photon emission computed tomography (SPECT) in evaluating patients with metastatic bone tumor. MATERIALS AND METHODS: We performed a meta-analysis of all available studies addressing the diagnostic accuracy of (18)F-Fluoride PET, (18)F-Fluoride PET/CT, BS planar, and BS planar and SPECT for detecting the metastatic bone tumor. We determined sensitivities and specificities across studies, calculated positive and negative likelihood ratios, and drew summary receiver operating characteristic curves using hierarchical regression models. We also compared the effective dose and cost-effectiveness estimated by data from the enrolled studies between (18)F-Fluoride PET or PET/CT and BS planar or BS planar and SPECT. RESULTS: When comparing all studies with data on (18)F-Fluoride PET or PET/CT, sensitivity and specificity were 96.2% [95% confidence interval (CI) 93.5-98.9%] and 98.5% (95% CI 97.0-100%), respectively, on a patient basis and 96.9% (95% CI 95.9-98.0%) and 98.0% (95% CI 97.1-98.9%), respectively, on a lesion basis. The Az values of (18)F-Fluoride PET or PET/CT were 0.986 for the patient basis and 0.905 for the lesion basis, whereas those of BS or BS and SPECT were 0.866 for the patient basis and 0.854 for the lesion basis. However, the estimated effective dose and average cost-effective ratio were poorer for (18)F-Fluoride PET or PET/CT than those of BS planar or BS planar and SPECT. CONCLUSION: (18)F-Fluoride PET or PET/CT has excellent diagnostic performance for the detection of metastatic bone tumor, but the estimated effective dose and average cost-effective ratio are at a disadvantage compared with BS planar or BS planar and SPECT.

[Assessment of diagnostic criteria for FDG-PET cancer screening program according to the interpretation of FDG-PET and combined examination].

OBJECTIVE: The aim of this study is to establish the diagnostic criteria for FDG-PET cancer screening program of four kinds of organ (breast, thyroid, lung and colon/rectum) according to the interpretation of FDG-PET cancer screening program of the case with proved clinical outcome. METHODS: Among FDG-PET cancer screening examinations performed in two PET centers during 2003 to 2006, two hundreds of examinations with proved clinical outcome were evaluated. Interpretation of breast ultrasonography, thyroid ultrasonography, chest CT and fecal occult blood testing, which were regarded as combined examinations, were performed together with the interpretation of FDG-PET images. RESULTS: As a result of the interpretation, localized FDG accumulating site in all four organs should be recommended for further inspections. In addition, essential point for diagnosis was considered as follows; (1) check over the slight localized FDG accumulation with screening of breast region, (2) combine chest CT with FDG-PET for the evaluation of lung region and (3) check up the shift of FDG accumulation between early and delayed phase with screening of colon/rectum region. CONCLUSIONS: According to the interpretation results of this study, we establish diagnostic criteria of FDG-PET and combined examination of four kinds of organ.