Faculty Bibliography

PURPOSE/OBJECTIVE:We performed a systematic review and meta-analysis on the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) derived from pretreatment F-FDG PET/CT in patients with esophageal cancer. METHODS:PubMed and EMBASE databases were searched until April 12, 2018, for studies that evaluated MTV or TLG as prognostic factors in esophageal cancer, with overall survival (OS) and event-free survival serving as the end points. Hazard ratios (HRs) were meta-analytically pooled using a random-effects model. Subgroup analyses based on the clinicopathological and PET variables were performed. RESULTS:In total, 16 studies with 1294 patients were included. The pooled HRs of MTV and TLG for OS were 2.26 (95% confidence interval [CI], 1.73-2.96) and 2.23 (95% CI, 1.73-2.87), respectively. Regarding event-free survival, the pooled HRs of MTV and TLG were 2.03 (95% CI, 1.66-2.49) and 2.57 (95% CI, 1.82-3.62), respectively. Metabolic tumor volume was found to be a significant prognostic factor for OS consistently across multiple subgroups classified based on stage, histological subtype, treatment, delineation of volume of interest, and the determination method of cutoff value, with pooled HRs ranging from 1.96 to 2.54. CONCLUSIONS:In patients with esophageal cancer, MTV and TLG derived from pretreatment F-FDG PET are significant prognostic factors. As prognostic biomarkers, volumetric metabolic parameters may bolster the role of F-FDG PET in the management of esophageal cancer.

OBJECTIVE:F-FDG PET) in patients with lung cancer. METHODS:PubMed and EMBASE databases were searched up to March 12, 2018, for original articles involving texture analysis for the prediction of prognosis in patients with lung cancer. Risk of bias in the studies was critically assessed using the QUIPS tool. The results of survival analysis in the included studies were compared. RESULTS:Of the 446 articles retrieved, 17 studies were eligible for inclusion. Our review suggests that the prognostic value of texture parameters in lung cancer remains unproven. Most studies had a moderate to high risk of bias. Texture parameters that described prognosis were not replicated across studies. Conflicting results on hazard ratios were found among the studies. This discrepancy is partly explained by false-positive findings originating from statistical error and variability caused by different methodologies used for image acquisition and processing in the included studies. CONCLUSION/CONCLUSIONS:F-FDG PET in lung cancer. Further studies implementing well-established methodologies and statistical evidence are warranted for proper validation of these promising imaging biomarkers.

OBJECTIVE:We describe a systematic review and meta-analysis of the performance of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) for detecting metastasis in ovarian cancer. METHODS:MEDLINE and Embase were searched for diagnostic accuracy studies that used ¹⁸F-FDG PET or PET/CT for pre-treatment staging, using surgical findings as the reference standard. Sensitivities and specificities were pooled and plotted in a hierarchic summary receiver operating characteristic plot. Potential causes of heterogeneity were explored through sensitivity analyses. RESULTS:Eight studies with 594 patients were included. The overall pooled sensitivity and specificity for metastasis were 0.72 (95% confidence interval [CI]=0.61-0.81) and 0.93 (95% CI=0.85-0.97), respectively. There was considerable heterogeneity in sensitivity (I²=97.57%) and specificity (I²=96.74%). In sensitivity analyses, studies that used laparotomy as the reference standard showed significantly higher sensitivity and specificity (0.77; 95% CI=0.67-0.87 and 0.96; 95% CI=0.92-0.99, respectively) than those including diagnostic laparoscopy (0.62; 95% CI=0.46-0.77 and 0.84; 95% CI=0.69-0.99, respectively). Higher specificity was shown in studies that confirmed surgical findings by pathologic evaluation (0.95; 95% CI=0.90-0.99) than in a study without pathologic confirmation (0.69; 95% CI=0.24-1.00). Studies with a lower prevalence of the FDG-avid subtype showed higher specificity (0.97; 95% CI=0.94-1.00) than those with a greater prevalence (0.89; 95% CI=0.80-0.97). CONCLUSION/CONCLUSIONS:Pre-treatment ¹⁸F-FDG PET/CT shows moderate sensitivity and high specificity for detecting metastasis in ovarian cancer. With its low false-positive rate, it can help select surgical approaches or alternative treatment options.

OBJECTIVE:F-FDG PET/CT parameters regarding the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in patients with uterine cervical cancer. MATERIALS AND METHODS:The PubMed and EMBASE databases were systematically searched until January 19, 2018. We included studies that evaluated pretreatment MTV or TLG as a prognostic factor in uterine cervical cancer with event-free (EFS) and overall survival (OS) as the endpoints. Effect sizes of the prognostic value of MTV and TLG were measured in terms of hazard ratio (HR) and were meta-analytically pooled. Multiple subgroup analyses stratified to clinicopathologic and PET/CT variables were performed to explore heterogeneity. RESULTS:Twelve studies including 660 patients were included. Prognoses were worse in patients with high MTV and TLG, with pooled HRs of 5.89 (95% CI, 3.85-9.01; p < 0.00001) and 5.82 (95% CI, 3.62-9.35; p < 0.00001), respectively, for EFS and 6.62 (95% CI, 3.44-12.73; p < 0.00001) and 7.75 (95% CI, 3.48-17.27; p < 0.00001), respectively, for OS. At multiple subgroups analyses, the prognostic values of MTV and TLG for EFS were consistently significant, with pooled HRs of 5.08-7.30 and 4.80-15.83, respectively. CONCLUSION:Volume-based FDG PET/CT parameters were significant prognostic factors in patients with uterine cervical cancer. In spite of clinical and methodologic differences across the studies, patients with high MTV or TLG had a higher risk of adverse events or death.

OBJECTIVE:The purpose of this study was to perform a systematic review and meta-analysis of a head-to-head comparison between the performance of biparametric MRI (bpMRI; only T2-weighted imaging and DWI) and that of multiparametric MRI (mpMRI; T2-weighted imaging, DWI, dynamic contrast-enhanced MRI) for the diagnosis of prostate cancer. MATERIALS AND METHODS:The PubMed and Embase databases were searched up to November 11, 2017. The search included diagnostic test accuracy studies that compared bpMRI and mpMRI for prostate cancer diagnosis with histopathologic findings from biopsy or radical prostatectomy as the reference standard. Methodologic quality was evaluated with the revised Quality Assessment of Diagnostic Accuracy Studies tool. Sensitivity and specificity were pooled by means of bivariate and hierarchic summary ROC (HSROC) modeling and graphically presented with HSROC plots. Meta-regression analysis and multiple subgroup analyses were used to compare the diagnostic performances of bpMRI and mpMRI. RESULTS:Twenty studies (2142 patients) were included. Pooled sensitivity and specificity were 0.74 (95% CI, 0.66-0.81) and 0.90 (95% CI, 0.86-0.93) for bpMRI and 0.76 (95% CI, 0.69-0.82) and 0.89 (95% CI, 0.85-0.93) for mpMRI. MRI protocol (bpMRI vs mpMRI) was not a significant factor in heterogeneity (p = 0.83). In 26 subgroups evaluated on the basis of stratification to clinicopathologic, study, and MRI characteristics, MRI protocol (bpMRI vs mpMRI) was not a significant factor in heterogeneity in any subgroup (p = 0.25-0.97). CONCLUSION:A head-to-head comparison showed that the performance of bpMRI was similar to that of mpMRI in the diagnosis of prostate cancer. Consistent results were found in multiple subgroup analyses.

PURPOSE:To evaluate the association of apparent diffusion coefficient (ADC), intravoxel incoherent motion (IVIM) MRI-derived parameters, and T2* relaxation time with histopathological changes observed during renal fibrogenesis in a rabbit model of unilateral ureter obstruction (UUO). METHODS:Twenty New Zealand White rabbits underwent baseline MRI followed by surgery (sham or UUO) and then follow-up MRI at postoperative day (POD) 0, 3, 7, and 14. Hematoxylin and eosin and Masson's trichrome staining was performed to evaluate cell density and area of fibrosis. Spearman rank correlation and Pearson correlation tests and one-way analysis of variance were used for statistical analyses. RESULTS:There was a continuous increase in the area of fibrosis and cell density: rho = 0.900 (95% confidence interval [CI] = 0.760, 0.960; p < 0.0001) and 0.904 (95% CI = 0.769, 0.962; p < 0.0001), respectively. There was a tendency for all MRI variables to decrease at POD 3 and partly recover at POD 7. ADC, D, f, and T2* relaxation time showed significant correlation with area of fibrosis and cell density (r = -0.5177 and -0.6962, -0.5395 and -0.7851, -0.7168 and -0.7902, and -0.6808 and -0.7212, respectively; p = 0.0052-0.0481) while D* did not (p = 0.1997 and 0.7853, respectively). CONCLUSIONS:ADC, IVIM MRI-derived parameters, and T2* relaxation time were significantly associated with the area of fibrosis and cell density during renal fibrogenesis in a rabbit model of UUO. After validation in future studies, MRI may have potential for noninvasive assessment modality of renal fibrosis.

CONTEXT: OBJECTIVE:Ga-PSMA PET on management of patients with prostate cancer. EVIDENCE ACQUISITION:Ga-PSMA PET in patients with prostate cancer. The quality of the studies was evaluated using the GRADE system. The proportion of management changes were pooled using random-effects model. Subgroup analyses and meta-regression analyses were performed to explore heterogeneity. EVIDENCE SYNTHESIS:Ga-PSMA PET. CONCLUSIONS: PATIENT SUMMARY:Ga-PSMA PET altered the management in approximately half of the patients.

Background Recent literature suggests that intratumoral hemorrhage detection may be helpful in differentiating papillary renal cell carcinoma (pRCC) from fat-poor angiomyolipoma (fpAML). Purpose To determine whether intratumoral hemorrhage detected using chemical shift magnetic resonance imaging (MRI) and T2*-weighted (T2*W) gradient echo (GRE) can be used to differentiate pRCC from fpAML. Material and Methods This retrospective study included 42 patients with pRCC (n = 28) and fpAML (n = 14) who underwent MRI followed by surgery. Two blinded radiologists independently assessed the presence of intratumoral hemorrhage using chemical shift MRI (decrease in signal intensity from opposed- to in-phase) and T2*W GRE ("blooming"). Consensus reading was determined for discrepant cases. MRI findings were compared using Chi-square test. Inter-observer agreement was assessed using kappa statistics. Results Inter-observer agreement was substantial for both sequences ( k = 0.622 and 0.793, P < 0.001). For chemical shift MRI, the prevalence of intratumoral hemorrhage was significantly greater in pRCC than in fpAML (71.4% versus 28.6%, P = 0.019 for reader 1; 64.3% versus 14.3%, P = 0.003 for reader 2; and 75% versus 21.4%, P = 0.002 for the consensus). T2*W GRE showed a similar tendency (46.4% versus 14.3%, P = 0.049 for both readers; and 50% versus 14.3%, P = 0.042 for the consensus). Using the consensus reading, sensitivity and specificity of determining pRCC were 75% and 78.6% for chemical shift MRI and 50% and 85.7% for T2*W GRE. Conclusion The prevalence of intratumoral hemorrhage identified from chemical shift MRI or T2*W GRE was significantly different between pRCC and fpAML. These hemorrhage-sensitive MRI sequences may be used as an adjunctive tool for discriminating between the two entities.

OBJECTIVE:To evaluate the proportion of pheochromocytomas meeting the criteria for adenoma on adrenal washout CT and the diagnostic performance of adrenal washout CT for differentiating adenoma from pheochromocytoma. METHODS:MEDLINE and EMBASE were searched to 28 March 2017. We included studies that used adrenal washout CT for characterisation of pheochromocytomas. Two independent reviewers assessed the methodological quality using Quality Assessment of Diagnostic Accuracy Studies-2. Proportions were pooled using an inverse variance method for calculating weights (random-effects). Sensitivity and specificity were pooled using hierarchical logistic regression modelling and plotted in a hierarchical summary receiver-operating-characteristics (HSROC) plot. RESULTS:Ten studies (114 pheochromocytomas) were included. The pooled proportion of pheochromocytomas meeting the criteria for adenomas was 35 % (95 % CI 20-51). For eight studies providing information on diagnostic performance, the pooled sensitivity and specificity for differentiating adenoma from pheochromocytoma were 0.97 (95 % CI 0.93-0.99) and 0.67 (95 % CI 0.44-0.84), respectively. The area under the HSROC curve was 0.97 (95 % CI 0.95-0.98). CONCLUSIONS:There was a non-negligible proportion of pheochromocytomas meeting the criteria for adenoma on adrenal washout CT. Although overall diagnostic performance was excellent for differentiating adenoma from pheochromocytoma, specificity was relatively low. KEY POINTS/CONCLUSIONS:• Non-negligible proportion of pheochromocytomas can be mistaken for adenoma. • Adrenal washout CT showed good sensitivity (97%) but relatively low specificity (67%). • Findings other than washout percentage should be used when diagnosing pheochromocytomas.

PURPOSE/OBJECTIVE:To evaluate the value of apparent diffusion coefficient (ADC) for determining parametrial invasion (PMI) in cervical cancer, by stratifying them into subgroups based on a Likert scale using T2-weighted imaging (T2WI). MATERIALS AND METHODS/METHODS:This retrospective study included 87 patients with FIGO stage IA2-IIB cervical cancer who underwent preoperative MRI followed by radical hysterectomy. Radiological PMI was assessed on T2WI using a six-point Likert scale and ADC values of the tumors were measured. MRI findings were compared between patients with and without PMI. Differences in ADC according to the Likert scale were also assessed. RESULTS:19 (21.8%) patients had pathological PMI. The prevalence of PMI was significantly associated with Likert scale (P < 0.001). ADC values significantly differed according to Likert scale (P < 0.001). However, only tumors with a Likert score of 0 (MRI-invisible) had significantly greater ADC than others (P < 0.001) while no significant difference was observed among tumors with Likert scores of 1-5 (P = 0.070-0.889). Patients with PMI had significantly lower ADC values than those without PMI (P = 0.034). However, no significant difference was seen between patients with and without PMI within each Likert score group (P = 0.180-0.857). CONCLUSION/CONCLUSIONS:T2WI-based Likert score for radiological PMI and ADC values of the tumor were significantly associated with pathological PMI. However, the apparent association seen between ADC values and PMI may be due to contribution of high ADC values of MRI-invisible tumors rather than reflecting their relationship.