Context Response Evaluation Criteria in Solid Tumors [RECIST (unidimensional)], World Health Organization [WHO (bi-dimensional)] and European Association for Study of the Liver [EASL (necrosis)] guidelines are commonly used to assess response following therapy for hepatocellular carcinoma (HCC). No universally accepted standard exists. Objectives To evaluate intermethod agreement between these 3 imaging guidelines and to introduce the concept of the “primary index lesion” as a biomarker for response. Design Single-center comprehensive imaging analysis. Setting and Participants 245 consecutive patients with HCC who were treated with chemoembolization or radioembolization between January 2000 and December 2008. Computed tomography and magnetic resonance imaging scans (N=1065) were reviewed to assess response in the “primary index lesion,” defined as the largest tumor targeted during first treatment. Main Outcome Measures Intermethod agreement (k statistics) between RECIST, WHO, and EASL guidelines response; correlation of WHO and EASL response in the primary index lesion with time to progression and survival. Results κ coefficients were 0.86(95% confidence interval [CI],0.80–0.92) between the WHO and RECIST guidelines, 0.24(95% CI, 0.16–0.33) between RECIST and EASL and 0.28 (95% CI, 0.19–0.36) between WHO and EASL. Disease progressed in 96 patients; 113 died. The hazard ratio for time to progression in responders compared with nonresponders was 0.36(95% CI, 0.23–0.57) for WHO, 0.38(95% CI, 0.24–0.58) for RECIST, and 0.38(95% CI, 0.22–0.64) for EASL. Hazard ratios for survival in responders compared with nonresponders in univariate and multivariate analyses were 0.46(95% CI, 0.32–0.67) and 0.55(95% CI, 0.35–0.84); they were 0.36(95% CI, 0.22–0.57) and 0.54(95% CI, 0.34–0.85) for EASL. Hazard ratios for survival in responders vs nonresponders in patients with solitary and multifocal HCC were 0.39 (95% CI, 0.19–0.77) and 0.51 (95% CI, 0.32–0.82) for WHO and 0.26 (95% CI, 0.10–0.67) and 0.47 (95% CI, 0.28–0.79) for EASL. Conclusions Among a group of patients with HCC, agreement for classification of therapeutic response was high between RECIST and WHO, but low between each of these and EASL. Application of these methods to measure response in a primary index lesion resulted in statistically significant correlations with disease progression and survival.

Purpose-We sought to study receiver-operating characteristics (ROC) of the European Association for the Study of the Liver (EASL), Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) guidelines of assessing response following locoregional therapies individually and in various combinations.Methods-Eighty-one patients with hepatocellular carcinoma underwent liver explantation following locoregional therapies. Response was assessed using EASL, RECIST and WHO. Kappa statistics were used to determine inter-method agreement. Uni/multivariate logistic regression analyses were performed to determine the variables predicting complete pathologic necrosis. Numerical values were assigned to the response classes: complete response=0, partial response=1, stable disease=2 and progressive disease=3. Various mathematical combinations of EASL and WHO were tested to calculate scores and their ROCs were studied using pathological examination of the explant as the gold standard.Results-Median times (95% CI) to WHO, RECIST and EASL response were 5.3 (4-11.5), 5.6 (4-11.5) and 1.3 months (1.2-1.5) respectively. Kappa coefficients for WHO/RECIST, WHO/ EASL and RECIST/EASL were 0.78, 0.28 and 0.31 respectively. EASL response demonstrated significant odds ratios for predicting complete pathologic necrosis on uni/multivariate analyses. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access

To correlate posttreatment radiologic and pathologic findings in patients who underwent transarterial chemoembolization before transplantation or resection. Thirty-five patients with postchemoembolization follow-up imaging underwent liver transplantation/resection. Pre-and posttreatment contrast-enhanced magnetic resonance imaging were used to evaluate radiologic findings. Imaging characteristics using World Health Organization (WHO) and European Association for the Study of the Liver (EASL) criteria after treatment were evaluated. Treated lesions were examined by pathology (gold standard) for the assessment of necrosis. Radiologic findings on magnetic resonance imaging were correlated to pathologic findings to assess the predictability by imaging of actual necrosis. Kappa (κ) statistics were used to determine intermethod agreement between WHO and EASL criteria. Fourteen (40%) of 35 lesions had biopsy-proven hepatocellular carcinoma. Thirteen (37%) of 35 target lesions showed complete pathologic necrosis. Complete pathologic necrosis was seen in 35% of lesions with pretreatment size <3 cm. Complete pathologic necrosis was seen in 1 (100%) of 1, 6 (67%) of 9, 6 (33%) of 18, and 0 (0%) of 7 of the lesions that exhibited complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by WHO criteria, respectively. Complete pathologic necrosis was seen in 9 (82%) of 11, 4 (36%) of 11, 0 (0%) of 8, and 0 (0%) of 5 of the lesions that showed CR, PR, SD, or PD by EASL criteria, respectively. EASL CR and WHO response were shown to have ≥85% specificity for predicting complete pathologic necrosis. The κ coefficient for agreement between WHO and EASL was 0.29. EASL and WHO criteria had minimal intermethod agreement. EASL CR and WHO response were able to predict pathologic necrosis.

BackgroundUp to a fifth of patients diagnosed with prostate cancer (PC) will develop castration-resistant prostate cancer (CRPC), which has been associated with a poor prognosis. The aim of this study was to consider the patient perspective as part of the overall treatment decision-making process for CRPC, given that an alignment between patient preference and prescribing has been shown to benefit patient outcomes. This study examines preferences of patients with CRPC in Japan for treatment features associated with treatments like RA-223, abiraterone, and docetaxel and to examine the extent to which treatment preferences may vary between symptomatic and asymptomatic patients.MethodsA two-phase research approach was implemented. In Phase 1, N = 8 patients with CRPC were recruited from a single hospital to complete a qualitative interview to provide feedback on the draft survey. In Phase 2, N = 134 patients with CRPC were recruited from five hospitals to complete a paper survey. The survey included 6 treatment choice questions, each asking patients to choose between two hypothetical treatments for their CRPC. Each treatment alternative was defined by the following attributes: length of overall survival (OS), time to a symptomatic skeletal event (SSE), method of administration, reduction in the risk of bone pain, treatment-associated risk of fatigue and lost work days. A hierarchical Bayesian logistic regression was used to estimate relative preference weights for each attribute level and mean relative importance.ResultsA total of N = 133 patients with CRPC completed the survey and were included in the final analysis. Patients had a mean age of 75.4 years (SD = 7.4) and had been diagnosed with PC a mean of 6.5 years prior (SD = 4.4). Over the attribute levels shown, fatigue (relative importance [RI] = 24.9 %, 95 % CI: 24.7 %, 25.1 %) was the most important attribute, followed by reduction in the risk of bone pain (RI = 23.2 %, 95 % CI: 23.0 %, 23.5 %), and OS (RI = 19.2 %, 95 % CI: 19.0 %, 19.4 %). Although symptomatic patients placed significantly more importance on delaying an SSE (p < .05), no other preference differences were observed.ConclusionsCRPC patients were more concerned about reduced quality of life from side effects of treatment rather than extension of survival, which may have implications for shared decision-making between patients and physicians.

Chronic kidney disease (CKD) occurs frequently after liver transplantation (LT) and is associated with significant morbidity and mortality. Thus, there is a pressing need to identify characteristics and biomarkers diagnostic of CKD to enable early diagnosis allowing preemptive interventions, as well as mechanistic insights into the progression from kidney injury to irreversible kidney failure. We analyzed 342 patients who had baseline GFR>60 at time of LT and are now >3 years post-LT. Risk factors for post-LT CKD were compared between 3 different groups defined by current GFR: >90 (n=40), 60–90 (n=146) and <60 (n=156) ml/min. Age, cyclosporine use, and pre-LT GFR were independently associated with new onset CKD. A subset (n=64) without viral/immune disease or graft dysfunction underwent multi-analyte plasma proteomic evaluations for correlation with CKD. Plasma proteomic analysis of two independent cohorts, test (n=22) and validation (n=42), identified 10 proteins highly associated with new onset CKD. In conclusion, we have identified clinical characteristics and a unique plasma proteomic signature correlating with new onset CKD after LT. These preliminary results are currently being validated in a prospective, multi-center study to determine if this signature precedes the onset of CKD and resolves with early interventions aimed at preserving kidney function.