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The association between radiological response and overall survival (OS) was retrospectively evaluated in patients treated with lenvatinib as a first-line systemic treatment for unresectable hepatocellular carcinoma. A total of 182 patients with Child–Pugh class A liver function and an Eastern Cooperative Oncology Group performance status of zero or one were enrolled. Radiological evaluation was performed using Response Evaluation Criteria in Solid Tumors (RECIST) and modified Response Evaluation Criteria in Solid Tumors (mRECIST). Initial radiological evaluation confirmed significant stratification of OS by efficacy judgment with both RECIST and mRECIST, and that initial radiological response was an independent prognostic factor for OS on multivariate analysis. Furthermore, in patients with stable disease (SD) at initial evaluation, macrovascular invasion at the initial evaluation on RECIST and modified albumin–bilirubin grade at initial evaluation on mRECIST were independent predictors of OS on multivariate analysis. In conclusion, if objective response is obtained at the initial evaluation, continuation of treatment appears desirable because prolonged OS can be expected; but, if SD is obtained at the initial evaluation, one should determine whether to continue or switch to the next treatment, with careful consideration of factors related to the tumor and hepatic reserve at the initial evaluation.

The oxygen evolution reaction (OER) plays a pivotal role in various renewable energy technologies. Thus, the development of efficient and stable electrocatalysts for OER is crucial. Metal-organic frameworks (MOFs) are highly promising catalysts for OER owing to their fascinating physicochemical properties. However, there is hardly any systematic exploration of the synergistic correlation between experimental tests and theoretical calculations to study MOF-based OER catalysts. This review systematically explores the evaluation criteria of the OER performance of MOF-based catalysts based on integrated experimental characterization and theoretical calculations. Furthermore, the recent representative developments in MOF-based OER catalysts, including an analysis of the intrinsic mechanisms underlying their exceptional OER catalytic performance using experimental and theoretical assessment methods, are presented. Finally, the key challenges faced by MOF-based catalysts are outlined, and insights into their future research directions are provided. This study offers theoretical guidance and practical strategies for the design of efficient and stable MOF-based catalysts for OER.

ObjectivesTo assess the inter-operator concordance and the potential sources of discordance in defining response to sorafenib in hepatocellular carcinoma (HCC).MethodsAll patients who received sorafenib between September 2008 and February 2015 were scrutinised for this retrospective study. Images were evaluated separately by three radiologists with different expertise in liver imaging (operator 1, >10 years; operator 2, 5 years; operator 3, no specific training in liver imaging), according to: response evaluation radiological criteria in solid tumours (RECIST) 1.1, modified RECIST (mRECIST) and response evaluation criteria in cancer of the liver (RECICL).ResultsThe overall response concordance between the more expert operators was good, irrespective of the criteria (RECIST 1.1, ĸ = 0.840; mRECIST, ĸ = 0.871; RECICL, ĸ = 0.819). Concordance between the less expert operator and the other colleagues was lower. The most evident discordance was in target lesion response assessment, with expert operators disagreeing mostly on lesion selection and less expert operators on lesion measurement. As a clinical correlate, overall survival was more tightly related with “progressive disease” as assessed by the expert compared to the same assessment performed by operator 3.ConclusionsDecision on whether a patient is a responder or progressor under sorafenib may vary among different operators, especially in case of a non-specifically trained radiologist. Regardless of the adopted criteria, patients should be evaluated by experienced radiologists to minimise variability in this critical instance.Key Points• Inter-operator variability in the assessment of response to sorafenib is poorly known.• The concordance between operators with expertise in liver imaging was good.• Target lesions selection was the main source of discordance between expert operators.• Concordance with non-specifically trained operator was lower, independently from the response criteria.• The non-specifically trained operator was mainly discordant in measurements of target lesions.

A series of hydrogeologic framework model (HFM)‐based steady‐ and transient‐state numerical simulations is performed first using a coupled subsurface flow‐transport numerical model to analyze groundwater flow and salt transport in an actual three‐dimensional complex coastal aquifer system before and during groundwater pumping. A series of analytic hierarchy process (AHP)‐based multi‐criteria evaluations is then performed applying a multi‐criteria decision‐making approach to determine optimal pumping location and rate for a new pumping well in the complex coastal aquifer system during groundwater pumping. The complex coastal aquifer system is composed of six anisotropic fractured porous geologic media (five rock formations and one fault) and three isotropic porous geologic media (three soil formations) and shows high geometric irregularity and significant heterogeneity and anisotropy of the nine geologic media. Results of the steady‐state numerical simulations show successful model calibration with 26 measured groundwater levels and two observed seawater intrusion front lines. The latter two are determined by spatial interpolation and extrapolation of electrical conductivity logging data and electrical resistivity survey data, respectively. Based on the status and prospect of necessary water uses and available groundwater resources, the field observations of groundwater and seawater intrusion, and the analyses of the steady‐state numerical simulation after the model calibration, six candidate pumping locations are selected for the new pumping well. In addition, from six preliminary individual transient‐state numerical simulations, maximum pumping rates at the six candidate pumping locations are calculated first, and a set of six incremental candidate pumping rates is then assigned at each of the six candidate pumping locations. Results of the transients‐state numerical simulations show that groundwater flow and salt transport are spatially and temporally changed, and seawater intrusion is further intensified by groundwater pumping. In addition, the magnitudes of such spatial and temporal changes and intensification are significantly different depending on the candidate pumping locations and rates. Results of the steady‐ and transient‐state numerical simulations also show that both complexity (geometric irregularity, heterogeneity, and anisotropy including the fault) and topography have significant effects on the spatial distributions and temporal changes of groundwater flow and salt transport in the coastal aquifer system before and during groundwater pumping. In addition, results of statistical estimations of the mesh Peclet and Courant numbers confirm acceptabilities of minimizing numerical dispersion in the steady‐ and transient‐state numerical simulations. Based on the analyses of the transient‐state numerical simulations, eight multiple criteria are chosen to judge, prioritize, and rank the six candidate pumping locations and six candidate pumping rates for optimal pumping. Results of the multi‐criteria evaluations determine the optimal pumping location and rate for the new pumping well among the six candidate pumping locations and six candidate pumping rates. In addition, results of consistency checks confirm consistencies of judgments in the multi‐criteria evaluations. Key Points Numerical simulations with successful model calibration show that spatial and temporal changes in groundwater flow and salt transport significantly depend on candidate pumping locations and rates Statistical estimations of the mesh Peclet and Courant numbers confirm acceptabilities of minimizing numerical dispersion in the numerical simulations Multi‐criteria evaluations determine optimal pumping location and rate, and consistency checks confirm consistencies of judgments in the multi‐criteria evaluations

A wide range of cancer immunotherapy approaches has been developed including non-specific immune-stimulants such as cytokines, cancer vaccines, immune checkpoint inhibitors (ICIs), and adoptive T cell therapy. Among them, ICIs are the most commonly used and intensively studied. Since 2011, these drugs have received marketing authorisation for melanoma, lung, bladder, renal, and head and neck cancers, with remarkable and long-lasting treatment response in some patients. The novel mechanism of action of ICIs, with immune and T cell activation, leads to unusual patterns of response on imaging, with the advent of so-called pseudoprogression being more pronounced and frequently observed when compared to other anticancer therapies. Pseudoprogression, described in about 2–10% of patients treated with ICIs, corresponds to an increase of tumour burden and/or the appearance of new lesions due to infiltration by activated T cells before the disease responds to therapy. To overcome the limitation of response evaluation criteria in solid tumors (RECIST) to assess these specific changes, new imaging criteria—so-called immune-related response criteria and then immune-related RECIST (irRECIST)—were proposed. The major modification involved the inclusion of the measurements of new target lesions into disease assessments and the need for a 4-week re-assessment to confirm or not confirm progression. The RECIST working group introduced the new concept of “unconfirmed progression”, into the irRECIST. This paper reviews current immunotherapeutic approaches and summarises radiologic criteria to evaluate new patterns of response to immunotherapy. Furthermore, imaging features of immunotherapy-related adverse events and available predictive biomarkers of response are presented.

To study the peculiarities of changes in functional indicators and body composition parameters of mixed martial arts (MMA) athletes of strike fighting style and a number of biochemical blood indicators during two months of using different intensity training load regimes, and to determine the most informative criteria for assessing adaptive body changes in these training conditions. We examined 40 MMA athletes (men) aged 20-22, who used mainly strike fighting style in their competitive activity, and divided them into 2 research groups (A and B), 20 athletes in each group. Group A athletes used medium intensity (  = 0.64), and group B-high intensity (  = 0.72) training load regime. To assess the adaptive body changes we applied methods of control testing of maximum muscle strength growth (1 RM), special training (the number of accurate kicks on the mannequin for 30 s), and bioimpedansometry. By monitoring biochemical parameters (testosterone, cortisol, creatinine, phosphorus, calcium, cholesterol, LDH) in the blood serum of athletes, we determined the peculiarities of adaptive-compensatory body reactions in response to training loads. The obtained results of special training increased during the study period by an average of 10.5% in group B athletes, but group A participants' results had no significant changes compared to basal data. The largest increase in the development of maximum muscle strength growth by an average of 44.4% was recorded after 2 months of research in group B. Group B athletes also had positive changes in body fat and fat-free mass indicators during the study which were two times higher than the results of group A. The laboratory studies and correlation analysis showed informative biochemical markers (cortisol, testosterone and creatinine) for assessing the condition of athletes in both groups before using high and medium training load regimes. The biochemical markers for assessing the adaptive-compensatory reactions of athletes in response to high-intensity physical stimuli at the beginning of the study were indicators of LDH and cholesterol, and in conditions of medium intensity it was LDH, testosterone and cortisol. After 2 months of study the set of biochemical markers assessing the adaptation processes before the load completely changed only in group B athletes and consisted of LDH, phosphorus, cholesterol, and calcium. At the same time, the set of biochemical criteria for assessing adaptive-compensatory reactions after training in group B athletes was completely changed compared with the data recorded at the beginning of the study. Defining the optimal set of criteria for assessing the adaptive-compensatory changes in MMA athletes of strike fighting style will allow in the shortest possible time to correct the parameters of the training load regime for accelerating the body functionality in the process of special power training.

Purpose Activity estimates should be accurately evaluated in phase 2 clinical trials to ensure appropriate decisions about proceeding to phase 3 trials. RECIST v1.1. progression-free survival (PFS) is a common endpoint in oncology; however, it can be influenced by assessment criteria and trial design. We assessed the value of central adjudication of investigator-assessed PFS times of participants in a double-blind, randomised phase 2 trial evaluating regorafenib versus placebo in advanced gastro-oesophageal cancer (AGITG INTEGRATE) to inform plans for central review in future trials. Methods We calculated the proportion of participants with a disagreement between the site investigator assessment and blinded independent central review and in whom central review resulted in a change, then evaluated the effect of central review on study conclusions by comparing hazard ratios (HRs) for PFS based on site review versus central review. Post-progression unblinding was assessed with similar methods. Simulation studies explored the effect of differential and non-differential measurement error on treatment effect estimation and study power. Results Disagreements between site assessments versus central review occurred in 8/147 (5.4%) participants, 5 resulting in amended date of progression (3.4%). PFS HRs (sites vs central review progression dates) were similar (0.39 vs 0.40). RECIST progression occurred in 82/86 (95%) of cases where post-progression unblinding was requested by the site investigator. Conclusions Blinded independent central review was feasible and supported the reliability of site assessments, trial results, and conclusions. Modelling showed that when treatment effects were large and outcome assessments blinded, central review was unlikely to affect conclusions.

Transarterial chemoembolization (TACE) has been the standard treatment for intermediate-stage, unresectable hepatocellular carcinoma (u-HCC). However, with recent advances in systemic therapy and the emergence of the concept of TACE-refractory or -unsuitable, the effectiveness of systemic therapy, as well as TACE, has been demonstrated for patients judged to be TACE-refractory or -unsuitable. In this study, the efficacy of lenvatinib and its combination with TACE after lenvatinib was investigated in 140 patients with intermediate-stage u-HCC treated with lenvatinib mainly because of being judged to be TACE-refractory or -unsuitable. Median overall survival (OS) and progression-free survival (PFS) were 24.4 and 9.0 months, respectively, indicating a good response rate. In multivariate analysis, modified albumin–bilirubin (mALBI) grade and up to seven criteria were identified as independent factors for OS, and mALBI grade and tumor morphology were identified as independent factors for PFS. While 95% of all patients were TACE-refractory or -unsuitable, the further prognosis was prolonged by the combination with TACE after lenvatinib initiation. These findings suggest that systemic therapy should be considered for intermediate-stage u-HCC, even in patients judged to be TACE-refractory or -unsuitable. The use of TACE after the start of systemic therapy may further improve prognosis.

Background Patients with hepatocellular carcinoma waiting for liver transplantation are commonly treated with locoregional treatments, such as TACE and ablation, to prevent tumor progression and dropout and to improve long-term outcome after transplantation. We wanted to prospectively assess feasibility of systemic antitumor treatment with sorafenib as neoadjuvant treatment for hepatocellular carcinoma while waiting for liver transplantation, evaluating tolerability, toxicity and posttransplant morbidity. We also wanted to evaluate perfusion CT parameters to assess tumor properties and response early after start of sorafenib treatment in patients with early hepatocellular carcinoma. Methods Twelve patients assigned for liver transplantation due to hepatocellular carcinoma, within the UCSF and who fulfilled other criteria, were included January 2012–August 2014. After baseline evaluation, sorafenib treatment was started. Treatment was evaluated by perfusion CT at 1, 4 and 12 weeks and thereafter every 8 weeks. Toxicity and quality of life was assessed at 1 and 4 weeks and every 4 weeks thereafter during treatment. Treatment was stopped when patients were prioritized on the transplantation waiting list or when intolerable side effects or tumor progress warranted other treatments. Posttransplant morbidity after 90 days was registered according to Clavien-Dindo. Results Baseline perfusion CT parameters in the tumors predicted the outcome according to RECIST/mRECIST at three months, but no change in CTp parameters was detected as a result of sorafenib. Sorafenib as neoadjuvant treatment was associated with intolerability and dose reductions. Therefore the prerequisites for evaluation of the sorafenib effect on both CT parameters and tumor response were impaired. Conclusions This study failed to show changes in CTp parameters during sorafenib treatment. Despite the curative treatment intention, tolerability of neoadjuvant sorafenib treatment before liver transplantation was inadequate in this study. Trial registration EudraCT number: 2010–024306-36 (date 2011-04-07).

Purpose We aimed to compare contrast-enhanced ultrasound (CEUS) with contrast-enhanced computed tomography (CECT) for evaluating the treatment response to transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). Materials and methods Treatment responses of 130 patients who underwent TACE were evaluated by CEUS and CECT. We initially compared the abilities of CEUS and CECT to detect residual tumour, which were confirmed by histology or angiography. Then, we compared the tumour response to TACE assessed by CEUS and CECT, according to Modified Response Evaluation Criteria in Solid Tumours (mRECIST). Results The sensitivity and accuracy of detecting residual tumour by CEUS vs. CECT were 95.9 % vs. 76.2 % ( p  < 0.001) and 96.2 % vs. 77.7 % ( p  < 0.001), respectively. For target lesions, 13 patients were observed as complete response (CR) by CEUS, compared to 36 by CECT ( p  < 0.001). For nontarget lesions, 12 patients were observed as CR by CEUS, compared to 22 by CECT ( p  = 0.006). For overall response, eight patients were observed as CR by CEUS, compared to 31 by CECT ( p  < 0.001). Conclusion The diagnostic performance of CEUS was superior to CECT for detecting residual tumour after TACE. In clinical, CEUS should be recommended as an optional procedure for assessing the tumour response to TACE. Key Points • The mRECIST are widely applied for evaluating the response of HCC . • Imaging method has been applied to assess the therapeutic response to TACE . • The diagnostic performance of CEUS was superior to CECT for residual tumours . • CEUS can be a valuable method for assessing tumour response to TACE .