Impact of liver-stiffness measurement on hepatocellular carcinoma development in chronic hepatitis C patients treated with direct-acting antivirals: A systematic review and time-to-event meta-analysis.

BACKGROUND AND AIM: Patients with chronic hepatitis C (CHC) treated with direct-acting antivirals (DAAs) are still at risk for developing hepatocellular carcinoma (HCC) even after achieving sustained virologic response (SVR). Liver-stiffness measurement (LSM) on imaging has been investigated as a predictor of HCC occurrence. OBJECTIVES: To provide systematic summary of the predictive value of LSM in predicting HCC occurrence in HCV patients treated with DAA. METHODS: A comprehensive literature search of the PubMed-MEDLINE and EMBASE databases was performed to identify studies that evaluated the predictive value of LSM in CHC patients treated with DAAs. Pooled hazard ratio (HR) comparing HCC occurrence between patients with positive and negative results on LSM was calculated for all studies and various subgroups. Subgroup analyses and meta-regression were performed. RESULTS: A review of 135 candidate articles identified eight eligible articles with a total of 3398patients for qualitative review and meta-analysis. The pooled HR for HCC occurrence determined by LSM was 3.43 (95% confidence interval [CI], 1.63-7.19) with heterogeneity (I2  = 81.87%, P < 0.001), thus indicating that LSM might be helpful for predicting HCC occurrence. In subgroup analyses, pooled HRs were different according to the study design (2.29; [95% CI, 0.96-5.45] for retrospective studies; 4.61 [95% CI, 2.44-8.71] for prospective studies), study population (4.00 [95% CI, 2.00-7.99] for CHC; 2.64 [0.99-7.00] for CHC with liver cirrhosis) and LSM parameter (3.17 [95% CI, 1.35-7.41] for baseline LSM; 4.19 [95% CI, 1.89-9.29] for others). In multivariate meta-regression, study design was the only influencing factor for pooled HR for HCC occurrence (P < 0.05). CONCLUSIONS: Consistent evidence demonstrated the predictive value of LSM for HCC occurrence in CHC patients treated with DAA. The significant influencing factor for risk of HCC occurrence indicated by LSM was study design.

Incidence of Pseudoprogression during Immune Checkpoint Inhibitor Therapy for Solid Tumors: A Systematic Review and Meta-Analysis.

BackgroundImmune checkpoint inhibitors (ICIs) have been increasingly used in cancer treatment, and a subset of patients undergo pseudoprogression. Recognizing the incidence of pseudoprogression is critical for clinical practice.PurposeTo evaluate by systematic review and meta-analysis the incidence of pseudoprogression in cancer treatment with ICIs, and compare the incidence according to response criteria, tumor types, and immunotherapeutic agents.Materials and MethodsMedline and Embase were searched to identify relevant studies published before December 31, 2018. Clinical trials, post hoc analysis of clinical trials, and prospective studies on ICI treatment in patients with malignant solid tumors were included. Pooled incidence of pseudoprogression for all included studies, per definition of pseudoprogression, cancer type, and drug type, was obtained by random-effects models with inverse variance weighting model.ResultsSeventeen studies with 3402 patients were analyzed. The pooled incidence of pseudoprogression was 6.0% (95% confidence interval: 5.0%, 7.0%). The definition of pseudoprogression were divided into four categories: progressive disease followed by partial response (PR) or complete response (CR) but not stable disease (SD) with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (six studies); progressive disease followed by SD or PR or CR with RECIST 1.1 (five studies); progressive disease followed by SD or PR or CR with RECIST 1.0 (three studies); and progressive disease followed by SD or PR or CR with immune-related response criteria (irRC) (three studies). Incidence of pseudoprogression varied from 4.5% to 8.0% per definition, ranged from 5.0% to 7.0% per cancer type, and was 5.6% with the monotherapy of programmed cell death-1 inhibitor.ConclusionThe overall incidence of pseudoprogression was 6.0% and was less than 10% in subgroup analyses according to the definitions of pseudoprogression, cancer type, and immune checkpoint inhibitor type. Varying definitions across trials and studies indicates the need for uniform criteria of pseudoprogression for solid tumors.© RSNA, 2020Online supplemental material is available for this article.See also the article by Dodd and MacDermott in this issue.

A cost-effectiveness analysis of the diagnostic strategies for differentiating focal nodular hyperplasia from hepatocellular adenoma.

OBJECTIVES: We evaluated the cost-effectiveness of a gadoxetic acid-enhanced MRI (EOB-MRI) strategy compared with conventional MRI strategy and biopsy to differentiate focal nodular hyperplasia (FNH) from hepatocellular adenoma (HCA). METHODS: A decision tree model was constructed to compare the cost-effectiveness of EOB-MRI, conventional MRI with extracellular contrast agents, and biopsy as the initial diagnostic modality in patients with incidentally detected focal liver lesions suspected of being FNH or HCA. We analysed the cost and effectiveness, i.e. probability of successful diagnosis of each strategy. Costs were based on utilisation rates and Medicare reimbursements in the USA and South Korea. RESULTS: In the base case analysis of our decision tree model, the effectiveness of the three strategies was similar. The cost of the EOB-MRI strategy ($1283 in USA, $813 in South Korea) was lowest compared with the biopsy strategy ($1725 in USA, $847 in South Korea) and the conventional MRI strategy ($1750 in USA, $962 in South Korea). One-way, two-way and probabilistic sensitivity analysis showed unchanged results over an acceptable range. CONCLUSIONS: EOB-MRI strategy is the most cost-effective strategy for differentiating FNH from HCA in patients with incidentally detected focal liver lesions in a non-cirrhotic liver. KEY POINTS: • The effectiveness of the three strategies was similar. • The cost of the EOB-MRI strategy was lowest. • EOB-MRI strategy is the most cost-effective for differentiating FNH from HCA.

Shear Wave Elastography as a Quantitative Biomarker of Clinically Significant Portal Hypertension: A Systematic Review and Meta-Analysis.

OBJECTIVE: To qualify shear wave elastography (SWE) as a biomarker for clinically significant portal hypertension (CSPH) beyond proof of concept, we aimed to accumulate and summarize the current evidence through systematic review and meta-analysis. MATERIALS AND METHODS: A computerized literature search was performed to identify studies from MEDLINE and EMBASE up to February 9, 2017. Studies on the diagnostic performance of liver stiffness measurements using SWE for CSPH with hepatic venous pressure gradient (HVPG) as the reference standard were included. Various aspects of SWE were comprehensively assessed. The summary diagnostic performance of SWE for the diagnosis of CSPH and the summary correlation coefficient between liver stiffness measured using SWE and HVPG were evaluated through a meta-analysis. RESULTS: Nine articles (including 746 patients) were retrieved. The diagnostic performance of SWE for the diagnosis of CSPH was fairly good, with a summary sensitivity of 85% (95% CI, 75-91%; I2 = 78.56%) and summary specificity of 85% (95% CI, 77-90%; I2 = 0%); the area under the ROC curve was 0.88 (95% CI, 0.85-0.91). The summary correlation coefficient between liver stiffness and HVPG measurements was 0.741 (95% CI, 0.658-0.825; I2 = 0%). These results support the value of SWE as a diagnostic biomarker for CSPH. However, there was significant heterogeneity in the imaging devices, protocols, liver stiffness measurement methods, and cutoff values used, which suggests that standardization is required. CONCLUSION: The consistent evidence favoring SWE as a biomarker for CSPH should be considered in the biomarker qualification process and management of patients with CSPH.

Performing Gadoxetic Acid-Enhanced MRI After CT for Guiding Curative Treatment of Early-Stage Hepatocellular Carcinoma: A Cost-Effectiveness Analysis.

OBJECTIVE: We determined the cost-effectiveness of two different diagnostic imaging strategies in guiding curative treatment of early-stage hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We developed a decision analytic model using as its starting point a cohort of patients aged 55 years with early-stage HCC detected at dynamic multiphasic CT and with Child-Pugh class A cirrhosis. The model compared two strategies on the initial workup: conventional CT strategy using dynamic multiphasic CT only and gadoxetic acid-enhanced MRI strategy using additional gadoxetic acid-enhanced MRI after initial CT. A Markov cohort model simulated a cohort of patients after curative or adjuvant treatment, with follow-up over the remaining life expectancy. We analyzed mean life-years gain, quality-adjusted life-years (QALYs), costs per person, and incremental cost-effectiveness ratio (ICER). To evaluate results, we performed one-way, two-way, and probabilistic sensitivity analyses. RESULTS: The life expectancies and QALY were 7.22 years and 5.08 for the conventional CT strategy and 7.79 years and 5.52 for the gadoxetic acid-enhanced MRI strategy, respectively. The expected costs were $99,770 for conventional CT and $105,025 for gadoxetic acid-enhanced MRI in the United States. The ICER with gadoxetic acid-enhanced MRI was $11,957, as opposed to that with conventional CT, which was lower than the cost-effectiveness threshold of $50,000/QALY. One-way, two-way, and probabilistic sensitivity analyses showed unchanged results over an acceptable range. CONCLUSION: Gadoxetic acid-enhanced MRI after CT is cost-effective for detecting additional HCC in patients with early-stage HCC who can undergo curative treatment (besides liver transplantation). The cost-effectiveness of gadoxetic acid-enhanced MRI may be considered in the management of patients with early-stage HCC during staging.

Comparison of screening strategies for prevalent vertebral fractures in South Korea: vertebral fracture assessment vs. spine radiography.

BACKGROUND: Vertebral Fracture Assessment (VFA) is a useful tool to detect the vertebral fracture (VF) with low cost and radiation exposure. We aimed to compare screening strategies including VFA and spine radiography (X-ray) for detecting VF in terms of clinical effectiveness, cost and radiation exposure. METHODS: Three screening strategies: 1) X-ray following VFA, 2) VFA only, and 3) X-ray only were compared using a Markov model based on administrative data from South Korea in a population aged ≥50 years. We compared the incidence of new VFs, cost-effectiveness of reducing new VFs and radiation exposure in each strategy. RESULTS: The incidence of new VFs was reduced in all screening strategies compared to no screening: 29.4% for women and 12.5% for men in both X-ray following the VFA and VFA only strategies and 35% for women and 17.5% for men in the X-ray only strategy. The X-ray following VFA strategy had the lowest cost, followed by the X-ray only, and VFA only strategies. The radiation doses for X-ray only were 2,647-2,989 µSv and 3,253-3,398 µSv higher than in the X-ray following VFA and VFA only strategies. The new VF prevention effect was greater in women, and more prominent in older people (women ≥ 70, men ≥ 80) than people ≥ 50 years. CONCLUSIONS: The X-ray following VFA strategy is a cost-effective option for screening prevalent VF to prevent new VF in people aged ≥50 years due to its high effectiveness, lowest cost, and least radiation exposure.

Hypervascular Transformation of Hypovascular Hypointense Nodules in the Hepatobiliary Phase of Gadoxetic Acid-Enhanced MRI: A Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this study is to evaluate the outcomes of hypovascular hypointense nodules in the hepatobiliary phase of gadoxetic acid-enhanced MRI and the risk factors for the hypervascular transformation of the nodules through a systematic review and meta-analysis. MATERIALS AND METHODS: We searched the Ovid-MEDLINE and EMBASE databases for published studies of hypovascular hypointense nodules in patients with chronic liver disease. The pooled proportions of the overall and cumulative incidence rates at 1, 2, and 3 years for the transformation of hypovascular hypointense nodules into hypervascular hepatocellular carcinomas (HCCs) were assessed by using random-effects modeling. Metaregression analysis was performed. RESULTS: Sixteen eligible studies with 944 patients and 1819 hypovascular hypointense nodules in total were included. The pooled overall rate of hypervascular transformation was 28.2% (95% CI, 22.7-33.6%; I2 = 87.46%). The pooled 1-, 2-, and 3-year cumulative incidence rates were 18.3% (95% CI, 9.2-27.4%), 25.2% (95% CI, 12.2-38.2%), and 30.3% (95% CI, 18.8-41.9%), respectively. The metaregression analysis revealed that the mean initial nodule size (cutoff value, 9 mm) was a significant factor affecting the heterogeneity of malignant transformation. CONCLUSION: Hypovascular hypointense nodules detected in the hepatobiliary phase of gadoxetic acid-enhanced MRI carry a significant potential of transforming into hypervascular HCCs. The size of nodules is a significant risk factor for hypervascular transformation.

The detectability of brain metastases using contrast-enhanced spin-echo or gradient-echo images: a systematic review and meta-analysis.

This study aimed to compare the detectability of brain metastases using contrast-enhanced spin-echo (SE) and gradient-echo (GRE) T1-weighted images. The Ovid-MEDLINE and EMBASE databases were searched for studies on the detectability of brain metastases using contrast-enhanced SE or GRE images. The pooled proportions for the detectability of brain metastases were assessed using random-effects modeling. Heterogeneity among studies was determined using χ (2) statistics for the pooled estimates and the inconsistency index, I (2) . To overcome heterogeneity, subgroup analyses according to slice thickness and lesion size were performed. A total of eight eligible studies, which included a sample size of 252 patients and 1413 brain metastases, were included. The detectability of brain metastases using SE images (89.2 %) was higher than using GRE images (81.6 %; adjusted 84.0 %), but this difference was not statistically significant (p = 0.2385). In subgroup analysis of studies with 1-mm-thick slices and small metastases (<5 mm in diameter), 3-dimensional (3D) SE images demonstrated a higher detectability in comparison to 3D GRE images (93.7 % vs 73.1 % in 1-mm-thick slices; 89.5 % vs 59.4 % for small metastases) (p < 0.0001). Although both SE or GRE images are acceptable for detecting brain metastases, contrast-enhanced 3D SE images using 1-mm-thick slices are preferred for detecting brain metastases, especially small lesions (<5 mm in diameter).

CHANGING FACE OF MEDICARE'S NATIONAL COVERAGE DETERMINATIONS FOR TECHNOLOGY.

OBJECTIVES: The Centers for Medicare and Medicaid Services (CMS) issues National Coverage Determinations (NCDs) for medical interventions expected to have a significant impact on Medicare, the health insurance program for US citizens aged 65 years and older and certain people with disabilities under the age of 65 years. The objective of this study was to evaluate NCDs issued from 1999 to 2013 to identify key trends, and to discuss implications for future CMS policy. METHODS: We used the Tufts Medical Center Medicare National Coverage Determination Database to examine characteristics of NCDs from 1999 through 2013. We examined various characteristics of NCDs, including: whether the intervention under review is used for prevention or treatment of disease, the type of intervention considered, evidence limitations cited by CMS, and coverage determination outcome. We evaluated longitudinal trends in categorical and continuous variables in the database, using Cochran-Armitage trend tests and linear regression, respectively. RESULTS: We found that NCDs increasingly focus on preventive care (p = 0.072), pertain to diagnostic imaging (p = 0.033), and evaluate health education/behavioral therapy interventions (p = 0.051). CMS increasingly cites the lack of relevant outcomes (p = 0.019) and the lack of applicability of study results to the Medicare population (p < 0.001) as evidence limitations. CMS less often restricts coverage to certain population subgroups in NCDs (p < 0.001), but increasingly applies coverage with evidence development policies (p < 0.001). CONCLUSIONS: Identified trends reflect broader changes in Medicare as CMS shifts its focus from treatment to prevention of disease, addresses potentially overutilized technologies, and attempts to issue flexible coverage policies.

Imaging features to distinguish malignant and benign branch-duct type intraductal papillary mucinous neoplasms of the pancreas: a meta-analysis.

OBJECTIVE: To systematically determine the imaging findings for distinguishing malignant and benign branch-duct type intraductal papillary mucinous neoplasms (BD-IPMNs), including mixed type, and their diagnostic value through meta-analysis of published studies. BACKGROUND: Management of BD-IPMNs, including mixed type, largely relies on imaging findings. The current knowledge on imaging findings to distinguish malignant and benign BD-IPMNs has weak evidence and is mostly from scattered individual retrospective studies. METHODS: Thorough literature search in Ovid-MEDLINE and EMBASE databases was conducted to identify studies where findings of computed tomography, magnetic resonance imaging, and endoscopic ultrasonography of BD-IPMNs with or without main pancreatic duct (MPD) dilatation were correlated with surgical/pathological findings. Review of 1128 article candidates, including full-text review of 102 articles, identified 23 eligible articles with a total of 1373 patients for meta-analysis. Dichotomous data regarding distinction between malignant and benign BD-IPMNs were pooled using random effects model to obtain the diagnostic odds ratios (DORs) and their 95% confidence intervals (CIs) of various individual imaging findings for diagnosing malignant BD-IPMN. RESULTS: Presence of mural nodules revealed the highest pooled DOR (95% CI) of 6.0 (4.1-8.8) followed by MPD dilatation [3.4 (2.3-5.2)], thick septum/wall [unadjusted, 3.3 (1.5-6.9); publication bias-adjusted, 2.3 (0.9-5.5)], and cyst size greater than 3 cm [2.3 (1.5-3.5)]. Multilocularity and multiplicity of the cystic lesions did not reveal statistically significant association with malignancy. CONCLUSIONS: Presence of mural nodules should be regarded highly suspicious for malignancy warranting a surgical excision whereas cyst size greater than 3 cm, MPD dilatation (5-9 mm), or thick septum/wall may better be managed by careful observation and/or further evaluation.

Comprehensive Analysis for Anti-Cancer Target-Indication Prioritization of Placental Growth Factor Inhibitor (PGF) by Use of Omics and Patient Survival Data.

The expression of the placental growth factor (PGF) in cancer cells and the tumor microenvironment can contribute to the induction of angiogenesis, supporting cancer cell metabolism by ensuring an adequate blood supply. Angiogenesis is a key component of cancer metabolism as it facilitates the delivery of nutrients and oxygen to rapidly growing tumor cells. PGF is recognized as a novel target for anti-cancer treatment due to its ability to overcome resistance to existing angiogenesis inhibitors and its impact on the tumor microenvironment. We aimed to integrate bioinformatics evidence using various data sources and analytic tools for target-indication identification of the PGF target and prioritize the indication across various cancer types as an initial step of drug development. The data analysis included PGF gene function, molecular pathway, protein interaction, gene expression and mutation across cancer type, survival prognosis and tumor immune infiltration association with PGF. The overall evaluation was conducted given the totality of evidence, to target the PGF gene to treat the cancer where the PGF level was highly expressed in a certain tumor type with poor survival prognosis as well as possibly associated with poor tumor infiltration level. PGF showed a significant impact on overall survival in several cancers through univariate or multivariate survival analysis. The cancers considered as target diseases for PGF inhibitors, due to their potential effects on PGF, are adrenocortical carcinoma, kidney cancers, liver hepatocellular carcinoma, stomach adenocarcinoma, and uveal melanoma.

CCR8 as a Therapeutic Novel Target: Omics-Integrated Comprehensive Analysis for Systematically Prioritizing Indications.

Target identification is a crucial process in drug development, aiming to identify key proteins, genes, and signal pathways involved in disease progression and their relevance in potential therapeutic interventions. While C-C chemokine receptor 8 (CCR8) has been investigated as a candidate anti-cancer target, comprehensive multi-omics analyzes across various indications are limited. In this study, we conducted an extensive bioinformatics analysis integrating genomics, proteomics, and transcriptomics data to establish CCR8 as a promising anti-cancer drug target. Our approach encompassed data collection from diverse knowledge resources, gene function analysis, differential gene expression profiling, immune cell infiltration assessment, and strategic prioritization of target indications. Our findings revealed strong correlations between CCR8 and specific cancers, notably Breast Invasive Carcinoma (BRCA), Colon Adenocarcinoma (COAD), Head and Neck Squamous Cell Carcinoma (HNSC), Rectum adenocarcinoma (READ), Stomach adenocarcinoma (STAD), and Thyroid carcinoma (THCA). This research advances our understanding of CCR8 as a potential target for anti-cancer drug development, bridging the gap between molecular insights and creating opportunities for personalized treatment of solid tumors.

Safety and Efficacy of Chimeric Antigen Receptor T-Cell Therapy for Glioblastoma: A Systemic Review and Meta-Analysis.

Background: Chimeric antigen receptor (CAR) T-cell therapy is a promising treatment option for patients with refractory hematological malignancies. However, its efficacy in glioblastoma remains unclear. Here, we performed a systematic review to summarize the safety and efficacy of CAR T-cell therapy in glioblastoma. Methods: The PubMed, EMBASE, and Cochrane databases were searched to identify articles published before June 30, 2021 describing the use of CAR T-cell therapy in glioblastoma. Information on the toxicity of CAR T-cell therapy was summarized. The pooled objective response rate (ORR) and overall survival (OS) of patients who underwent CAR T-cell therapy were estimated using a random-effects model with an inverse-variance weighting model and quantile estimation method, respectively. Results: Of 397 articles identified, eight studies including 63 patients with recurrent glioblastoma treated with various CAR T-cell regimens were included in the analysis. Six (9.5%) patients developed cytokine release syndrome (grade ≤2), and 16 (25.4%) experienced non-critical neurological events. The pooled ORR was 5.1% (95% confidence interval [CI], 0.0-10.4; I 2 = 0.05%), and the pooled median OS was 8.1 months (95% CI, 6.7-9.5; I 2 = 0.00%). Conclusion: Although CAR T-cell therapy is a relatively safe therapeutic option in patients with glioblastoma, it shows marginal efficacy, suggesting that further research is necessary for its translation into clinical practice for the treatment of recurrent glioblastoma.

Evolution of Radiological Treatment Response Assessments for Cancer Immunotherapy: From iRECIST to Radiomics and Artificial Intelligence.

Immunotherapy has revolutionized and opened a new paradigm for cancer treatment. In the era of immunotherapy and molecular targeted therapy, precision medicine has gained emphasis, and an early response assessment is a key element of this approach. Treatment response assessment for immunotherapy is challenging for radiologists because of the rapid development of immunotherapeutic agents, from immune checkpoint inhibitors to chimeric antigen receptor-T cells, with which many radiologists may not be familiar, and the atypical responses to therapy, such as pseudoprogression and hyperprogression. Therefore, new response assessment methods such as immune response assessment, functional/molecular imaging biomarkers, and artificial intelligence (including radiomics and machine learning approaches) have been developed and investigated. Radiologists should be aware of recent trends in immunotherapy development and new response assessment methods.

Treatment Efficacy of Immune Checkpoint Inhibitors for Patients with Advanced or Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis.

The treatment efficacy of immune checkpoint inhibitors (ICIs) in colorectal cancer (CRC) has been reported heterogeneously across clinical trials. We conducted a systematic review and meta-analysis to evaluate the efficacy of ICIs in patients with advanced/metastatic CRC. Ovid-Medline was searched to identify clinical trials providing the efficacy outcomes of overall response rate (ORR) or disease control rate (DCR). The pooled ORR and DCR were estimated across all studies and subgroups. Meta-regression was performed to find the influencing factors for treatment efficacy. A total of thirty studies (1870 patients) were eligible. The overall ORR and DCR were 20.1% and 58.5%, respectively, but these results were heterogeneous across studies. Multivariate meta-regression revealed that microsatellite phenotype (odds ratio of MSI-H/dMMR versus MSS/pMMR: 1.67, p < 0.001) and drug regimen (odds ratio of monotherapy versus combination therapy: 1.07, p = 0.019) were the source of heterogeneity and also significantly influenced factors for the efficacy of the treatment. Although the efficacy of ICIs as a first-line therapy was higher than that of ICIs as the second- or more-line therapy (ORR: 51.5% vs. 13.4%, DCR: 85% vs. 49.5%), multivariate regression showed that the line of therapy was not a significant factor for the treatment efficacy. Our study suggests that the microsatellite phenotype and drug regimen, rather than the line of treatment, are the primary factors influencing the treatment response among advanced/metastatic CRC patients treated with an ICI-based regimen.

Impact of pseudoprogression and treatment beyond progression on outcome in patients with non-small cell lung cancer treated with immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICI) have become an important treatment option for non-small cell lung cancer (NSCLC). We aimed to evaluate the clinical impact of pseudoprogression (PsP) and treatment beyond RECIST1.1-defined progressive disease (TBP) on outcome in NSCLC patients treated with ICI. Methods: NSCLC patients treated with ICI between Mar 2016 and July 2018 were recruited in a consecutive manner. Response was assessed every 8-12 weeks using RECIST1.1 and iRECIST. Based on iRECIST, PsP was defined as progressive disease (PD) on RECIST1.1 subsequently reset to non-PD categories. Using log-rank test, progression-free survival (PFS) was compared between patients with and without PsP, and overall survival (OS) was compared between patients treated with and without TBP. The impact of TBP on OS was evaluated through multivariate Cox proportional hazard models. Results: Of the 189 patients, seven (3.7%) experienced PsP which mostly occurred approximately 3 months after baseline. The median PFS was significantly longer in patients with PsP (not reached) than those without PsP (3.8 months, P = .02). Among patients who demonstrated PD according to RECIST1.1, median OS was significantly longer in patients with TBP (17.2 months) than those without TBP (7.4 months, P < .001). On multivariate analysis adjusting other covariates, TBP (HR, 0.4; 95% CI, 0.2-0.7) remained as a significant protective factor for mortality. Conclusion: PsP occurred in 3.7% of NSCLC patients under ICI treatment. Based on iRECIST scheme, PsP and TBP may be associated with survival benefit.

The incidence of ALK inhibitor-related pneumonitis in advanced non-small-cell lung cancer patients: A systematic review and meta-analysis.

INTRODUCTION: We evaluated the incidence of pneumonitis in clinical trials of anaplastic lymphoma kinase (ALK) inhibitors in patients with advanced non-small cell lung cancer (NSCLC) and compared the incidence among different cohorts, in order to identify possible predisposing factors for ALK inhibitor-related pneumonitis. METHODS: MEDLINE and EMBASE search up to 1/30/18 using the keywords, "alectinib", "ceritinib", "crizotinib", "brigatinib", and "lung cancer", resulting in a total of 20 eligible cohorts with 2261 patients treated with ALK inhibitor monotherapy for advanced NSCLC. The pooled incidences of all-grade, high-grade, and grade 5 pneumonitis were calculated. Subgroup analyses were conducted with meta-regression using study-level covariates. RESULTS: The overall pooled incidence of pneumonitis was 2.14% (95% CI: 1.37-3.34) for all grade, 1.33% (95% CI: 0.80-2.21) for high grade, and 0.22% (95% CI: 0.09-0.52) for grade 5 pneumonitis. The incidence was significantly higher in studies from Japan compared to studies of non-Japan origin, for all-grade (6.25% vs 1.14%, p < 0.001) and high-grade pneumonitis (3.31% vs 0.39%, p < 0.001). Multivariate meta-regression demonstrated the cohorts from Japanese studies had significantly higher odds of pneumonitis for all-grade (odds ratio [OR]: 4.329 [95% CI: 1.918, 9.770], p < 0.001) compared to those of non-Japan origin, after adjusting for types of ALK inhibitors. CONCLUSIONS: The overall incidence of ALK inhibitor pneumonitis was 2.14% in patients with advanced NSCLS. The patients from Japanese cohorts had a higher incidence of ALK-inhibitor pneumonitis, which indicates the need for increased awareness and caution for pneumonitis in Japanese patients treated with ALK inhibitors.

Technical Performance of Two-Dimensional Shear Wave Elastography for Measuring Liver Stiffness: A Systematic Review and Meta-Analysis.

OBJECTIVE: To assess the technical performance of two-dimensional shear wave elastography (2D-SWE) for measuring liver stiffness. MATERIALS AND METHODS: The Ovid-MEDLINE and EMBASE databases were searched for studies reporting the technical performance of 2D-SWE, including concerns with technical failures, unreliable measurements, interobserver reliability, and/or intraobserver reliability, published until June 30, 2018. The pooled proportion of technical failure and unreliable measurements was calculated using meta-analytic pooling via the random-effects model and inverse variance method for calculating weights. Subgroup analyses were performed to explore potential causes of heterogeneity. The pooled intraclass correlation coefficients (ICCs) for interobserver and intraobserver reliability were calculated using the Hedges-Olkin method with Fisher's Z transformation of the correlation coefficient. RESULTS: The search yielded 34 articles. From 20 2D-SWE studies including 6196 patients, the pooled proportion of technical failure was 2.3% (95% confidence interval [CI], 1.3-3.9%). The pooled proportion of unreliable measurements from 20 studies including 6961 patients was 7.5% (95% CI, 4.7-11.7%). In the subgroup analyses, studies conducting more than three measurements showed fewer unreliable measurements than did those with three measurements or less, but no intergroup difference was found in technical failure. The pooled ICCs for interobserver reliability (from 10 studies including 517 patients) and intraobserver reliability (from 7 studies including 679 patients) were 0.87 (95% CI, 0.82-0.90) and 0.93 (95% CI, 0.89-0.95), respectively, suggesting good to excellent reliability. CONCLUSION: 2D-SWE shows good technical performance for assessing liver stiffness, with high technical success and reliability. Future studies should establish the quality criteria and optimal number of measurements.

Systemic review: agreement between the latent tuberculosis screening tests among patients with rheumatic diseases.

BACKGROUND/AIMS: To estimate the level of agreement and positivity rates of latent tuberculosis infection (LTBI) tests prior to the use of tumor necrosis factor (TNF) inhibitors in relation to underlying rheumatic diseases and endemic tuberculosis levels. METHODS: The Ovid-Medline, Embase, and Cochrane Libraries were searched for articles before October 2013 involving LTBI screening in rheumatic patients, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), juvenile idiopathic arthritis (JIA), and psoriatic arthritis. RESULTS: In pooled analyses, 5,224 rheumatic patients had undergone both a tuberculin skin test (TST) and an interferon-gamma release assay (IGRA) before TNF inhibitors use. The positivity of TST, QuantiFERON-TB Gold In Tube (QFT-GIT), and T-SPOT.TB (T-SPOT) tests were estimated to be 29%, 17%, and 18%, respectively. The agreement percentage between the TST and QFT-GIT, and between the TST and T-SPOT were 73% and 75%. Populations from low-to-moderate endemic TB presented with slightly less agreement (71% between TST and QFT-GIT, and 74% between TST and T-SPOT) than patients from high endemic countries (73% between TST and QFT-GIT, and 81% between TST and T-SPOT). By underlying disease stratification, a lower level of agreement between TST and QFT-GIT was found among AS (64%) than among JIA (77%) and RA patients (73%). CONCLUSION: We reaffirm the current evidence for accuracy of LTBI test done by TST and IGRA among rheumatic patients is inconsistent. Our stratified analysis suggests different screening strategies might be needed in clinical settings considering the endemic status in the patient's country of origin and the precise nature of underlying diseases.

Pneumonitis in advanced non-small-cell lung cancer patients treated with EGFR tyrosine kinase inhibitor: Meta-analysis of 153 cohorts with 15,713 patients: Meta-analysis of incidence and risk factors of EGFR-TKI pneumonitis in NSCLC.

PURPOSE: Pneumonitis is a significant toxicity of EGFR tyrosine kinase inhibitors (EGFR-TKI) in non-small-cell lung cancer (NSCLC) patients. We studied the incidence of pneumonitis in clinical trials of EGFR-TKI published in 2003-2017, and performed subgroups analyses to identity predisposing factors. METHODS: Ovid-MEDLINE and EMBASE search up to 4/17/17 using the keywords, "erlotinib", "gefitinib", "afatinib", "osimertinib", and "lung cancer", resulted in a total of 153 eligible trial cohorts with 15,713 advanced NSCLC patients treated with EGFR-TKI. The pooled incidence of all-grade, high-grade, and grade 5 pneumonitis was obtained. Subgroup analyses were performed with meta-regression using study-level covariates. RESULTS: Among the patients without prior exposure to EGFR-TKI, the overall incidence was 1.12% (95% CI:0.79-1.58%) for all-grade, 0.61% (95% CI:0.40-0.93%) for high-grade, and 0.20% (95% CI:0.11-0.38%) for grade 5 pneumonitis. The incidence was significantly higher in Japanese studies compared to studies of non-Japan origin, for all-grade (4.77% vs. 0.55%, p < 0.001), high grade (2.49% vs. 0.37%, p < 0.001), and grade 5 pneumonitis (1.00% vs. 0.18%, p < 0.001). Multivariate analyses demonstrated higher odds of pneumonitis in Japanese studies for all-grade (odds ratio [OR]: 5.04; 95% CI:3.14-8.11, p < 0.001), high-grade (OR: 4.45; 95% CI:2.50-7.93, p < 0.001), and grade 5 pneumonitis (OR: 4.55; 95% CI:2.20-9.44, p < 0.001) compared to others, after adjusting for types of EGFR-TKI and lines of therapy. In patients with EGFR retreatment analyzed separately, the pooled incidence was 1.13% (95% CI:0.40-3.15%) for all-grade, 0.49% (95% CI:0.21-1.11%) for high-grade, and 0.16% (95% CI:0.04-0.65%) for grade 5 pneumonitis. CONCLUSIONS: The overall incidence of EGFR-TKI pneumonitis was 1.12% in patients without prior exposure to EGFR-TKI, and 1.13% in EGFR-TKI retreatment group. The cohorts from Japan had significantly higher incidence of pneumonitis, providing insights for further mechanistic studies.