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BACKGROUND: Current guidelines lack recommendations for the use of immunotherapy and immune-related biomarkers for hepatocellular carcinoma (HCC). We aim to provide reliable evidence of the association of survival with HCC immunotherapy and to demonstrate that genomic mutation signature could be an effective biomarker to predict immunotherapy efficacy of HCC patients. METHODS: We conducted a meta-analysis of 17 randomized trials with 2055 patients and an individual patient-level analysis of 31 patients. Trial data were identified in PubMed, EMBASE and Cochrane Central library, and individual patient data were obtained from the cBioPortal database. Overall survival (OS) and progression-free survival (PFS) were assessed with the hazard ratio (HR) and 95% CI. This study is registered with PROSPERO, number CRD42018083991. RESULTS: The meta-analysis showed that compared to conventional therapy, immunotherapy resulted in prolonged OS (HR =0.65, P

Xi Lin,1 Cai Chang,2,3 Changjun Wu,4 Qin Chen,5 Yulan Peng,6 Baoming Luo,7 Lina Tang,8 Jing Li,9 Jihui Zheng,10 Ruhai Zhou,11 Guanghe Cui,12 Ao Li,13 Xuemei Wang,14 Linxue Qian,15 Jianxing Zhang,16 Chaoyang Wen,17 Joel Gay,18 Huili Zhang,18 Anhua Li,1 Yaling Chen2,3 1State Key Laboratory of Oncology in Southern China, Department of Ultrasound, Sun Yat-Sen University Cancer Center, Guangzhou 510060, P. R. China; 2Department of Ultrasound, Fudan University Shanghai Cancer Center, Shanghai 200032, P. R. China; 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, P. R. China; 4Department of Ultrasound, First Affiliated Hospital of Harbin Medical University, Harbin 150001, P. R. China; 5Department of Ultrasound, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, Chengdu 610072, P. R. China; 6Department of Ultrasound, West China Hospital of Sichuan University, Chengdu 610041, P. R. China; 7Department of Ultrasound, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510235, P. R. China; 8Department of Ultrasound, Fujian Provincial Cancer Hospital, Fuzhou 350014, P. R. China; 9Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang 110004, P. R. China; 10Department of Ultrasound, The Fourth Affiliated Hospital of China Medical University, Shenyang 110032, P. R. China; 11Department of Ultrasound, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo 315040, P. R. China; 12Department of Ultrasound, Binzhou Medical University Hospital, Binzhou 256603, P. R. China; 13Department of Ultrasound, Jiangsu Province Hospital, Nanjing 210029, P. R. China; 14Department of Ultrasound, The First Hospital of China Medical University, Shenyang 110001, P. R. China; 15Department of Ultrasound, Beijing Friendship Hospital of Capital Medical University, Beijing 100050, P. R. China; 16Department of Ultrasound, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou 510120, P. R. China; 17Department of Ultrasound, First Affiliated Hospital of PLA General Hospital, Beijing 100037, P. R. China; 18Supersonic Imagine, Aix-en-Provence, France Purpose: This study aimed to investigate the value of shear wave elastography (SWE) for characterization of breast masses in a Chinese population. Patients and methods: Two thousand two hundred seventy-three women consented to be prospectively enrolled for the characterization of breast masses with ultrasound and SWE. Breast masses were known from symptoms, palpability, and/or previous imaging screening with mammography and/or ultrasound. Correlation of SWE qualitative and quantitative features with malignancy risk and impact on diagnostic performance of combining SWE features were assessed, and the Breast Imaging Reporting and Data System (BI-RADS) scoring was calculated using histopathology as reference. Results: Data of 2,262 masses (median size: 13 mm; range: 1.3–50) from 2,262 patients (median age: 43 years; range: 18–91) were investigated, of which 752 (33.3%) were malignant. Sensitivity and specificity of BI-RADS diagnosis were 97.5% (733/752) and 54.8% (827/1,510), respectively. By logistic regression, the combination of maximum elasticity (Emax) measurements with BI-RADS assessments increased the area under the receiver operating characteristic curve from 0.908 (95% CI: 0.896–0.920) to 0.954 (95% CI: 0.944–0.962). Using Emax of 30 kPa or lower to selectively downgrade BI-RADS 4a masses to follow-up, and Emax of 160 kPa or higher to selectively upgrade BI-RADS 3 lesions to biopsy, specificity significantly increased from 54.8% (827/1,510) to 66.1% (998/1,510) (P

Background Diabetic foot ulceration is receiving more attention because of its high amputation and mortality rate. It is essential to establish the frequency of amputations in people with diabetes after any change to the management of diabetic foot care. The present study aim to compare the frequency of lower-extremity amputations in patients with diabetes foot ulcer over a ten-year period. Methods Six hundred forty eight patients with diabetes foot ulcer were retrospectively studied from 2004 to 2013. The clinical features, laboratory results and the lower-extremity amputations were recorded. Major amputation was defined as amputations above the ankle while minor amputation was amputations below the ankle in the present study. Results Patients with diabetic foot ulcer were old (age 66.96 ± 11.96 years), with a long duration of diabetes (10.30 ± 6.94 years), high HbA1c (9.19 ± 2.62 %), SBP (144.05 ± 24.18 mmHg), DBP (79.53 ± 11.88 mmHg), LDL-C (2.71 ± 0.93 mmol/L) and had great frequency of neuropathy (62.7 %), retinopathy (45.0 %), nephropathy (39.5 %) and PAD (33.2 %). From 2004 to 2013, the frequency of all lower-extremity amputations is 12.0 % (5.2 % major amputation, 6.8 % minor amputation). The frequency of major amputations decreased from 9.5 % in 2004 and 14.5 % in 2005 to less than 5.0 % after 2006. In particular, there was a significant decline in major amputations of diabetic foot patient with Wagner 3 to 4 wounds. The frequency rate of major amputations in diabetic foot patient with Wagner 3 to 4 wounds fell from 35.7 % in 2004 to 4.4 % after 2007. The change in frequency of minor amputations was fluctuation. Conclusion This study demonstrates that the introduction of a multidisciplinary team, coordinated by an endocrinologist and a podiatrist, for managing diabetic foot disease is associated with a reduction in the frequency of major amputations in patients with diabetes.

Purpose The purpose of this study was to compare the efficacy and safety of cilostazol versus acetylsalicylic acid (ASA) for amelioration of lower limb ischemia in type 2 diabetes. Design Prospective, randomized positive-controlled open clinical trial. Subjects and setting Eighty-nine patients with type 2 diabetes mellitus and symptoms of lower limb ischemia (perceptions of coldness of the lower limbs, numbness, intermittent claudication, or pain at rest) present for 6 months or more that had not significantly changed within the past 3 months participated in the study. All subjects had an initial transcutaneous oxygen pressure (TcpO2) of less than 40 mm Hg in the foot when measured in the supine position. Subjects included 46 males and 43 females; their ages ranged from 35 to 80 years. Methods Participants were randomly allocated to 2 groups, one was treated with cilostazol 100 mg taken twice daily (n = 48), and a second group took 100 mg of ASA daily (n = 41) for 8 weeks. Clinical assessment included measurement of transcutaneous oxygenation, and symptoms associated with lower limb ischemia. Blood analyses included a full blood panel, coagulation screen, renal function tests, hepatic function tests, and lipid profiles. All tests were performed at baseline and repeated at 8 weeks. Results Age, duration of diabetes, diabetic complications, lower limb ischemic symptoms, TcpO2, and smoking status did not differ between the 2 groups. In contrast, TcpO2 significantly improved from 37.1 ± 11.9 mm Hg to 42.0 ± 9.7 mm Hg in the cilostazol-treated group (P .05). Ischemic symptoms such as intermittent claudication (P = .009), perception of limb coldness (P = .008), and pain at rest (P = .017) showed greater improvement in the cilostazol-treated group when compared to subjects treated with ASA. Approximately 10% of patients treated with cilostazol experienced adverse side effects (palpitations, headache, diarrhea). Cilostazol was not found to have significant detrimental effects in hematologic or biochemical indices, including renal, hepatic, and blood coagulant function tests. Conclusions We found that 8 weeks of treatment with cilostazol 100 mg daily was safe and well tolerated for the treatment of type 2 diabetes with lower limb ischemic disease.

e16129Background: The role of immune biomarkers in predicting benefits of hepatocellular carcinoma (HCC) was still controversial. We was aimed to investigate the prognostic value of immune biomarke...

e16125Background: The role of adjuvant interferon, tumor vaccines or cellular immunotherapies in patients with hepatocellular carcinoma (HCC) continues to be debated. This study aimed to assess the...

1 Background: Previous clinical data suggested that the tumour-infiltrating lymphocytes (TILs) were predictive in breast cancer treated with adjuvant chemotherapy; however, clinical relevance has yet to be established. We hypothesized that TILs would be associated with overall survival (OS) and disease-free survival (DFS) after anthracycline/taxane-based adjuvant chemotherapy in breast cancer subtypes. Methods: PubMed and EMBASE were searched until March 2017 for studies that investigated the association of TILs with survival for anthracycline/taxane-based adjuvant chemotherapy in breast cancer. OS and DFS were combined using random-effects meta-analysis and calculated as combined hazard ratio (HR) with 95% credible intervals (CIs). The PROSPERO registry number is CRD42017072133. Results: Twelve studies comprising 9,023 patients were eligible for analysis. Six were prospective adjuvant trials (n = 7686) and six were retrospective studies (n = 1337). Pooled analysis indicated that high TILs have no significant predictive association in overall population (DFS, HR = 0.87, 95% CI, 0.70 – 1.08; OS, HR = 0.98, 95% CI, 0.89 – 1.07), Luminal A/B (DFS, HR = 0.99, 95% CI, 0.94 – 1.04; OS, HR = 1.01, 95% CI, 0.92 – 1.12), and HER2–positive patients (DFS, HR = 0.84, 95% CI, 0.71 – 1.00; OS, HR = 0.89, 95% CI, 0.77 – 1.02), but were related to improved DFS (HR, 0.81; 95% CI, 0.73 – 0.89) and OS (HR, 0.74; 95% CI, 0.66 – 0.84) in triple negative breast cancer (TNBC) patients. Additionally, increasing TILs were not significantly associated with reduced risk of relapse in HER2-positive patient through adjuvant trastuzumab (HR, 0.97; 95% CI, 0.93 – 1.01). Conclusions: This meta-analysis provides an evidence that TILs predicts survival to anthracycline/taxane-based adjuvant chemotherapy in TNBC patients and suggests that predictive benefit seemed to be influenced by breast cancer subtypes as well.

168 Background: Treatment with immune checkpoint inhibitors is becoming the standard of care for patients and it was approved for the treatment of non-small-cell lung cancer (NSCLC) growing at a rapid pace. However, selecting patients who are appropriate for therapy and which therapeutic strategies to use can be challenging. Methods: We searched for randomized clinical trials (RCTs) investigating immune checkpoint inhibitors versus observation in patients with advanced NSCLC until September 2017. Overall survival (OS) and progression-free survival (PFS) were pooled by meta-analysis. The GRADE system was used to describe the quality of evidence. Results: The analysis included 11 trials with 5,538 unique patients. High- to moderate-quality evidence indicated that immune checkpoint inhibitors extended NSCLC survival and PFS, expressed as hazard ratios (HRs) (OS: 0.79, P = 0.000; PFS: 0.78, P = 0.000). High- to moderate-quality evidence revealed prolonged OS and PFS were similar across preplanned subgroups in patients with squamous (0.77, P = 0.000 and 0.74, P = 0.001) or nonsquamous disease (0.76, P = 0.003 and 0.73, P = 0.041), EGFR wild-type positive status (0.67, P = 0.000 and 0.59, P = 0.010), current or former smokers (OS: 0.83, P = 0.009), and male (0.79, P = 0.000 and 0.67, P = 0.023). Increasing improvement in OS was associated with increasing PD-L1 expression (TC3 or IC3 HR 0.54, P = 0.000; TC2/3 or IC2/3 HR 0.62, P = 0.007; TC1/2/3 or IC1/2/3 HR 0.64, P = 0.000; TC0 and IC0 HR 0.72, P = 0.017; high- to moderate-quality evidence). In exploratory subgroup analysis suggest that there was advantageous of immune checkpoint inhibitors in previous definitive chemotherapy compared with chemoradiotherapy, with concurrent administration of chemotherapy (OS as HR: P = 0.001, P = 0.006, respectively). Conclusions: This large and comprehensive analysis produced firm evidence that immune checkpoint inhibitors extended advanced NSCLC survival and PFS, while in some patients with EGFR wild-type positive status, current or former smokers, male and higher PD-L1 expression had substantial benefit. The benefits from therapy appear to be influenced by preceding definitive therapy and concurrent chemotherapy.

2 Background: Current guidelines have limited information regarding tumour-infiltrating lymphocytes (TILs) were predictive in breast cancer survival treated with neoadjuvant chemotherapy, although some studies suggest a benefit. We quantify the prognostic value of this biomarker for neoadjuvant chemotherapy in patients with breast cancer. Methods: PubMed and EMBASE were searched until March 2017 for studies that investigated the association of TILs with survival for anthracycline/taxane-based neoadjuvant chemotherapy in breast cancer. Overall survival (OS) and disease-free survival (DFS) were combined using random-effects meta-analysis calculated as combined hazard ratio (HR) with 95% credible intervals (CIs). The interaction test was adopted in order to determine the differential effect according to the histology subtypes and TILs subsets. The PROSPERO registry number is CRD42017072133. Results: We identified 16 studies comprising 2,523 patients were entitled. According to histology subtypes analysis indicated that TILs were not prognostic markers for DFS and OS in overall population, but high TILs were related to improved DFS (HR = 0.73, 95% CI, 0.63 – 0.86) and OS (HR = 0.65, 95% CI, 0.51 – 0.83) in triple negative breast cancer (TNBC) patients, and high TILs were also related to better DFS (HR = 0.62, 95% CI, 0.40 – 0.96) in HER2–positive patients. For TILs subsets, our results indicated that high TILs were prognostic markers for DFS (HR = 0.94, 95% CI, 0.89 – 0.98) and OS (HR = 0.74, 95% CI, 0.58 – 0.94). In an ad-hoc analysis, increasing CD8+ lymphocytes were associated with improved DFS (HR = 0.46, 95% CI, 0.33 – 0.65) and OS (HR = 0.41, 95% CI, 0.24 – 0.71), high CD8/FOXP3 ratio was correlated with prolonged DFS (HR = 0.43, 95% CI, 0.29 – 0.63) and OS (HR = 0.45, 95% CI, 0.26 – 0.76), while rich FOXP3+ lymphocytes were associated with reduced DFS (HR = 1.47, 95% CI, 1.01 – 2.15) in overall population. Conclusions: The present results reveal TILs as a predictor of survival to anthracycline/taxane-based neoadjuvant chemotherapy in breast cancer patients. Furthermore, predictive benefit appears to be influenced by breast cancer subtypes and TILs subsets as well.

194 Background: Immune checkpoint inhibitors selection in advanced melanoma is complicated further, with choices among anti-CTLA4 or anti-PD-1 therapeutic antibodies options. We aimed to evaluate the clinical benefits of immune checkpoint inhibitors for discussing evidence-based treatment strategies by a meta-analysis of randomized clinical trials (RCTs) data. Methods: We searched for RCTs investigating immune checkpoint inhibitors in patients with advanced melanoma until September 2017. Hazard ratios (HRs) was estimated for overall survival (OS) and progression-free survival (PFS). The quality of the evidence was evaluated with the GRADE framework. Results: Overall, 18 RCTs including a total of 8,917 patients were identified. Immune checkpoint inhibitors versus placebo or observation prolonged PFS (HR = 0.59, 95% confidence interval (CI) 0.44 to 0.78, P < 0.0001) and OS (HR = 0.77, 95% CI 0.72 to 0.84, P < 0.0001). The combination immunotherapy had significantly higher benefit than monotherapy for PFS (HR = 0.75, 95% CI 0.61 to 0.92, P = 0.005) and OS (HR = 0.70, 95% CI 0.61 to 0.79, P < 0.0001). Treatment with anti-PD-1 monoclonal antibody was associated with improved PFS (HR = 0.61, 95% CI 0.59 to 0.69, P < 0.0001) and OS (HR = 0.66, 95% CI 0.58 to 0.77, P < 0.0001) compared with anti-CTLA-4 monoclonal antibody. According to BRAF status analysis, there was a PFS benefit of immune checkpoint inhibitors versus placebo or observation (mutant, HR = 0.58, 95% CI 0.35 to 0.96, P = 0.035; wild–type, HR = 0.52, 95% CI 0.43 to 0.69, P = 0.001), anti-PD-1 outperformed anti-CTLA-4 checkpoint inhibitor (mutant, PFS HR = 0.64, 95% CI 0.51 to 0.79, P < 0.0001; wild–type, PFS HR = 0.58, 95% CI 0.47 to 0.71, P < 0.0001); and combination compared with single-agent immunotherapy (mutant, HR = 0.38, 95% CI 0.15 to 0.98, P = 0.046; wild–type, HR = 0.40, 95% CI 0.23 to 0.69, P = 0.001). Conclusions: This analysis provides an evidence that immune checkpoint inhibitors enhanced OS and PFS in patients with advanced melanoma, as well as combination immunotherapy and anti-PD-1 monoclonal antibody appear to be clinically beneficial option preference.

Ultrasonography, the preferred imaging modality for breast diseases, has merits such as absence of radiation, high diagnostic accuracy, and convenience for follow-up, thus playing an important role in clinical diagnosis and management. The American College of Radiology (ACR) proposed Breast Imaging-Reporting and Data System (BI-RADS ) and has updated for several times. Gradually, the BI-RADS has been accepted and adopted by ultrasound physicians at all levels of hospitals in China, and it has played a certain role in improving the diagnostic level of breast ultrasound in China. In order to standardize breast ultrasound application and raise the status of ultrasound in clinical decision-making of breast diseases, based on the latest edition of ACR BI-RADS Atlas 2013, the committee has reached the “Expert Consensus on Clinical Frequently Asked Questions in Breast Ultrasonography”on a number of controversial Frequently Asked Questions (FAQs) in clinical practice (hereafter referred to as “Consensus”), and will be dedicated to updating the contents of the “Consensus”, through further experience in clinical practice and the advent of new information from further studies. This consensus is only for reference purposes for medical personnel, and the processes outlined are not mandatory by law.

Ultrasound-measured inferior vena cava (IVC) and abdominal aorta (Ao)-associated parameters have been used to predict volume status for decades, yet research focusing on the impact of individual physical characteristics, including gender, height/weight, body surface area (BSA), and age, assessed simultaneously on those parameters in Chinese children is lacking. The aim of the present study was to explore the impact of individual characteristics on maximum IVC diameter (IVCmax), Ao, and IVCmax/Ao in healthy Chinese children. From September to December 2015, 200 healthy children from 1 to 13 years of age were enrolled. IVCmax and Ao diameters were measured by 2D ultrasound. We found that age (years), height (cm), weight (kg), waist circumference (cm), and BSA (m2) were positively correlated with IVCmax and Ao. Multivariate linear regression showed that age was the only independent variable for IVCmax (mm) in female children, height was the only independent variable for IVCmax in male children, and age was the only independent variable for Ao in both females and males. IVCmax/Ao was not significantly influenced by the subjects’ characteristics. In conclusion, IVCmax and Ao were more susceptible to subjects’ characteristics than IVCmax/Ao. IVCmax/Ao could be a reliable and practical parameter in Chinese children as it was independent of age, height, and weight.