bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative pembrolizumab for MSI high, EBV positive or PD-L1 positive locally advanced gastric cancer followed by surgery and adjuvant chemoradiation with pembrolizumab: Interim results of a phase 2 multi-center trial (NCT03257163).
Authors: Kennedy Timothy , Shah Mihir Maheshkumar , In Haejin , Chuy Jennifer W. , Moore Dirk F. , Kooby David A. , Kabarriti Rafi , Szabo Stephen M. , Hochster Howard S. , Jabbour Salma K. 
Published: June 2021

e16111 Background: Despite advances in therapy, outcomes of patients with gastric cancer in the US remain poor. Recent data demonstrated that certain subtypes of gastric cancer are less responsive to perioperative chemotherapy. Preliminary data suggest that patients with microsatellite unstable tumors (MSI-H), EBV expressing tumors, and tumors with high PD-L1 expression may benefit from immunotherapy. We initiated a clinical trial to evaluate the benefit of PD-1 checkpoint immunotherapy in this subset of patients with resectable gastric cancer. Methods: Interim analysis performed on this phase 2 multi-institutional clinical trial (NCT03257163) is presented. Patients with clinically staged T2-T4, N0-N3, M0 gastric adenocarcinoma are evaluated for loss of mismatch repair proteins, expression of EBV or PDL1 expression with CPS > 1%. Consented patients receive 2 cycles of neoadjuvant pembolizumab followed by surgical resection. Following surgery, patients receive adjuvant chemoradiation (45 Gy) with 5 cycles of capecitabine and concurrent pembrolizumab, followed by up to 1 year of pembrolizumab. The primary endpoint is disease-free survival. Results: Of the 15 patients currently enrolled (planned enrollment = 40), 6 patients were MSI-H, 2 EBV (+), and 7 had PDL1 expression with CPS > 1%. Two patients did not undergo surgical resection as 1 patient was found to have peritoneal disease at time of exploration and second was deemed too frail to proceed with surgery. In the 13 patients who underwent surgical resection, all are alive without evidence of recurrent disease (follow up 1 month – 22 months). After 2 cycles of pembrolizumab, 2 patients with MSI-H tumors had pathologic complete response. Clinical T stage was downstaged in 5 patients and clinical N stage was downstaged in 2 patients. PD-1 checkpoint immunotherapy was well tolerated with minimal need for dose reduction and limited toxicity. Conclusions: Early results from our phase 2 clinical trial show immunotherapy to be well tolerated with limited toxicity. Following 2 cycles of pembrolizumab, 2 patients with MSI-H had complete pathologic response and above a third of our patients were downstaged. No recurrences have been observed in the short-term follow-up of surgically resected patients. Clinical trial information: NCT03257163.
Lenvatinib plus pembrolizumab versus lenvatinib in patients with unresectable hepatocellular carcinoma: A real world study.
Authors: Lee I-Cheng , Wu Chi-Jung , Chen San-Chi , Chao Yee , Huang Yi-Hsiang 
Published: June 2021

e16138 Background: The combination of lenvatinib (LEN) and pembrolizumab (PEMBRO) showed promising response rates and survival in a phase 1b trial for patients with unresectable hepatocellular carcinoma (HCC). Whether LEN plus PEMBRO provides better outcomes than LEN monotherapy remains unclear. The aim of this study was to compare the outcomes of LEN plus PEMBRO versus lenvatinib monotherapy in patients with unresectable HCC in the real world setting. Methods: A total of 123 patients with unresectable HCC were retrospectively enrolled, including 61 patients with LEN monotherapy and 62 patients with LEN plus PEMBRO. We evaluated progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) by RECIST 1.1 and modified RECIST (mRECIST) criteria. Results: One hundred and one (82.1%) patients were in BCLC stage C and 81 (65.9%) patients received LEN or LEN plus PEMBRO as first line setting. During a median follow-up period of 8.0 months, 71 (57.7%) and 31 (25.2%) of patients had disease progression and death, respectively. The median PFS was 8.4 and 4.9 months in the LEN plus PEMBRO and LEN monotherapy groups, respectively (p = 0.033). The median OS was not reached in the LEN-PEM group and was 17.2 months in the LEN monotherapy group (p = 0.064). Patients with LEN plus PEMBRO had higher objective response rate (ORR: 34.4% vs 23.7% by RECIST 1.1, p = 0.277; 57.4% vs 32.2% by mRECIST, p = 0.010) and higher disease control rate (83.6% vs 62.7% by RECIST 1.1, p = 0.017; 85.2% vs 62.7% by mRECIST, p = 0.009). In subgroup patients with BCLC stage C, LEN plus PEMBRO provided significantly longer PFS (9.1 vs 4.8 months, p = 0.008), higher ORR (60% vs 33.3%, p = 0.015) and higher DCR (88% vs 60.4%, p = 0.004) by mRECIST criteria. Conclusions: LEN plus PEMBRO provides significantly better ORR, DCR and PFS then LEN monotherapy for patients with unresectable HCC.
A novel sub-staging system for prognosis prediction of Barcelona clinic liver cancer C stage hepatocellular carcinoma: 10 years observational study.
Authors: Mo Zhiqiang , Mai Qicong , He Jian , Chen Xiaoming 
Published: June 2021

e16139 Background: This study sought to propose a novel sub-staging system which could predict prognosis of patients with Barcelona clinic liver cancer (BCLC) C stage Hepatocellular carcinoma (HCC). Methods: Between January 2008 and September 2018, 806 patients with BCLC-C stage HCC were assessed retrospectively. The significance of clinical variables in predicting prognosis were statistical analysis. A prognostic sub-staging system of BCLC-C stage HCC was developed according to prognosis-related factors. The predictive performance was subsequently validated. Results: In training set, tumor burden (TB) >50%, type III/IV portal vein tumor thrombus (PVTT), extrahepatic metastasis (M) and Child-Pugh (CP) B class were independently associated with overall survival (OS). According to those prognosis-related factors, a novel sub-staging system of BCLC-C stage was “linear predictor= TB+PVTT+M+CP”, which had good performance in predicting OS in both training and validation set. The thirtieth percentile and the third quartile of the linear predictor, namely 6 and 12, were selected as cut-off values, stratifying patients into different OS after interventional therapy (IT) or sorafenib therapy (ST), specifically, ≤6: 43.7 months for IT, 32.0 month for ST;＞6 but＜12: 43.7 months for IT, 32.0 month for ST; ≥12: 43.7 months for IT, 32.0 month for ST. Conclusions: The novel sub-staging system of BCLC-C stage HCC may stratify patients for suitable therapy and predict individual survival with favorable performance and discrimination.
Healthcare utilization and costs in hepatocellular carcinoma (HCC) patients treated at a large referral center in Washington (WA) State.
Authors: Shankaran Veena , Chennupati Shasank , Sanchez Hayley , Sun Qin , Aly Abdalla , Marcus Healey , Seal Brian S. 
Published: June 2021

e16149 Background: Though the treatment landscape for HCC has changed significantly in the last several years with the refinement of liver-directed therapy techniques and the introduction of multiple new drugs, few studies have investigated the impact of the changing treatment landscape on lifetime treatment costs, particularly in Barcelona Clinic Liver Cancer (BCLC) stage C disease. We therefore sought to investigate real-world clinical characteristics, treatment patterns, healthcare use, and costs in patients with HCC treated at a single high-volume institution in WA. Methods: We conducted a retrospective cohort study of patients diagnosed with HCC between 2007 and 2018 at a single clinical cancer center using a database containing abstracted data from the electronic medical record (EMR) linked to cancer registry data and health claims from commercial insurance plans, Medicare, and Medicaid. We described clinical characteristics, including BCLC stage and Child Pugh score, and treatment patterns. We investigated the mean per patient lifetime treatment costs by BCLC stage using Kaplan-Meier cost estimator methods. Results: The final cohort included 215 patients, majority white (71%), male (68%), and with underlying hepatitis C (61%). Most patients had either Child Pugh A (76%) or B (20%) liver disease and BCLC A (45%), B (20%), or C (19%) stage HCC. Only 40% of BCLC C patients received systemic chemotherapy. Mean per patient lifetime costs were highest in BCLC A ($289,318) and BCLC C ($255,430) patients and lowest in BCLC D ($123,701) patients (Table). Surgical costs, hospital costs, imaging, and outpatient visits were the major contributors to total lifetime costs in BCLC A patients. Chemotherapy costs were highest in BCLC C patients, but still were not the predominant area of spending. Conclusions: In a WA state cohort of HCC patients, mean lifetime costs were highest in patients with BCLC A disease, largely driven by surgery and hospital costs. As utilization of newer and less toxic therapies in BCLC C patients increases, mean lifetime costs in this group may surpass other stages.[Table: see text]
Serum neutrophil/lymphocyte ratio as a potential predictor of treatment response for immune checkpoint inhibitors in patients with advanced hepatocellular carcinoma.
Authors: He Jian , Mo Zhiqiang , Mai Qicong , Chen Xiaoming 
Published: June 2021

e16156 Background: Neutrophil to lymphocyte ratio (NLR) has been shown to associate with tumor progression. The present study was to investigate the role of NLR on predicting the treatment response for immune checkpoint inhibitors (ICIs) therapy in patients with advanced hepatocellular carcinoma (HCC). Methods: We retrospectively reviewed 81 patients received ICIs for advanced HCC from January 2017 to July 2019. We analyzed whether pre- and first 3 weeks post- treatment serum NLR level was associated with ICIs outcome. Results: In this study, the pre-treatment NLR level ranged from 0.64 to 14.93 among 81 patients. The cut-off level of NLR was set as the median value of 2.79. The objective response rate (ORR) in the patients with NLR＜2.79 (low NLR) was 25.0%, which was significantly better than that of patients with NLR ≥2.79 (high NLR) (7.3%, P ＝0.03). Compared to patients with high NLR, patients with low NLR exhibited significantly longer median progression-free survival (PFS) (3.7 vs 3.0 months, P ＝0.004) and median overall survival (OS) (10.3 vs 7.5 months, P ＝0.001). Multivariate analysis revealed high NLR was an independent unfavourable prognostic factor for PFS (hazard ratio [HR] = 1.857, 95% confidence interval [CI] = 1.093-3.154; P = 0.022) and OS (HR = 2.267, 95% CI = 1.221-4.207; P = 0.009). For the patients with high pre-treatment NLR level, ICIs outcome was stratified more clearly by first 3 weeks post- treatment NLR level. Conclusions: The pre- and first 3 weeks post- treatment serum NLR level could be considered as a predictive factor of treatment response for ICIs in patients with advanced HCC.
Association of gut microbiota and metabolites with tumor response to immune checkpoint inhibitors in patients with unresectable hepatocellular carcinoma.
Authors: Lee Pei-Chang , Wu Chi-Jung , Hung Ya-Wen , Lee Chieh-Ju , Chao Yee , Hou Ming-Chih , Kuo Yu-Lun , Chou Shih-Hsuan , Huang Yi-Hsiang 
Published: June 2021

e16165 Background: Immunotherapy with checkpoint inhibitors (ICI) is a promising treatment for unresectable hepatocellular carcinoma (HCC), but lack of effective biomarker to predict treatment response. Gut microbiome could modulate tumor response to immunotherapy in melanoma; but its effects on HCC are still unclear. Methods: From May 2018 to April 2020, 94 patients received ICI treatment for unresectable HCC (uHCC) in Taipei Veterans General Hospital, the feces samples were prospectively collected before ICI treatment. Finally, 20 patients with radiology proven objective tumor responses (OR; 3 complete responses and 17 partial responses) following immunotherapy, and 21 randomly selected patients with progressive disease (PD) were enrolled for fecal microbiota and metabolites investigation. In addition, feces from 17 healthy volunteers were taken as normal control. Results: Although the alpha diversity was not significantly different among groups, the principal component analysis of Bray-Curtis distance showed a significant clustering of fecal microbiota between HCC patients and healthy volunteers. The significant bacterial dissimilarity was observed between OR and PD patients following immunotherapy (p = 0.016 and 0.019 by Anoism and Adonis tests, respectively). According to linear discriminant analysis (LDA) effect size (LEfSe), a prominence of Prevotella usually regarded as a pathogenic bacterium, was more abundant in HCC patients with PD to ICI treatment. While Veillonella, Lachnospiraceae, Lachnoclostridium, Lactobacillales, Streptococcaceae and Ruminococcaceae were predominant in patients with OR (LDA score [log10] > 3). In addition, primary bile acids, including murocholic acid, α and β-muricholic acids, and secondary bile acids, including ursodeoxycholic acid, ursocholic acid, tauro-ursodeoxycholic acid, and taurohyocholic acid were significantly dominant in the feces of patients with OR to ICI treatment. Correlation network analysis in patients with OR showed significant linkages between Lachnoclostridium, Ruminococcus and secondary bile acids. Conclusions: Fecal microbiota and bile acids are associated with the response to immunotherapy for uHCC patients. These findings highlight the potential role of microbiota as a biomarker and strategy to enhance response to immunotherapy by modifying gut microbiota for uHCC.
The efficacy and safety of lenvatinib for advanced hepatocellular carcinoma in China: A retrospective, real-world study.
Authors: Yang Xin-Rong , Guo De-Zhen , Chen Fei-Yu , Fan Jia , Jian Zhou 
Published: June 2021

e16182 Background: Hepatocellular carcinoma (HCC) is one of the most common malignancy with dismal outcomes. Recently, lenvatinib have been approved as the first-line therapy for unresectable HCC. However, the efficacy and safety of lenvatinib with the combination of other therapy such as transarterial chemoembolization (TACE) and immune checkpoint inhibitor (ICI) therapy was still unclear. Methods: A multicenter retrospective study was conducted and 158 HCC patients treated with lenvatinib from four medical centers were enrolled between November 2018 and December 2020. According to the treatment combined with lenvatinib, all patients were classified into four groups, including lenvatinib monotherapy (LEN) group, combined ICI (c-ICI) group, combined TACE (c-TACE) group and combined ICI and TACE (c-ICI-TACE) group. Objective response rate (ORR) and disease control rate (DCR) were assessed. Overall survival (OS) and time to progression (TTP) were calculated and compared among different groups. Results: All patients (n = 158) were classified into LEN group (n = 40), c-ICI group (n = 42), c-TACE group (n = 39) and c-TACE-ICI group (n = 37). In all patients, the ORR and DCR was 29.1% and 74.1%. The median OS and TTP were 21.8 and 6.2 months, respectively. Four groups showed significant differences in ORR and DCR rates. Specifically, c-ICI-TACE group have significantly higher ORR and DCR rate compared with LEN group (ORR: 12% vs. 38%, P = 0.002; DCR: 60% vs. 89%, P = 0.004). Kaplan-Meier analysis identified that LEN group, c-ICI group, c-TACE group and c-TACE-ICI group showed significantly different TTP (median TTP: 5.0 vs. 6.6 vs. 4.9 vs. 9.5 months; P = 0.021), but similar OS (median OS: 21.8 vs. 19.6 vs. 17.5 months vs. unreached; P = 0.180). Further investigation revealed lenvatinib combined with ICI could prolong TTP compare with lenvatinib without ICI (median TTP: 8.4 vs. 5.0 months; P = 0.019), but it had no significant impact on OS (median OS: unreached vs. 20.1 months; P = 0.300). c-ICI-TACE group showed both better TTP and improved OS compared with other three groups (median TTP: 9.5 vs. 5.2 months; P = 0.004; median OS: unreached vs. 20.1 months; P = 0.034). Univariate and multivariate analysis confirmed that c-ICI-TACE was an independent protective factor for OS (hazard ratio: 0.226; 95% confidence interval: 0.10-0.50; P < 0.001) and TTP (hazard ratio: 0.55; 95% confidence interval: 0.32-0.95; P = 0.032). Most patients (152/158, 96.2%) showed adverse events (AEs) during lenvatinib treatment and the grade 3 AE occurred in 45 patients (28.5%). No significant difference of AE (P = 0.569) and grade 3 AE (P = 0.572) was found among four groups. Conclusions: Lenvatinib was an effective treatment for patients with HCC. Lenvatinib combined ICI could prolong the TTP, while lenvatinib combined ICI and TACE could improve both TTP and OS. Combined therapy wouldn’t escalate the AE and grade 3 AE rates.
Healthcare utilization and outcomes in HIV versus non-HIV patients with hepatocellular cancer: A nationwide analysis.
Authors: Asotibe Jennifer C , Achebe Ikechukwu , Sherazi Syed Ali Amir , Warraich Muhammad-Sheharyar , Attar Bashar , Gupta Shweta , Mullane Michael Russell 
Published: June 2021

e16189 Background: Hepatocellular Carcinoma (HCC) remains a leading cause of cancer related mortality and has a 5-year survival after diagnosis of under 20%. HIV-HCC patients are reported to present with advanced disease and shorter survival compared to non-HIV-HCC patients. HIV has not been known to have a direct causal relationship with HCC but chronic immunosuppression, direct effects of HIV virus on liver parenchyma and use of hepatotoxic antiretroviral medications are thought to contribute to the pathogenesis of HCC (Curr Opin HIV AIDS 2017;12:20-25). We studied differences in outcomes and healthcare utilization between HIV and non-HIV-HCC from a national database. Methods: Healthcare Cost Utilization Project (HCUP) National Inpatient Sample (NIS) database was queried to identify all HIV and non-HIV HCC admissions between 2016-2018. The groups were compared for socio-demographic differences, inpatient mortality, length of stay (LOS) and total hospital charges (THC). Secondary outcomes studied were rates of acute kidney injury (AKI), encephalopathy, anemia, upper GI Bleed (LGIB), tumor lysis (TLS), portal hypertension (PH), sepsis, septic shock (SS), neutropenia and protein energy malnutrition (PEM). Statistics were performed using the t-test, univariate and multivariate logistic regression. Results: A total of 845 HIV-HCC and 88,805 non-HIV-HCC inpatient admissions were identified. Compared to non-HIV-HCC, HIV-HCC patients were significantly younger (mean age 59.3 vs 64.7 years, p < 0.0001) with fewer over 65 years old (21.9 % vs 47.4%, p < 0.0001), more males (87.6% vs 74.3%, p < 0.0002) and African American (AA) (44.8% VS 15.9%, p < 0.0001). HIV-HCC cohort were more likely to be treated at a teaching hospital (89% vs 81%, p < 0.035) and had higher comorbidity burden as defined by a high Charlson comorbidity index (p < 0.01) compared to non-HIV-HCC. Odds of adjusted inpatient mortality (aOR= 0.47, CI = 0.27–0.82, p = 0.007) was significantly lower in HIV-HCC with similar LOS (6.5 vs 6.1 days, p = NS) and THC ($85,930 vs $84,592, p = NS) compared to non-HIV-HCC. While rates of neutropenia (2.96% vs 0.62%, p < 0.001) and PEM (26.0% vs 16.3%, p = 0.01) were higher in HIV-HCC, rates of other secondary outcomes were similar compared to non-HIV cohort. Conclusions: HIV-HCC patients are younger, AA, and men with significantly lower inpatient mortality and similar healthcare utilization compared to non-HIV-HCC, despite higher rates of PEM and neutropenia, possibly reflecting advancements in HIV-HCC treatment, and contributed to by younger age and treatment at teaching hospitals. Further studies are needed to evaluate and assess the effect of co-infection with hepatitis on HIV-HCC outcomes which was not evaluated in present study and investigate interventions aimed to reduce complications like PEM and neutropenia to further improve outcomes.
Real-world efficacy and safety of lenvatinib-base therapy for patients with unresectable hepatocellular carcinoma in China: A multicenter retrospective analysis.
Authors: Mai Qicong , Chen Song , Shi Feng , Mo Zhiqiang , He Jian , Guo Wenbo , Chen Xiaoming 
Published: June 2021

e16192 Background: Lenvatinib has been approved as a first-line systemic for advanced hepatocellular carcinoma (HCC) after the randomized phase III REFLECT trial. The aim of this study was to assess the lenvatinib-base treatment patterns and safety in real-world clinical settings in China. Methods: In this multicenter retrospective study, A total of 278 patients with unresectable HCC were treated with lenvatinib-base treatment between October 2018 and November 2020 were analyzed. Therapeutic effect was determined using the RECIST 1.1 and mRECIST criteria. Progression free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAE) were also evaluated. Results: Of 278 unresectable HCC patients (median age: 56.1±11.9 years), 220 (79.1%) had cirrhosis caused by HBV infection. 215 (77.3%) and 63 (22.7%) patients were classified as Child-pugh A and B class, respectively. 233 (83.8%) and 45 (16.2%) patients received lenvatinib in first-line and second-line systemic therapies, respectively. 223 (80.2%) patients were treated with lenvatinib plus arterially directed therapy (TACE or HAIC of FOLFOX) and 55 (19.8%) were treated with lenvatinib alone. The objective response rate were 34.9% (RECIST) and 47.5% (mRECIST), while the disease control rate were 75.5%. With a median follow-up period of 12.8 months, the median PFS and OS were 7.8 months (95% CI 7.1–8.4) and 17.2 months (95% CI 14.9–19.6), respectively. Results from the multivariate analysis showed that the significant independent favorable prognosis factors were tumor burden< 50% (P=0.033), Child–Pugh A class (P<0.01), AFP level <200ng/mL (P=0.045), the combination with lenvatinib and arterially directed therapy (P<0.01). TRAE occurred in 219 of 278 patients (78.8%), most common TRAE were hypertension (n=118; 42.4%) and hand-foot skin reaction (n=91; 32.7%). The most common grade 3–4 TARE were hypertension (n=23; 8.3%), decreased appetite (n=18; 6.5%), AST elevation (n=14; 5%), and diarrhea (n=14; 5%) across all study patients. Conclusions: In this multicenter real-world study, lenvatinib-base treatment could be accomplished with well tolerated and response for unresectable HCC patients. Combination with arterially directed therapy could likely improve the overall survival.