bluuebunny/crossref_metadata_2025_split huggingface dataset:
The mutational pattern of homologous recombination (HR) related genes and its relevance to response to immunotherapy in gastric cancer.
Authors: Fan Yue , Ying HaiFeng , Wu Xueying , Mao Beibei , Zhang Henghui 
Published: May 2020

e16579 Background: Although therapeutic strategies based on immune checkpoint inhibitors (ICIs) have been introduced for gastric cancer (GC), there is still a pressing need to find potential predictive therapeutic biomarkers beyond PD-L1 expression to help patients to derive more benefit from these therapies. Homologous recombination deficiency (HRD) could modify tumor immune microenvironment by increasing the presence of tumor-infiltrating lymphocytes (TILs) indicating that HRD might be a biomarker of immunotherapies. Our aim was to analyze the mutational pattern of HR related genes in a large Chinese GC cohort and its relevance to tumor immune profile and clinical response to immunotherapy. Methods: A panel of 543 cancer related genes was used to analyze the genomic profiling of Genecast cohort which is consisted of 484 Chinese patients with GC. The correlation between HR-gene mutations and tumor immunity or clinical outcome using two GC genomics datasets (TCGA and MSK-GC) by the bioinformatic approach. Results: Fifty-one of 484 (10.54%) patients had at least one somatic mutation in HR-gene, ATM (16/484, 3.31%), ATRX (14/484, 2.89%), and ATR (13/484, 2.69%) were among the top mutated HR-gene in Genecast cohort. Mutations in HR-gene are associated with elevated TMB, enhanced immune activity, and microsatellite instability (MSI) status. In MSK-GC cohort, including a total of 49 patients who had stomach adenocarcinoma (STAD) or gastroesophageal junction adenocarcinoma (GEJ) and treated with ICIs, HR-mut GC (n = 12) had a significantly better OS than HR-wt GC (n = 37) (log-rank test, P = 0.034). Conclusions: Our data suggests that detection of somatic mutations of HR-gene could expand the proportion of patients who might get benefit from immune checkpoint blockade therapy response.
Variability in multimodality treatment influences survival in non-metastatic gastric cancer patients.
Authors: Hoang Tuyen , Dayyani Farshid , Alfaro Ariceli , Huynh Jasmine , Ji Jingran , Ko Andrew H. , Cho May Thet , Hiyama Darryl 
Published: May 2020

e16588 Background: While gastric cancer is a leading cause of cancer-related mortality in Eastern Europe and Asia, it is less common in the United States. Recommendations regarding optimal treatment of non-metastatic gastric cancer (nmGC) with regard to type and extent of surgery, choice and sequence of chemotherapeutic agents, and use of radiation therapy vary somewhat depending on geographic location. To determine how variability in treatment practices affects patient outcomes, we conducted a retrospective study to evaluate clinical outcomes in nmGC patients treated at four high-volume academic institutions. Methods: California Cancer Registry of demographic and clinical data were collected for nmGC patients who underwent surgery with curative intent from 2010-2018. We conducted chart reviews of the patients’ electronic health records to validate clinical factors and outcomes. We performed multivariable Cox regressions to determine prognostic factors for outcomes. Results: Demographics of study cohort (n = 326): mean age 66 years; 64% male; 44% Caucasian, 35% Asian, 16% Latino. Tumor stage: 48% loco-regional (pT4 or pN1+) versus 52% localized (pT1-3, pN0). Histology: 47% intestinal, 30% diffuse, 8% mixed, 15% unknown. Surgery: number of recovered lymph nodes varied from 0 to 60 in any tumor stage. Chemotherapy: 20% neoadjuvant, 25% adjuvant, 16% perioperative, 39% none. Multimodality therapy: 44% surgery only, 31% chemotherapy, 25% chemotherapy and radiation. With a median follow-up after surgery of 6 years, 24% of patients developed recurrence and 40% had died. Compared to open surgery, laparoscopic surgeries was associated with lower lymph node recovery (median = 15 vs 19, p = .0042), which in turn was associated with a significant decrease in overall 5-year survival after adjusted for tumor stage (hazard ratio HR = 1.9, p = .0012). Timing of chemotherapy and addition of radiation therapy to chemotherapy did not confer further improvements in survival. In contrast, greater lymph node recovery plus chemotherapy were associated with improved survival in patients with loco-regional tumors (HR = 0.3, p = .0020). Conclusions: This study highlights major practice differences in the management of nmGC across providers and institutions. Further efforts should be made to standardize the use of chemotherapy and adequate recovery and assessment of lymph nodes in this patient population.
Impact of immunotherapy use in patients with stage IV biliary carcinoma.
Authors: Rojas Mariajose , Komiya Takefumi , Sharma Neil R. , Powell Emily 
Published: May 2020

e16597 Background: Most patients with cholangiocarcinoma have non resectable disease at the time of diagnosis and usually die within 6-12 months. The 5-year survival rate is very low (about 5%), and since most patients present with advanced disease at time of diagnosis, treatment includes chemoradiation and biliary stenting. Recently, trials with immunotherapy (IO) for treatment of advanced cancer have shown promising results as alternative therapeutic options. Despite indications in other solid tumors, the role of IO is unknown for biliary cancer. Methods: Using National Cancer Database (NCDB), cases of Stage IV biliary cancers (including gallbladder and cholangiocarcinoma) diagnosed in the period of 2014-2016 with at least 30-day follow up were analyzed. The following clinical demographics were included: age (younger than 70 vs. older than 70), sex (male vs. female), race (whites vs. others), insurance (uninsured vs. insured), liver metastasis (Yes vs. No). We also analyzed data regarding cancer treatment, including radiation (Yes vs. No), chemotherapy (Yes vs. No), and IO (Yes vs. No). Survival analysis was performed using Kaplan-Meier curves and Log-rank tests. A p-value < 0.05 was considered significant. Results: Among 6,344 eligible cases, 57 patients were treated with IO. No significant association between use of IO and clinical demographics was observed except for use of chemotherapy (p = 0.001) and primary location (gallbladder vs. others, p = 0.042). Chemotherapy was administered in 52 (91%) and 4112 (65%) of cases in IO and non-IO groups, respectively. Use of IO was associated with improved overall survival in both univariate and multivariate analyses (p = 0.0005and 0.0156, respectively). Median overall survival (in months) was 14.0 in the IO group vs 7.0 in the non-IO group. Landmark analysis in the IO group showed 12 and 24-month survival of 56.1% and 19.3% respectively, as compared with 27.8% and 7.6% in the non-IO group. Conclusions: This retrospective data analysis using a large cancer database suggests that use of IO could improve survival in patients with advanced biliary cancer. More studies will be needed in the future to validate these results.
Lenvatinib plus hepatic arterial infusion of modified FOLFOX regime in patients with advanced hepatocellular carcinoma.
Authors: Mai Qicong , Mo Zhiqiang , Shi Feng , Chen Xiaoming 
Published: May 2020

e16603 Background: Recently, Sorafenib plus hepatic arterial infusion chemotherapy (HAIC) of modified FOLFOX regime has shown promising results for patients with advanced hepatocellular carcinoma. Lenvatinib is also the first-line treatment for advanced hepatocellular carcinoma, it has shown the better objective response rate (ORR) and longer progression free survival (PFS) than sorafenib. This retrospective study evaluated the combination of lenvatinib plus HAIC of modified FOLFOX regime in patients with advanced hepatocellular carcinoma. Methods: This study retrospectively enrolled and analyzed 24 patients from Nov 2018 to May 2019 from Guangdong provincial people’s hospital. Patients with advanced hepatocellular carcinoma were treated with 8 mg(≤60kg) or 12mg( > 60kg) lenvatinib once daily plus HAIC of modified FOLFOX regime (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2400 mg/m2 for 46 hours, every 3 weeks). Best response according to the RECIST 1.1 and mRECIST criteria. PFS, overall survival (OS) and treatment-related adverse events(TRAE) were also evaluated. Results: 24 patients(median age: 49.2 years) underwent a total of 91 cycles of HAIC therapy (mean: 3.79; range: 2-8). 22 (91.7%) patients had cirrhosis caused by HBV infection.17(70.8%) patients were diagnosed with vascular invasion and 7 (29.2%) were both vascular invasion and extrahepatic spread. 20 (83.3%) patients were classified as Child-pugh A class and 4 (16.7%) patients were Child-pugh B class. The ORR were 58.3% (RECIST) and 66.7% (mRECIST), the disease control rate (DCR) was 79.2% (RECIST/mRECIST). With a median follow-up period of 11.3 months, the median PFS was 8.1 months. 6-, 9-, and 12-months OS rates were 91.7, 83.3%, and 75%, respectively. TRAE occurred in 20 of 24 patients (83.3%), most common TRAE were hypertension (41.7%) and hand-foot skin reaction(25%). No grade 3/4 TRAE was observed. Conclusions: Lenvatinib plus HAIC of modified FOLFOX regime was well tolerated and had shown promising ORR, PFS and 6-, 9-, and 12-months OS rates in advanced hepatocellular carcinoma. A prospective large-scale trial is needed to justify these results. [Table: see text]
To biopsy or to not biopsy, that is the question: A single-center retrospective analysis of outcomes of liver biopsy with hepatocellular carcinoma and other liver diseases.
Authors: Lee Sophia Seo-hyeon , Yang Wei , Rowe Julie Haewon 
Published: May 2020

e16606 Background: Unlike other malignancies, hepatocellular carcinoma (HCC) is most often diagnosed radiologically, based on previous studies suggesting complication rates of 1.4%-3.4% (e.g., bleeding) and concerns regarding “tumor seeding.” Lack of tissue for analysis has led to a lag in understanding the molecular biology of HCC. Molecular characterization of biopsies may allow HCC subtyping in order to personalize medicine, thus the potential of liver biopsy’s safety and utility needs to be reassessed. Methods: We performed a retrospective review of patients who underwent biopsy for suspected HCC or other liver diseases between Jan 1, 2010 and Jan 1, 2020. Demographics and clinical data including comorbidities, renal function, ascites, hepatic encephalopathy, varices, and labs including hemoglobin, WBC, platelets, sodium, creatinine, liver function test and coagulation studies were collected. Child Pugh (CP) and MELD-Na scores were calculated. Adherent medications at the time of biopsy and type of biopsy with any complications were included. Results: A total of 427 patients underwent liver biopsy. Patient characteristics are given in the table. Most patients (97%) underwent core needle biopsy. Biopsy complication rate was 1.23% (n = 5); these included bleeding (80%, n = 4), hospitalization (60%, n = 3), infection (20%, n = 1), and death (20%, n = 1). In the 5 patients, increased creatinine was associated with bleeding complications; however, one patient was on dialysis (Cr = 11.20), and this should be interpreted with caution. Existing comorbidities, concurrent medication use (including anticoagulants), CP and MELD-NA score, and lab findings were not associated with biopsy complications. Conclusions: To our knowledge, this review is first to demonstrate a low complication rate of 1.23% in suspected HCC patients who underwent liver biopsy in the current era of improved radiological techniques. This is consistent with historical data in liver disease patients. Comorbidities, being on anticoagulants, CP and MELD scores do not predict for biopsy complications. Higher creatinine was associated with more complications, but this needs to be examined in a larger study. Biopsy should be considered a valuable tool in understanding the molecular profiles of HCC, which could lead to more novel treatment. [Table: see text]
Correlation of serum PIVKA-II and AFP level with portal vein tumor thrombus and BCLC stage in newly diagnosed hepatocellular carcinoma patients.
Authors: Gandham Goutham , Jayamohanan Hridya , Ponnada Bharadwaj , Kumar Anil , S Sudhindran , Keechilat Pavithran 
Published: May 2020

e16608 Background: Protein Induced by Vitamin K Absence-II (PIVKA-II) is a tumor marker specific for hepatocellular carcinoma (HCC). PIVKA-II levels correspond with HCC oncogenesis and disease progression. Portal vein tumor thrombus (PVTT) in patients with HCC is a significant factor that affect treatment and prognosis. In this study we assessed the predictive value of PIVKA-II and AFP for vascular invasion and BCLC stage in newly diagnosed HCC patients. Methods: We retrospectively reviewed records of newly diagnosed HCC patients at a tertiary hospital in India between January 2019 to December 2019. Clinical details, BCLC stage, radiological imaging records, serum levels of PIVKA-II and AFP at the time of diagnosis were obtained from medical records. Diagnostic accuracy and cut-off value of PIVKA-II in patients with portal invasion were calculated using receiver operator curve (ROC) analysis. Multiple pairwise comparisions between BCLC stage with PIVKA-II and AFP levels were analysed using Kruskal-Wallis test. Results: Out of 162 newly diagnosed HCC patients 42(25.9%) were detected with PVTT on imaging such as contrast-enhanced computed tomography or magnetic resonance imaging at the time of diagnosis.120(74.1%) patients without PVTT were taken as controls for the analysis. Serum level of PIVKA-II in HCC patients with PVTT was significantly higher than in HCC patients without PVTT (1152.57 mAU/ml vs 146.39 mAU/ml; p = 0.001). AUROC of PIVKA-II was 0.796 (95%CI 0.70-0.892, p = 0.000).The optimal cut-off value of PIVKA-II was 271.81 mAU/ml with a sensitivity of 78.6% and specificity of 52.4%, and the diagnostic accuracy was 59.98%. AUROC of AFP was 0.619 (95%CI 0.59-0.72, p = 0.001). Median PIVKA-II value increased from BCLC stage A to D. Kruskal-Wallis test showed a significant difference of PIVKA-II levels between all stages except stage A and B (p values for stage A-B (0.297), A-C (0.000), A-D(0.000),whereas for AFP results were significant only between stages A and C (p values for stage A-B (0.348), A-C (0.003), A-D(0.206). Conclusions: Serum PIVKA-II level appears as a good predictive marker for PVTT and BCLC stage when compared to AFP which may guide therapeutic strategy and assessment of prognosis in newly diagnosed HCC patients.
Efficacy and safety of immune checkpoint inhibitors (ICIs) in unresectable hepatocellular carcinoma (HCC): A systematic review and meta-analysis of randomized clinical trials (RCTs).
Authors: Jácome Alexandre A. , De Castro Ana Carolina Guimaraes , Solar Vasconcelos João Paulo , Silva Maria Helena Cruz Rangel , Lessa Marco Antonio Oliveira , Moraes Eduardo Dias de , Andrade Aline Chaves , Ferreira Barbara Sodre Figueiredo , Lima Frederico M. T. , Bulcao Marcela Lima , Ferreira Artur Rodrigues , Fogacci De Farias Joao Paulo , Prolla Gabriel , Garicochea Bernardo 
Published: May 2020

e16631 Background: ICIs have ushered a new era in cancer therapy, but their efficacy in HCC is uncertain. Single-arm phase II studies with sorafenib-refractory patients have suggested clinical activity of nivolumab and pembrolizumab, which have become FDA-approved therapies. Nevertheless, the overall effect of ICIs compared with the standard of care (SOC) in unresectable HCC patients is still unknown. Methods: We systematically searched PubMed, Cochrane Library, Web of Science, LILACS, and ASCO and ESMO Meeting Proceedings in the last 10 years for RCTs that have compared the efficacy of ICIs versus the SOC in the systemic therapy of unresectable HCC. Outcomes of interest included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3-4 treatment-related adverse events (TRAEs). A summary hazard ratio (HR) of OS and PFS was calculated using 95% confidence intervals (CI) by fixed-effects model. The likelihood of ICIs being associated with ORR and TRAEs was expressed by odds ratio (OR) and 95% CI using a random-effects model (PROSPERO ID 162599). Results: Of the 2,334 studies yielded by the search, 3 studies were retained (KEYNOTE-240, CheckMate-459, and IMbrave150), totaling 1,657 patients (985 ICIs versus 672 SOC). Two studies compared ICIs versus sorafenib in 1st line setting, and one study compared with placebo in 2nd line. The ICIs studied were pembrolizumab, nivolumab, and atezolizumab. RCTs with anti-CTLA4 have not been reported. Two studies evaluated ICIs as monotherapy, and one study investigated the association with bevacizumab. Compared with the SOC (sorafenib in 1st line or placebo in 2nd line), ICIs significantly improved OS (HR: 0.78, 95% CI 0.68 – 0.89, p = 0.0002), PFS (HR: 0.79, 95% CI 0.71 – 0.89, p < 0.0001), and ORR (OR: 2.82, 95% CI 2.02 – 3.93, p < 0.0001). ICIs were associated with a lower probability of grade 3-4 TRAEs when compared to sorafenib (OR: 0.44, 95% CI 0.20 – 0.96, p = 0.04). No significant heterogeneity was found among studies when OS and ORR were analyzed, but it was found in the analysis of PFS and TRAEs. Conclusions: ICIs demonstrated superior efficacy and safety compared to the standard therapy of patients with unresectable HCC. The analysis of ICIs as monotherapy and combination therapy increased the heterogeneity among studies. The association of anti-angiogenic therapy with ICIs improved the survival benefit of immunotherapy and should become the new SOC in the 1st line systemic therapy of unresectable HCC.
Novel systemic therapies in hard to treat fibrolamellar hepatocellular carcinoma.
Authors: Gliksberg Ariel , O'Grady Claire , Kent Paul 
Published: May 2020

e16653 Background: Fibrolamellar Carcinoma (FLC) is a very rare liver malignancy of young adults without underlying liver disease (0.02 per 100,000 in the US).. Complete resection is the primary therapy, but recurrence rates are still > 50%. Currently there are no established systemic treatments, especially for high-risk disease (unresectable, relapse, progression, or metastatic disease). At our institution triple therapy “TT” with Nivolumab/5FU/Interferon α-2b is our first line, followed by other novel combination therapies such as Gemcitabine/Oxaliplatin/Lenvantinib (GOL) or Nivolumb/Lenvantinib/Quecertin (NLQ). Objective: To evaluate the tolerability and early response of multi-agent systemic therapies in patients with high-risk FLC. Methods: Data from all patients with FLC who received systemic therapies from 5/2018 to 2/2020 was reviewed to assess tolerability, survival and toxicity. Results: Nineteen patients were treated with systemic therapies of which 16 (10F, 6M median age of 19) were evaluable based on follow up scans. Between our 16 patients they had relapsed 28 times, 12 had metastatic disease and 7 had tried 2+ systemic therapies. RECIST 1.1 objective response (CR+PR) and tumor control (CR+PR+SD) are 44% and 69%. Since starting multi-agent therapy, all 6 patients who had previously been treated with monotherapy, have already exceeded their previous longest time to progression. Thirteen patients were treated with “TT” [12.5 median cycles (6-38)]. Three patients were treated with NLQ including 2 who failed TT. Of these, the 1 evaluable patient achieved CR. Two patients were treated with GOL, 1 who failed TT and one who was post liver transplant, both had sustained PR of 6 and 9 months. Subsequently one died and one achieved CR. For the 6 patients who achieved remission before or during therapy, only 1 has relapsed. To date the period of response is already 68% longer than the previous best length of response. There was 1 withdrawal due to grade 3 colitis and 2 dose adjustments. All experienced mild adverse effects, most commonly fever, headache, and hypertension, with 3 patients with grade 3 toxicities. Conclusions: FLC is a devastating disease with patients often relapsing even after successful surgical remission. Currently there is a need for tolerable systemic therapies. Although at our institution, TT is our frontline therapy, there are other combinations of immunochemotherapies that we have used to treat FLC with preliminary success and minimal toxicities. Our early results show that multi-agent systemic therapy in hard-to-treat FLC is worthy of further study.
Controversial risk factors for cholangiocarcinoma.
Authors: Sarmini Muhammad Talal , Baidoun Firas , Saad Anas M , Gad Mohamed , Alhaj Moustafa Muhamad 
Published: May 2020

e16662 Background: Cholangiocarcinoma (CCA) is a relatively rare malignancy accounting for 3% of gastrointestinal cancers in the US. While multiple risk factors for CCA are established and well-studied, other potential risk factors are still controversial and not well established. Herein, we used a large national database to investigate possible risk factors and associations. Methods: We used the National Inpatient Sample (NIS) database to review all admissions between 2011 and 2015. We grouped patients based on the presence and absence of CCA using the appropriate ICD-9 codes. We used multivariate logistic regression to assess the association between obesity, alcohol abuse, smoking, diabetes mellitus (DM), and non-alcoholic fatty liver disease (NAFLD). Results: We reviewed 30,955,295 admissions of which 20,030 had CCA. CCA Patients were older compared to the rest of the patients (mean age 67 years ±12.8 vs. 57±20.6, P < .001) and had less female patients (48% vs 59%, P < .001). Patients’ characteristics are shown in the table. After adjusting for viral hepatitis B (HBV), viral hepatitis C (HCV), liver cirrhosis, inflammatory bowel disease (IBD), primary sclerosing cholangitis (PSC), and bile duct stones, logistic regression showed DM to be proportionately associated with CCA (OR = 1.04, 95%CI[1.01-1.08], P < .001), whereas alcohol, smoking and obesity were all inversely associated with CCA; OR = 0.75, 95%CI [0.69-0.81], P < .001, OR = 0.75, 95%CI [0.71-0.79], P < .001 and OR = 0.71, 95%CI [0.67-0.75], P < .001, respectively. In addition, compared to whites, Hispanic and Asian/Pacific Islander races were proportionally associated with CCA; OR = 1.27, 95%CI [1.21-1.34], P < .001, and OR = 1.79, 95%CI, [1.67-1.92], P < .001, respectively, while black race was inversely associated with CCA (OR = 0.85, 95%CI [0.81-0.89], P < .001). Conclusions: In our large database study, we found that patients with diagnosis of DM or being from certain minority ethnic groups are associated with increased incidence of CCA. Other factors like alcohol and smoking were associated with decreased incidence of CCA, but those factors may be under reported. This raises the need for further evaluation for these factors and their effect on CCA incidence and outcomes in those specific groups. [Table: see text]