bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical characteristics and outcomes of signet ring cell carcinoma of the stomach: A retrospective analysis of SEER database.
Authors: Ellithi Moataz , Elnair Radowan , Abdullah Hafez Mohammad 
Published: May 2020

e16572 Background: Signet ring cell carcinoma (SRCC) of the stomach accounts for 8 to 30% of all gastric cancers, however the incidence has been rising. We performed a Surveillance, Epidemiology and End Results (SEER) database analysis to further characterize the biology and clinical aspects of this entity, in comparison to gastric adenocarcinoma (AC). Methods: Surveillance, Epidemiology and End Results (SEER) 18 database was used to obtain data on age, gender, ethnicity, survival, and tumor characteristics of 5,424 US patients diagnosed with gastric SRCC between 2012-2016 and these were compared to 40,657 patients with other gastric adenocarcinoma (AC) subtypes diagnosed during the same period. Results: The gender distribution of both types of cancer was similar with males making up 51.8% of gastric SRCC and 48.3% of gastric AC patients. Median age of diagnosis was 63 years for gastric SRCC as compared to 65 years for gastric AC patients. The age of diagnosis distribution for both types was similar with patient <40 years (7.2% versus 6.2% respectively), 40-60 years (34% versus 32% respectively), 60-80 years (44.6% versus 45.15% respectively) and at > 80 years (14.4% versus 16.6% respectively). Among the SRCC patients, 70.9 % were Caucasians, 15.5% were Asians/Pacific Islanders, and 11.6% were African-Americans. Amongst gastric AC patients, Caucasians made up 76% of the patients, while African-Americans made up 12.9% and Asian/Pacific Islanders made up 9.2 % of the patients. Median OS was 10 months for gastric SRCC compared to 24 months (p < 0.001) for gastric AC. Racial differences in overall survival (OS) was noted. The median OS in Caucasians, African-American, Asian/Pacific Islander, and Native American populations was 11,11,15,7 months respectively (p < 0.001). Conclusions: Gastric SRCC has significantly worse survival as compared to AC with median OS of 10 months vs 24 months. It is more common in patients with Asian/Pacific Islander ancestry as compared to gastric AC. There is a significant racial disparity in survival outcomes with significantly shorter survival in patients with Native american ancestry.
The impact of surgery induced immune-nutritional change on the outgrowth of micrometastasis after potentially curative resection for gastric cancer.
Authors: Aizawa Masaki , Yabusaki Hiroshi , Matsuki Atsushi , Bamba Takeo , Nakagawa Satoru 
Published: May 2020

e16581 Background: Whereas radical resection for gastric cancer is only life-saving option, resulting host response have been suggested to trigger the outgrowth of previously disseminated foci at distant anatomical sites via alteration of anti-tumor immunity. The prognostic nutrition index (PNI) which was calculated as 10 × serum Alb concentration (g/dL) + 0.005 × peripheral total lymphocyte count (/µL) is a surrogate marker of inflammation related nutritional decline and the imbalance of T lymphocyte differentiation. The aim of study was to evaluate the impact of perioperative change of PNI. Methods: The medical record of 567 gastric cancer patients who matched with the following inclusion criteria, R0 resection between 2006 and 2018, no preoperative anticancer treatment, pStage IB-IIIC according to UICC TNM classification and no other organ cancer at surgery, was identified from the prospectively maintained database. The postoperative laboratory data was routinely evaluated at POD 1, 3, 7 and first visit after discharge (AD). The PNI was compared through the perioperative course. Then the predictive value of low PNI-AD which defined as PNI < 40 on the relapse free survival (RFS) after surgery was estimated by COX proportional hazards analysis. Results: The median value of PNI at base line, 1, 3, 7 POD and AD was 51.0, 35.9, 34.0, 38.3 and 48.2, respectively. The PNI as significantly decreased at 1, 3 and 7 POD. Though the PNI at AD had a proclivity to recover, which was still significantly lower than that at base line. During observation period after surgery, the recurrence was encountered in 80 patients. The 5-year RFS rate in patients of pStage IB (n = 164), II (n = 228) and III (n = 175) was 97.4%, 88.9% and 64.7%, respectively. The multivariate analysis identified female gender (HR: 1.715, 95%CI; 1.018-2.890, p = 0.04), pT3-4 (HR:3.620, 95%CI; 2.011-6.518, p < 0.01), pN1-3 (HR:2.741, 95%CI; 1.428-5.263, p = 0.02), vessel invasion (+) (HR:2.666, 95%CI; 1.681-4.229, p < 0.01), PNI-AD < 40 (HR:1.833, 95%CI; 1.002-3.352, p = 0.04) were independent predictors of recurrence. The low PNI-AD was significantly related to the recurrence in the population of pStage III, but not in pStage IB and II. Conclusions: The retardation of postoperative recovery of PNI might evoke the distant metastasis.
Efficacy of immune check point inhibitors (ICIs) in metastatic gastric or gastroesophageal junction (GEJ) cancer by patient subgroups: A systemic review and meta-analysis.
Authors: Goldvaser Hadar , Sternschuss Michal , Moore Assaf , Perl Gali , Brenner Baruch , Kundel Yulia 
Published: May 2020

e16587 Background: Patients with metastatic gastric or GEJ cancer have short duration of response to chemotherapy and poor outcome. Treatment with ICIs has been investigated for this population with inconsistent results. It is uncertain whether the effect of ICIs is comparable in different subgroups. Methods: Randomized controlled trials (RCTs) that compared standard treatment to treatment with ICIs, either as a monotherapy or in combination with chemotherapy, for metastatic gastric or GEJ cancer were identified. Hazard ratios (HRs) and 95% confidence intervals (CI) for overall survival (OS) were extracted and pooled in a meta-analysis using generic inverse variance and random effects modelling. Pre-specified subgroups included: patients’ age at time of randomization (age < /≤ 65 years versus ≥/ > 65 years), gender (female versus male), ethnicity (Asians versus the rest of the world), Eastern Cooperative Oncology Group performance status (0 versus 1), primary tumor location (gastric versus GEJ) and histological subtype (diffuse versus other subtypes). Data on progression free survival (PFS) and on OS in patients with programmed death ligand (PDL1) positive were also collected. Results: Four RCTs comprising 1,765 patients were analyzed. Treatment with ICIs compared to standard therapy did not significantly improve OS (HR = 0.84, 95% CI 0.66-1.07, p = 0.17), PFS (HR = 1.22, 95% CI 0.75-1.96, p = 0.52), or OS in patients with PDL1 positive disease (HR = 0.86, 95% CI 0.73-1.02, p = 0.08). The effect of ICIs on OS was similar in all subgroups. Non-significantly greater effect sizes were seen in younger patients (HR = 0.82 versus 0.86, p for subgroup difference 0.80), male (HR = 0.81 versus 0.97, p = 0.32), performance status 0 (HR = 0.84 versus 0.88, p = 0.81), GEJ tumors (HR = 0.76 versus 0.89, p = 0.44) and non-diffuse subtype (HR = 0.71 versus 0.79, p = 0.62). Conclusions: Compared to standard treatment, ICIs in metastatic gastric or GEJ cancer did not improve OS significantly. As none of the evaluated subgroups has shown increased magnitude of effect to ICIs, other biomarkers for ICIs response are desired in order to optimize the risk versus benefit balance of these patients.
Safety and efficacy of lenvatinib in HCC beyond second-line treatment.
Authors: Jefremow André , Wiesmüller Marco , Rouse Rachel Amande , Dietrich Peter , Kremer Andreas Emanuel , Waldner Maximilian Josef , Neurath Markus Friedrich , Siebler Jurgen 
Published: May 2020

e16592 Background: Until 2018 sorafenib was the only first-line systemic treatment option for advanced hepatocellular carcinoma (HCC). Ten years later a new agent, called lenvatinib, showed equal efficiency in comparison to sorafenib. Currently sorafenib and lenvatinib are options for first line treatment with regorafenib, cabozantinib and ramucirumab (if alpha fetoprotein > 400 ng / ml) as second-line treatment choices. The first published results from Imbrave150-trial shows promising effects regarding the combination of atezolizumab and bevacizumab for first line treatment in advanced HCC. This highlights the question for reasonable sequence therapies. Yet, it has so not been demonstrated, if lenvatinib is an option for a treatment line beyond the second. Methods: We identified 5 patients with advanced HCC from our hospital, who had been treated with local ablative procedures as well as at least three different systemic therapies with still excellent clinical performance status before receiving lenvatinib. Retrospective analysis was performed to examine clinical and radiologicresponse rates as well as side effects. Results: 3/5 patients achieved regression in at least third treatment lines. One patient showed stable disease, and only one of these five patients showed a mixed response. The toxicity profile was heterogeneous. One patient developed a mild hand-foot syndrome. Another one evolved hypertension. Developing of proteinuria led to stop treatment in one patient. One patient showed psychiatric disorder, which was possibly associated with lenvatinib. Response was independent of the underlying cause of HCC. Conclusions: Lenvatinib is a promising agent for treating advanced HCC in a later treatment line and revealed a tolerable toxicity profile.
Combination therapy with lenvatinib and anti-PD-1 antibodies for unresectable or advanced hepatocellular carcinoma: A real-world study.
Authors: Sun Hui-Chuan , Zhu Xiao-Dong , Huang Cheng , Shen Ying-Hao , Ge Ning-Ling , Chen Yi , Tan Chang-Jun , Zhou Jian , Fan Jia 
Published: May 2020

e16610 Background: Combination therapy of anti-angiogenic therapy and anti-PD-1 antibody had shown promising anti-tumor effects for advanced hepatocellular carcinoma (HCC) in clinical trials. Here we report the effectiveness and safety of the combination therapy of lenvatinib and anti-PD-1 antibodies in a cohort of unresectable or advanced HCC pts. Methods: From Sep 2018 to Jan 2020, 77 consecutive pts received a combination treatment of lenvatinib and an anti-PD-1 antibody. Lenvatinib was given 8 mg/d regardless of patient body weight and anti-PD-1 antibody was used either q2wk (nivolumab or camrelizumab) or q3wk (pembrolizumab, sintilimab or toripalimab). pts who completed at least one efficacy and safety assessment were eligible for this study. Tumor response were evaluated with abdominal contrast-enhanced MRI/CT and/or chest CT every 2 mo (± 1 wk). Laboratory tests were monitored every 2-3 wk. Results: 59 pts were eligible for this study. Of them, 1 (1.7%) were BCLC stage A, 10 (16.9%) were BCLC stage B, 48 (81.4%) were BCLC stage C (including 20 pts in China Liver Cancer [CNLC] stage IIIa and 28 in CNLC stage IIIb). 43 (72.9%) pts were treated as first-line therapy. The table below shows efficacy results. R0 resection was performed in 6 (10.2%) pts due to tumor regression. By the data cut-off date, 13 pts died, and mOS was not mature. Overall, the combination treatment was well tolerated. 28 (47.5%) pts had at least one ≥ grade 3 treatment-emergent adverse event. 3 (5.1%) pts died from immune-related adverse events, 2 of them died from immune-related adverse events after hepatectomy. Conclusions: The combination of lenvatinib + anti-PD-1 antibody is effective and well-tolerated in pts with HCC as first-line or second-line treatment. It is also noted that initially unresectable HCC may be converted to resectable HCC following this combination treatment. [Table: see text]
Distinct clinical and genetic characteristics of AFP-negative hepatocellular carcinoma patients infected by HBV or HCV.
Authors: Zhang Bixiang , Duan Jingxian , Li Yingmei , Ding Zeyang , Zhang Zhanguo , Chen Shifu 
Published: May 2020

e16620 Background: The serum level of alpha-fetoprotein (AFP) is a key biomarker in hepatocellular carcinoma (HCC) screening regardless of the high false-negative rates. Studies have characterized AFP negative HCC patients, however, the differences between HBV and HCV infected AFP negative HCC patients have not been discussed. Methods: The clinical profiles and whole-exome sequencing data of 243 patients were downloaded from the TCGA database. Patients were divided into 4 groups based on their virus infection status and serum AFP measurements as indicated in the table. The mutation profiles and clinical features of the patients were analyzed. Results: In the HBV infected groups, the AFP+ patients carried significantly larger tumors (n = 17, 85.88±11.87 mm) compared to the AFP- patients (n = 13, 49.08±8.933 mm, p = 0.026). The HBV+ AFP+ group exhibited the prevalence of vascular invasion (VI, 76%, 13/17) while less than half of the patients in the HBV+ AFP- group developed VI (46%, 6/13). The WES results identified shared mutations in more than 10% of patients in each group. It appeared that 126 shared mutations were restricted to the HBV+ AFP+ group, they are involved in the regulation of ion transmembrane transport (p < 0.001) and interaction between L1 and Ankyrins (p < 0.0001). Only 51 shared mutations were exclusive to the HBV+ AFP- group, they majorly affect developmental growth (p < 0.001) and skeletal system development (p < 0.01). In contrast, the tumor sizes of HCV+ AFP+ and HCV+ AFP- patients are similar (55.18±7.781 vs 48.19±5.564, p = 0.47), while the VI rate is higher in the HCV+ AFP- group (63%, 17/29, Table). In total, 11 shared mutations were restricted to the HCV+ AFP+ group, several of the genes were involved in the generation of precursor metabolites and energy (p < 0.01) and activation of immune response (p < 0.01). 27 shared mutations were exclusive to the HCV+ AFP- group, the enrichment analysis showed that they are related to the regulation of synapse organization (p < 0.0001) and the regulation of chromosome organization (p < 0.01). Conclusions: HBV and HCV infection were associated with distinct clinical features among the AFP positive and AFP negative patients. The differences were underpinned by the mutations exclusive to each group, and they were involved in distinct molecular and cellular functions. [Table: see text]
The role of targeted therapy (TKI) in the treatment of advanced hepatocellular carcinoma (aHCC) in the era of immunotherapy: Real-world data using AI analytics from an academic medical center.
Authors: Wong Rachel Su Jen , Wu Jiaxuan , Leen Alisha Joan , Tey Glenn Jin Chong , Asokumaran Yugarajah , Chan Gloria , Siddappan Chidambaram , Jeyasekharan Anand Devaprasath , Chee Cheng Ean , Yong Wei-Peng , Ngiam Kee Yuan , Sundar Raghav 
Published: May 2020

e16623 Background: The management of aHCC has evolved dramatically in recent years, with new agents like immunotherapy receiving regulatory approval. As we begin incorporating these drugs into routine clinical practice, data on real-world sequencing of therapies and clinical outcomes are needed. Methods: We utilised the DISCOVERYAI platform, a virtual machine containing de-identified patient electronic health records to review HCC patients treated at the National University Health System, Singapore from January 2015 to December 2019. We then identified those who received systemic therapy and correlated their clinical outcomes. Results: In total, 395 HCC patients were identified; 75 received surgery, 174 received loco-regional therapy and 102 referred for consideration of systemic therapy. Of those considered for systemic therapy, median age was 65 years (range 23-87); 88% male (n = 90); hepatitis B/hepatitis C/non-hepatitis, 41(40.2%)/ 10(9.8%)/ 51(50.0%). 75.5% (n = 77) of them received systemic therapy with a TKI and/or immunotherapy. 39% (n = 30) of these received second-line treatment. Child-Pugh score at start of treatment was A5/A6/B7/B8, 38(49.3%)/ 32(41.6%)/ 5(6.5%)/ 2(2.6%) respectively. In the first-line, 66% (n = 51) received TKI and 34% (n = 26) received immunotherapy. Amongst those treated with first-line TKI, 45% (n = 23) received second-line therapy; 65% (n = 15) immunotherapy, 35% (n = 8) another TKI. Of those treated with first-line immunotherapy, 27% (n = 7) received second-line TKI. At a median follow-up of 35 months, first-line median progression-free survival (mPFS) for TKI vs immunotherapy was 3.7 vs 3.1 months (HR 0.73; 95% CI, 0.40-1.33; p = 0.31). mPFS for second-line immunotherapy vs TKI was 4.0 vs 2.9 months (HR 0.43; 95% CI, 0.19-0.96; p = 0.04). When comparing sequencing of therapies, the combined first and second mPFS for TKI-immunotherapy/TKI-TKI/immunotherapy-TKI is 9.5/7.6/7.6 months respectively (log-rank test, p = 0.71). Those patients that received both immunotherapy and TKI had significantly higher overall survival (OS) compared to those receiving only immunotherapy or only TKI or none (mOS NR vs 10.1 vs 13.2 vs 4.7 months; p < 0.001). Conclusions: TKI remains an important pillar of treatment in aHCC in the era of immunotherapy. While immunotherapy provides long durable responses and benefit in a minority of patients, the majority appear to benefit from TKI. Biomarker studies are needed to discern treatment algorithms for aHCC.
Genomic architecture of gallbladder cancer: Results of a first prospective study.
Authors: Patel Amol , Singh H P , Pandalanghat Suresh , Kumar Manish , Guleria Bhupesh , Mathighatta Shivarudraiah Shivashankara Swamy 
Published: May 2020

e16628 Background: Rarity in western countries precluded Gallbladder cancer (GBC) from prospective research. Comprehensive Genomic profiling carries potential to determine oncogenic pathways, driver mutations and possible resistance mechanisms. This study is evaluating the role of comprehensive genomic profiling and role of targeted therapies therein. Methods: This is a single center, prospective, study conducted from Aug2018-Dec2019. All consecutive patients of unresectable and/or metastatic GBC of age ≥18 years were enrolled. Hybrid capture based comprehensive genomic profiling was performed by Foundation Medicine CDx. Microsatellite instability and PDL1 expression were studied. Results: Median age was 56 years (range:26-83) with male to female ratio of 1:1.6. NGS information was available for 50 patients. ERBB pathway was aberrated in 44% of patients. ERBB2 & ERBB3 amplification was seen in 9(18%) and 2(4%) patients respectively. ERBB2 mutations were present concurrently with amplification in 3 patients. MET amplification was present in 3 (6%) PIK3CA mutations were seen in 14% of cases. PIK3CA mutations were independent of ERBB aberrations. FGFR2 mutation, FGFR2 and FGFR3 amplification was present in one patient each. NF1 and NF2 mutations were seen in three and two patients respectively. Median TMB (n = 39) was 5 mut/Mb with range of 1-14 mut/Mb. PDL1 (n = 31) of ≥ 1% was present in 32% of cases and it ranged from 1-100%. MSI (n = 39) was stable in all cases. Other somatic mutations and/or amplifications are shown in Table. Conclusions: GBC is enriched in 28% of patients with ERBB2 & ERBB3 amplifications and/or mutations. FGFR2 mutation is rare in GBC. PIK3CA aberrations are common. Phase 2 trial of frontline Trastuzumab combined with chemotherapy is ongoing. [Table: see text]
Association of immune related adverse events with superior outcomes in patients with hepatocellular carcinoma (HCC) treated with nivolumab.
Authors: Ostios-Garcia Lorena , Ramiro-Cortijo David , Peters Mary Linton Bounetheau , Bullock Andrea J. 
Published: May 2020

e16630 Background: Nivolumab, an anti-PD1 antibody, is FDA approved in patients (pts) with HCC. Anti-PD-1 promotes hyperstimulation of host immunity and is associated with a spectrum of toxicities known as immune-related adverse events (irAEs). In other malignancies, higher rates of irAEs are associated with improved cancer outcomes. This study shows correlation between irAEs and efficacy in pts with HCC treated with nivolumab. Methods: Demographic and toxicity data were collected retrospectively on all pts with HCC treated with nivolumab at a single institution from Jan 2012 – Sept 2019. Response was evaluated using RECISTv1.1. Adverse events were assessed according to CTCAEv5.0. Categorical variables were assessed by Fisher's exact test. Survival was estimated with the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate analyses were performed by the Cox-regression model. Results: 30 pts were treated; irAEs were detected in 16 (53%). There was no difference in baseline characteristics among those who did and did not experience irAEs (Table). The most frequent irAEs were elevated AST/ALT (n = 7; 44%), rash (n = 4; 25%), and hypothyroid (n = 4; 25%). 3 G3 (rash and transaminitis) and 1 G4 AE (pured red cell apalasia) were observed. Among all pts, overall response rate (RR) and disease control rate (DCR) were 13 and 50%, respectively. Median progression free survival (PFS) and overall survival (OS) were 27 and 56 weeks (w), respectively. The RR and DCR were higher among irAEs vs non-irAEs, although this did not reach statistical significance (RR 25 vs 0%; p = 0.05; DCR 62 vs 35%; p = 0.19). Median PFS and OS were longer in those with irAEs vs non-irAE; PFS 33 vs 16 w (HR: 0.26; CI 95%: 0.076-0.89; p = 0.028); (OS 69 vs 21 w HR: 0.18; CI 95%: 0.05-0.58; p = 0.002). On multivariate analysis, viral etiology was associated with prolonged PFS (p = 0.002) and MELD was associated with reduced OS (p = 0.004). Conclusions: Development of irAEs was associated with prolonged PFS and OS in pts with HCC treated with nivolumab. Further study is needed to determine whether type of irAE, onset time, or duration affect cancer outcomes. [Table: see text]
AST-to-APOA ratio to predict overall survival in hepatocellular carcinoma receiving TACE.
Authors: Chen Yongjian , Li Xing , Chen Jie , Qin Gang , Qiao Yidan , Huang Shaozhuo 
Published: May 2020

e16637 Background: Current guidelines lack definitive evidences about the predictive capability of clinical parameters for transcatheter arterial chemoembolization (TACE). The aim of this study was to comprehensively investigate the predictive factor among stage I-IV liver hepatocellular carcinoma (LIHC) patients after TACE. Methods: We investigated the clinical features of 211 stage I-IV patients with LIHC in discover group and 341 patients in validation group. Overall survival (OS) was estimated using the Kaplan-Meier method and the log-rank test. Results: Univariate Cox regression revealed that Monocyte count, TNM stage and AST-to-APOA ratio (AAR) were associated with unfavorable OS. AAR was identified as an independent predictor of OS using multivariate analysis. Kaplan-Meier curve demonstrated that patients with AAR < 50 displayed better prognosis. The median follow-up time was 17.1 (95%CI, 14.4 to 19.3) months, 3-year overall survival was 55.9% in the low AAR group versus 28.6% in the high AAR group, and there was significant difference in OS (Hazard ratio [HR] 0.47, 95%CI 0.33 to 0.67, P < 0.001). The AAR showed predictive ability for OS (12-month, AUC = 0.707). These findings were successfully validated in validation group (HR 0.62, 95%CI 0.46 to 0.84, P = 0.002; 12-month AUC = 0.636). Conclusions: AAR was an independent predictor among LIHC patients after TACE. Patients with lower AAR were optimal candidates for TACE.