bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world experience of pembrolizumab plus lenvatinib in unresectable hepatocellular carcinoma in Taiwan.
Authors: Wu Chi-Jung , Hung Ya-Wen , Lee Pei_Chang , Lee ChiehJu , Chen Ming Huang , Chao Yee , Hou Ming-Chih , Huang Yi-Hsiang 
Published: May 2020

e16627 Background: Multi-kinase inhibitors and immune checkpoint inhibitors (ICIs) are treatment options of systemic therapy for unresectable hepatocellular carcinoma (HCC). Targeted therapy can potentially enhance T cell infiltration and activation, consequently, cooperate with ICIs to produce synergistic anti-tumor effects. The ongoing clinical trial shows promising data by combining pembrolizumab with lenvatinib for advanced HCC. The study tried to evaluate the treatment response and adverse events of pembrolizumab plus lenvatinib for HCC in real-world setting. Methods: From Jul. 2019, patients who received pembrolizumab plus lenvatinib for unresectable HCC in a tertiary medical center in Taiwan were prospectively enrolled. The status of HCC was either in advanced HCC or failed by prior locoregional treatment. The dosage of pembrolizumab was 100mg every 3 weeks. The starting dose of lenvatinib was 10mg per day then titrating to weight-based dose according to recommendation. Patients who had received at least 2 cycles of pembrolizumab were evaluated in this report. The tumor response was assessed with Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST (mRECIST). The treatment related adverse events (TRAEs) were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: Till the end of Jan. 2020, 27 patients had received at least 2 cycles of pembrolizumab, and 17 had evaluable post-treatment images either by CT or MRI. There were 6 (22.2%) in BCLC B, and 21 (77.8%) in BCLC C. Of them, 17 (63%) were treated as the first-line systemic treatment, 8 as the second-line and 2 as the third line systemic treatment. Of the 17 cases with post-treatment image studies, there were 6 (35.3%) in partial response (PR), 7 (41.2%) in stable disease (SD), and 4 (23.5%) in progressive disease (PD) by RECIST v1.1; and 1 (5.8%) in complete response (CR), 9 (52.9%) in PR, 3 (17.6%) in SD and 4 (23.5%) in PD by mRECIST, respectively. The objective response rate (ORR) and disease control rate (DCR) by mRECIST were 58.7% and 76.5%, respectively. The most common TRAEs in any grade were hypertension 24 (88.4%), palmar-plantar syndrome 19 (70.4%), hypothyroidism 19(70.4%). The Grade 3/4 TRAEs were 3 (11.1%) with psoriasis-like skin reaction, 3 (11.1%) with hypertension and 2 (7.4%) with palmar-plantar syndrome. Conclusions: Pembrolizumab plus lenvatinib can produce excellent ORR and DCR with tolerable safety profiles. Such combination could be a promising strategy for unresectable HCC in the future.
Landscape of immune-checkpoint inhibitors in hepatocellular carcinoma: A systematic review with meta-analysis.
Authors: Shek Dmitrii , Read Scott A. , Nagrial Adnan , Gao Bo , Ahlenstiel Golo 
Published: May 2020

e16632 Background: The WHO estimates that liver cancer will cause 1 million deaths by 2030. Hepatocellular carcinoma (HCC) is a primary liver malignancy causing 4.3% of all cancer deaths in 2019 in Australia. Kinase inhibitors are standard of care (SoC) for metastatic HCC with median overall survival (mOS) of < 13 months. This meta-analysis primarily aimed to determine objective response rate (ORR) of immune-checkpoint inhibitors (ICIs) in advanced HCC. Methods: Potentially relevant clinical studies were identified through PUBMED, Scopus, ASCO and ESMO databases. Studies evaluating ICIs in patients with HCC and reporting efficacy outcomes were considered as eligible. Publication bias was assessed with Funnel plots. Data analysis was performed employing fixed and random effects model depending on study heterogeneity evaluating by I2 statistic. STATA v16 software was used for all statistical considerations. Results: 12 single arm phase II/III studies and 2 randomized clinical trials on ICIs in HCC were included into this analysis. First-line ICI: Primary forest plot established the median ORR was 26.2% (95% CI 24.7 to 27.9) in patients treated with first line ICIs monotherapy; in comparison, ORR of current SoC sorafenib is 2-3% and lenvatinib 18.8%. Moreover, nivolumab resulted in 9.8 months of OS in Child-Pugh class B (CPB) patients, previously eligible only for supportive care due to a low efficacy of sorafenib (mOS < 4.5 months). Second-line ICI: Secondary forest plot established that nivolumab at 1 mg/kg with ipilimumab 3 mg/kg Q3W resulted in mOS of 23 months with ORR of 32% in sorafenib-progressors. In comparison, current second line SoC regorafenib has mOS of 10.6 months and ORR of 17%. Conclusions: This meta-analysis suggests that ICIs may be superior (ORR) to SoC sorafenib in advanced HCC, particularly nivolumab. Secondly, nivolumab with ipilimumab were confirmed to provide higher OS in sorafenib progressors as compared to regorafenib. Of note, many of the studies included were only available in abstract form and final reporting is pending. Nevertheless, our results support higher efficacy of ICIs in HCC patients.
Demographic trends and in-hospital mortality data in patients with hepatocellular carcinoma.
Authors: Adepoju Bolanle , Perimbeti Stuthi , Kyung Daniel , Styler Michael , Jain Maneesh Rajiv 
Published: May 2020

e16648 Background: Hepatocellular carcinoma (HCC) remains the 4th leading cause of cancer related mortality in the US. The incidence of HCC in the US appears to be increasing in specific demographic subgroups (Caucasian males, Hispanics and in the Southern US). Older studies identified substantial racial and ethnic differences in treatment and survival in HCC. There is a lack of large scale studies exploring the mortality patterns in patients hospitalized with HCC. Methods: The National Inpatient Sample was used to extract admissions for HCC using the ICD-9 code 155.0 from the years 2010 to 2014. The sample was weighted to approximate the full inpatient population of the U.S. over the 5-year interval. Univariate analysis was performed to determine the frequency distribution and bivariate analysis was performed using Chi Square test to determine the in-hospital mortality percentage. Results: A total of 52,868 (weighted = 262845) admissions were extracted from the years 2010 to 2014. While the number of patients admitted with HCC steadily increased over the 5-year study period, the overall in-hospital mortality decreased significantly from 9.35% to 7.68% (p < 0.0001). The mortality was highest for patients with African American ethnicity at 11.2% and for uninsured patients at 13%. The mortality rate among patients in the low income group (0-25th percentile) was 10.2 %, significantly higher (p = 0.0005) than other income groups. Conclusions: Even though the incidence of in-hospital mortality in HCC patients is decreasing, there appears to be a disparity in mortality data among patients of low socioeconomic status, self-pay or uninsured status and among African Americans. Our study further confirms the persistence of racial,economic and social disparities and highlights the need for additional equity research to understand the reasons for these differences and to improve outcomes for these subgroups of patients.
Hepatobiliary tumors in adolescents and young adults: Site, age and gender distribution.
Authors: Wong Evelyn , Goh Wei Lin , Hong Jiancheng , Wong Victoria , Quah Daniel , Tan Yee Pin , Tan Yung Ying , Chan Jason Yongsheng , Somasundaram Nagavalli , Harunal Rashid Mohamad Farid Rin , Poon Eileen Yi Ling 
Published: May 2020

e16651 Background: Hepatobiliary cancer is one of the common cancers within Asia with 80% of global cases occurring in the continent alone. Currently little is known about the incidence of hepatobiliary cancer in the Adolescent and Young Adults (AYA). In this population, hepatobiliary cancer may present in an insidious manner due to low suspicion and management may result in a higher likelihood of survivors with long-term treatment-related toxicities. We aim to highlight the clinicopathological features and treatment outcomes in this age-group in an Asian high-volume tertiary cancer institution. Methods: Patients diagnosed between the age of 16-39 with hepatobiliary cancers between 1st January 2015 to 31st December 2019 in a single-centre institution in Singapore were included in this study. Results: There was a total of 84 AYA patients with hepatobiliary tumours who were referred to our institution. Median age of diagnosis was 35 years old (n = 84). 32 patients (38.1%) had hepatocellular carcinoma, 22 patients (26.2%) had biliary tract tumours, 11 patients (13.1%) had neuroendocrine cancers while 19 patients (22.6%) had other tumour types (Figure 1). Male incidence was highest in all hepatobiliary AYAs (n = 56, 66.7%, p = 0.002) and hepatocellular carcinomas (n = 25, 78.1%, p = 0.001) (Table). 65 patients (77.4%) remain alive as of 31st December 2019. Conclusions: Patterns of hepatobiliary incidence differ between sexes. In the young AYA population, hepatocellular precursor cells may have sex-specific features affecting malignant potentials. More studies should be done to further elucidate the genomic and epidemiology of hepatobiliary tumours in the younger population of patients to better outcomes in this population. [Table: see text]
Effect of neoadjuvant immunotherapy and targeted therapies on surgical resection in patients with solid tumors: A systematic review and meta-analysis.
Authors: Serrano Aybar Pablo Emilio , Tywonek Kasia , Faisal Noor , Lee Sandra , Alfayyadh Ali , O'Neill Connor , Gundayao Marylrose , Ruo Leyo , Parpia Sameer , Meyers Brandon M. 
Published: May 2020

e16656 Background: Neoadjuvant immunotherapy with anti-programmed cell death protein-1 (PD-1) or anti-programmed cell death ligand-1 (PD-L1) and tyrosine kinase inhibitor (TKI) therapy is currently being used to treat certain solid tumours prior to surgery. Neoadjuvant therapy may cause delays to resection potentially losing a window of opportunity. We explored the pooled proportion of patients with solid tumours receiving neoadjuvant therapy who completed planned surgical resection. Methods: Medline, CENTRAL and Embase databases were searched for single arm or randomized controlled trials studying neoadjuvant PD-1/PD-L1 immunotherapy or TKI therapy. Random-effects model was used to estimate the pooled proportion of patients undergoing planned resection, and weights were estimated using inverse variance method. Statistical heterogeneity was calculated using the I2 and chi-squared test. Results: From 368 relevant articles, eleven studies with a total of 382 patients receiving neoadjuvant PD-1 immunotherapy (n = 234) or neoadjuvant TKI therapy (n = 148) were analyzed. The types of tumours included hepatocellular carcinoma (1 study), renal cell carcinoma (8 studies), bladder carcinoma (1 study) or non-small cell lung cancer (1 study). The pooled proportion of patients who completed planned surgery after neoadjuvant therapy was 95% (95% CI 0.92 to 0.99). The overall partial response rate prior to surgery was 12% (95% CI 0.07 to 0.16) in the PD-1 therapy group and 46% (95% CI -0.12 to 1.03) in the TKI group. The pooled serious adverse events rate was 17% (95% CI 0.02 to 0.32) in the PD-1 therapy group and 29% (95% CI -0.10 to 0.68) in the TKI group. For all patients receiving neoadjuvant therapy, the pooled median overall survival was 23.41 months (95% CI 16.21 to 30.62) and median progression free survival was 7.46 months (95% CI 4.41 to 10.51). Conclusions: Neoadjuvant PD-1 or TKI therapy prior to surgery for solid tumours is safe, does not delay surgical resection and can result in a partial radiological response prior to surgery.
Blood levels of steroid hormone precursors allow differentiation between pancreatic adenocarcinoma and neuroendocrine tumors.
Authors: Aleynov Viacheslav A. , Frantsiyants Elena M. , Bandovkina Valeria A. , Cheryarina Natalia D. , Trifanov Vladimir S. , Sanamyants Sergey V. , Averkin Mikhail A. , Kit Oleg I. , Shaposhnikov Alexander V. , Fomenko Yuriy A. , Petrov Dmitry S. 
Published: May 2020

e16692 Background: The activity of some enzymes involved in the synthesis and transformation of sex hormones changes in some tumor tissues of the pancreas, which can affect the circulating concentrations of these hormones in the blood. The purpose of the study was to determine the possibility of differential diagnosis of pancreatic cancer at primary examination. Methods: Levels of 17OHP and DHEAS were measured by RIA in the blood of 25 men with chronic pancreatitis (CP), 34 patients with pancreatic adenocarcinoma (PA) and 15 patients with pancreatic neuroendocrine tumors (PNET). The results were compared with the levels in 23 healthy donors. All patients gave voluntary informed consent for the study. Results: Men with CP did not show statistically significant changes in 17OHP and DHEAS. The levels in pancreatic cancers were lower than in donors: in PA, DHEAS was 1.6 times and 17OHP - 1.4 times lower than the norm. DHEAS in PNET was 2.4 times lower than the norm and 1.5 times lower than in PA. 17OHP in PNET was 6.4 and 4.5 times lower, respectively. Conclusions: Measuring DHEAS and 17OHP in the blood can serve as an informative laboratory test for predictor assessment of the nature of pancreatic disease.
Effect of neuroendocrine component in pancreatic adenocarcinoma on blood levels of steroid hormones.
Authors: Aleynov Viacheslav A. , Frantsiyants Elena M. , Bandovkina Valeria A. , Cheryarina Natalia D. , Trifanov Vladimir S. , Chernyak Maksim N. , Mezentsev Stanislav S. , Grechkin Fedor N. , Katsieva Tanzila Beksultanovna , Kit Oleg I. , Shaposhnikov Alexander V. , Petrov Dmitry S. , Fomenko Yuriy A. 
Published: May 2020

e16695 Background: 90% of pancreatic cancers are adenocarcinomas. Pancreatic neuroendocrine tumors (PNET) are much less common. However, some adenocarcinomas carry a neuroendocrine component and have an effect on the hormonal profile of the body. The purpose of the study was to analyze the content of steroid hormones and ACTH in the blood of patients with pancreatic cancer in dependence on the neuroendocrine component presence. Methods: Standard RIA methods were used to measure blood level of testosterone (T), estradiol (E2), progesterone (P4), cortisol and ACTH in 10 patients with pancreatic adenocarcinoma (PA), 12 patients with PNET and 20 patients with PA with a neuroendocrine component (PA+NEC). The results were compared with the levels in 23 healthy donors. All patients gave voluntary informed consent for the study. Results: Levels of all measured hormones were elevated in the blood of patients with PA: T by 1.8 times, P4 by 4.8 times, E2 by 2.7 times, cortisol by 2 times and ACTH by 2.5 times, compared to donors. In PNET, E2 was 1.5 times (p < 0.05) lower, and T 1.6 times (p < 0.05) higher than in donors. Levels of P4, ACTH and cortisol in PNET were similar to normal values. In PA+NEC, T was decreased by 1.3 times, P4 and ACTH increased by 1.4 and 2.2 times respectively. E2 and cortisol were similar to normal values. Conclusions: The hormonal profiles of patients with PNET and PA differ, except T with blood levels increasing in both tumors. The presence of NEC in PA decreases blood levels of T and normalizes E2 and cortisol.
Comprehensive study of genetic features of pancreatic neuroendocrine tumors.
Authors: Trifanov Vladimir S. , Kit Oleg I. , Gvaldin Dmitry Yu. , Timoshkina Natalya N. , Sanamyants Sergey V. , Myagkov Roman E. , Gaziev Umar Muhmadovich , Fomenko Yuriy A. , Petrov Dmitry S. 
Published: May 2020

e16699 Background: Pancreatic neuroendocrine tumors (panNETs) are a heterogeneous, relatively rare type of neoplasm which distinguishes a long clinical course in a large number of cases, that leads to the fact that the prevalence rate of NETs is one of the highest. The purpose of this study was a research the mutational profiles of panNETs of various grades of malignancy and to search for new candidate genes involved in the oncogenic processes of this pathology. Methods: The study included a retrospective group of 24 patients (10 men, 14 women, median age - 60 years old) with a diagnosis of panNET, treated in the RRIO from 2011 to 2018. Comprehensive cancer panel (409 genes) were used for NGS procedure on the NextSeq 550 platform(Illumina, USA). To work with raw data, we used the standard pipeline proposed by BaseSpace (Illumina, USA). Interpretation of the identified variants was carried out in accordance with the recommendations of the Association for Molecular Pathology, American Society of Clinical Oncology and College of American Pathologists. Results: 119 mutations in 54 genes were detected in samples of panNETs. 26 genetic variations were characterized as new, not previously described for panNETs. 18% of the mutations were activating, 35% of the variants led to a loss of function of the encoded protein, 52% were not classified. Candidate genes that have not been previously described in the literature and which are potentially involved in pancreatic oncogenesis are identified: CREB1, TCF12, PRKAR1A, BCL11A and BUB1B. The largest number of mutational events occurred in the genes responsible for histone methylation; in addition, 38% described genetic alterations in the regulation of the SMAD2/3 signaling pathway. Conclusions: According to the NGS study of panNETs of low and moderate malignancy in the Russian cohort, a unique spectrum of 119 mutations was obtained, of which 26 were not previously described. The discovered molecular genetic changes in the signaling pathways underline the importance of impaired epigenetic control of transcription in pancreatic oncogenesis and open up new prospects for targeted therapy.
GETNE-SILVELUL study: A new immunohistochemical score (SPI) in patients (pts) with pancreatic neuroendocrine tumors (PanNET) treated with everolimus or captem.
Authors: Viudez Antonio , Crespo Guillermo , Gómez-Dorronsoro Maria Luisa , Benavent Marta , Hernando Jorge , Goñi Saioa , García Beatriz , Sevilla Isabel , Alonso Vicente , González-Borja Iranzu , Lopez Carlos , Custodio Ana , Hernandez Irene , Llanos Marta , Carmona Alberto , Pérez-Sanz Jairo , López San Vicente Borja , De Jesus-Acosta Ana 
Published: May 2020

e16707 Background: Previously our group showed the potential use of a score based (SPI) on MGMT, NDRG-1 and PHLDA-3 immunohistochemistry (IHC) expression as predictor of outcome in operated PanNET (Viúdez et al. Oncotarget 2016). The present retrospective multicenter project is analyzing the predictive/prognosis role of MGMT, NDRG-1 and PHLDA-3 in patients treated with advanced PanNET treated CAPTEM or everolimus. Methods: IHC nuclear staining for MGMT and PHLDA-3 is being scored as 0, 1-5%, 6-50% and ≥ 51%. For NDRG-1, we are using a cytoplasmic score from 0 to 2 based on distribution pattern (null, patched or diffuse). Results: 60 of 105 pts have been fully analyzed., most of then women (53%) and median age of 63 (27-79). 30 pts were treated with CAPTEM and 30 pts with everolimus. Median previous lines were 1 (21,7% received chemotherapy previously), and 91,7% pf pts had ki67 < 20%. 65,5%, 10,2% and 29,1% were null for MGMT, NDRG-1 and PHLDA-3 IHC analysis. In the entire cohort K-M analysis showed significant differences for PFS or OS based on best response observed (p = 0,0001) and number previous lines received (p = 0,05), respectively. In pts treated with CAPTEM, log rank analysis showed significant differences for PFS (p = 0,047 HR:4,63 CI95%: 1,023-20,990) and OS (p = 0,040 HR:5,433 CI95%: 1,082-27,266) based on our SPI. Similar, although not significant, results were observed in everolimus-treated cohort for PFS (p = 0,529) and OS (p = 0,592) according to SPI. Conclusions: As it was described previously in operated PanNET, our SPI also seems to own predictive role in pts with advanced PanNET treated with CAPTEM or everolimus. More mature results of our work are needed and will be presented during 2020 ASCO Annual Meeting.
A phase II study of anlotinib with cediranib as a second-line treatment for patients with advanced biliary tract cancers (aBTCs).
Authors: Zhao Ruihua , Zong Hong , Jin Shuiling , Zhong Qian , Jiang Miao , Jin Ming , Li Rui , Jiang Guozhong 
Published: May 2020

e16712 Background: Gemcitabine combined with cisplatin (GP) is currently used as a standard first-line chemotherapy regimen for aBTCs, However, the median overall survival (mOS) is only about 11.7 months, and there is no standard treatment option for patients who failed GP therapy. In this study, we aimed to investigate the efficacy and safety of anlotinib with cediranib as a second-line treatment for patients with aBTCs. Methods: A monocenter single-arm phase II study was conducted at the First Affiliated Hospital of Zhengzhou University. Patients with measurable aBTCs and progressed on GP were enrolled in this study. Patients received cediranib 200mg, on day1 + anlotinib 12mg on day1-14, Q3W until disease progression, intolerance of toxicity, investigator/patient decision to withdraw or other reasons specified in the protocol. Response (RECIST1.1) was assessed every 8 weeks. Plasma, stool and tumor tissues were collected for exploratory analyses. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and drug safety. Results: We planned to include 20 patients. So far 9 patients were enrolled in this study, 66.7% (6/9) were men, 33.3% were women. The median age was 56y (43y-61y). The primary sites of the tumor were intrahepatic biliary (66.7%, 6/9) and gallbladder (33.3%, 3/9). At data cutoff (Dec 14, 2019), the median duration of follow-up was 2.5mos (range, 1.2 to 4) and all of the patients were still under treatment. 8 patients have undergone at least one efficacy evaluation, of which 2 (25%) PR, 5 SD (62.5%), DCR was 87.5% ((7/8). An SD patient had a long-term intermittent fever, which considered to be tumor fever, the body temperature returned to normal after 1 cycle of treatment. 1 patient was considered to be undefined because, at the first evaluation, the liver lesions were reduced however the lymph nodes in the retroperitoneum were enlarged. The median PFS and OS not yet reached. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 11.1% (1/9) of patients. TRAEs led to discontinuation in 1 patient (grade 3 hypertension). TRAEs led to dose reduction of anlotinib in 2 patients. No TRAEs were fatal. Conclusions: The primary result showed that the combination of anlotinib and cediranib was well tolerated and demonstrates encouraging efficacy than historical control in second-line treatment for aBTC. Updated data, including safety, efficacy, and biomarkers will be presented. Clinical trial information: ChiCTR1900022003 .