bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the gastric microbiome in gastric cancer patients and in non-tumorous patients.
Authors: Bang Eun Joo , Choi Hyuk Soon , Lee Jae Min , Kim Eun Sun , Keum Bora , Jeen Yoon Tae , Chun Hoon Jai 
Published: January 2022

349 Background: Gastric cancer is the fifth most common cancer worldwide and it is the most commonly diagnosed cancer in Korea. The most clearly known microbiologic risk factor is Helicobacter pylori infection. Chronic inflammation of gastric mucosa accelerates a cascade of chronic active gastritis, multifocal atrophy intestinal metaplasia, gastric dysplasia and gastric adenocarcinoma. Studies proved H. pylori reduces microbial diversity, but it is reversible with H. pylori eradication. Thus, we could assume gastric carcinogenesis may not solely depend on H. pylori. In this study, we analyzed and compared gastric microbiome in gastric cancer patients and non-cancer patients to find changes between the two groups. Additionally, we analyzed microbial diversity of cancerous lesions and para-cancerous lesions in the cancer group in an effort to reveal the role of microbiome in carcinogenesis. Methods: Gastric mucosa collected by biopsy during esophagogastroduodenoscopy (EGD) from 10 patients with gastric cancer and 18 non-cancer patients. Gastric biopsies were obtained from the margin of cancer and para-cancerous lesions in cancer patients. In control group, samples were obtained from antrum with normal mucosal morphology. DNA was extracted from the gastric mucosal tissues and 16s rRNA genes were amplified. Then they were analyzed by microbiome analysis program. Results: Higher number of species was detected in the control group (average of 97.75 species) compared to the cancer group (average of 73.4 species). The gastric cancer microbiome was showed reduced microbial diversity compared to that of control group. Fusobacteria was more dominant in cancer group and Rhodobacterales was found more prominent in control group. We compared microbial diversity of the cancer lesion and the para-cancerous lesion within the cancer group and higher number of species was detected in non-tumorous lesion. Conclusions: Gastric microbiome of non-tumorous patients was more diverse and the composition of species was different between the two groups. These results suggest that microbial dysbiosis may be involved in gastric carcinogenesis. Further studies should include more detailed analysis of spatial and temporal composition and the comparison between different pathologic types and tumor location are necessary. Better understanding of microbial differences and changes in healthy and gastric cancer patients could verify the carcinogenesis of gastric cancer.
Survival prediction using radiomic signatures in metastatic gastric and esophageal adenocarcinoma (GEA).
Authors: Allen Michael J , Sertic Andrew , Liu Zhihui (Amy) , Liu Zijin , Suzuki Chihiro , Panov Elan David , Ma Lucy Xiaolu , Bach Yvonne , Jang Raymond Woo-Jun , Chen Eric Xueyu , Darling Gail Elizabeth , Yeung Jonathan , Swallow Carol Jane , Brar Savtaj Singh , Kalimuthu Sangeetha , Wong Rebecca , Veit-Haibach Patrick , Elimova Elena 
Published: January 2022

357 Background: Radiomic characterisation of tumour phenotypes can generate image-driven biomarkers that potentially aid in clinical decision-making. We sought to identify radiomic features in metastatic GEA that may be predictive for survival outcomes. Methods: A retrospective analysis between 2009-20 identified patients (pts) with metastatic GEA. All pts received chemotherapy (CTx), with a ‘baseline’ and 8-12 week ‘on-treatment’ contrast-enhanced CT chest/abdomen/pelvis performed. Radiomic analysis was performed with LIFEx (livexsoft.org). Population demographics and clinical outcomes were recorded. Univariable Cox proportional hazards model (UVA) assessed clinical variables (n=26) predictive of overall survival (OS) and progression-free survival (PFS) with p=0.05 indicating significance. Multivariable Cox model (MVA) was used to assess radiomic features (n=78) in the presence of clinical variables. Concordance index (C-index) was calculated to assess model performance (≥0.7 = high predictive accuracy). A ‘validation’ cohort analysis was performed to validate the model. Results: 166 pts were identified (primary cohort n=143; validation cohort n=23). 123 had de-novo metastatic disease, 43 recurrence following curative-intent therapy. In the primary cohort the median age was 58.1y, 101 (71%) were male, 120 (84%) were non-Asian and 131 (92%) were ECOG 0-1. Similar demographics were observed in the validation cohort. Both ‘baseline’ and ‘on-treatment’ scans UVA identified Her2 status, ethnicity, and the number of CTx cycles as predictive of PFS, while ECOG, brain metastases, neutrophil count (ANC), albumin and number of CTx cycles were predictive of OS. ‘Baseline’ model analysis for PFS and OS identified consistent radiomic features (HUskewness; HUpeakSphere), with an observed C-index 0.6 and 0.657 respectively. No radiomic features were identified on ‘on-treatment’ PFS analysis. ‘On-treatment’ OS analysis is shown in the table with 3 radiomic features (SHAPE Surface; SHAPE Compacity; PARAMS ZSpatial-Resampling) predictive for OS. The C-index is 0.76. Analysis of the validation cohort supported the model (C-index 0.815) for ‘on-treatment’ OS. Conclusions: Radiomic analysis identified a number of features associated with PFS and OS. The features specifically identified on ‘on-treatment’ scans were highly predictive for OS. Our analysis suggests radiomic features in addition to clinical variables can be predictive of outcome in patients with metastatic GEA receiving CTx.[Table: see text]
Definitive chemoradiation for oligometastatic esophageal cancer patients.
Authors: Puckett Lindsay , Matoska Thomas , Jurkowski Lauren , Banerjee Anjishnu , Martinez Enrique , Kodali Divya , Shukla Monica , Linsky Paul , Gasparri Mario , Chakrabarti Sakti , George Ben , Shreenivas Aditya V. 
Published: January 2022

359 Background: When esophageal cancer (EC) is metastatic at diagnosis, prognosis is poor, with 5-year survival of ̃5%. NCCN guidelines recommend palliative treatment or best supportive care. However, guidelines do not stratify by the extent of metastatic disease. Oligometastatic (oligo) disease has been shown in some cancers to portend better survival and more aggressive treatment options may be appropriate. Preliminary data has shown this may be the case for oligo EC, however, consensus recommendations remain palliative in intent. This study aims to compare overall survival (OS) in oligo EC patients treated with a definitive approach (chemoradiotherapy [CRT]) to those treated with purely palliative intent. Methods: Patients with oligo (any histology, ≤5 metastatic foci) EC treated in a single academic hospital between 2009-2020 were retrospectively analyzed in 2021. Patients were divided into definitive and palliative treatment groups; definitive CRT was defined as radiation therapy >40 Gy and >2 cycles of chemotherapy (CT) (+/- induction CT). OS was calculated by measuring the time from the date of diagnosis to the date of death or last follow-up. Survival curves between groups and by various prognostic factors were compared using the log rank test. Results: Of 77 Stage IVB patients, 35 met the pre-specified oligo definition. Of these, 18 received definitive CRT, and 17 palliative treatment (Table). With a median follow-up of 60.8 months, median OS for definitive CRT and palliative groups were 91.4 and 8.2 months, (p<0.01), translating into 5-year OS of 57.7% (95%CI: 33.5-82.0%) vs. 7.5% (95%CI: 0.0-21.6%), respectively. Prognostic factors correlated with increased OS included lower ECOG performance status (PS) (p<0.01), induction CT (p<0.01), N stage (p<0.01), adenocarcinoma (vs. squamous cell carcinoma) (p<0.05), diagnosis in 2013 or later (p<0.05), younger age (p<0.05), and > lymphocyte-to-monocyte ratio (p<0.05). Factors not associated with OS included neutrophil-to-lymphocyte ratio (p=0.39), T-stage (p=0.9), primary site (GEJ, distal, mid, or cervical) (p=0.07), tumor grade (p=0.83), type of spread (hematogenous, lymphatic, or local invasion) (p=0.69), sex (p=0.22), and HER2 status (p=0.07). Conclusions: Within our population, oligo EC patients treated with definitive CRT had significantly improved OS as compared to those treated with palliative only intent. These results suggest there may be a sub-population of oligo EC that would benefit from more aggressive treatment paradigms; thus, further evaluation is warranted.[Table: see text]
A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1.
Authors: Oh Do-Youn , He Aiwu Ruth , Qin Shukui , Chen Li-Tzong , Okusaka Takuji , Vogel Arndt , Kim Jin Won , Suksombooncharoen Thatthan , Lee Myung Ah , Kitano Masayuki , Burris III Howard A. , Bouattour Mohamed , Tanasanvimon Suebpong , Zaucha Renata , Avallone Antonio , Cundom Juan , Rokutanda Nana , Xiong Julia , Cohen Gordon , Valle Juan W. 
Published: January 2022

378 Background: BTC is a rare, heterogenous cancer with poor prognosis. Reports on immunogenic features of BTC suggest checkpoint inhibition may result in antitumor immune responses, and limited clinical activity has been seen with single agents in advanced settings. Durvalumab (PD-L1 inhibitor) + GemCis showed promising antitumor activity in advanced BTC in a phase 2 study. TOPAZ-1 (NCT03875235) is the first global phase 3 study to evaluate first-line immunotherapy + GemCis in advanced BTC. Methods: In this double-blind study, pts previously untreated for unresectable locally advanced, recurrent, or metastatic BTC were randomized 1:1 to receive durvalumab (1500 mg every 3 weeks [Q3W]) or placebo + GemCis (Gem 1000 mg/m2 and Cis 25 mg/m2 on Days 1 and 8 Q3W) for up to 8 cycles, followed by durvalumab (1500 mg Q4W) or placebo until disease progression or unacceptable toxicity. Randomization was stratified by disease status (initially unresectable, recurrent) and primary tumor location (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer). The primary objective was to assess overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Results: At data cutoff for this interim analysis (11 August 2021), 685 pts were randomized to durvalumab + GemCis (n=341) or placebo + GemCis (n=344; Table). The primary objective was met: durvalumab + GemCis significantly improved OS vs placebo + GemCis (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.66–0.97; p=0.021). PFS was also significantly improved with durvalumab vs placebo (HR, 0.75; 95% CI, 0.64–0.89; p=0.001). ORR was 26.7% with durvalumab and 18.7% with placebo. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 62.7% of pts receiving durvalumab and 64.9% of pts receiving placebo. TRAEs led to discontinuation of any study medication in 8.9% of pts receiving durvalumab and 11.4% of pts receiving placebo. Conclusions: In pts with advanced BTC, durvalumab + GemCis significantly improved OS and PFS vs placebo + GemCis with manageable safety, indicating durvalumab + GemCis may be a new first-line standard of care regimen. Clinical trial information: NCT03875235. [Table: see text]
Phase 3 randomized, open-label, multicenter study of tremelimumab (T) and durvalumab (D) as first-line therapy in patients (pts) with unresectable hepatocellular carcinoma (uHCC): HIMALAYA.
Authors: Abou-Alfa Ghassan K. , Chan Stephen Lam , Kudo Masatoshi , Lau George , Kelley Robin Kate , Furuse Junji , Sukeepaisarnjaroen Wattana , Kang Yoon-Koo , Dao Tu V. , De Toni Enrico N. , Rimassa Lorenza , Breder Valeriy Vladimirovich , Vasilyev Alexander , Heurgue Alexandra , Tam Vincent , Mody Kabir , Thungappa Satheesh Chiradoni , He Philip , Negro Alejandra , Sangro Bruno 
Published: January 2022

379 Background: A single priming dose of T (anti-CTLA-4) added to D (anti-PD-L1) in the STRIDE (Single T Regular Interval D) regimen, formerly T300+D, showed encouraging clinical activity and limited toxicity in a phase 2 uHCC study (Study 22, NCT02519348), suggesting single exposure to T is sufficient to improve upon D activity. HIMALAYA (NCT03298451) evaluated the efficacy and safety of STRIDE or D vs sorafenib (S) in uHCC. Methods: HIMALAYA is an open-label, multicenter, phase 3 study, in which pts with uHCC and no prior systemic therapy were initially randomized to STRIDE (T 300 mg plus D 1500 mg [one dose] plus D 1500 mg every 4 weeks [Q4W]), D (1500 mg Q4W), S (400 mg twice daily), or T 75 mg Q4W (4 doses) plus D 1500 mg Q4W (T75+D). Recruitment to T75+D ceased after a planned analysis of Study 22 showed T75+D did not meaningfully differ from D. The primary objective was overall survival (OS) for STRIDE vs S. The secondary objective was OS noninferiority (NI) of D to S (NI margin: 1.08). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR; RECIST v.1.1), duration of response (DoR), and safety. Results: In total, 1171 pts were randomized to STRIDE (N=393), D (N=389), or S (N=389). At data cutoff (DCO), the primary objective was met: OS was significantly improved for STRIDE vs S (hazard ratio [HR], 0.78; 96% confidence interval [CI], 0.65–0.92; p=0.0035; Table). D met the objective of OS NI to S (HR, 0.86; 96% CI, 0.73–1.03). ORRs were higher for STRIDE (20.1%) and D (17.0%) than for S (5.1%). No new safety signals were identified. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 25.8% (STRIDE), 12.9% (D), and 36.9% (S) of pts. Grade 3/4 hepatic TRAEs occurred in 5.9% (STRIDE), 5.2% (D), and 4.5% (S) of pts. No TRAE of esophageal varices hemorrhage occurred. Rates of TRAEs leading to discontinuation were 8.2% (STRIDE), 4.1% (D), and 11.0% (S). Conclusions: HIMALAYA was the first large phase 3 trial with a diverse, representative uHCC population and extensive long-term follow-up to assess both mono- and combination immunotherapy. D was noninferior to S with favorable safety. The combination of a single priming dose of T plus D in STRIDE displayed superior efficacy and a favorable benefit-risk profile vs S. STRIDE is a proposed, novel, first-line standard of care systemic therapy for uHCC. Clinical trial information: NCT03298451. [Table: see text]
Lenvatinib combined with transarterial chemoembolization as first-line treatment of advanced hepatocellular carcinoma: A phase 3, multicenter, randomized controlled trial.
Authors: Peng Zhenwei , Fan Wenzhe , Zhu Bowen , Li Jiaping , Kuang Ming 
Published: January 2022

380 Background: LAUNCH is a multicenter, randomized, open-label, parallel-group phase 3 trial, aiming to assess the efficacy and safety of lenvatinib plus TACE compared with lenvatinib alone as first-line therapy in patients with advanced hepatocellular carcinoma (HCC). Methods: Patients with advanced HCC were randomly assigned in a 1:1 ratio to receive either lenvatinib plus TACE (LEN-TACE group) or lenvatinib alone (LEN group). Randomized stratification factors include: Eastern Cooperative Oncology Group performance status score (0 vs. 1), tumor thrombus (presence vs. absence), body weight (<60 vs. ≥60kg) and site. In both Len group and LEN-TACE group, patients received oral lenvatinib after randomization within 3 days. The initial dose is 12 mg/day for patients weighing ≥ 60 kg, and 8 mg/day for patients weighing < 60 kg. TACE was started one day after initial lenvatinib in LEN-TACE group and then performed on-demand according to the condition of the tumor and liver function. The primary endpoint were overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate (ORR, the proportion of patients with complete response or partial response according to mRECIST), and adverse events. The deadline for interim analysis of data is September 20, 2021. Results: Overall, 338 patients from 12 hospital in China were randomly assigned to receive either lenvatinib plus TACE (n = 170) or lenvatinib (n = 168). The median follow-up duration was 18.4 months (95% confidence interval [CI] 13.7-23.1 months) in the LEN-TACE group and 17.0 months (95% CI 14.2-19.8 months) in the LEN group. The median OS was 17.8 months (95% CI 16.1–19.5) for the lenvatinib-TACE group and 11.5 months (95% CI 10.3–12.7) for the lenvatinib group (stratified hazard ratio [HR] for death = 0.45, 95% CI 0.33–0.61, P<0.001). The median PFS was significantly longer in the LEN-TACE group than in the LEN group (10.6 vs. 6.4 months, HR[hazard ratio]=0.43, P<0.001). Lenvatinib plus TACE improved ORR compared to lenvatinib alone (54.1% vs. 25.0, P<0.001). The following grade 3–4 AEs were more frequently in the lenvatinib-TACE group than in the lenvatinib group: ALT increased (30 [17.6%] vs. 2 [1.2%], P<0.001), AST increased (39 [22.9%] vs. 3 [1.8%], P<0.001), hyperbilirubinemia (16 [9.4%] vs. 5 [3.0%], P=0.014). Conclusions: In conclusion, this trial showed that the combination of lenvatinib plus TACE can improve clinical outcomes and may be the new first-line treatment for patients with advanced hepatocellular carcinoma. Clinical trial information: NCT03905967.
Responses to immunotherapy in hepatocellular carcinoma patients with nonalcoholic steatohepatitis cirrhosis.
Authors: Chang Jeremy , Ryan Joseph S , Ajmera Veeral , Ting Stephanie , Tamayo Pablo , Burgoyne Adam 
Published: January 2022

389 Background: Hepatocellular carcinoma (HCC) is the most rapidly growing cause of cancer-related mortality in the United States. Recent preclinical studies suggest that immunotherapy agents targeted at programmed cell death protein 1 (PD-1) do not lead to tumor regression in HCC with underlying nonalcoholic steatohepatitis (NASH). However, further clinical studies are needed to clarify the impact of immunotherapy on patients with NASH-related HCC. Methods: This was a single center, retrospective study analyzing the best responses to immunotherapy in patients with HCC and underlying cirrhosis due to NASH. Patients were divided into 2 groups: those with HCC related to NASH cirrhosis and those with HCC without NASH cirrhosis. All patients received immunotherapy, either as a single agent or in combination with other cancer-directed therapy, with response assessments conducted during their treatment courses. Results: A total of 79 patients were included in this study. There were 15 patients in the NASH cirrhosis-related HCC group and 64 patients in the HCC group without NASH cirrhosis. When analyzing the best disease responses to immunotherapy, 7 patients (46.7%) with HCC and NASH cirrhosis were found to have disease progression as their best responses compared to 7 patients (10.9%) who had HCC without NASH cirrhosis (risk ratio 4.27, p = 0.004). In addition, for the group without NASH cirrhosis, 57 patients (89.1%) experienced disease control (stable disease, partial response, or complete response) from immunotherapy versus 8 patients (53.3%) in the NASH cirrhosis-related HCC group (risk ratio 1.67, p = 0.004). There were no notable differences in patient age, gender, or immunotherapy agents received between the two groups, but there was a significantly greater proportion of patients of Hispanic ethnicity in the HCC group with NASH cirrhosis (p = 0.006, full patient characteristics listed in the table). However, when looking at all individuals in the study, patients of Hispanic ethnicity were not found to have a significantly higher risk of disease progression compared to non-Hispanic patients (p = 0.07). Conclusions: There were significantly higher rates of disease progression as the best response to immunotherapy in patients with HCC and NASH cirrhosis compared to those without NASH cirrhosis. With the expanded use of immunotherapy in HCC patients, further prospective studies are needed to clarify the impact of underlying liver disease etiology on immunotherapy response.[Table: see text]
Treatment of hepatocellular carcinoma with tyrosine kinase inhibitors: Real-world outcomes from the West of Scotland.
Authors: Naylor Gregory , McLaren Alistair , Graham Janet , Evans T.R. Jeffry 
Published: January 2022

390 Background: Sorafenib, lenvatinib and regorafenib have proven efficacy in patients with HCC in randomised clinical trials. First line sorafenib significantly improves overall survival (OS) and disease control rates vs. placebo (SHARP) whilst lenvatinib (REFLECT) is non-inferior to sorafenib in terms of OS. Second line regorafenib improves OS versus placebo (RESORCE). Real world outcomes are often inferior to randomised controlled trial data. Consequently we investigated the outcomes of real world patients with HCC treated with multi-kinase inhibitors in our regional tertiary-referral centre. Methods: All patients with advanced HCC treated with sorafenib, lenvatinib or regorafenib as monotherapy from 4 December 2015 to 16 September 2020 were included. The Information Governance (Caldicott) guardian approved access to patients records. Median OS (mOS) and treatment duration (mDoT) were calculated using Kaplan-Meier estimate; baseline patient characteristics and information on dosing regimen, dose interruptions and modifications, were also collected. Results: The SHARP trial achieved mOS and mDoT of 10.7 and 5.3 months. 26% required dose reductions and 44% dose interruptions. Our patients achieved mOS of 7.98 and mDoT 2.62 months; 35% required a dose reduction and 48% a dose interruption. Mean daily dose (MDD) was not given in SHARP but was 663.8mg in REFLECT; 728mg sorafenib was achieved in West of Scotland (WOS). In REFLECT, lenvatinib patients had mOS and mDOT of 13.6 and 5.7 months; our patients had a mOS of 9.55 and mDoT of 3.68 comparatively. 37% and 40% had dose reductions and interruptions in REFLECT vs. 50% and 44% in WOS. Our patients had a MDD of 10.9 mg (12mg/day) and 6.88mg (8mg/day) lenvatinib vs. 10.5mg and 7.0mg in REFLECT. In RESORCE, mOS and mDOT of 10.6 and 3.6 months was acheived in regorafenib patients vs. 9.52 and 3.42 months in WOS. 68% needed drug interruption or reduction vs. 53% in WOS and MDD of regorafenib was 144·1mg vs. 148.3mg in our population. Conclusions: Consistent with other real world experiences our data demonstrate reduced mOS and mDoT times compared to trials. This is despite maintaining good dose intensity. On average, mOS was 2.6 months less in our population vs. trial data. This may be explained by etiological differences of underlying liver disease or treatment of less highly selected patients. Our patients tended to be older, have poorer PS and Child Pugh scores compared with trials. Our data lack control arms, preventing interpretation of whether improved survival outcomes over placebo are maintained. Interestingly our data mirror the results of REFLECT where lenvatinib treatment was maintained for longer periods compared to sorafenib, despite higher numbers of dose interruptions. Our data also confirm that observed within RESORCE where, remarkably, patients treated with second line regorafenib achieved mOS similar to those treated in the first line setting.