bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of circulating tumor cells in stage III colorectal cancer patients under three or six months of adjuvant therapy.
Authors: Messaritakis Ippokratis , Koulouridi Asimina , Sfakianaki Maria , Vogiatzoglou Konstantinos , Gouvas Nikolaos , Tsiaousis Ioannis , Athanasakis Elias , Xynos Evangelos , Sougklakos Ioannis , Boukovinas Ioannis 
Published: June 2022

e15601 Background: The duration of adjuvant oxaliplatin-combination treatment in stage III colorectal cancer (CRC) patients is still debatable. Circulating Tumor Cells (CTCs) have been proposed as a potential markers for detection of micrometastatic disease. The aim was to compare the elimination rate of CTCs in patients treated with three- and six-months treatment with FOLFOX or CAPOX, in stage III CRC patients. Methods: Peripheral blood samples were collected from 132 patients at baseline, after three (for all patients) and after six months (for those under six months treatment). Surgical specimens were collected from all patients for the evaluation of their genetic profiling using Sanger sequencing (Ras/Raf) and fragment analysis (microsatellite instability status). The detection and number of circulating tumor cells (CTCs) were evaluated using double immunofluorescence and a real time-polymerase chain reaction assay, at all three time points. Results: Median age of the patients was 62 years, 59.8% were males, 92.7% had a colon/sigmoid tumor location, 24.4% had tumor on the right colon and 99.2% had a good performance status (PS). Of all patients, 44.3% and 55.7% were treated with FOLFOX and CAPOX, respectively; patients received treatment for three and six months, were equally distributed. KRAS, NRAS and BRAFmutations were detected in 41.5%, 2.1% and 12.8%, respectively; whereas MSI-High status was detected in 9.8% of the patients. CTCs were detected in 43.2%, 42.4% and 54.2% of the patients, at baseline, after three and six months of treatment, respectively. Both positivity rate ( p< 0.001) and absolute number of CTCs ( p= 0.022) were decreased between baseline and three months of treatment. Moreover, a significant increase was observed both on the positivity rate ( p= 0.053) and absolute number of CTCs ( p< 0.001) between three and six months of treatment. Following Cox regression analysis, BRAF status and the detection of CTCs are significantly correlated with decreased time to progression. Conclusions: To conclude, the current study indicates that 3 months of adjuvant treatment is at least as efficacious as 6 months in eliminating CTCs. However, the increase of both the rate and number of positive CTCs after three months of treatment might highlight the emergence of resistant cancer cell clones.
Single-agent neoadjuvant immunotherapy of PD-1 antibody in resectable mismatch repair-deficient/microsatellite instability-high colorectal cancer.
Authors: Huang Jun , Pei Fengyun , Wu Jingjing , Zhao Yandong , He Wan , Shi Tianhao , Huang Meijin 
Published: June 2022

e15605 Background: PD-1 blockade has been recommended as first-line therapy for non-resectable or metastatic mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC). However, the safety and efficacy of neoadjuvant immunotherapy of PD-1 blockade for resectable dMMR/MSI-H CRC remains unclear. Methods: From June 2020 and March 2021, eight resectable dMMR/MSI-H CRC patients treated in the 6th Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) were enrolled. All patients accepted 6 doses (200mg/dose, every 3 weeks) of Sintilimab injection (Innovent, LTD) before radical laparoscopic resections. The clinical and pathological data of the 8 patients was analyzed retrospectively. Results: All patients were confirmed dMMR by immunohistochemistry (IHC). However, 87.5% (7/8) of the patients were confirmed MSI-H and 12.5% (1/8) was confirmed microsatellite stable (MSS) by NGS. After 6 doses of neoadjuvant anti-PD-1 therapy, 87.5% (7/8) of the patients achieved pathological complete response (pCR), and the 7 patients were confirmed both dMMR and MSI-H. The rest 12.5% (1/8) who achieved major pathological response (mPR), with residual tumor <1%, was dMMR but MSS. None of the patients had immunotherapy-related adverse events (irAE) of grade 3 or above (CTCAE; version 5.0). 75.0% (6/8) of the patients had grade 1/2 irAE. No operational mortality or complications were found within 30 days after surgery. Conclusions: Single-agent neoadjuvant immunotherapy of PD-1 antibody was safe and effective in resectable dMMR/MSI-H CRC. Double confirmation of both dMMR and MSI-H status was necessary before PD-1 blockade therapy in dMMR/MSI-H CRC patients.
First-line therapy for gastric cancer with bone marrow metastasis and disseminated intravascular coagulation with infusional fluorouracil and weekly docetaxel: A multicenter, phase II clinical trail.
Authors: Zhai Xiaohui , Cao Taiyuan , Li Shanshan , Lin Xiaoru , Xiao Jian 
Published: June 2022

e16004 Background: Gastric cancer (GC) with bone marrow metastasis (BMM) and disseminated intravascular coagulation (DIC) is a special subtype of gastric cancer which has highly aggressive characteristic and extremely poor prognosis. Case reports showed chemotherapy achieved survival benefit but prospective trial is still urgently needed. Methods: This is a multi-center phase II clinical trial. Infusional fluorouracil of 200mg/m2/day, D1-21 (LD-FU) with docetaxel 25mg/m2, D1,D8,D15 will be administered to chemo-naïve metastatic GC with BMM and DIC every four weeks. The primary endpoint is the hematology response rate (HeRR) defined as the rate of platelet count restored to 100X109/L or higher. The secondary endpoints are time to HeR, duration of HeR, one-month mortality, overall survival, toxicity and the quality of life. Results: Until Feb 1, 2022, 11 gastric cancer patients with BM and DIC were enrolled in this trail and 8 patients reached the hematology response. The HeRR is 72.72%(8/11) and the media time to HeR is 13.5 days (11-20days). The rate of grade 1or to oral mucositis is 36.36%(4/11) and there is no grade 3 or 4 treatment toxicity. Conclusions: This is the first prospective clinical trail to evaluate the safety and efficacy of chemotherapy for advanced GC patients with BMM and DIC and will provide high level evidence to guide clinical practice. Clinical trial information: NCT04547153.
Safety and efficacy of anti-VEGF antibodies in the treatment of advanced gastric carcinomas.
Authors: Vorla Mounica , Akbar Usman Ali , Sheikh Daniya , Masthan Shameera Shaik , Pusa Mounika , Bamboria Aditya , Barham Saman , Dab Ammar Yaser , Qazi Shaheryar , Khan Adil , Anwer Rana Usman , Akinti Oluwasegun , Anwer Faiz 
Published: June 2022

e16005 Background: The prognosis of gastric cancer remains poor despite advances in diagnostic techniques, neoadjuvant chemo radiotherapy and surgery. This led to the development of Anti-Vascular Endothelial Growth Factor inhibitors (Anti-VEGF), which inhibit angiogenesis, inducing a state of dormancy in the tumors. In this review, we studied the safety and efficacy of Ramucirumab (RAM) and Bevacizumab (BVZ). Methods: Following the PRISMA guidelines, we searched the literature on PubMed, Cochrane, Embase & clinicaltrials.gov. A total of 311 articles were screened, and 4 studies were included. Results: When compared to placebo, in the two Phase III trials enrolling 1020 participants,RAM enhanced overall survival (OS) and progression-free survival (PFS). RAM treatment was associated with fewer hematological adverse effects, such as anemia. In addition, when administered in conjunction with CTx, bevacizumab (BVZ) improved OS (12.1m Vs 10.1m in one trial), but more clinical studies are needed to consolidate these findings. In both phase III studies with BVZ, anemia and neutropenia were shown to be less common, as shown in the table. Conclusions: Anti-VEGF inhibitors have shown to be effective in treating advanced or relapsed GC or GE CAs with minimal adverse effects. However, high-quality large prospective randomized clinical studies are still needed.[Table: see text]
ScRNA-seq based copy number variations (CNVs) detection identified TPSB2 and TPSAB1 as prognostic biomarkers in Gastric Cancer(GC).
Authors: Wang Tao , Zheng Liuqing , Wang Qian , Xiao Shanshan ,   Hangzhou Repugene Technology Co,.Ltd
Published: June 2022

e16021 Background: Gastric Cancer (GC) is the third leading cause of cancer-related mortality around the world, with a relatively poor prognosis. Single-cell RNA-sequencing (scRNA-seq) is a powerful tool to analyze tumor microenvironment at a comprehensive resolution, revealing previously uncharacterized molecular complexities. CNVs detection based on scRNA-seq data can reveal genome heterogeneity, therefore identify prognostic biomarkers at the single cell level. Methods: ScRNA-seq data from publicly available dataset (Anuja S et.al, CCR 2020) with 3 gastric cancer tissues, and 3 paired adjacent normal tissues was used. We inferred CNVsusing non-malignant cells as reference to estimate the mutations of malignant cells based on InferCNV package. Survival analysis was made by Kaplan-Meier method on TCGA-STAD (Stomach adenocarcinoma) cohort to identify the CNV genes with prognostic ability. To further explore these genes, their correlations with CD8+T cells marker ( CD8A) and malignant marker ( EPCAM) were analyzed based on the Spearman Correlation Method. Results: From a total of 11,459 cells, comprising 3 gastric cancer tissues (7,634 cells), and 3 paired adjacent normal tissues (3,825 cells), we identified 23 clusters that belonged to different types of cells including Endothelial, Epithelial, Fibroblast, B cells, Myeloid cells, T cells and NK cells. InferCNV analysis predicted 5 CNV regions and 209 CNV genes according to the heterogeneity between malignant and non-malignant cells. Survival analysis based on RNA-seq data from TCGA-STAD cohort, enabled us to narrow down the list of candidate biomarkers to 22 genes with prognostic ability. Among them, the specific functions of TPSB2 and TPSAB1 in GC, especially in their prognosis value, remain unclear. Downregulations of these 2 genes were both associated with longer progression-free survival (PFS). More specifically, expression profiles of gene TPSB2 and TPSAB1 were positively correlated with Epithelial marker genes (p = 0.02 and 0.03 respectively) but negatively correlated with CD8+ T lymphocytes (p = 0.02 and 0.11 respectively). Conclusions: Our analysis suggested that the high expressions of gene TPSB2 and TPSAB1 are associated with poor prognosis in GC patients. And these two genes are correlated with low T lymphocyte infiltration and an immune-suppressive environment, which could be possible prognosis biomarkers to identify patients with a more aggressive tumor evolution.
Greater expression of THBS2 and VACN in gastric carcinoma compared to gastritis.
Authors: Fan Zhisong , Feng Li , Liu Linnan , Li Dan , Liu Jiayin , Zuo Jing , Wang Yudong , Han Jing , Zhang Xue , Wang Long 
Published: June 2022

e16026 Background: Gastric carcinoma (GC) is one of the most common cancers with the lowest survival rate in the world. The development from gastritis to GC may be related to genetic factors, but the specific molecular mechanism is not clear. The present study aimed to explore the gene difference between GC and gastritis. Methods: Two gene expression profiles including GC and gastritis were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between GC and gastritis were explored. Through pathway enrichment of DEGs, hub genes were identified. The prognosis significances of hub genes for GC patients were analyzed by overall survival (OS) analysis. Animal models of gastritis and GC were constructed and immunofluorescence and RT-PCR were used to verify the distinct expression of hub genes between the two diseases. Finally, the correlations between hub genes and GC were understood based on BP neural network. Results: A total of 62 DEGs was identified between GC and gastritis. Eight hub genes were identified, including MSLN, FGA, SPP1, THBS2, SPARC, FN1, IGFBP7 and VCAN. Except SPP1, the high expression of the other seven hub genes predicted poor OS for GC patients. In mouse model, the mRNA expression of SPP1, FN1, IGFBP7, THBS2 and VCAN were significantly higher in GC group than that in gastritis group. No matter in mouse model or in Human Protein Atlas, the protein expression of THBS2 and VCAN in GC was higher than that in gastritis. Based on the strong correlation among THBS2, VACN and GC suggested by BP neural network, it was speculated that the expression levels of THBS2 and VACN may be a predictor of GC. Conclusions: Compared with gastritis, THBS2 and VACN are highly expressed in GC. THBS2 and VACN may be potential biomarkers and therapeutic targets for GC.
Outcomes of neoadjuvant and definitive CROSS (carboplatin and paclitaxel chemoradiotherapy) in oesophageal cancer.
Authors: Iqbal Samreen , Atkinson Victoria , Arneil Melissa , Andelkovic Vladimir , Roberts Kate Elizabeth 
Published: June 2022

e16033 Background: This is a retrospective analysis of outcomes in patients with oesophageal cancer treated with either neoadjuvant or definitive CROSS chemoradiotherapy (CRT) at the Princess Alexandra Hospital between 2016-2020. Methods: Data was collected from a single centre using the electronic medical records system. Patient demographics, oesophageal cancer characteristics, treatments and outcomes were recorded. Results: 90 patients were identified–75% were male and the average age at diagnosis was 64 years. Higher tumour grade, nodal stage or grade of oesophageal cancer was associated with lower average overall survival (OS). 68% had oesophageal adenocarcinoma (Adeno) and 31% had oesophageal squamous cell carcinoma (SCC). Of those with Adeno, 69% received neoadjuvant CROSS and 31% definitive CROSS. 32% of those with SCC received neoadjuvant CROSS with 64% receiving definitive CROSS therapy. Routine adjuvant chemotherapy was not delivered post CRT. 81% of those with Adeno treated with neoadjuvant CROSS proceeded to surgery compared to 100% of those with SCC treated similarly. Only 19% of patients did not complete CRT however 67% of patients experienced some toxicity and 43% required hospitalisation during the course of therapy. Average weight loss during therapy was 6.4kg. 27% of patients required enteral nutrition and they had a lower OS (20 months) compared to those that did not require nutritional support (25 months). Of those with Adeno, 50% of patients who received neoadjuvant CROSS experienced relapse compared to 74% in patients who received definitive CROSS. For the SCC cohort, 22% of those who received neoadjuvant CROSS relapsed compared to 44% who received definitive CROSS. Average time to relapse (from end of CRT) was greatest for those with SCC receiving neoadjuvant CROSS (16 months) and worst for those with SCC receiving definitive CROSS (7 months). Average OS for patients with Adeno who received definitive CROSS was 18 months compared to 27 months for those who received neoadjuvant CROSS. For patients with SCC, the average OS for those who received definitive CROSS was 18 months compared to 29 months for those treated with neoadjuvant CROSS. Of those with Adeno, 63% of those treated with definitive CROSS and 38% of those treated with neoadjuvant CROSS died secondary to their disease. For patients with SCC, 44% of those treated with definitive CROSS died whilst everyone who received neoadjuvant CROSS was alive at study conclusion. Conclusions: The best outcomes were seen in patients with SCC treated with neoadjuvant CROSS; this group had the highest OS (29 months), the lowest relapse rate (22%) and all patients were alive at the end of the study. The pivotal CROSS study by Shapiro et al. also demonstrated better outcomes in the SCC cohort, with this analysis further comparing definitive vs neoadjuvant CROSS. A limitation however is the comparatively shorter follow up period.
Systematic genomics-based approach for developing new therapeutics and diagnostics for esophageal cancer.
Authors: Daigo Yataro , Takano Atsushi , Nakamura Yusuke 
Published: June 2022

e16034 Background: As the prognosis of advanced esophageal cancer patients is still poor after standard therapies, development of new molecular therapies with minimum risk of adverse events and cancer biomarkers for companion diagnostics is eagerly awaited. Methods: We have been screening new therapeutic target molecules and biomarkers for esophageal cancers as follows; i) To identify highly expressed genes in esophageal cancers by gene expression microarray analysis, ii) To verify the target molecules for their low expression in normal tissues, iii) To validate the clinicopathological significance of their protein expression by tissue microarray covering 265 esophageal cancers, and iv) To confirm their function for the growth and/or invasive ability of esophageal cancer cells by siRNAs and gene transfection assays. Results: We identified dozens of candidate oncoproteins and selected ESOC1 (esophageal cancer-associated oncoprotein 1) that has a methyltransferase domain. We first confirmed its in vitro methyltransferase activity. Immunohistochemical analysis showed that ESOC1 positivity was detected in 68.5% of esophageal cancers and associated with tumor size. Moreover ESOC1 positivity was an independent prognostic factor for patients with esophageal cancer. Knockdown of ESOC1 expression by siRNAs suppressed growth of esophageal cancer cells. Exogenous expression of ESOC1 increased the growth of mammalian cells. Therefore, ESOC1 is likely to be a prognostic biomarker and therapeutic target for esophageal cancers. Conclusions: Systematic genomics-based approach could be useful for the selection of novel candidate cancer biomarkers and therapeutic targets for small molecules, antibodies, nucleic acid drugs, and immunotherapies.
Microbiome associations between esophageal adenocarcinoma and esophageal squamous cell carcinoma.
Authors: Wang Qian , Liu Yang , Xiao Shanshan , Wang Tao ,   Hangzhou Repugene Technology Co,.Ltd
Published: June 2022

e16050 Background: Microbiomes in tumor environment are thought to be associated with outcomes of precision therapy. Esophageal squamous cell carcinoma (ESCC) and Eophageal adenocarcinoma (EA) are the two subtypes of esophageal cancer. Although gene mutation and expression profiles have been well characterized, the microbial set between them are poorly studied. Methods: The microbial dataset of the identified species and their relative abundance using whole genome sequencing (WGS) and whole exome sequencing (WES) was obtained from TCMA database, which includes 17 EA samples and 32 ESCC samples. To investigate the microbial difference between EA and ESCC, The alpha diversity (Shanno and Simpson index) and beta diversity (PCoA, NMDS, Adonis) were calculated using the identified species to examine the overall difference between the two subtypes. The student's t-test were used to examine the relative abundance of single species Using the identified differential abundant microbial species, correlation analysis were performed to investigate whether synergistic effects exist for some species between the two subtypes. Moreover, taxonomy set enrichment analysis was used to find out whether the differential genus between EA and ESCC were associated with cancers. Finally, cox regression was used to investigated differential species between EA and ESCC affected the survival rate of EA group or ESCC group. Results: Through alpha and beta diversities, we didn’t find overall difference between EA and ESCC both in WGS and WES datasets. However, seventeen and two differential abundance species were found using Student’s t-test in WGS and WES datasets, respectively. The relative abundances of the differential species were mostly higher in ESCC than in EA. Correlation analyses showed that prevotella sp. HMSC069G02 and prevotella sp. HMSC077E08 were highly correlated. There were eight differential species ( prevotella aurantiaca, prevotella dentalis, prevotella marshii, etc.) were found in WGS and two species ( prevotella sp. C561, prevotella pleuritidis) in WES, respectively. The ten species all belong to prevotella genus, and taxon set enrichment analysis showed prevotella genus was associated with esophageal cancer, implies the identified differential species may be different in ESCC and EA patients. Among them, prevotella dentalis and prevotella buccae were found to be potentially risk factors in ESCC after Cox regression. Conclusions: This study investigated the microbiome difference between EA and ESCC cancers. Although we didn’t find the overall difference between the two subtypes, our preliminary results showed there exist some differential species between two subtypes. We found prevotella dentalis and prevotella buccae were the potential risk factors in ESCC, and the results can help further understand the therapy outcome differences between EA and ESCC from the microbial aspect.
Systematic literature review and meta-analysis of clinical outcomes for previously treated patients with advanced gastric or gastroesophageal junction cancer.
Authors: Abderhalden Lauren , Frederickson Andrew , Lang Brain M , Mojebi Ali , Wu Ping , Gozman Alexander , Malbecq William , Jin Fan , Amonkar Mayur 
Published: June 2022

e16054 Background: Standard of care treatment in advanced (unresectable and/or metastatic) gastric or gastroesophageal junction (GEJ) cancer includes chemotherapies with or without targeted therapies. While there have been many studies undertaken in this patient population, there exists uncertainty around the efficacy of these treatments. A systematic literature review and meta-analysis were conducted to assess clinical outcomes of chemotherapies with or without targeted therapies. Methods: A systematic literature review was conducted through mid-2021 to identify relevant studies using Embase, MEDLINE, and Cochrane Central Register of Controlled trials (January 1, 2000–July 6, 2021) with additional searches of recent annual ASCO and ESMO conferences. Eligible studies included randomized controlled trials (RCTs), controlled clinical trials, and non-randomized clinical trials of any pharmacologic treatments licensed by the FDA or EMA among patients (≥18 years age, Eastern Cooperative Oncology Group performance score 0 or 1) previously treated for advanced gastric or GEJ cancer and who had progressed on prior treatment (i.e., ≥2L). A meta-analysis of objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were conducted among RCTs of relevant therapies for ≥2L gastric cancers. The ORR meta-analysis was performed using the Freeman-Tukey double arcsine transformation. For time-to-event outcomes, published Kaplan-Meier curves for OS and PFS were digitized to create pseudo- individual patient data. A meta-analysis of the resulting pooled survival curves for OS and PFS were conducted following the methodology of Combescure et al. (2014). Results: Of the 214 studies identified, 42 RCTs (77 trial arms) evaluating relevant therapies including 7,256 participants were included in the meta-analysis of ORR. The random effects pooled estimate of ORR was 15.0% (95% confidence interval [CI]: 12.7-17.5%). Median PFS (32 studies; 61 survival curves) was 3.5 months (95% CI: 3.2-3.7) with PFS rates at 6, 12, and 24 months of 25.8% (95% CI: 23.1-28.8%), 7.3% (95% CI: 6.0-8.9%), and 0.7% (95% CI: 0.4-1.0%), respectively. Median OS (34 studies; 64 survival curves) was 7.9 months (95% CI: 7.4-8.5) with OS rates at 6, 12, and 24 months of 62.5% (95% CI: 59.0-66.2%), 30.4% (95% CI: 27.7-33.3%), and 6.7% (95% CI: 5.4-8.4%), respectively. Conclusions: The standard treatments have demonstrated limited efficacy in previously treated patients with advanced gastric or GEJ cancers. Newer treatments (e.g., immunotherapies) to address this unmet medical need should be thoroughly investigated and evaluated.