bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-hospital retrospective study comparing gastric adenocarcinoma in Hispanic versus non-Hispanic patients.
Authors: Zarrinkhoo Erfan , Klingbeil Kyle D. , Condamoor Shreya , Park Joon , Jackson Nicholas , Chiu Victor , Kadera Brian E. 
Published: June 2023

e16027 Background: Gastric cancer is one of the most prevalent malignancies in the United States and carries a particularly high rate of mortality. In the United States, the overall gastric cancer rate continues to decline amongst Caucasian and African American patients; however, it remains static amongst Hispanic patients. While numerous studies have been conducted to better understand the underlying causes leading to the disproportionate incidence of gastric cancer among Hispanics, it is still not well understood. This retrospective study sought to compare the clinicopathological features and overall survival of Hispanic patients with gastric adenocarcinoma with non-Hispanic patients treated in three safety-net county hospitals in Southern California. Methods: This is a retrospective cohort study of 123 patients with newly diagnosed gastric adenocarcinoma who were treated at three safety-net county hospitals in Southern California between 2010 and 2022. The subjects were categorized as Hispanic and non-Hispanic. Clinical, pathological, and survival data were obtained from the patient chart and compared. Results: Of the 123 patients included in the study, 87 (71%) were Hispanic. At time of diagnosis, Hispanic patients were found to be significantly younger than non-Hispanics (55.4 +/- 13.5 vs 60.8 +/- 12.2, p-value 0.03). They were also more likely to be misdiagnosed (defined as greater than one prior encounter of misdiagnosis within six months) relative to non-Hispanics (26% vs 14%, p-value 0.007) despite no differences in insurance/PCP status. Hispanic patients were more likely to present with metastatic disease (65% vs 30%, p-value <0.001), and were found to have a higher rate of peritoneal carcinomatosis (30% vs 8%, p-value 0.01). Hispanics were also more likely to present with disease in the gastric antrum (47% vs 19%, p-value 0.004) and have a higher rate of diffuse subtype histology (32% vs 22%, p-value 0.05). Similar rates of Helicobacter pylori infection were found within the tissue biopsy sample using Warthin Starry stain amongst Hispanic and non-Hispanic patients (17% vs 17%). Lastly, the mortality rate was higher in Hispanics relative to non-Hispanics at time of last contact (65% vs 35%, p-value <0.001). Conclusions: Upon comparing clinicopathological features and mortality among gastric cancer patients who were treated in multiple safety net county hospitals, there were significant differences noticed in Hispanic American patients. Relative to non-Hispanics, Hispanic patients were more likely to be misdiagnosed, more likely to present with metastatic disease, and have higher rates of mortality despite no disparities in insurance and PCP status. Further investigation is warranted regarding possible risk factors including exposures to possible environmental triggers or if there is a genetic predisposition in Hispanic populations.
First-line envafolimab plus SOX chemotherapy for PD-L1 positive metastatic or recurrent gastric adenocarcinoma: A multi-centre, single-arm phase II clinical trial.
Authors: Liangjun Zhu 
Published: June 2023

e16029 Background: Clinical evidence for PD-L1 positive metastatic or recurrent gastric adenocarcinoma patients were relatively limited in clinic, which limited the development of evidence-based medicine for these patients. Immune checkpoint inhibitor (ICI) therapy has been established as the standard treatment for advanced gastric carcinoma patients recently. Envafolimab is the first approved subcutaneous single-domain PD-L1 antibody, which has been commercialized in China for the treatment of MSI-H/dMMR advanced solid tumors. This study aimed to investigate the efficacy and safety of Envafolimab plus SOX chemotherapy for metastatic or recurrent gastric adenocarcinoma, aiming to provide further reference for clinical rational drug use for this population. Methods: This multi-centre, single-arm, open-label study was conducted to evaluate the efficacy and safety of Envafolimab in metastatic or recurrent gastric adenocarcinoma. A total of 38 patients with histologically confirmed advanced gastric adenocarcinoma were enrolled. Patients will receive Envafolimab (300 mg, s.c., day 1) plus chemotherapy (oxaliplatin 130 mg/m2, i.v., day 1, and S-1 40mg, BSA＜1.25 m2、50mg 1.25 m2＜BSA＜1.5 m2、60 mg BSA＞1.5m2, p.o., twice daily, days 1-14) every 3 weeks for 6 cycles, followed by maintenance treatment with Envafolimab plus S-1 until disease progression (PD), unacceptable toxicity, or patient refusal. Eligible patients must be histologically confirmed, advanced metastatic gastric adenocarcinoma or recurrent gastric adenocarcinoma after prior surgical treatment. Other key inclusion criteria were previously untreated, HER2-negative, PD-L1 positive (Combined Positive Score (CPS)≥1), ECOG performance status of 0 or 1, and adequate organ function. Patients with any prior ICI therapy, abnormal AFP elevation, or microsatellite-instability-high (MSI-H) status will be excluded. The primary endpoint was objective response rate (ORR) based on the RECIST version 1.1, and the secondary endpoints were progression-free survival (PFS), overall survival (OS), etc. Adverse events were evaluated using the CTCAE v5.0 criteria. Results: Overall, thirteen patients were consecutively enrolled from March, 2022 to September 2022 and involved in this study. The median age was 62.7 years. At present, eight patients were included for efficacy analysis, and nine for safety evaluation. The ORR was 50%, and DCR was 87.5%, based on RECIST v1.1. Survival data are not mature at present. The most common TRAEs were elevated AST (75%), elevated ALT (65%) and leukopenia (42.5%). No treatment-related deaths occurred. Conclusions: Envafolimab plus chemotherapy is a promising and tolerable therapeutic regimen for patients with metastatic or recurrent gastric adenocarcinoma. Clinical trial information: NCT05237349 .
Artificial intelligence model for predicting the efficacy of sintilimab plus chemotherapy in treating patients with esophageal squamous cell carcinoma.
Authors: Wang Kefeng , Wu Duoguang , Wang Wenjian , Lei Kai , Liang Ruihao , Tan Binghua , Hu Xueting , Li Lin , Lyu Yingcheng , Wang Zhizheng , Zeng Yanwu , Pang Fei , Wang Kai , Lin Huayue , Wang Minghui 
Published: June 2023

e16030 Background: Blockade of programmed cell death 1 (PD-1) could induce tumor regression in patients with advanced esophageal squamous cell carcinoma (ESCC), although little is known about the biomarker to guide immunochemotherapy. In this study, we sought to evaluate the efficacy and discover biomarkers and establish an artificial intelligence (AI) model to predict the efficacy of the combination of sintilimab and chemotherapy in the treatment of patients with ESCC. Methods: Fifty-nine (59) patients enrolled in our study received chemotherapy with sintilimab and follow-up data were available. Treatment outcomes were assessed using the Response Evaluation Criteria in Solid Tumors (v1.1). Eleven (11) clinicopathologic characteristics including age, albumin, HLA-1 evolutionary divergence (HED), TMB, body mass index (BMI), neutrophil-lymphocyte ratio (NLR), platelets, hemoglobin, stage, sex, leukocyte, lymphocyte and therapy were collected. Results: Thirty-four (34) patients with ESCC who received sintilimab as first-line chemotherapy had a median follow-up of 13.7 (range, 0.53-35.57) months. At the time of analysis, six (6, 17.6%) patients were still receiving treatment, 24 patients achieved PR, and the confirmed ORR was 67.65%. Four (4) patients had SD and the DCR was 79.41%. Median PFS (mPFS) was 10.06 months. Median overall survival (mOS) was 23.27 months. The mPFS of the PD-L1 positive population was significantly better than that of the PD-L1 negative population (19.23 months vs. 6.57 months, p = 0.046). There was no significant difference in mPFS and mOS between the high and low TMB groups. Patients were divided into response (CR or PR) and non-response (SD or PD) groups according to their response to combined immunotherapy. The response rate of patients with wild-type MET was higher than that of patients with MET mutation (75% vs. 25%, p=0.0889). Compared to patients with wild-type BRCA2, patients with mutant BRCA2 had a significantly shorter mPFS (4.2 months vs. 13.3 months, p=0.027). Based on the efficacy data and 11 additional clinicopathologic characteristics of the 59 patients who received sintilimab in combination with chemotherapy, a random forest AI model was constructed to predict response to immunochemotherapy. Patients were randomly divided into a training set and a test set in a 6:4 ratio. In the test set, the top three predictive biomarkers were HED, age, and BMI. The area under the curve of the predictive model in the test set was 0.82. Conclusions: Sintilimab combined with chemotherapy could be an effective treatment for advanced ESCC, and an AI model based on multiple clinical features at baseline could predict the efficacy of immunochemotherapy. Further studies with larger sample size are needed to validate our findings.
TQB2450 plus anlotinib combined with paclitaxel and cisplatin as first-line treatment of advanced esophageal squamous cell carcinoma (ESCC): Update results of a single-arm, multicenter phase Ⅱ trial.
Authors: Wang Junsheng , Li Ning , Guo Yanzhen , Cheng Yufeng , Li Baosheng , Luo Su-xia 
Published: June 2023

e16034 Background: PD-1 inhibitors plus chemotherapy are the standard regimens of first-line treatment in advanced ESCC. Anlotinib, a multi-target TKI effectively inhibiting angiogenesis and improving tumor microenvironment, had been demonstrated to have promising efficacy and tolerable toxicity whether combined with chemotherapy as first-line treatment or monotherapy as second-line in advanced ESCC. TQB2450 is a novel humanized anti-PD-L1 monoclonal antibody. We have conducted a phase II trial to evaluate the efficacy and safety of anlotinib combined with TQB2450, cisplatin and paclitaxel as first-line therapy in advanced ESCC. Here is the update results with more enrolled patients and longer follow-up period. Methods: Eligible patients (pts) with previously untreated unresectable locally advanced or metastatic ESCC received TQB2450 (1200mg, iv, d1, q3w) plus anlotinib (10mg, po, d1~14, q3w) combined with paclitaxel (135mg/m2, iv, d1, q3w) and cisplatin (60~75mg/m2, iv, d1~3, q3w) for 4 - 6 cycles as initial therapy. Patients without progressive disease (PD) continued to receive same dose of anlotinib plus TQB2450 as maintenance therapy until PD or unacceptable toxicity. The primary endpoint was PFS (RECIST version 1.1). Secondary endpoints included iPFS (iRECIST), ORR (RECIST version 1.1), DCR, DOR and safety. Results: From September 2021 to August 2022, 50 pts were enrolled with a median age of 64 years (range 41-74), male (39/50, 78%) and ECOG PS 1 (39/50, 78%). At the data cutoff date of January 16, 2023, 45 pts were tumor response evaluable, among whom, 3 pts achieved complete response, 34 had partial response and 8 had stable disease. The ORR was 82.2% (95% CI: 68.0%, 92.0%) and the DCR was 100.0% (95% CI: 92.1%, 100.0%). Median PFS was not reached. The incidence of grade 3-4 treatment emergent adverse events (TEAEs) was 66% (33/50), mainly included neutropenia (34%, 17/50), leukopenia (20%, 10/50) and hypertension (20%, 10/50), platelet count decreased (6%, 3/50). There was no grade 5 TRAE. 17 pts (34%, 17/50) occurred treatment related serious AEs. Conclusions: TQB2450 plus anlotinib combined with paclitaxel and cisplatin showed significant efficacy and manageable safety profile as first-line treatment in advanced ESCC, which might provide a new treatment strategy for ESCC patients. Clinical trial information: NCT05013697 .
18F-FDG PET and CT identifiers of high-risk lesions in the stomach and esophagus.
Authors: EighaeiSedeh Ashkan , Kako Bashar , Deffler Caitlin , Ng Thomas , Catalano Onofrio Antonio , Mahmood Umar , Heidari Pedram , Abdar Esfahani Shadi 
Published: June 2023

e16036 Background: Assessing the significance of incidentally found increased 18F-FDG uptake in the stomach and esophagus on PET/CT has long been a challenge. Currently, there is no clear guideline to assist clinicians with distinguishing malignant from benign uptake. This study aims to compare various PET and CT characteristics used separately and collectively, to identify high-risk foci of uptake. Methods: 18F-FDG PET/CT images from August 2018 to October 2022 were reviewed and patients who completed a follow up EGD due to incidentally found increased gastroesophageal uptake were included in this study. To identify high-risk foci, the following PET and CT characteristics were used: 1) uptake intensity, using lesion SUVmax relative to mediastinal blood pool and liver SUVmean values (≤ blood pool = 0, > blood pool but < liver = 1, ≥ liver = 2); 2) uptake pattern (diffuse = 0, segmental = 1, focal = 2); 3) eccentricity (circumferential= 0, eccentric = 1); and CT correlation score (normal = 0, thickening = 1, mass = 2). Cut-off values were determined using receiver operating characteristic (ROC) curves. Benign and malignant uptake were compared to histological findings using Pearson’s chi-square test. Results: Incidental uptake in the stomach and/or esophagus were noted in 473/7805 (6.1%) patients of which 89 (18.8%) had a follow up EGD and were included in this study. Uptake intensity did not differentiate benign and malignant as SUVmax was greater than background tissues in all cases (Score =2). Uptake pattern, eccentricity, and CT-correlation of PET were significantly different between benign and malignant foci ( p < 0.001, p < 0.001, and p < 0.001, Chi-square). Using cut-off scores from ROC curves, the predictive value of different PET/CT characteristics in identifying high-risk foci was reviewed. Conclusions: PET eccentricity along with anatomic CT correlative findings, offer similar value in predicting high-risk uptake foci to uptake pattern, eccentricity, and CT correlation combined. These are both, however, superior to other PET/CT characteristics used alone or in combination. [Table: see text]
Updated results of the phase 1 I-FLOAT trial: Safety and efficacy of combining genotype-guided irinotecan with 5FU, leucovorin, oxaliplatin and docetaxel (gFOLFOXIRITAX) in advanced upper GI cancers.
Authors: Paydary Koosha , Loew Colton , Desgardin Aurelie , Shergill Ardaman , Reizine Natalie Marie , Robinzine Chanelle , Racette Christine , Ignatiev Elena , Neerukonda Anu Radha , Ji Yuan , Polite Blase N. , Liao Chih-Yi 
Published: June 2023

e16038 Background: 5FU, Oxaliplatin (ox), irinotecan (iri) and docetaxel (tax) are each active in upper GI cancers; however, combination of all 4 agents (FOLFOXIRITAX) has not been studied. UGT1A1 polymorphisms may predispose to Iri toxicity. We sought to determine the maximum tolerated dose (MTD) in the 1st month of therapy (tx) among each of the low (L), intermediate (I) and high (H) risk UGT1A1 genotype (UGT) groups. We report the updated results of the I-FLOAT trial. Methods: Previously untx’d advanced upper GI cancer patients (pts) with ECOG PS 0/1 received gFOLFOXIRITAX (+ trastuzumab if HER2+) with pegfilgrastim. 5FU 2400mg/m2 over 46 hrs, LV 400mg/m2, Ox 85mg/m2, and Tax 25mg/m2 were given IV Q14 days. UGT-L, I, and H risk groups received starting Iri dose levels (DL1) of 120, 105 and 45mg/m2, respectively; Iri doses were escalated in each UGT group by 15mg/m2 increments and Tax to DL2 of 37.5mg/m2 using a I3+3 novel design (Liu & Ji. J Biopharm Stat 2020). Other endpoints included overall safety (thru up to 8 cycles before maintenance 5FU +/- Iri/tras), ORR (RECIST1.1) & ctDNA response (>50% decrease in highest MAF) by G360 (Guardant Health). Results: From 6/30/2020-1/1/2023, 27 pts (11F, 16M) enrolled: median age 51 (range 21-76); 9 ECOG PS 1, UGT-L:I:H with 6:18:3 pts; 12 esophageal, 6 gastric, 8 pancreatic, and 1 bile duct cancer; 3 pts HER2+; 22 metastatic, 5 locally advanced unresectable. The median (range) of albumin and neutrophil-to-lymphocyte ratio (NLR) were 3.9 mg/dL (3.2-4.7) and 4.06 (1.89-27.6), respectively; 81% (22/27) of pts had a NLR > 2.88, a poor prognostic marker. Dose limiting toxicities (DLTs) were seen in 5 pts: one G3 diarrhea (UGT-H, DL1/DL1 Iri/Tax), two G3 sepsis not neutropenic (one UGT-I, DL2/DL2 Iri/Tax; and one UGT-I, DL3/DL1 Iri/Tax), one G3 fatigue (UGT-I DL2/DL2 Iri/Tax) and one G3 diarrhea and neutropenic fever (UGT-L DL4/DL1 Iri/Tax). MTD has not been reached in any UGT TAX DL1 cohorts to date; currently enrolling UGT-H Iri/Tax DL1/DL1, UGT-I DL4/DL1, & UGT-L DL4/DL1. The most frequent any Gr tx related toxicities: diarrhea (78%), fatigue (74%), nausea (70%), neuropathy (67%), anorexia (52%), elevated LFT (48%), anemia (37%), vomiting (37%). Of evaluable pts across all cohorts, PR/CR was seen in 18/22 (82%) patients, with 2 (9%) SD and 2 (9%) PD for a disease control rate of 91%. Of evaluable pts, best ctDNA response was seen in 12/13 (92%). Conclusions: gFOLFOXIRITAX continues to demonstrate tolerability at initial DLs of Iri/Tax. Efficacy is promising and could be an aggressive approach in upper GI cancers with high relapse risk in curative-intent settings. Clinical trial information: NCT04361708 .
Paclitaxel + ramucirumab versus paclitaxel alone in patients with squamous-cell carcinoma of the esophagus, refractory or intolerant to combination therapy with fluoropyrimidine and platinum-based drugs: Final results from the randomized phase 2 IKF-S627/RAMOS trial of the AIO.
Authors: Scheck Magdalena , Goetze Thorsten Oliver , Ettrich Thomas Jens , Schmalenberg Harald , Clemens Michael , Mahlberg Rolf , Heeg Steffen , Kanzler Stephan , Hapke Gunnar , Thuss-Patience Peter C. , Kestler Angelika , Treschl Anne , Frost Gregg , Schiemer Moritz , Junge Sabine , Pauligk Claudia , Al-Batran Salah-Eddin , Lorenzen Sylvie 
Published: June 2023

e16043 Background: Ramucirumab (Ram) in combination with docetaxel is an approved 2nd-line treatment in patients (pts) with squamous cell carcinomas (SCC) of the lung (REVEL study) and with paclitaxel for esophagogastric adenocarcinoma (RAINBOW study). In SCC of the esophagus, nivolumab is currently the only evidence-based 2nd-line treatment option. This study evaluates the safety and efficacy of the combination of Ram plus paclitaxel. Methods: This prospective, randomized, open-label, multicenter, phase II trial evaluated paclitaxel plus Ram (Ram 8 mg/kg d1 and d15 and paclitaxel 80 mg/m2 d1, 8, 15) Arm A vs. paclitaxel alone (80 mg/m2 d1, 8, 15) Arm B, both q4w. Primary endpoint was overall survival rate at 6months (mos) (OS@6), main secondary endpoints were OS, PFS, objective response rate (ORR) and safety. Results: From 3/2019 to 4/2021, 21/186 planned pts were treated within the study protocol (Arm A 11 pts; Arm B 10 pts) in 10 German centers. Due to slow accrual, the study was terminated prematurely. Median age was 63y, 71% were male and 86% had relevant concomitant disease. Pts. received a median of 9 and 10 cycles Arms A and B, respectively. The most common treatment related AEs in Arm A were leucopenia (54.5%), fatigue (27.3%) and peripheral sensory neuropathy (18.2%). Treatment related adverse events (AEs) ≥ grade 3 occurred in 27% in Arm A and 50% in Arm B with neutropenia being most frequent in Arm B (n=3; 30%). Serious adverse events (SAE) occurred in 36% and 50% in Arms A and B respectively. Median follow-up was 9 months (0.7 – 32.4 months). OS@6 in Arm A was 73% for Ram/paclitaxel and 50% for paclitaxel. However, the study design did not allow for statistical comparison of the arms. ORR (CR+PR 18% vs. 20%) and DCR (55% vs. 60%) were in the same range, as well as median PFS (3.8 vs. 3.5 mos) and OS (12.1 vs. 9.2 mos), for Arms A and B, respectively. Conclusions: Ram and Paclitaxel is considered to show an acceptable tolerability and numerically improved OS@6. Due to the small number of pts the current trial must be considered exploratory and more data are needed in this indication. Clinical trial information: NCT03762564 .
Co-occurrence of mutations and related signal pathway analysis of CCND1 amplification in esophageal squamous cell cancer.
Authors: Pang Qingsong , Zhang Wencheng , Zhang Tian , Chen Xi , Zhao Fangdong , Li Jiacheng , Dong Jie , Liu Yang , Wang Qian , Xiao Shanshan , Wang Tao 
Published: June 2023

e16044 Background: Profiling molecular subtypes was usually necessary for cancer patients to facilitate better treatment strategy. Esophageal squamous cell cancer (ESCC) has four subtypes including cell cycle pathway activation (CCA), NRF2 oncogenic activation (NRFA), immune suppression (IS), and immune modulation (IM). CCND1 amplification is one of the important molecular biomarkers for CCA subtype. Previous research showed that CCND1 amplification was associated with immune resistance in ESCC. The co-occurred mutations and related signaling pathways are of great interest to study molecular mechanism in ESCC. Methods: This study enrolled 50 ESCC patient samples comprising 19 whole exome sequencing (WES) samples, 18 whole genome sequencing (WGS) samples and 13 NGS panel (667 genes) samples. To use all the samples, the minimal set of 667 genes was analyzed in detail for gene amplifications and mutations. Kaplan-Meier (KM) survival analysis was applied to study the prognosis associations with the frequently occurred amplifications including CCND1, FGF3, FGF4 and FGF19, etc. Gene expression profiles were then investigated by RNA-Seq sequencing on ESCC cell lines with CCND1 (K30-N) and without CCND1 gene (K30-S, knocked out). PCA analysis was applied to explore the differences between K30-S and K30-N, and KEGG and GO enrichment analysis were performed on the differential expressed genes (DEGs). All analyses were carried out through R4.1.0. Results: The mutational profiles showed that TP53, CCND1, FGF4, FGF19, FGF3, and CDKN2A/B were the most frequently mutated genes in ESCC patients, with the mutation frequencies of 62%, 58%, 56%, 50%, 48% and 40%, respectively. Among those genes, CCND1 and FGF3/4/19 co-occurred amplifications presented in almost all the samples and no other co-existent gene amplifications were identified. The CCND1 and FGF3/4/19 amplification patients were associated with worse prognosis. A total of 1494 differential expressed genes were identified between K30-N and K30-S cell lines, including 998 up-regulated genes and 496 down-regulated gene in K30-S cell line. KEGG enrichment analysis showed that these DEGs were mainly enriched in MAPK signaling pathway, p53 signaling pathway, mTOR signaling pathway and etc. GO enrichment analysis revealed that these differential genes are mainly enriched in cell growth, developmental cell growth, Ras protein signal transmission. Those results were consistent with CCA molecular subtype and highlighted the important role of CCND1 in ESCC subtype classification. Conclusions: This study demonstrated that CCND1 and FGF3/4/19 amplifications frequently co-occurred in ESCC and they were associated with worse prognosis. Signal pathway analysis showed CCND1 play important roles in subtype classification of ESCC.