bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revolutionizing outcome prediction for immunotherapy with vision transformer-based pathomics signature in esophageal squamous cell cancer.
Authors: Li Butuo , Qin Wenru , Wang Linlin 
Published: July 2024

e16049 Background: Immune checkpoint inhibitors (ICIs) has notably enhanced the survival prospects for patients with esophageal squamous cell carcinoma (ESCC), however the clinical benefit was limited to only a small portion of patients. This study aimed to perform a deep learning signature based on H&E-stained pathological specimens for the purpose of identifying effective markers that can accurately predict the clinical benefit of ICIs among patients with ESCC. Methods: ESCC patients receiving PD-1 inhibitors from Shandong Cancer Hospital were included. Whole slide images (WSIs) of H&E-stained histological specimens of included patients were collected, and subsequently randomly allocated into two sets: a training set comprising 70% of the samples, and a validation set consisting of the remaining 30%. The labels of images were defined by the progression-free survival (PFS) with the interval of 4 months. The pretrained ViT model was used for patch-level model training, and all patches were projected into probabilities after linear classifier. Then the most predictive patches were passed to RNN for final patient-level prediction to construct ESCC-pathomics signature (ESCC-PS). Accuracy rate and survival analysis were performed to evaluate the performance of ViT-RNN survival model in validation cohort. Results: 163 ESCC patients receiving PD-1 inhibitors were included for model training. There were 486,188 patches of 1024*1024 pixels from 324 WSI images of H&E-stained histological specimens after image pre-processing. The training cohort consisted of 120 patients with a total of 227 images, while the validation cohort comprised 43 patients and featured 97 images. Notably, both groups exhibited balanced baseline characteristics between them. The ESCC-PS achieved an accuracy of 84.5% in the validation cohort, and could distinguish patients into three risk groups with the median PFS of 2.7, 4.8 and 16.7 months (P < 0.001). The multivariate cox analysis revealed ESCC-PS could act as an independent predictor of survival from PD-1 inhibitors (P < 0.001). A combined signature incorporating ESCC-PS and expression of PD-L1 shows significantly improved accuracy in outcome prediction of PD-1 inhibitors compared to ESCC-PS and PD-L1 anlone, with the area under curve value of 0.952, 0.924, 0.648 for 6-month PFS and C-index of 0.816, 0.806, 0.66, respectively. Conclusions: The outcome supervised pathomics signature based on deep learning has the potential to enable superior prognostic stratification of ESCC patients receiving PD-1 inhibitors, which convert the images pixels to an effective and labour-saving tool to optimize clinical management of ESCC patients.
Immune checkpoint inhibitor plus chemotherapy versus chemotherapy alone in HER2-negative advanced gastric or gastroesophageal junction cancer: A systematic review and meta-analysis of randomized controlled trials.
Authors: Oliveira João Pedro , Silva Isadora Mamede Mendes da , de Liz Caio Dabbous , Maia Melissa , Oliveira Audrey Cabral Ferreira de , Alves Ana Caroline Fonseca 
Published: July 2024

e16052 Background: Synergistic effects of immune checkpoint inhibitors (ICI) and chemotherapy (CTX) have been documented, demonstrating promising efficacy across diverse cancer types. This report presents a meta-analysis aimed at assessing the effectiveness and safety profile of ICI plus CTX in patients diagnosed with Human Epidermal Growth Factor Receptor type 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) cancers. Methods: PubMed, EMBASE, Cochrane Central, and ASCO Abstracts databases were systematically searched for randomized controlled trials comparing PD-1 or PD-L1 inhibitors plus CTX with CTX alone in patients diagnosed with HER2-negative gastric or GEJ cancers. The assessed outcomes included Progression-Free Survival (PFS) and Overall Survival (OS), stratified by PD-L1 Combinated Positive Score (CPS) in tumors, as well as any Adverse Events (AE) and Treatment-Related Adverse Events (TRAE) graded as ≥ 3. Statistical analysis employed a random effects model in R version 4.3.2, with heterogeneity assessed using the I2 statistic. Results: We conducted a meta-analysis comprising 6 RCTs involving 5,520 patients, among whom 2,766 received PD-1 or PD-L1 inhibitors in combination with chemotherapy. This combined regimen demonstrated significant improvements in both general PFS (HR 0.73; 95% CI [0.68; 0.78]; p < 0.01) and OS (HR 0.77; 95% CI [0.71; 0.84]; p < 0.01). Specifically, the combination of ICI with CTX exhibited enhanced PFS across various subgroups, including CPS ≥ 5 (HR 0.66; 95% CI [0.59; 0.75]; p < 0.01), CPS ≥ 10 (HR 0.75; 95% CI [0.65; 0.87]; p < 0.01), and CPS ≤ 1 (HR 0.75; 95% CI [0.69; 0.82]; p < 0.01). Median OS similarly reflected this improvement in CPS ≥ 5 (HR 0.71; 95% CI [0.63; 0.81]; p < 0.01) and CPS ≥ 10 (HR 0.66; 95% CI [0.57; 0.75]; p < 0.01) subgroups, albeit not in the CPS ≤ 1 subgroup (HR 0.91; 95% CI [0.77; 1.08]; p = 0.29). Furthermore, no significant differences were observed in the incidence of adverse events (AE) (RR 1.01; 95% CI [0.99; 1.04]; p = 0.221), while grade 3 or more treatment-related adverse events (TRAE) were slightly higher in the ICI plus CTX group (RR 1.15; 95% CI [1.01; 1.32]; p = 0.038). Conclusions: These findings indicate that the combination of ICI with CTX demonstrates superior efficacy compared to CTX alone in HER2-negative gastric or GEJ cancer. However, this efficacy trend is not maintained in patients with PD-L1 CPS ≤ 1 tumors. Moreover, the absence of differences in AE and the slight increase in TRAE in the ICI plus CTX group still further supports the safety profile of this combination therapy.
Association between homologous recombination deficiency (HRD) gene mutations and the efficacy of venadaparib in combination with irinotecan as third- or fourth-line treatment in patients with metastatic gastric cancer (mGC).
Authors: Ryu Min-Hee , Kim Hyung-Don , Oh Do-Youn , Lee Keun-Wook , Rha Sun Young , Kim Seung Tae , Lee Won Sik , Hong Min Ju , Lee Myongjae , Roh Eun-Jihn , Ha Kyoung Soo 
Published: July 2024

e16057 Background: Tumors with homologous recombination deficiency (HRD) have been suggested to be associated with a favorable response to poly (adenosine diphosphate [ADP]–ribose) polymerase (PARP) inhibitors. The aim of this exploratory analysis was to evaluate the association between the presence of HRD gene mutations and the efficacy of venadaparib, a novel PARP inhibitor, plus irinotecan in patients with mGC who had failed at least at least 2 lines of therapy. Methods: This was an exploratory analysis from a multi-national, phase 1b trial of venadaparib plus irinotecan in patients with mGC (NCT04725994). Tumor response was evaluated according to RECIST v. 1.1. Genomic analysis was conducted using ctDNA (GuardantOMNI Gene Panel version 1.0, Redwood City, CA) on Day 1 pre-dose. Results of the exploratory genomic analysis, which includes pathogenic or deleterious mutations of following genes: BRCA1/2, ATM, ATR, PALB2, RAD51, RAD51B/C/D, CHEK1/2, POLD1/2/3/4, BARD1, BRIP1, were analyzed with the efficacy outcomes. Results: In the dose-finding part of the clinical study, 26 patients were enrolled:13 had received two prior treatments and 13 had received three prior treatments, respectively. Of the 26 patients enrolled, 7 (26.9%) had mutations involved in HRD (4 with ATM, 1 with BRCA2, 1 with BARD1, and 1 with ATR mutations, respectively), and were treated with varying doses of venadaparib plus irinotecan. Among the 7 patients with a mutation in HRD genes, an objective response rate (ORR) was 57.1%, and median progression free survival (mPFS) was 5.6 months (95% confidence interval [CI] 1.2–not reached). For those without a mutation in HRD genes (n = 19), 1 patient achieved partial response and 13 achieved stable disease as best response with a mPFS of 4.0 (95% CI 2.9-5.5) months. Conclusions: Venadaparib in combination with irinotecan showed promising efficacy outcomes in patients with mGC, especially for those with mutations of HRD-related genes. Further development of this combination may consider a biomarker-based approach. Clinical trial information: NCT04725994 . [Table: see text]
Effectiveness and safety analysis of serplulimab-based regimens in patients with HER2-negative advanced gastric cancer from a real-world retrospective study.
Authors: Ding Qian , Wu Mengyao , Yu Danlei , Sun Di , Li Na , Tao Min , Zhu Hong 
Published: July 2024

e16058 Background: Immune checkpoint inhibitors (ICIs) combined with chemotherapy are currently the preferred regimen for the treatment of HER-2 negative advanced gastric cancer. Serplulimab, an anti-PD-1 inhibitor, has been conditionally approved for the treatment of adult advanced gastric cancer. Because of the diverse nature of patients (pts), patient-centered, individualized treatment require accumulation of experience for real-world applications. Methods: We retrospectively studied 42 HER2-negative advanced gastric adenocarcinoma pts whose safety profiles of regimen containing serplulimab could be evaluated from April 2022 to October 2023 in the First Affiliated Hospital of Soochow University. Individualized treatment regimens mainly included serplulimab combined with one or two selected drug(s) from platinum, taxanes, and fluoropyrimidines. Results: Cut-off on January 30th, 2024, 30 pts (71.4%) received serplulimab based regimens as the first line (1L), 12 pts (28.6%) received the second or more line (≥2L) therapy. The characteristics were as follows: the median age, 66 years (range 35-80 years); male/female 33 (78.6%)/9(21.4%); ECOG performance status 0-1/38, ≥2/4. The median follow-up was 5.7 months (range 0.2-22.3 mos). A total of 227 cycles of treatment was administrated with a median of 4 cycles (range 1-17). Among the pts evaluable for RECIST 1.1, ORR and DCR were 42.9% and 69.0% respectively. There were 3 pts with 3 or more metastatic lesions achieved PR. Nine 1L pts and one 2L pt receiving serplulimab combined with dual chemotherapy containing platinum achieved disease control more than a year. We also tracked 11 pts who experienced grade 1-2 immune-related adverse events (irAEs) reaped over 6 months PFS. Two of four pts who stopped immunotherapy but maintained 1 or 2 cycles of original combined chemotherapy obtained PFS for more than a year. Median PFS and DoR have not reached. The most common grade 3/4 AEs was myelosuppression (7.1%), increased aminotransferases (4.7%) and elevated creatinine (2.3%). 15 (35.7%) pts experienced immune-related adverse events (irAEs) of any grade including aminotransferase elevation, increased creatinine, but no grade 3 or higher irAEs observed. Conclusions: The real-world data analysis shows that serplulimab-based flexibly combination according to patient status, achieving tumor control in diverse pts while ensuring drug safety. We successfully validated the effectiveness and safety of chemo-immunotherapy strategy in real-world practice. [Table: see text]
Efficacy, safety and DNA methylation analysis of cadonilimab combined with taxane and cisplatin as the first-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC): An open-label, multicenter phase II trial– Updated results from AK104-IIT-014.
Authors: Qu Wang , Gao Jing , Zhang Bo , Liu Yun , Guo Yijia , Yang Mudan , Huang Jing 
Published: July 2024

e16064 Background: Immune checkpoint inhibitors combined with chemotherapy has become the current first-line standard treatment for advanced ESCC, while still having a lot of room for improvements in objective responses and survival. Cadonilimab, a bispecific antibody simultaneously targeting PD-1 and CTLA-4, may further boost anti-tumour activity with a satisfied safety profile. Here, we present the updated data for the safety and efficacy of Cadonilimab combination therapy as the first-line treatment in advanced ESCC. Methods: Treatment-naïve patients (pts) with unresectable locally advanced or metastatic ESCC were eligible for inclusion. Cadonilimab (10mg/kg, iv, d1, q3w) combined with paclitaxel or nab-paclitaxel (175 mg/m2, iv, d1, q3w) and cisplatin (65 to 75 mg/m2, iv, d1, q3w) were administrated for up to 6 cycles, then Cadonilimab (10mg/kg, iv, d1, q3w) monotherapy continued as maintenance until progressive disease or unacceptable toxicity, with a maximum of 24 months. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety. Plasma cell-free DNA samples were collected before and after treatment and prepared for DNA methylation level sequencing. Results: At updated analysis (cut-off: February 5, 2024), 35 pts were enrolled with a median age of 61 years (range 44-75), 82.9% were male, 57.1% had PD-L1 CPS<10 and 88.6% had distant metastases. In the efficacy-evaluable population (n = 29), 5 pts reached complete response (CR), 21 pts had partial response (PR) and 3 pts had stable disease (SD). The ORR was 89.7% (95%Cl: 71.5%-97.3%) and the DCR was 100.0% (95%Cl: 85.4%-100.0%). Among evaluable pts with PD-L1 CPS≥10 and PD-L1 CPS<10, the ORR were 100.0% (12/12) and 81.3% (13/16), respectively. SEPT9 methylation was significantly higher in patients with CR or PR compared to patients with SD (33.28% vs 3.87%, p < 0.001). The median PFS and OS was still not reached. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 9 (25.7%) pts. The most common TRAEs were neutropenia (17.1%), leukopenia (5.7%) and hyponatremia (5.7%). Immune-related adverse events were observed in 9 pts (25.7%). Three pts (8.6%) suffered from serious adverse events, and no grade 5 TRAEs or death were observed. Conclusions: The updated results suggested that bispecific antibody AK104 combined with taxane and cisplatin as first-line treatment showed promising anti-tumor activity and manageable safety in patients with advanced ESCC. DNA methylation level might be a potential biomarker for guiding patient outcomes. Follow-up is ongoing for survival analysis. Clinical trial information: NCT05522894 .
The clinical significance of PRMT8 expression in esophageal squamous cell carcinoma and the influence on prognosis.
Authors: Liu Sihan , Zuo Jing , Zhang Xue 
Published: July 2024

e16066 Background: Protein arginine methyltransferase 8 (PRMT8), a member of protein arginine methyltransferases, is an enzyme catalyzing the methylation of arginine residuals of histones and non-histone proteins to serve as one of many critical post-translational modications (PTMs). Esophageal squamous cell carcinoma (ESCC) is the third most common cancer type of the gastrointestinal tract with poor prognosis. Abnormal arginine methylation modifications are closely associated with the development of ESCC and can exert oncogenic effects by regulating a variety of cellular processes. However, the expression of PRMT8 in ESCC and its influence on prognosis is currently unknown. Methods: After passing the application and obtaining the approval of the hospital ethics review committee and obtaining the informed consent of all patients and their families, we collected 46 cases of renal cell carcinoma diagnosed in the Fourth Hospital of Hebei Medical University from 2018 to 2023, and postoperative pathological reports of all patients confirmed to be ESCC. We followed the selected patients and obtained complete data. All the pathological specimens of the selected patients were resectioned and then subjected to immunohistochemical examination to observe the expression differences of PRMT8 in ESCC, and parallel semi-quantitative analysis. Finally, the data of the patients were statistically built. Results: PRMT8 is mainly stained on the plasma membrane of tumor cells. The difference in expression levels between ESCC and normal tissue adjacent to the cancer was statistically significant (P < 0.01). This study found that the patient’s gender, age, tumor side have no correlation with the expression levels of PRMT8 (P > 0.05), while the three indicators of tumor size, TNM stage, and lymph node metastasis are positively correlated with the expression levels of PRMT8 and the difference is statistically significant (P < 0.01). Moreover, the positive staining of PRMT1 in ESCC was significantly correlated with poor prognosis of ESCC patients. Conclusions: The expression of PRMT8 is highly expressed in ESCC and associated with aberrant clinicopathological characteristics and poor prognosis. PRMT8 is a potential target for the stratification and treatment of ESCC.
Concordance of PD-L1 combined positive score (CPS) analysis between primary gastric cancer and matched peritoneal metastasis.
Authors: Massa Valentina , Salani Francesca , Grelli Giada , Genovesi Virginia , Vivaldi Caterina , Signorini Francesca , Ugolini Clara , Filice Maria Elena , Bernardini Laura , Cesario Silvia , Caccese Miriam , Graziani Jessica , Bartalini Linda , Berra Dario , Mangogna Francesco , Nardini Vincenzo , Masi Gianluca , Fornaro Lorenzo 
Published: July 2024

e16068 Background: Peritoneum represents one of the most common metastatic sites of gastroesophageal adenocarcinoma (GEA) and is associated with poor prognosis. Programmed death-ligand 1 (PD-L1) expression is a recognized predictive biomarker of response to immune checkpoint inhibitors (ICIs) in the first-line setting. However, data from pivotal trials showed poorer clinical efficacy of ICIs in the sub-set of patients with peritoneal involvement, regardless of PD-L1 score magnitude. Here, we investigated the temporal and spatial heterogeneity of PD-L1 expression between primary tumor and matched peritoneal metastasis. Methods: PD-L1 expression according to CPS was determined by immunohistochemistry using VENTANA PD-L1 (SP263) assays on formalin-fixed paraffin-embedded (FFPE) tumor tissues derived from 22 patients treated at our institution for advanced GEA from September 2015 to August 2023. Concordance rate of PD-L1 expression between primary tumor and matched peritoneal metastasis using PD-L1 CPS cut-off of 1 and 5 was reported (spatial heterogeneity); additionally, concordance between PD-L1 value before and after the administration of systemic treatments was analyzed (temporal heterogeneity). Results: 12(54.5%)/5(22.7%) primary tumor samples and 12(54.5%)/1(4.5%) peritoneal metastases showed PD-L1 CPS ≥ 1/ ≥ 5, respectively. Concordance of PD-L1 CPS between primary and peritoneal specimens was 54.5% and 72.7% according to CPS cuts-off of 1 and 5, respectively, highlighting marked spatial heterogeneity. High concordance rate (94%) was reported between negative PD-L1 CPS primary tumor samples and matched peritoneal metastases, against the cut-off of CPS ≥ 5; in contrast, none of the positive primary tumor samples retained PD-L1 expression in the peritoneum. Evident temporal heterogeneity of PD-L1 expression was also observed, with 56% concordance against CPS ≥ 5 in the pre- versus post-treatment comparison. Conclusions: PD-L1 expression in GEA is characterized by spatial and temporal heterogeneity which is more prominent for lower CPS cut-offs values. This evidence could hamper its role as predictive biomarker for ICIs. The high intra-patient discordance rate of PD-L1 CPS expression between positive primary tumor samples and matched peritoneal metastases suggests that peritoneal specimens should not be recommended as the preferred source for PD-L1 assessment.
Life expectancy of patients with early gastric cancer who underwent curative gastrectomy: Comparison with the general population using the Korean Statistical Information Service database.
Authors: Ko ChangSeok 
Published: July 2024

e16077 Background: Although clinical trials have reported the long-term survival of patients with early gastric cancer, data comparing their life expectancy with that of the general population is scarce. Our study estimated these patients’ life expectancy and analyzed the differences in life expectancy between patients with early gastric cancer and the general population. Methods: We enrolled patients who underwent curative gastrectomy and were diagnosed with pathologic stage 1 gastric cancer at Asan Medical Center from the gastric cancer registry. We determined patients’ survival status through the national health insurance system. Their life expectancy was analyzed and compared with that of the general population, utilizing data from the Korean Statistical Information Service database. Results: This cohort comprised 8,637 patients and 64.7% were men. Approximately 17.3% of participants were aged 70 years and older. Approximately 20% of patients underwent total gastrectomy. Life expectancy was favorable among women. Across all age groups, women’s life expectancy generally exceeded 80 years. Male patients showed a reduced life expectancy, typically 4-10 years shorter than their female counterparts. The average life expectancy of male patients aged over 80 years who underwent total gastrectomy was about 5 years, whereas that of their female counterparts was approximately 7 years. Female patients undergoing distal gastrectomy did not demonstrate a statistically significant variance in life expectancy compared to the general population. Conclusions: This study provided comprehensive life expectancy data, organized by age, sex, and type of gastrectomy in a large stage 1 gastric cancer cohort. Elderly patients undergoing total gastrectomy with limited life expectancy may benefit from considering alternative treatment options instead of total gastrectomy.