bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endoscopic prediction of depth of tumor invasion in early gastric cancer in the upper third of the stomach.
Authors: Moon Hee Seok , Cnuhgi Cnuhgi 
Published: January 2023

406 Background: The endoscopic features of early gastric cancer (EGC) arising from the upper third of the stomach (upper body, fundus, and cardia) has not been well studied. If EGC in the upper third of the stomach can be predicted to have invaded the mucosal (M) or submucosal (SM) layer, endoscopic or surgical treatment can be determined. This study evaluated the endoscopic features of EGC in the upper third of the stomach as well as risk factors for SM invasion. Methods: We retrospectively reviewed patients' medical records from a single tertiary hospital (Daejeon) and investigated endoscopic findings and clinical data. Patients with EGC in the upper third of the stomach who underwent surgery or endoscopic resection between January 2016 and April 2022 were included. Logistic regression was used to determine the risk factors of the SM cancer group. Results: In total, 173 patients were enrolled in this study: 94 with SM cancer and 79 with M cancer. Risk factors for SM invasion determined by univariate logistic regression were clubbing of converging folds (OR 6.279, p=0.000), fusion of converging folds (OR 9.179, P=0.000), irregular nodule in the central lesion (OR 2.336, p=0.016), margin with elevation (OR 2.520, P=0.031), and ulceration (OR 9.686, p=0.000). However, in the multivariate logistic regression analysis, only ulceration was identified as a risk factor (OR 6.598, p=0.007). Conclusions: In EGC occurring in the upper third of the stomach, ulceration is a risk factor for SM invasion. Surgical treatment should be considered if this characteristic is present.
Anlotinib combined with paclitaxel and cisplatin as neoadjuvant treatment for esophageal squamous cell carcinoma (ESCC).
Authors: Jiang Gongqian , Wang Guolei 
Published: January 2023

409 Background: Preoperative chemoradiotherapy before esophagectomy in esophageal squamous cell carcinoma (ESCC) can obtain significant survival benefits for patients compared with surgery alone. The antiangiogenic drugs have shown efficacy in many cancers including esophageal cancer. The benefits of antiangiogenic drugs in neoadjuvant therapy for ESCC still worth exploring. Anlotinib was an effective second-line monotherapy for ESCC in China and the combination of anlotinib and chemotherapy might be a promising strategy as neoadjuvant treatment. Methods: This was a single-arm, non-interventional study. Patients diagnosed stage II-III ESCC confirmed by histopathology would be enrolled(N=30). Patients received neoadjuvant therapy with anlotinib (12 mg, po, d1-14, 21 days per cycle) combined with paclitaxel (135 mg/m2 iv d1, 21 days per cycle) and cisplatin (60-75mg/m2 iv d1, 21 days per cycle). The primary endpoints were pathologic complete response (pCR) rate, rate of R0 resection and disease-free survival (DFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR) and safety profile. Results: From July 2020 to September 2022, 20 pts (15 males and 5 females) were enrolled with a median age of 66 years (range: 48-75). 12 pts (60%) had ECOG PS 1, 8 pts had ECOG PS 2. 17/1/2 pts received 2/3/4 cycles of neoadjuvant treatment respectively. In best overall response assessment, ORR was 95% and DCR was 100%. Among them 18 pts underwent esophagectomy and all of them obtained R0 resection, as the rate of R0 resection was 90%. 6 pts (30%) were confirmed to be pCR. The median DFS was not yet available. The safety profile suggested that 3 (15%) pts occurred grade 1-2 treatment-related adverse events (TRAEs), including decreased leukocyte count (5%), diarrhea (5%), nausea and vomiting (5%). No grade ≥3 TRAEs were observed. Conclusions: The preliminary results of this study show promising efficacy and safety of anlotinib combined with paclitaxel and cisplatin as neoadjuvant therapy for patients with esophageal squamous cell carcinoma. More ESCC patients would be recruited in the future. Clinical trial information: ChiCTR2100054374 .
MicroRNAs (miRs) as biomarkers of resistance to trastuzumab in HER2-positive oesophago-gastric cancer: Sub-study within the Planning Treatment for Oesophago-Gastric Cancer—A Randomised Maintenance Therapy Trial (PLATFORM).
Authors: Lote Hazel , Mousoullou Florentia , Vlachogiannis George , Fong Caroline , Satchwell Laura , Peckitt Clare , Begum Ruwaida , Kidd Shannon , Cromarty Susan , Gordon Anderley , Fribbens Charlotte Victoria , Watkins David J. , Rao Sheela , Chau Ian , Starling Naureen , Cunningham David , Valeri Nicola 
Published: January 2023

419 Background: A predictive biomarker for resistance to trastuzumab in HER2 positive oesophago-gastric cancer would refine patient selection. Our preclinical studies suggest that patients with HIGH baseline plasma miR-148a-3p levels will experience shorter Overall Survival (OS), Progression Free Survival (PFS), and worse Progression Free Rates (PFR) than those with LOW plasma miR-148a-3p levels. Methods: This sub-study is a prospective biomarker analysis of baseline plasma samples for HER2 positive advanced oesophago-gastric cancer patients registered within Arm B1 of the Phase 2 open label, multicentre, randomised PLATFORM trial (NCT02678182). All HER2 positive patients assessable for clinical response and miR signatures were included. Copies of miR-148a-3p and miR-16 per ml of plasma were quantified using Digital Droplet Polymerase Chain Reaction (ddPCR). OS as primary endpoint for miR-148a-3p LOW (≤median) versus HIGH (>median) was analysed using Kaplan-Meier curves and Cox model regression. Secondary endpoints were PFS and PFR. OS and PFS are from start of 1st line therapy; PFR are from start of maintenance trastuzumab. Sensitivity analysis normalised miR-148a-3p to miR-16. Results: Of 63 patients with analysable lab samples and available survival data, normalisation was possible for 41 patients. Median follow-up was 38 months. There was no statistically significant relationship between OS and miR-148-3p copies/μl of ddPCR reaction LOW versus HIGH (n= 62, Hazard Ratio (HR) 0.98, p=0.933), PFS (n=62, HR 1.08, p=0.759) or PFR (n=31, Odds Radio (OR) 0.67, p=0.577). Normalised miR-148a-3p (NmiR-148a-3p) LOW versus HIGH demonstrated a statistically significant difference in PFR at 3 months (n=23, OR=0.11, p=0.027) but no difference in OS or PFS. A model adjusting for primary tumour site, metastatic disease and number of sites demonstrated a statistically significant difference in PFR at 3 months (aOR=0.03, p=0.029). Conclusions: Patients with HIGH NmiR-148-3p have 0.03 times the odds of being progression-free at 3 months than patients with LOW NmiR-148a-3p in this population, when adjusted for key factors. Limitations include small sample size and normalisation. Clinical trial information: NCT02678182 . [Table: see text]
Sex differences in the clinicopathological and molecular biological features of gastric cancer.
Authors: Terashima Masanori , Yagi Taisuke , Hatakeyama Keiichi , Furukawa Kenichiro , Fujiya Keiichi , Tanizawa Yutaka , Bando Etsuro , Yamaguchi Ken 
Published: January 2023

421 Background: The prevalence of gastric cancer is higher in males than in females. Reports have revealed that female gastric cancer patients exhibit some distinctive features, such as a high proportion of undifferentiated cancer and poor survival outcomes. The therapeutic effects of anti-PD-1 antibody have also been reported to be different between males and females. However, precise differences in molecular profiling features between males and females are yet to be reported. To elucidate sex differences in the clinicopathological and molecular biological characteristics of gastric cancer, we performed whole-exon sequencing and comprehensive gene expression analysis. Methods: We compared the clinicopathological factors and disease-specific survival (DSS) in 499 patients who underwent gastrectomy for gastric cancer between January 2014 and April 2019, excluding those with special types of gastric cancer and R2 resection. We also performed whole-exome sequencing using peripheral blood and tumor tissue, gene panel testing, and transcriptome analysis of tumor and nontumor tissues. Results: Among the 499 patients, 358 were male and 141 were female. Women had significantly more undifferentiated and M-region cancers (P < 0.05 for both). In terms of gene mutations, TP53 mutations were significantly more common in males (P = 0.002), whereas CDH1 (P = 0.005), PIK3CA (P = 0.046), and ERBB3 (P = 0.021) mutations were significantly more common in females. Expression profiles reflecting the tumor microenvironment were classified into two groups: T cell high group (290 patients) and T cell low group (209 patients), via cluster analysis. Men in the T-cell high group had significantly better DSS than those in the T-cell low group (P = 0.005), whereas no significant difference was observed among women in the T-cell high and low groups (P = 0.402). Among the 136 genes significantly upregulated in the T-cell high group, CCL18 (P = 0.048) gene was significantly upregulated in males and CD8A (P = 0.026) gene was upregulated in females. Conclusions: TP53 mutations were more common in male patients with gastric cancer, whereas CDH1, PIK3CA, and ERBB3 mutations were more common in female patients with gastric cancer. Additionally, women did not demonstrate good survival outcomes even in the T-cell high group considered to have enhanced tumor immunity.
Multidimensional characterization of early-stage gastric cancer: Preliminary results of MIMETIC trial.
Authors: Catanese Silvia , Catozzi Carlotta , Macandog Angeli Dominique , Fazio Nicola , Fumagalli Uberto , De Roberto Giuseppe , De Pascale Stefano , Funicelli Luigi , Sabbatini Annarita , Gnagnarella Patrizia , Nezi Luigi , Gervaso Lorenzo , Cella Chiara Alessandra 
Published: January 2023

422 Background: Gastric adenocarcinoma (GA) represents a leading cause of cancer death worldwide. For localized and locally advanced (LA) GA, accounting for 30% of new diagnoses, surgery, with or without peri-operative chemotherapy (CTX), remains the cornerstone of treatment. Nevertheless, the cure rate remains unsatisfactory. Genomic biomarkers have been tested to tailor anticancer treatments, but no one is able to guide the treatment choice in GA. Gut microbiota represents an emerging area of investigation in cancer, as a key modulator of host immune response. However, its role in GA on treatment tolerability and outcome is not unraveled. Additionally, radiomics, which can perform massive data mining to increase diagnostic power, and extensive dietary assessment are fast-growing tools. Our aim is to set an innovative approach to mapping the interaction among nutrition, microbiome, genomics, and radiomics and correlate them with clinical outcomes. Methods: We are conducting a prospective observational trial in GA patients (pts), candidates to receive peri-operative CTX or upfront surgery. For each patient, we longitudinally collect blood, fecal and salivary samples, alongside clinical and nutritional information. Additionally, past dietary consumption is measured using the food frequency questionnaire. At baseline, CT scan for staging, radiomic analysis, upper digestive endoscopy with biopsy, and molecular biomarkers are performed. Additional samples are taken from tumor and surrounding normal mucosa (1 to 3 cm) for microbiome analysis. Genomic DNA from stool, buccal and gastric tissue samples will be extracted and subjected to 16S metagenomic sequencing. Taxonomic and functional features within and between anatomical compartments will be correlated with clinical and radiomic data. Results: Here, we are presenting preliminary data of fecal samples from 35 GA pts in comparison with a cohort of healthy subjects (HCs) collected at our Institution. Pts’ characteristics are outlined here. We observed that the structure of the gut microbiota of GA pts is distinct from HCs in terms of beta diversity, and this difference is maintained after CTX. In particular, GA’s microbiota was enriched in S. anginosus, among other taxa. Conclusions: Our preliminary data support the feasibility of the study. The differences in structure and composition of the gut microbiota of GA pts compared to HCs confirm previous reports while providing the rationale for developing gut microbiota profiling into a non-invasive biomarker, to implement early diagnosis and prevention. The study is ongoing and actively recruiting.[Table: see text]
Development of a novel chimeric oncolytic viral platform, CF33 and its derivatives, for peritoneal-directed CF33-OV treatment of gastric cancer peritoneal carcinomatosis.
Authors: Yang Annie , Zhang Zhifang , Chaurasiya Shyambabu , Park Anthony K , Jung Audrey , Lu Jianming , Kim Sang-In , Priceman Saul , Fong Yuman , Woo Yanghee 
Published: January 2023

428 Background: Peritoneal carcinomatosis (PC) is a deadly end-stage manifestation of gastric cancer (GC). CF33, a chimeric oncolytic virus, and its genetically modified derivatives have shown exclusive cancer selectivity and oncolytic potency against various solid tumors. Intravenous and intratumoral CF33-hNIS and CF33-hNIS-antiPDL1 have entered phase I trials to treat triple-negative breast cancer and unresectable solid tumors. Here, we investigated the antitumor activities of CF33-OVs against GCPC. Methods: We infected six GC cell lines, including both intestinal-type (AGS and MKN-74) and diffuse-type (KATO III, MKN-45, SNU-1, and SNU-16) with CF33, CF33-GFP, or CF33-hNIS-antiPDL1 at various multiplicities (MOI 0.01, 0.1, 1.0 and 10.0) to examine viral proliferation and cytotoxicity by using standard plaque assay and cell proliferation assay. We performed immunofluorescence imaging and flow cytometric analysis to verify virus-encoded gene expression and blockade of PD-L1 binding by virus-encoded anti-PD-L1 scFv. A mouse model of peritoneal dissemination xenograft of SNU-16-ffluc cells was set up to evaluate the antitumor activity of intraperitoneal (IP) CF33-hNIS-antiPDL1 treatment (3x105 pfu x 3 doses). Results: CF33-OVs showed dose-dependent infection, replication, and killing of human GC cell lines. Immunofluorescence imaging showed virus-encoded GFP, hNIS, and anti-PD-L1 scFv expression in CF33-OV-infected GC cells. GC cell surface PD-L1 binding was blocked by virus-encoded anti-PD-L1 scFv. In the xenograft model, IP CF33-hNIS-antiPDL1 treatment significantly reduced peritoneal tumors (p<0.0001), decreased amount of ascites (62.5% PBS vs. 25% CF33-hNIS-antiPLD1), and prolonged animal survival (p<0.01). Conclusions: CF33-OVs demonstrate effective antitumor activity and can deliver functional proteins in vitro and in vivo. CF33-hNIS-antiPDL1 treatment induced sustained regression of GCPC and prolonged survival. These promising preclinical results support peritoneal-directed strategies with CF33-hNIS-antiPDL1 in GCPC patients.
Intertumor heterogeneity of locally advanced gastric cancer.
Authors: Belyak Natalia P. , Kutukova Svetlana , Orlova Rashida , Kaledina Ekaterina , Androsova Alexandra , Zhukova Natalia V. 
Published: January 2023

435 Background: The aim of the present study was to determine to the effect of HER2, dMMR, PD-L1 status in the primary tumor and in metastasis to the regional lymph node of GC patients. Methods: A total of 44 patients with primary loco-regional (N+) gastric adenocarcinoma were recruited, and two formalin-fixed paraffin-embedded (FFPE) tumor-containing blocks of each patient (one block with primary tumor and one block with metastasis to the regional lymph node)were selected for HER2, dMMR, PD-L1 (CPS) immunohistochemical (IHC) assay. Clinicopathological characteristics were recorded, and intertumoral heterogeneity of HER2, dMMR, PD-L1 IHC expression was determined. Results: The study included 19 women and 25 men, 30 patients had Laurén’s intestinal type of cancer, 14 had a Laurén’s diffuse type. In 5 patients (11.4%) overexpression of Her-2 neu was detected, and heterogeneity was detected in all five cases: in three patients with HER2 overexpression in the primary tumor, no overexpression was detected in the metastasis to the regional lymph node, in two cases overexpression was detected in the metastasis, while no overexpression was observed in the primary tumor. 2 patients showed signs of dMMR (4.5%), in one case, heterogeneity in dMMR status was also revealed: signs of dMMR in the primary tumor and its absence in regional metastasis (pMMR). Assessment of PD-L1 status was carried out using the CPS formula. Ten patients (22.7%) had a negative PD-L1 status (CPS=0) both in the primary tumor and in regional metastasis. Positive PD-L1 status in the primary tumor: in 24 patients CPS= 0-5 (54.5%), in 5 patients CPS= 5-10 (11.4%) and 5 patients CPS= 10 or more (11.4% ). Positive PD-L1 status in regional lymph node metastasis: in 24 patients CPS= 0-5 (54.5%), in 5 patients CPS= 5-10 (11.4%) and in 5 patients CPS= 10 or more ( 11.4%). In 5 cases (11.4%) marked heterogeneity in PD-L1 status between the primary tumor and its regional metastasis (1 case with dMMR heterogeneity). Conclusions: The research findings in this paper indicate that the intertumoral heterogeneity of HER2 overexpression is common in GC patients, We highly recommend multi-block HER2 assessment for accurate diagnosis of GC. Given the rarity of status detection dMMR, a study in a larger number of patients is required, however, our data also confirm the presence of heterogeneity in dMMR status, and probably the possibility of metastasis of a more aggressive pMMR clone. Heterogeneity in PD-L1 status is quite rare and amounted to only 11.4%, which also has important practical significance.
Clinicopathological features of HER2-low expressed advanced gastric cancers.
Authors: Nakayama Izuma , Takahari Daisuke , Chin Keisho , Wakatsuki Takeru , Ooki Akira , Ogura Mariko , Fukuda Koshiro , Osumi Hiroki , Fukuoka Shota , Shinozaki Eiji , Yamaguchi Kensei 
Published: January 2023

459 Background: The DESTINY-Breast04 data demonstrated the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) was also effective for metastatic breast patients (pts) with HER2-low expression. Now that the HER2-low expressed cancer is categorized as an independent subset in breast cancer patients. It is unknown whether patients with the HER2-low expression are distinguishable from the HER2 negative or positive and are potential candidates for the anti-HER2 therapy in advanced gastric cancer (AGC) patients. Methods: We retrospectively reviewed the medical records of AGC pts who received standard chemotherapy with platinum containing regimens as the first-line treatment between Jan, 2011 and Dec, 2018 at the Cancer Institute Hospital of the JFCR. AGC pts were classified according to the HER2 status using immunohistochemistry (IHC) and in situ hybridization (ISH) as follows; HER2 negative (IHC 0), HER2-low (IHC 1+ or 2+/ISH-) and HER2 positive (IHC2+/ISH+ or 3+). This study was conducted to investigate the clinicopathological features and prognosis of HER2-low AGC pts compared with HER2 negative and positive. Results: A total of 734 AGC pts were received HER2 testing and classified into three groups according to HER2 status (HER2 negative; n=410, HER2-low; n=154, HER2 positive; n=170). The proportion of male (negative; 61.5%, low; 63.6% and positive; 69.4%), intestinal histology (negative; 21.0%, low; 44.2% and positive; 59.8%), liver metastases (negative; 18.3%, low; 24.8% and positive; 46.5%), higher serum CEA level (>ULN) (negative; 32.2%, low; 41.6% and positive; 56.5%) and higher serum CA19-9 level (>ULN) (negative; 34.1%, low; 36.7% and positive; 56.5%) were gradually increased along with HER2 expression level. The proportion of peritoneum metastasis (negative; 56.3%, low; 44.8% and positive; 21.8%) was decreased along with the HER2 expression level. One hundred and fifty-two pts (89.4%) received combination chemotherapy with trastuzumab in the first-line treatment. Sixteen pts received trastuzumab in the HER2-low (n=3) and HER2 negative (n=13) in the clinical trial. The median survival time (MST) of pts with HER-low was the same with that of HER2 negative (15.7ms). The statistically significant difference was observed in OS between the HER2-low and HER2 positive (HR 1.43 95% CI: 1.12-1.83, P=0.003). Conclusions: AGC Pts with HER2-low have intermediate clinicopathological features between HER2 negative and positive. A Novel effective anti-HER2 therapy for the HER2-low expressed tumor would be warranted in AGC treatment.
Prognostic value of mismatch repair deficiency in patients receiving first-line fluoropyrimidine plus platinum chemotherapy for metastatic, recurrent, or locally advanced unresectable gastric cancer.
Authors: Oh Chung Ryul , Kim Eo Jin , Chae Heejung , Park Young Soo , Ryu Min-Hee , Kim Hyung-Don , Kang Yoon-Koo 
Published: January 2023

461 Background: In localized gastric cancer (GC), deficient mismatch repair (dMMR) tumors reportedly have a favorable prognosis. However, a potentially detrimental effect of the dMMR status was suggested in patients treated with adjuvant chemotherapy. It remains unclear whether the mismatch repair (MMR) status can impact clinical outcomes in patients with metastatic GC (mGC) receiving palliative chemotherapy. We examined the impact of the MMR status on survival outcomes of patients with HER2-negative mGC receiving first-line fluoropyrimidine plus platinum (FP) chemotherapy. Methods: We reviewed patients with histologically confirmed metastatic, recurrent, or locally advanced unresectable adenocarcinoma of the stomach or gastroesophageal junction receiving first-line FP chemotherapy between January 2015 and August 2018 at Asan Medical Center, Korea. MMR status was correlated with clinical characteristics and survival outcomes for patients with available MMR immunohistochemistry results. Results: Of 895 patients, we analyzed 543 with available MMR protein expression results, and dMMR was detected in 4.4% (n=24). Patients with dMMR exhibited a significantly higher median age than those with proficient MMR (pMMR) (64 vs. 58 years, p=0.044). No signet ring cell carcinoma (SRCC) was detected among dMMR tumors, whereas SRCC was found in 17.5% of pMMR tumors. Based on our prognostic model (Koo DH et al, 2011), only 4.2% of patients with dMMR were classified as the poor-risk group (vs. 16.8% of patients with pMMR, p=0.097). No significant difference in progression-free survival (PFS) was noted between patients with dMMR and pMMR tumors (median, 5.6 vs. 5.8 months, p=0.266). Patients with dMMR tumors tended to have better overall survival than those with pMMR tumors; this difference was not statistically significant (median, 17.9 vs. 12.2 months, p=0.183). In the good-risk subgroup, patients with dMMR tumors had a significantly worse PFS than those with pMMR tumors (median, 5.6 vs. 9.2 months, p=0.009); multivariate analysis revealed that MMR status was an independent factor for poor PFS in this subgroup. Conclusions: Survival outcomes of dMMR mGC did not differ from pMMR in patients who received first-line FP chemotherapy. However, in the good-risk subgroup, patients with dMMR tumors had a significantly shorter PFS than those with pMMR, suggesting a potentially reduced efficacy of cytotoxic chemotherapy in these patients.