bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tislelizumab combined with POFI (irinotecan, paclitaxel, oxaliplatin and 5-FU/levoleucovorin) as first-line treatment of advanced gastric/gastroesophageal junction adenocarcinoma (AGC): Preliminary results of a single-arm, open-label phase I/II trial (SYLT-023).
Authors: Lin Rongbo , Zaisheng Ye , Changhua Zhuo , Wei Shenghong - , Li Zhixiong , Zhao Shen , Su Liyu 
Published: January 2024

331 Background: Tislelizumab is a humanised IgG4 monoclonal antibody with high affinity and binding specificity for PD-1. Combined with fluoropyrimidine + platinum (XELOX or FP), it is approved in China as first-line treatment of advanced gastric cancer (AGC). Both irinotecan and paclitaxel have also shown antitumor activity in advanced gastric/gastroesophageal junction adenocarcinoma. In this phase I/II study, we explore the safety, tolerability, and efficacy of tislelizumab + irinotecan, paclitaxel, oxaliplatin and 5-FU (POFI) as first-line treatment of HER-2 negative, pMMR AGC. Methods: In a phase I dose finding study using a standard 3+3 design, subjects received four escalating dose levels (dl) of irinotecan/paclitaxel (mg/m2): 135/45 (dl #1), 150/45 (dl #2), 135/67.5 (dl #3), and 135/90 (dl #4) in combination with tislelizumab 200 mg plus oxaliplatin 85 mg/m2, levoleucovorin 200 mg/m2, and 5-FU 2400 mg/m2 for 46 hours every 2 weeks. Primary endpoints were safety, tolerability, and recommended phase 2 dose (RP2D). Results: Fifteen subjects with treatment naïve AGC were enrolled (3 each in dl #1, dl #2, and dl #3 and 6 in dl #4). The median age was 65 years (range 36-72); 80% were male. Two subjects (13.3%) were diagnosed with gastroesophageal junction cancer, 9 (60%) had poorly differentiated disease, and 5 (33.3%) had liver metastasis. PD-L1 CPS scores were: 5 (n=5); 1 (n=1); and 0 (n=9). All subjects were evaluated for dose-limiting toxicity (DLT). One DLT (grade 4 neutropenia) occurred within 28 days in dl #4. No maximum tolerated dose was reached; the RP2D was dl #4. All subjects had ≥1 treatment-related adverse event (TRAE) and 10 (66.7%) had ≥1 grade 3-4 TRAE per NCI CTC-AE 5.0. The most frequent grade 3-4 TRAEs were neutropenia (n=8; 53.3%), anemia (n=2; 13.3%), and increased glutamyl transpeptidase (n=2 pts; 13.3%). Confirmed objective response rate in 13 subjects with measurable disease was 100% (1 complete response [CR], 12 partial responses [PR]) per RECIST 1.1. Of the 2 subjects with non-measurable disease, one was a CR and the other was non-CR/non-PD. Survival data are immature. Conclusions: Tislelizumab+POFI was well tolerated and showed preliminary antitumor activity. A phase II study at the RP2D is ongoing. Clinical trial information: NCT05319639 .
Impact of adding nivolumab to first-line chemotherapy in patients with advanced gastric cancer.
Authors: Utsumi Mai , Yukami Hiroki , Okemoto Dai , Kadono Toru , Yamaguchi Toshifumi , Goto Masahiro , Nishikawa Hiroki 
Published: January 2024

334 Background: Nivolumab plus chemotherapy (Nivo-Chemo) is the standard treatment for advanced gastric cancer based on the results of CheckMate 649 trial and ATTRACTION-4 trial. However, real-world data on the efficacy of Nivo-Chemo are limited. This study aimed to assess the efficacy of Nivo-Chemo in the clinical practice setting by comparing it to chemotherapy alone. Methods: We retrospectively reviewed the medical records of patients with advanced gastric cancer who received palliative chemotherapy in our hospital between 2017 and 2023. The inclusion criteria were as follows: age ≥ 20 years; histologically confirmed advanced unresectable or recurrent gastric/gastro-esophageal junction adenocarcinoma; HER2 negative or unknown; and no prior treatment. Patients were divided into two groups based on their first-line treatment: the Nivo-Chemo group and chemotherapy alone (Chemo) group. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were assessed. Results: Of 78 patients, 52 patients were in the Chemo group and 26 patients were in the Nivo-Chemo group. Median age were 69 years (range 30–83) and 67 years (range 39–76) in the Chemo group and Nivo-Chemo group. Eastern Cooperative Oncology Group performance status (ECOG PS) was 0/1/2 in 18/27/7 patients (35%/52%/13%) in the Chemo group and in 17/8/1 patients (65%/31%/4%) in the Nivo-Chemo group. Histological type (Intestinal type/diffuse type) was 19/33 (37%/63%) in the Chemo group and 8/18 (31%/69%) in the Nivo-Chemo group. Combined positive score (CPS) was assessed in 21 patients in the Nivo-Chemo group. The CPS <1/1-5/>5 was in 3/10/8 (12%/38%/31%). In the Chemo group, 28 patients (54%) received anti-PD-1 monotherapy after progression of first-line chemotherapy. The median PFS was 5.7 months in the Chemo group and 6.0 months in the Nivo-Chemo group (HR 0.88, 95% CI 0.50-1.55, p = 0.66). The median OS was 15.0 months in the Chemo group and 18.6 months in the Nivo-Chemo group (HR 0.76, 95% CI 0.37-1.53, p = 0.44). The ORR was 50% in the Chemo group and 54% in the Nivo-Chemo group, while the DCR was 63% and 69%, respectively. Conclusions: In clinical practice, the addition of nivolumab to chemotherapy tended to provide a survival benefit compared to chemotherapy alone.
Anlotinib combined with penpulimab and nab-paclitaxel as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): A single-arm, open-label phase II clinical trial.
Authors: Chang Zhiwei , Liu Xiao-Lei , Yu Dan-Dan , Han Hui-Qiong , He Jian , Wang Rui-Rui , Qin Yan-ru 
Published: January 2024

340 Background: Recently, PD-1 blockades combined with dual chemotherapy in first-line setting exhibited encouraging efficacy for patients with ESCC. However, the safety profile of conventional dual chemotherapy remained unsatisfactory. Therefore, PD-1 blockades combined with anti-angiogenic tyrosine kinase inhibitors (TKIs) and single chemotherapy regimen might be a promising strategy. Anlotinib, a novel multitarget TKI primarily targeting VEGFR1-3, demonstrated promising therapeutic activity as first-line combination therapy or second-line monotherapy for patients with ESCC in China clinically. Therefore, this study was designed to explore the efficacy and safety of anlotinib combined with penpulimab (PD-1 blockade) and nab-paclitaxel as first-line therapy in advanced ESCC. Methods: Patients with previously untreated metastatic or locally advanced ESCC were recruited and treated with anlotinib (12mg, po, d1~14, q3w) and penpulimab (200mg, iv, d1, q3w) plus nab-paclitaxel (220mg/m2, iv, d1, q3w) until disease progression or unacceptable toxicity. The tumor response was assessed according to RECIST 1.1 using CT scans every two cycles. Adverse events were recorded by severity in accordance with the NCI CTC AE Version 5.0. The predefined sample size was 30. Primary endpoint was PFS and secondary endpoints included safety, ORR, DCR and OS. Results: From Jul 2022 to Aug 2023, a total of 23 patients were enrolled, 19 patients who had received first tumor response were included in this analysis. The best overall response indicated that there were 14 PR (73.7%), 2 SD (10.5%) and 3 NE (15.8%). Therefore, the preliminary ORR was 73.7% (95%CI: 48.8%-90.9%), DCR was 84.2% (95%CI: 60.4%-96.6%). Median PFS of the 19 patients was not yet reached. Additionally, safety profile exhibited that the regimen was tolerable. The most common treatment-emergent adverse events among the 23 patients with the incidence >20% were leukopenia (30%) and anemia (30%). Common grade ≥3 treatment-emergent adverse events were leukopenia (9%), glutamic-pyruvic transaminase was elevated (4%), glutamic oxaloacetic transaminase increased (4%), hypertension (4%) and diarrhea (4%). Conclusions: The combination of anlotinib plus penpulimab and nab-paclitaxel as first-line therapy for advanced ESCC demonstrated promising efficacy and manageable safety profile. The conclusions needed to be confirmed in subsequent trials.
Advantages of robotic surgery for advanced gastric cancer in short-term outcomes: A single-center retrospective study using propensity score matching.
Authors: Komatsu Masaru , Yura Masahiro , Yoshida Mitsumasa , Habu Takumi , Nagata Hiromi , Kinoshita Takahiro 
Published: January 2024

343 Background: The advantages of robotic gastrectomy (RG) for gastric cancer are being demonstrated. However, there are few reports that have focused on advanced gastric cancer and examined the advantages of RG for laparoscopic gastrectomy (LG). We conducted the following study to clarify the advantages of RG for advanced gastric cancer. Methods: This single-center retrospective study reviewed the clinical data of 1531 patients who underwent either RG or LG from 2014 to 2023. 473 patients were with clinically diagnoses as having advanced gastric cancer. They were divided into the RG group (n = 143) and the LG group (n = 330). Propensity score matching was employed to adjust the background of the two groups, as covariates of age, gender, BMI, surgical method (distal gastrectomy/total gastrectomy), stage (early cancer/advanced cancer), and presence or absence of preoperative chemotherapy. Then, the treatment results were compared and examined. Results: 130 patients in each group were extracted by propensity score matching. There were no significant differences in age, gender, and ECOG-PS between the two groups. Compared to the LG group, the RG group had more cases with deeper invasion depth ≥T3 (93.1 vs 84.6%, P = 0.04), more D2 dissection (96.9 vs 88.5%, P = 0.01), and longer operative time (339.5 vs 294.5min, P <0.01). The number of retrieved lymph nodes was larger (49.5 vs. 44, P <0.01) in the RG group. Importantly, in the RG group, there were fewer complications with Clavien-Dindo (CD) classification ≥Grade II (11.5 vs 21.5%, P = 0.04) and CD classification ≥Grade III (0.8% vs 6.9%, P = 0.01). Postoperative hospital stay was shorter (8 vs 9 days, P = 0.01) in the RG group. Conclusions: RG for advanced gastric cancer has the potential to reduce complications compared to LG. Long-term survival outcomes should be investigated.
Use of novel cancer staging model to analyze healthcare costs of commercially insured patients with colorectal cancer.
Authors: Smith Rebecca , Cao Xiting , Cuyun Carter Gebra , Pope Andreyah , Fayyaz Ifrah , Ellenberg Phil , Miller-Wilson Lesley-Ann , Limburg Paul J. , Pyenson Bruce 
Published: January 2024

35 Background: Earlier colorectal cancer diagnosis can improve patient outcomes, but the payer cost impact of earlier stage at cancer diagnosis is not well understood because stage information is not directly available in administrative claims data. This data gap impairs researchers’ ability to fully evaluate the financial impact of earlier neoplasia detection resulting from colorectal cancer screening. In prior work, we used SEER-Medicare data to develop machine learning algorithms to assign AJCC stages to colon (CC) and rectal (RC) cancer patients using treatment flags derived from claims data. These algorithms were 83% (CC) and 69% (RC) accurate at assigning incident cancer patients to their SEER-recorded AJCC stage. This new work applied those validated algorithms to commercial claims data to study the healthcare costs by stage of patients identified with incident CC or RC. Methods: Newly diagnosed CC and RC patients were identified in Milliman’s 2019-2020 Consolidated Health Cost Guidelines Sources Data for commercially insured patients. Patients were assigned a cancer stage using a claims-based predictive multinomial logistic regression model (R Statistical Software - v4.1.2 R Core Team 2021; nnet package - Venables and Ripley 2002). Allowed medical and pharmacy costs were summarized by month, starting from each patient’s initial claim with a cancer diagnosis through the end of the patient’s enrollment or through September 2022. Patients with each cancer type were then grouped by stage, and mean cumulative costs at 12-, 24-, and 36-months were calculated. Results: CC patients with stage 4 disease incur costs over 4x greater than those with stages 2B or lower and 1.7x greater than patients with stages 2B/3 during the first year after diagnosis. Cost differentials by stage are smaller among patients with RC. RC patients with stage 4 disease incur costs 2.2x greater than those with stages 2B or lower and 1.3x greater than patients with stages 2B/3 over the first year after diagnosis. For both CC and RC, substantial differences in cost persist over a 3-year period post-diagnosis. Conclusions: We applied a novel cancer staging model to commercial claims to estimate patients’ healthcare costs by stage at diagnosis. CC and RC patients’ costs increase substantially as their stages at diagnosis increase. In addition to improving patient outcomes, diagnosis of CC and RC at earlier stages among commercial patients could reduce treatment costs. [Table: see text]
Updated pooled analyses of first-line anti-PD1/PD-L1 inhibitors plus chemotherapy in advanced esophageal squamous cell carcinoma.
Authors: Vilbert Maysa , Priantti Jonathan N , Madeira Thiago , Moraes Francisco Cezar A , Tojjari Alireza , Sahin Ibrahim Halil , Cavalcante Ludimila , Saeed Anwaar 
Published: January 2024

366 Background: Advanced and metastatic esophageal squamous cell carcinoma (ESCC) patients have limited treatment options and poor prognosis. Recently, several studies demonstrated the clinical benefit of combining immune checkpoint inhibitors (ICI) and chemotherapy (CT), leading to its approval in the first-line setting. Since then, efforts have been made to identify the patients who may benefit the most or not from the combination of ICI plus CT. Methods: We searched PubMed, Scopus, and the Cochrane Library for randomized clinical trials investigating first-line ICI plus chemotherapy (CT) for advanced or metastatic ESCC patients. Outcomes of interest included: overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and OS according to gender, PD-L1 expression (<1% / ≥1%), and PD-L1 CPS (<10 / ≥10). We used I2 statistics to assess heterogeneity, and the fixed-effect model was used to pool studies. Results: Eight studies were included with 4,702 patients. Of them, most had an ECOG 0 or 1, and were younger than 65 years (62%), male (77%), and Asian (78%). Metastatic disease was diagnosed in 75% of patients. ICI plus CT was administered to 58%, and 43% received CT +/- placebo. Median follow-up ranged from 7.1 to 22.6 months. ICI plus CT significantly improved all efficacy outcomes compared to CT alone: decreasing the risk of death by 32% (HR for OS: 0.68; 95%CI 0.63-0.74; p<0.00001); reducing the risk of progression or death by 38% (HR for PFS: 0.62; 95%CI 0.58-0.67; p<0.00001); and increasing the objective response rate (risk difference: 0.17; 95%CI 0.14-0.20; p<0.00001). A survival benefit was seen across all subgroup analyses, but it was significantly higher in patients with PD-L1 ≥1% compared to those with PD-L1 <1% (reduction in the risk of death of 38% versus 23% respectively, p=0.03). OS was not significantly different between males versus females, or PD-L1 CPS≥10 versus CPS<10. Conclusions: Our large systematic review and meta-analysis support the efficacy and survival benefit of ICI plus CT as first-line therapy for all ESCC patients, regardless of gender or PD-L1 expression.
The implication of failure patterns after neoadjuvant chemoradiotherapy with small involved-field in esophageal squamous cell carcinoma.
Authors: Shin Hyunju , Oh Dongryul , Noh Jae Myoung , Yang Kyungmi 
Published: January 2024

376 Background: In this study, we aimed to analyze failure patterns, the clinical and biological prognostic factors for treatment outcomes, and evaluate the feasibility of involved-field irradiation (IFI) in patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (CCRT). Methods: We retrospectively reviewed the medical records of 511 patients diagnosed with ESCC and underwent neoadjuvant CCRT and radical esophagectomy between January 2016 and February 2022 at Samsung Medical Center. For IFI, the clinical target volume (CTV) was defined as the primary gross tumor volume (GTV) plus a 2.0-3.0 cm longitudinal margin and a 0.5-1.0 cm circumferential margin, as well as the GTV of lymph nodes (LN) plus a 0.5-1.0 cm margin. For elective nodal irradiation (ENI), the CTV encompassed supraclavicular, mediastinal, or abdominal LN regions based on the primary tumor location. IFI was applied in most cases (98%). The failure patterns, loco-regional control (LRC), and survival outcome were analyzed. Regional lymph nodes (LNs) were defined and classified according to the AJCC 8th edition. Non-regional LNs were defined as metastatic LNs in neck, thorax, abdominal area except regional LNs. Results: With a median follow-up of 44.4 months, 213 (41.7%) patients experienced recurrence. The first recurrent sites were locoregional (LR) in 98 patients (19.2%), non-regional LN in 81 (15.9%), and distant organs in 152 (29.7%). Among the 98 patients with LR recurrence, RT in-field failure occurred in 53 (10.4%) patients, in & out-field failure in 18 (3.5%), and out-field failure in 27 (5.3%). In 27 cases of out-field failure only, LR recurrent lesion could be included in the target volume in 7 (1.4%) cases if ENIs were applied. Among the 27 patients, 10 received salvage treatment and 2 did not experience further recurrence. The analysis for the detailed LN recurrence showed that the upper mediastinal and supraclavicular LNs were the most frequent area, regardless of the primary tumor location and other clinical factors. Among 213 recurrent cases, 54 (10.5%) recurred in upper paratracheal LN and 40 (7.8%) in supraclavicular LN. The 5-year LRC rates, disease-control rates, and overall survival (OS) rates were 77.5%, 53%, and 54.3%, respectively. Multivariate analysis revealed that gender, age, cStage, ypStage, and resection margin status were independent prognostic factors for OS. Conclusions: Neoadjuvant CCRT using IFI with a small margin showed favorable treatment outcomes and out-field recurrence that the traditional ENI field could cover accounted for a small portion; thus, it might be feasible in the neoadjuvant setting. However, we need to consider that the upper mediastinal and supraclavicular areas were the most frequent recurrence sites.
PD1 and CD39 expression on tumor infiltrating lymphocytes in patients with gastric cancer.
Authors: Okayama Takafumi , Tsukamoto Nobuo , Suzuki Toshihiro , Mochizuki Kiyotaka , Sano Junichi , Nagata Hiromi , Terajima Daiki , Habu Takumi , Yoshida Mitsumasa , Sato Kazuma , Fujiwara Naoto , Yura Masahiro , Fujita Takeo , Shimomura Manami , Oonuki Kazunobu , Fukuda Kyoko , Uemura Yasushi , Nakatsura Tetsuya , Kinoshita Takahiro 
Published: January 2024

377 Background: Activation and clonal expansion of tumor antigen-specific T cells in cancer patients are crucial for immunotherapies. Recent reports indicate that CD39 is a marker to distinguish tumor-reactive CD8 T cell populations from bystander populations. In gastric cancer (GC), anti-CD39 antibody, anti-PD-1 antibody, and FOLFOX combination therapy may be effective therapy at AACR 2022. Methods: We retrospectively reviewed the data of 62 GC patients who underwent gastrectomy at our hospital (2017 - 2018) and examined their rejected specimen’s immune-microenvironment using immunohistochemistry. Then we prospectively enrolled 16 GC patients. Their tumor tissue and tumor-infiltrating lymphocytes (TILs) were extracted from surgical specimens, these fractions were subjected to the RNA-seq analysis ( n = 3), CD107a degranulation assay ( n = 7) and 3H-Thymidine incorporation assay ( n = 7). Results: The densities of CD39+CD8 TILs positively correlated with the densities of CD4 T cells and B-cells in GC tissues ( P = 0.01, < 0.01, respectively). Furthermore, higher densities of CD39+CD8 TILs in GC patients were associated with better overall survival ( P < 0.01). We classified TILs into four groups based on expression levels of the PD-1 and CD39. The proportion of CD39+CD8 T cells was significantly higher in GC tissues than their PBMCs ( n = 13) and non-cancerous tissues ( n = 4). CD39+PD-1+CD8 (DP) TILs in primary tumors were elevated expression of multiple inhibitory receptors such as LAG3, TIGIT and reduced expression of IL-2 by RNA-seq analysis. T cells expanded in vitro from DP-TILs ( n = 5) efficiently recognized autologous tumor cells in CD107a assay compared with other populations, and considered to be tumor-reactive T cells fraction. However, since these DP TILs in primary tumors show exhausted phenotypes, capacities to kill tumor are expected to be reduced in the tumor-microenvironment (TME). By adding ATP to the DP-TILs in vitro at the concentration reported in the TME, we observed reduction of cell proliferation by 3H-thymidene incorporation assay and of degranulation by CD107a assay, and we observed recovery of these changes by adding anti-CD39 inhibitory antibody. Conclusions: DP-TILs may have superior T cell receptors recognizing tumor-antigens and contribute to tumor eradication, especially when administrated anti-CD39 antibody.
Dysbiosis in gastric mucosal microbiota associated with gastric carcinogenesis.
Authors: Kim Byung-Wook , Choe Younghee , Kim Joon Sung , Na Soo-Young 
Published: January 2024

381 Background: Gastric microbiota, including H. pylori, may play a role in the development of gastric cancer. This study aimed to investigate the gastric microbiota throughout the stages of gastric carcinogenesis, encompassing atrophic gastritis, gastric dysplasia, and gastric adenocarcinoma. Methods: From December 2021 to August 2023, we collected gastric mucosal tissue samples from patients with atrophic gastritis, gastric dysplasia, and early gastric cancer. Subsequently, we conducted 16S rRNA gene profiling through next-generation sequencing. We compared alpha-diversity and beta-diversity within each group and analyzed the taxonomic composition. Results: This study included a total of 98 patients, comprising 16 with atrophic gastritis, 23 with low-grade dysplasia, 15 with high-grade dysplasia, and 44 with early gastric cancer. The H. pylori infection status was comparable across all groups. While there was a difference in alpha diversity between tumor lesions and normal stomach lesions, it did not reach statistical significance. Notably, Phyllobacterium was dominant in early gastric cancer, Prevotella in high-grade dysplasia, and Kocura in low-grade dysplasia. Furthermore, within the early gastric cancer group, Bacillus was widely distributed in cases of undifferentiated type adenocarcinoma. Conclusions: The analysis of microbiota collected from Korean stomach tissue revealed distinct microbial distributions across the various stages of gastric carcinogenesis.