bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world treatment patterns, testing patterns, and clinical outcomes of first-line (1L) therapy for metastatic gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma (mGC/GEJC/EAC).
Authors: Kakehi Sumie , Betts Keith A. , Nie Xiaoyu , Kitchen Sophie A. , Ray Saurabh 
Published: January 2024

275 Background: GC/GEJC/EAC are among the leading causes of cancer-related morbidity and mortality worldwide. Nivolumab + fluoropyrimidine- + platinum-containing chemotherapy (NIVO+chemo) has demonstrated superior efficacy in patients with advanced non-HER2-positive (HER2-) GC/GEJC/EAC versus chemo alone in the CheckMate 649 trial. The objective of this study was to characterize real-world treatment and PD-L1 testing patterns in the 1L setting for mGC/GEJC/EAC since the FDA approval of NIVO+chemo on April 16, 2021. Methods: This retrospective observational study used the electronic medical record data from the ConcertAI Patient360 database. Adult patients with HER2- mGC/GEJC/EAC and 1L initiation date (index date) between April 16, 2021 and October 31, 2022 were included. PD-L1 testing patterns and 1L regimens were described overall and stratified by PD-L1 testing. The analyses of clinical outcomes are currently ongoing. Results: A total of 161 patients with mGC/GEJC/EAC met the inclusion criteria. The median age at index was 67.0 years, 76.4% were male, and the median follow-up time from index date was 6.7 months. 81 (50.3%) patients had evidence of receiving at least one PD-L1 test (median [interquartile range] time from first test to 1L initiation: 0.4 [-0.1, 1.0] months) among whom 28 (34.6%) had the first test documented after 1L initiation. Overall, 1L immunotherapy-based regimens were received by 63 (39.1%) patients, with NIVO+chemo being the most common (n = 47; 29.2%). 1L fluoropyrimidine- + platinum-containing chemotherapy and other chemotherapies were received by 51 (31.7%) and 42 (26.1%) patients, respectively. Among patients with evidence of PD-L1 testing, 31 (38.3%) received NIVO+chemo, and 37 (45.7%) received chemotherapy alone. Among those without evidence of PD-L1 testing, 56 (70.0%) received chemotherapy alone, and 16 (20.0%) received NIVO+chemo. Conclusions: These preliminary findings show an early uptake of NIVO+chemo in the advanced or metastatic GC/GEJC/EAC patient population. With a majority of PD-L1 untested patients receiving chemotherapy only as 1L therapy, there is an opportunity for these patients to potentially benefit from immuno-oncology containing regimens. Further analyses are needed to characterize the chemotherapy only treated patient population.
Changes in circulating immune biomarkers following nivolumab with or without ipilimumab for metastatic anal cancer (NCI9673).
Authors: Morris Van K. , Ochieng Joshua , Ciombor Kristen Keon , Polite Blase N. , Mukherjee Sarbajit , Krauss John C. , Shields Anthony F. , Aranha Olivia , Hays John L. , Kazmi Syed Mohammad Ali , Weinberg Benjamin Adam , Benson Al B. , Lieu Christopher Hanyoung , Iqbal Syma , Hochster Howard S. , Xiao Lianchun , Haymaker Cara L. , Eng Cathy 
Published: January 2024

3 Background: Approximately 25% of patients (pts) with squamous cell carcinoma of the anal canal (SCCA) develop metastatic disease. The ETCTN-led NCI9673 phase II trial evaluated PFS of the anti-PD-1 antibody nivolumab (N) with or without the anti-CTLA-4 antibody ipilimumab (I) in metastatic SCCA. We analyzed serial blood samples from NCI9673 for immune biomarker profiling following N or N+I. Methods: PBMCs from 47 pts (24 N, 23 N+I) were collected at pretreatment (N=47), week 9 (N=26), and at progression (N=15). Immune cell populations - effector CD4 T cells, CD8 T cells, natural killer (NK) cells, and regulatory T cells - were analyzed by flow cytometry for immune inhibitory (PD-1, CTLA-4, TIM-3, LAG-3, TIGIT) and immune stimulatory (OX40, ICOS) expression. Mean expression (as percentage of cells with any expression) for each biomarker at a matched time point was compared between the N and N+I arms by a corrected student’s t test, with an alpha= .10 for significance. Changes in mean expression for each biomarker were compared by one-way ANOVA. Results: Mean TIGIT expression at baseline was highest on CD4 and CD8 T-cells relative to other immune checkpoint biomarkers (p< .0001 for all subsets; see Table). N+I was associated with higher TIGIT expression on CD4 cells at progression than for N alone (21.3% vs. 10.9%, p=.08). Among NK cells, TIGIT expression decreased at progression relative to baseline for N (14.1% vs. 5.9%, p=.06). Relative to non-responders, responders to N had OX40 expression that increased on CD4 T cells but decreased on NK cells at week 9 relative to baseline. Conclusions: In previously metastatic SCCA pts, TIGIT expression was greater on CD4 and CD8 T cells and was modulated on differing immune cell populations according to treatment arm. These data not only implicate T and NK cells in mediating treatment effect following single agent and/or combination immunotherapy, but also support the exploration of TIGIT as a potential novel target for treatment of metastatic SCCA.[Table: see text]
The overall safety and short-term efficacy of nivolumab plus ipilimumab for advanced esophageal squamous cell carcinoma.
Authors: Shiraishi Kazuhiro , Yamamoto Shun , Yoshinami Yuri , Ohara Akihiro , Itoyama Mai , Yokoyama Kazuki , Honma Yoshitaka , Kashiraha Tairo , Kurita Daisuke , Ishiyama Koshiro , Oguma Junya , Igaki Hiroshi , Daiko Hiroyuki , Kato Ken 
Published: January 2024

329 Background: Although nivolumab plus ipilimumab (Nivo+Ipi) is strongly recommended as 1st-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC), tumor proportion score (TPS) should be considered. Despite the efficacy, patients who received Nivo+Ipi often experienced serious immune related adverse events (irAEs). However, there are few data on safety and short-term efficacy of Nivo+Ipi in real world. Methods: We retrospectively collected data of pts who received Nivo+Ipi for advanced ESCC between May 2022 to July 2023 in the National Cancer Center Hospital. We evaluated adverse events by CTCAE v5.0 and multivariate analysis using a logistic regression model. estimated overall response rate (ORR) by RECIST v1.1 and progression-free survival (PFS). Results: Thirty pts were subjects in this study. The characteristics were as follows: median age (range): 63.5 (36-80) years, male/female: 24/6, metastatic/recurrent: 3/27, ECOG PS 0/1≤: 16/14, PD-L1 TPS 1%≤: 17, number of organs with metastases 1/2≤: 13/17, treatment-line 1st/2nd≤ 6/24 Median follow-up time was 5.0 months (mo) (reverse Kaplan-Meier, 95%CI; 3.0-8.3 mo). Any grade and grade 3≤ irAEs were observed in 12 (40.0%) and in 5 pts (17.9%), respectively. In grade 3≤ irAEs, AST/ALT elevation (n=2, 7.1%), adrenal insufficiency (n=1, 3.6%), pneumonitis (n=1, 3.6%), myositis (n=1, 3.6%), encephalopathy (n=1, 3.6%), stevens-Johnson syndrome (n=1, 3.6%) were reported. The pts who received systemic steroid therapy was 8 pts (28.6%). Two pts received high-dose steroid with methyl-prednisolone, 1 g/body for 3 days, four pts needed steroid therapy with prednisolone, 1-2 mg/kg and two pts added mycophenolate mofetil. No treatment-related deaths were reported. For the pts who received Nivo+Ipi as a first-line treatment (n=6), 3 pts (50%) achieved partial response and 2 pts (33.3%) had stable disease. 6-mo PFS rate of the 1st line pts was 63%. For the pts who received Nivo+Ipi in later-line, the ORR and the median PFS were 33.3% and 2.6 mo (95%CI; 1.4-3.9 mo), respectively. Fifteen pts received subsequent systemic therapy, which consisted of taxane (12 pts), fluoropyrimidine plus platinum (2 pts) and 1 pt continued Nivo+Ipi beyond progression. Conclusions: Our study may demonstrate a consistent incident of irAEs in pts who received Nivo+Ipi in the real world, compared to the results of the CheckMate 648. Despite of the short time of follow-up period, 1st-line treatment with Nivo+Ipi appeared to be more efficacious than Nivo+Ipi used as a later-line treatment.
Clinical significance of time interval between surgery and adjuvant chemotherapy in patients with gastric cancer after gastrectomy: A population-based cohort study using a nationwide claims database.
Authors: Maeng Chi Hoon , Kim Hoseob , Kim Mina 
Published: January 2024

333 Background: Adjuvant chemotherapy can reduce recurrence rates by eradicating microscopic metastases which may persist after curative resection. However, the optimal time interval (TI) between the surgery and chemotherapy remains controversial. Methods: The data were obtained from the NHIS of Korea. We included patients who underwent gastrectomy for gastric cancer between 2013 and 2018. To determine the optimal cut-off point of TI, a restricted cubic spline cox regression model was established, and categorized the population into three groups based on TI: the early group (≤ 20 days), the reference group (21-34 days), and the late group (≥ 35 days) with the reference interval group having the lowest mortality and recurrence. Propensity score matching was performed for each group. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Results: During the study period, 98,556 patients underwent surgery for gastric cancer. After excluding ineligible participants, 6,602 patients were included in the analysis. The median DFS and OS did not differ significantly between the early and reference groups ( p=0.7258 and p=0.6056, respectively). In comparison between the late and reference groups, the median DFS was significantly lower in the late group ( p=0.0079). 5-year DFS were 77.6% and 81.3% in the late and reference groups, respectively. Furthermore, the late group showed worse OS than the reference group ( p=0.0336). OS at 5-year were 82.1% and 85.0% in the late and reference groups, respectively. In the multivariable analysis, DFS in the late group retained inferiority (aHR 1.138, 95% CI: 1.003-1.292, p=0.045). OS showed a worse trend without significance compared to the reference group (aHR 1.138, 95% CI: 0.984-1.317, p=0.0805). Conclusions: Adjuvant chemotherapy after gastrectomy in patients with gastric cancer should be initiated within five weeks of surgery. A delay of more than five weeks may have a detrimental effect on the subsequent disease course.
Subgroup analyses of the effect of ramucirumab in pretreatment with immune checkpoint inhibitor in RINDBeRG: A randomized clinical trial in third- or further-line treatment of gastric cancer.
Authors: Kawabata Ryohei , Sakai Daisuke , Kadowaki Shigenori , Tsuduki Takao , Suzuki Takahisa , Masuzawa Toru , Shimozaki Keitaro , Tsuda Masahiro , Yamada Takeshi , Yamaguchi Toshifumi , Ueda Shugo , Kito Yosuke , Hirose Toshiharu , Kawase Tomono , Nomura Takashi , Nishikawa Kazuhiro , Kawakami Hisato , Shimokawa Toshio , Boku Narikazu , Satoh Taroh 
Published: January 2024

339 Background: To confirm synergistic effect of immune checkpoint blockade and anti-angiogenesis in cancer treatment, we evaluated the effect of pretreatment with immune checkpoint inhibitors to ramucirumab plus irinotecan versus irinotecan in the third or later line treatment beyond progression after ramucirumab for advanced gastric cancer from the RINDBeRG trial. Methods: Patients received ramucirumab at 8 mg/kg plus irinotecan at 150 mg/m2 or irinotecan alone. End points were compared between treatment arms and pretreatments with nivolumab (NIVO+, n = 226) or without nivolumab (NIVO-, n = 169). Results: The overall survival hazard ratio was 0.84 (95 % confidence interval, 0.64-1.12) in the NIVO+ population and 1.05 (95 % confidence interval, 0.76-1.44) in the NIVO- population. The progression-free survival hazard ratio was 0.67 (95 % confidence interval, 0.51-0.87) in the NIVO+ population and 0.83 (95 % confidence interval,0.61-1.12) in the NIVO- population. The objective response rate was higher for ramucirumab plus irinotecan in both populations (NIVO+ population, 17.5 % vs 28.8 %; NIVO- population, 10.9 % vs 14.5 %). Safety profiles of the ramucirumab plus irinotecan arm were similar between populations. Conclusions: Progression-free survival and objective response rate improvements were observed for ramucirumab plus irinotecan in both populations and these benefits were enhanced with prior nivolumab therapy. Clinical trial information: jRCTs051180187 .
Phase II study of GEN-001 in combination with avelumab in patients with PD-L1–positive locally advanced, or metastatic gastric cancer (GC) or gastroesophageal junction cancer (GEJC) who have progressed after second-line (2L) and beyond (GEN001-201 study).
Authors: Lee Jeeyun , Jung Minkyu , Lee Keun-Wook , Ryu Min-Hee , Kwon Minsuk , Park Kyung Mi , Yoon Young-Kwang , Kim Mincheol , Park Hansoo 
Published: January 2024

368 Background: The relationship between gut microbiota and the response to immune checkpoint inhibitors is likely due to cross-reactivity between microbial and tumor antigens, enhancing dendritic cell (DC) activation, antigen presentation, and inflammatory cytokine production. GEN-001 is a live biotherapeutic product (LBP) consisting of a lyophilized formulation of a strain of Lactococcus lactis. This study is designed to investigate the safety and efficacy of GEN-001 in combination with avelumab (the PD-L1 inhibitor) for patients with PD-L1 positive advanced GC/GEJC. Methods: This is an open-label, single arm, phase II clinical trial for PD-L1 positive (CPS ≥1) patients with unresectable, locally advanced, or metastatic GC/GEJC who have progressed after second-line and beyond. All patients were treated with GEN-001 (9x1011 CFU, administered as oral once daily) in combination with avelumab (800 mg, administered as an intravenous infusion every two weeks) until progressive disease, unacceptable toxicity, death, or withdrawal. Tumor response was assessed every 8 weeks for 6 months and every 12 weeks thereafter. The primary endpoint was objective response (OR); secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. Results: As of August 31, 2023, a total of 42 patients were enrolled. 37 patients have been assessed for response. The confirmed partial response (PR) and unconfirmed PR were achieved by 5 patients and 1 patient respectively, 8 patients have experienced as stable disease (SD). Median PFS and median OS were 1.73 months (95% confidence interval [CI]: 1.67-2.37 months) and 7.9 months (95% [CI]: 6.07-NE months). Treatment-related adverse events (TRAEs) of any grade occurred in 12 patients (28.6%) and Grade ≥3 TRAEs occurred in 2 patients (4.8%) out of 42 patients. Conclusions: Treatment of patients with GC/GEJC with GEN-001 in combination with avelumab in the ≥ 3L setting showed promising antitumor activities with an overall manageable safety profile. The results from this trial will be updated about its effects on clinical outcome, including survival, safety, and biomarker findings. Clinical trial information: NCT05419362 .
Detection of early-stage gastrointestinal cancers by micronuclei DNA from erythrocytes.
Authors: Sun Haobo , Yao Xingyun , Han Yuehua , Jiao Yurong , Kong Xiangxing , Liu Chengcheng , Guo Qingqu , Meng Fei , Liang Honghao , Fan Xiuqin , Li Jun , Gao Xiaofei 
Published: January 2024

382 Background: Gastrointestinal (GI) cancers account for over a third of cancer deaths. However, their early detection remains a challenge. Micronuclei (MN) are extranuclear bodies containing damaged chromosome segments indicative of genomic instability. Increased MN frequency in hematopoietic cells is observed in patients with solid tumors. We have developed a method (WO2021/228246 A1) for purifying and characterizing micronuclei DNA (mnDNA) in erythrocytes from peripheral blood. Here, we evaluated the potential of mnDNA for early-stage GI cancer detection, including colorectal (CC) and gastric (GC) cancers. Methods: Peripheral blood (1 ml) was collected from healthy donors (HD) and cancer patients mnDNA isolation and purification from erythrocytes. Participants were randomly divided into training, validation and independent test cohorts in a 7:2:1 ratio, maintaining similar cancer types, CC/GC/HD ratio, gender and age distribution. Distinct mnDNA features between cancer patients and HDs were identified using sequencing data. Logistic regression algorithms were applied using these features for cancer detection. Results: The study enrolled 1046 participants, including 419 HDs, 366 CC and 261 GC cases. Of these, over half were diagnosed with early-stage diseases; TNM stage I accounted for 38.7%, stage II for 22.8%, stage III for 30.5% and stage IV for 8.0%. The cancer detection model with mnDNA features yielded an overall accuracy of 84.8%, with a sensitivity of 84.1% and specificity of 85.7%. For individual caner types, sensitivity was 89.2% for CC and 76.9% for GC. For early-stage (stage I-II) CC and GC, the model demonstrated sensitivities of 88.9% and 76.5%, respectively, at 85.7% specificity. Conclusions: Unlike cell-free DNA, mnDNA are chromosomal fragments in the cytoplasm. The abundance of erythrocytes in peripheral blood provides an easily accessible source for mnDNA enrichment. This pilot study illustrates the potential of mnDNA as a tool for early GI cancer detection, contributing to large-scale efforts towards developing an effective GI cancer screening test.
Survival trends in gastric cancer in Brazil: Real-life data from a large cancer center.
Authors: Brito Angelo Borsarelli Carvalho , Mendonca e Silva Diego Rodrigues , Curado Maria Paula , Durant Lais Corsino , Taboada Rodrigo Gomes , Pelosof Adriane Graicer , Diniz Alessandro Landskron , Coimbra Felipe José Fernández , Felismino Tiago Cordeiro 
Published: January 2024

413 Background: Gastric cancer (GC) is the fourth leading cause of cancer deaths globally. There is a paucity of real-life data on GC in Brazil. Our study aimed to evaluate survival trends in gastric adenocarcinoma (GA) in a large cancer center in Brazil during 2000-2017. Methods: Based on our Hospital Cancer Registry Database, all individuals diagnosed with GA between 2000 and 2017, and treated at A.C. Camargo Cancer Center, were retrospectively included. The primary objectives were to describe the patient demographics, clinicopathological characteristics, treatment modalities, and survival trends during four separate periods of diagnosis (2000-2004; 2005-2009; 2010-2014; and 2015-2017). χ2 test was performed between two specified periods (2000-2004 and 2015-2017) to compare categorical variables. Overall survival (OS) curves were stratified by four separate periods and compared with log-rank tests. Results: The current analysis comprises a retrospective cohort of 1406 patients (552 female and 854 male individuals). Across all periods, most patients were men aged 50 to 69 and presented with Lauren’s intestinal subtype. There were significant differences between staging groups during the study. Specifically, between 2000-2004, stage IV varied from 43.6% to 32.8% in 2015-2017 (P<0.001). The most substantial variation in nonmetastatic cases occurred in stage II, comprising 9.4% of cases from 2000-2004 and rising to 24.8% in 2015-2017 (P<0.001). Concerning treatment modalities, we observed an increased utilization of a combined approach involving chemotherapy and surgery throughout the investigation. Specifically, from 2000-2004, only 12% of patients received a multimodal treatment regimen consisting of chemotherapy and surgery, whereas, between 2015-2017, this proportion increased to 36.3% (P<0.001). Also, patients receiving surgery + radiotherapy + chemotherapy varied from 12.4% of patients in 2000-2004 to 4.5% in 2015-2017 (P<0.001). When the entire cohort was analyzed, the predicted 5-year OS of patients with GA between 2000-2004 was 27.8%, which increased to 53.9% in the period from 2015-2017 (P<0.001). Among females, 5-year OS increased from 31.3% between 2000-2004 to 58.5% between 2015-2017 (P=0.001). Among males, 5-year OS increased from 25.2% to 51.0% in the same comparison (P<0.001). Conclusions: Our hospital-based data shows an upward trend in survival rates across patients with GA. We observed that 5-year OS almost doubled among men and women during the analyzed period. Recent improvements in staging methods and treatment have increased cure rates. Nevertheless, further investigation is essential to determine significant differences in OS between males and females.
Analysis of patients (pts) with unresectable hepatocellular carcinoma (uHCC) and Child–Pugh (CP)-B liver function treated with regorafenib in routine clinical practice in the observational REFINE study.
Authors: Kim Yoon Jun , Merle Philippe , Finn Richard S. , Kudo Masatoshi , Klümpen Heinz-Josef , Lim Ho Yeong , Pinter Matthias , Babajanyan Svetlana , Khan Javeed , Awan Maria , Özgürdal Kirhan , Qin Shukui 
Published: January 2024

452 Background: Pts with HCC and compromised liver function are typically excluded from clinical trials. The REFINE real-world study (NCT03289273) assessed a more varied pt population treated with regorafenib than the phase 3 RESORCE trial.1 Median overall survival (OS) in REFINE was 13.2 months and treatment-emergent adverse events (TEAEs) were consistent with RESORCE. We present a subgroup analysis of outcomes in pts from REFINE with CP-B liver function. Methods: REFINE is an international, prospective observational study of pts with uHCC for whom the decision to treat with regorafenib according to the local health authority approved label was made by their physician before enrollment. The primary endpoints were safety (Medical Dictionary for Regulatory Activities v25) and dose modifications due to drug-related TEAEs. Secondary endpoints included OS and duration of treatment (DoT). Results: Of 1005 evaluable pts, 123 (12%) were classified as CP-B at study entry, with most being CP-B7 (Table). Of the CP-B pts, 40/123 (9%), 9/123 (18%), and 58/123 (15%) initiated regorafenib at 160 mg, 120 mg, and 80 mg, per day, respectively. Median DoT with regorafenib was 2.3 months in CP-B pts and 3.7 months in the overall cohort. Incidence rates of TEAEs in CP-B pts and the overall cohort were similar (93% and 92%) and TEAEs were drug-related in 70% and 74% of pts, respectively. Grade 3–4 TEAEs occurred in 41% of CP-B pts and 39% of the overall cohort and were drug-related in 27% and 26% of pts, respectively. Serious TEAEs were observed in 48% of CP-B pts and 37% of the overall cohort, and were drug-related in 11% and 9% of pts, respectively. Drug-related TEAEs led to less frequent dose modifications in CP-B pts than in the overall cohort (28% vs 37%), but more frequent permanent discontinuations (28% vs 16%). Median OS in CP-B pts was 6.3 (95% confidence interval [CI] 4.9, 7.8) months and in CP-B7 pts was 6.7 (95% CI 5.1, 8.7) months. Conclusions: In REFINE, pts with uHCC and CP-B liver function had similar rates of grade 3–4 TEAEs, but a higher occurrence of serious TEAEs due to underlying cirrhosis led to more frequent permanent discontinuations in CP-B pts. Median OS in CP-B7 pts was comparable with OS in CP-B pts overall. The evaluation of prognostic models to identify CP-B pt subgroups who may benefit from regorafenib treatment is a subject for further research. 1. Kim YJ, ILCA 2022. [Table: see text]