bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of time-of-day on nivolumab monotherapy infusion in patients with metastatic gastric cancer.
Authors: Ishizuka Yasunobu , Narita Yukiya , Sakakida Tomoki , Wakabayashi Munehiro , Kodama Hiroyuki , Honda Kazunori , Masuishi Toshiki , Taniguchi Hiroya , Kadowaki Shigenori , Ando Masashi , Tajika Masahiro , Muro Kei 
Published: January 2024

268 Background: Nivolumab monotherapy, an immune checkpoint inhibitor, is a standard of care for patients with metastatic gastric cancer (mGC) as a later-line treatment. Several studies have suggested that the circadian rhythm is essential in immune system function, including anti-cancer immunity. This study evaluated whether the time-of-day patterns of nivolumab infusion alter the efficacy of mGC treatment. Methods: This study retrospectively analyzed 298 consecutive mGC patients who received nivolumab monotherapy at a single institution between December 2014 and December 2022. Patients were divided into early (EA)- and late (LA)-nivolumab infusion groups: EA group = ≥70% of their infusions before 14:00, and LA group = <70% of their infusions before 14:00. Treatment efficacy (overall response rate [ORR], disease control rate [DCR], progression-free survival [PFS], and overall survival [OS]) was evaluated. Multivariate analyses included variables with P values <0.1 in univariate analyses. Results: A total of 248 patients were eligible; 140 were classified as having EA, and 108 as having LA. Most baseline characteristics were similar between EA and LA. In contrast, the median infusion time was earlier in EA than in LA (11:50 vs. 14:22). The median follow-up time was 9.0 months (range, 1.2–64.7 months). ORR and DCR were significantly higher in the EA than in the LA among 149 patients with measurable lesions (ORR, 16.9% vs. 3.3%, P=0.01; DCR, 47.2% vs. 20.0%, P<0.01). Patients with EA had significantly better prognoses than those with LA in terms of PFS (median PFS, 2.3 vs. 1.6 months.; hazard ratios [HR], 0.65; P<0.01) and OS (median OS, 7.6 vs. 3.9 months.; HR, 0.64; P<0.01). EA patients received the subsequent chemotherapy more frequently than those in LA (54% vs. 32%; P<0.01). Multivariate analyses, including factors such as age, ECOG performance status, histological type, ascites, modified Glasgow Prognostic Score, and timing of nivolumab infusion, showed that EA was an independent prognostic factor for PFS (adjusted HR, 0.66; P<0.01) and OS (adjusted HR, 0.62; P<0.01). Conclusions: Our data suggest that efforts to schedule nivolumab infusions before mid-afternoon could be considered in daily practice.
Recurrence-free survival as a surrogate for overall survival in esophageal squamous cell carcinoma: Nationwide real-world data from Japan.
Authors: Okui Jun , Nagashima Kengo , Matsuda Satoru , Sato Yasunori , Okamura Akihiko , Kawakubo Hirofumi , Muto Manabu , Kakeji Yoshihiro , Kono Koji , TAKEUCHI HIROYA , Watanabe Masayuki , Doki Yuichiro , Bamba Takeo , Fukuda Takashi , Fujiwara Hitoshi , Sato Shinsuke , Noma Kazuhiro , Miyata Hiroshi , Fujita Takeo , Kitagawa Yuko 
Published: January 2024

269 Background: One of the limitations of the established gold standard, overall survival (OS), is that it requires an extended follow-up period. Addressing this challenge involves investigating appropriate statistically and clinically relevant surrogate endpoints. However, there is a paucity of studies using real-world data (RWD) to explore surrogacy in patients with esophageal squamous cell carcinoma (ESCC). Our study aims to investigate whether recurrence-free survival (RFS) is a valid surrogate endpoint for OS in surgically resectable advanced ESCC patients, utilizing a comprehensive nationwide database in Japan. Methods: The ESCC patients who received neoadjuvant CF (cisplatin and 5-fluorouracil) or DCF (docetaxel, cisplatin and 5-fluorouracil) at 58 Japanese esophageal centers certified by the Japan Esophageal Society were retrospectively reviewed. Kendall's tau between RFS and OS was used at the individual level, and the coefficient of determination was used at the institutional level to assess surrogacy. Additionally, surrogacy between each short-term postoperative endpoint (pathological complete response [pCR] or pathological grade) and OS was investigated using novel statistical methods. Results: Our study encompassed 3154 ESCC patients who underwent subtotal esophagectomy from 2010 to 2015. The cStage I/II/III/IVA/IVB (due to supraclavicular lymph node metastasis) was 224 (7.1%), 1008 (32.0%), 1664 (52.8%), 117 (3.7%), and 140 (4.4%), respectively. The 5-year OS and RFS rate for the entire cohort was 56.6% and 47.7%, respectively. In the primary analysis, a strong correlation between RFS and OS was found (Kendall's tau = 0.797, 95% confidence interval [CI]: 0.782 to 0.812) at the individual level. Subgroup analysis revealed that the better the pathological response, the higher the tau value. An adjusted R2 of 100.0% (95% CI: 40.2 to 100.0) was obtained with the meta-regression model at the institutional level. The surrogate threshold effect was 0.703. Tau between pCR or pathological grade and OS were -0.025 (95% CI: -0.335 to 0.285) and 0.062 (95% CI: -0.086 to 0.209), respectively. Conclusions: The present study was the first nationwide RWD investigation to demonstrate a strong correlation between RFS and OS in surgically resectable ESCC patients who underwent neoadjuvant chemotherapy (NAC). Notably, this correlation was more pronounced in patients who had a more effective response to NAC. These findings hold promise for expediting the development of novel neoadjuvant treatment by shortening the duration of clinical trials.
Clinical presentation and delay to diagnosis and treatment in Mexican patients with gastric cancer.
Authors: Hernandez-Felix Jorge Humberto , Meneses-Medina Mónica I. Isabel , Jiménez Meza Marco Antonio , Conde Flores Emilio , Rosas Camargo Vanessa , Huitzil Melendez Fidel David David 
Published: January 2024

291 Background: Gastric cancer is the fifth leading cause of cancer-related deaths in Mexico. Diagnosis is often made at advanced stages, resulting in a poor prognosis. The delay from the onset of the first symptom to diagnosis and treatment could influence the poor prognosis of gastric cancer patients (pts) in our country. In Mexico, information on this topic is limited. We aim to investigate the time delay between the onset of symptoms, histological diagnosis, and initiation of oncological treatment in pts with gastric adenocarcinoma. Methods: We conducted a retrospective review of the clinical records at our institution of all pts with confirmed histological diagnosis of gastric adenocarcinoma (GC) treated between Jan 2005 and Dec 2017. Overall Survival (OS) was estimated using the Kaplan-Meier method. Groups were compared using Log-Rank test. Results: We included 270 pts with confirmed histopathological diagnosis of GC, 53.3% (n=144) women, median age 58 years (IQR 25-75); 44% (n=121) reported family history of cancer, 39.6% (n=107) smoking, H. pylori infection was documented in 22% (n=61). Symptoms before diagnosis were present in 98.5% (n=266) of pts, most common were: weight loss 77.4% (n=209), fatigue 51.9% (n=140), early satiety 51.1% (n=138), nausea 48.9% (n=132), vomiting 48.1% (n=130), dysphagia 21.5% (n=58), and gastrointestinal bleeding 37.8% (n=102). The most common method for histological diagnosis was endoscopy with biopsy in 86.7% (n=234). The median time between the onset of symptoms and histopathological diagnosis was 4.21 (IQR 2.25–8.48) months (m), between the onset of symptoms and the initiation of oncological treatment 5.28 (IQR 2.86–9.52) m, and between histopathological diagnosis and oncological treatment 0.60 (IQR 0.13–1.21) m. 72.6% (n=196) of cases were stage IV, 14.1% (n=38) stage III, 8.1% (n=22) stage II, 4.8% (n=13) and stage 0 or I. The median OS for the entire cohort was 7.2 m, 3.7 m for stage IV, 17.3 m for stage III, and 84 m for stage I. Median OS for stage II was not reached, and it was 58% at 5 years. Symptoms associated with worse or better survival are shown in table. Conclusions: Reducing delays in histopathological diagnosis from symptom onset could lead to earlier detection and curative treatments. Identifying alarm signs and appropriate patient navigation would enable earlier diagnosis and early treatment. [Table: see text]
Real-world (RW) effectiveness of nivolumab plus chemotherapy (NIVO+chemo) in patients (pts) with advanced or metastatic gastric carcinoma, gastroesophageal junction carcinoma, or esophageal adenocarcinoma (GC/GEJC/EAC).
Authors: Chau Ian , Barzi Afsaneh , Zhang Ying , You Min , Bertwistle David , Davis Catherine , Chen Clara 
Published: January 2024

295 Background: In the CheckMate 649 trial, NIVO+chemo demonstrated superior efficacy vs chemo alone in pts with previously untreated, advanced, non-human epidermal growth factor receptor 2 positive GC/GEJC/EAC. Our study was the first to evaluate the RW adoption patterns and effectiveness of NIVO+chemo as a first-line (1L) treatment of advanced GC/GEJC/EAC in the immediate period after NIVO approval in this setting. We report the 18-mo follow-up results. Methods: Pts in the United States ≥ 18 years of age with previously untreated advanced or metastatic GC/GEJC/EAC receiving NIVO+chemo or chemo alone (FOLFOX or CAPEOX) between 04/01/2021 and 12/31/2022 were identified in the Flatiron Health database. Pts were followed from the start of 1L therapy to death, loss of data availability, or the end of data abstraction, whichever occurred first. Results: 528 pts were eligible for the analysis (231 [44%] NIVO+chemo, 297 [56%] chemo). The prevalence of PD-L1 combined positive score (CPS) ≥ 5 before the 1L therapy was 55% for NIVO+chemo and 27% for chemo. Baseline demographic and clinical characteristics were comparable between treatment groups in the overall cohort and the CPS subgroups. Median follow-up (interquartile range) was 6.0 (2.4−9.8) mo for NIVO+chemo and 6.1 (2.5−9.7) mo for chemo. There were 87 (37.7%) deaths in the NIVO+chemo cohort and 138 (46.5%) in the chemo cohort. NIVO+chemo demonstrated superior overall survival (OS) in the overall cohort, with a 12-mo OS rate of 53.3% vs 38.1% for chemo and a 2.6-mo improvement in median OS (12.6 [95% confidence interval (CI), 10.2−17.9] mo vs 10.0 [8.9−11.5] mo, P = 0.047). Univariate Cox regression analysis of OS yielded a hazard ratio (HR) of 0.76 (95% CI, 0.58−1.00; P = 0.048) and multivariate Cox regression yielded an HR of 0.74 (95% CI, 0.56−0.98; P = 0.033) for NIVO+chemo vs chemo. There was also a consistent trend toward OS benefit with NIVO+chemo vs chemo in all CPS subgroups (Table). Multivariate analysis in the CPS ≥ 1 subgroup yielded a HR of 0.51 (95% CI, 0.30−0.89) for NIVO+chemo vs chemo but was not feasible in other subgroups due to sample size. Conclusions: NIVO+chemo showed superior OS vs chemo alone in previously untreated pts with advanced GC/GEJC/EAC in the RW setting. A trend toward OS benefit was also observed in all CPS subgroups, which will be further examined in future analyses with larger samples and longer follow-up. Clinical trial information: NCT02872116 . [Table: see text]
A multi-institutional prospective study to compare postoperative quality of life of patients who undergo proximal or total gastrectomy for early gastric cancer (CCOG1602).
Authors: Hojo Yumiko , Kanda Mitsuro , Mochizuki Yoshinari , Tanaka Chie , Ito Seiji , Watanabe Takuya , Sueoka Satoshi , Ishiyama Akiharu , Yamada Takanobu , Oshima Takashi , Hattori Masashi , Koike Shinya , Ishigure Kiyoshi , Teramoto Hitoshi , Murotani Kenta , Kodera Yasuhiro 
Published: January 2024

296 Background: Proximal gastrectomy (PG) has become an increasingly preferred procedure for treating early cancer in the upper third of the stomach when oncological safety is ensured, with expectation for improvement of nutritional status and quality of life (QOL) attributable to the remnant stomach. Although few studies compare postoperative outcomes of patients who undergo total gastrectomy (TG) and PG based on questionnaires, their significant limitations include the retrospective design, use of a questionnaire not specific to a postgastrectomy setting, and observation at a fixed time or after a short postoperative period. Methods: A multi-institutional prospective study (CCOG1602) of patients who undergo PG or TG for cStage I gastric cancer was conducted. We used the Post-Gastrectomy Syndrome Assessment Scale (PGSAS)-37 and The European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC-QLQ-C30) to evaluate the changes in body weight and QOL over a 3-year postoperative period. The primary endpoint was the weight loss rate 3 years after surgery. Results: We enrolled 109 patients from 18 institutions and selected 65 and 19 patients for inclusion in the TG and PG groups, respectively. There were no differences in age, sex, or preoperative body mass index between the TG and PG groups. Mean postoperative weight loss rates were 16.0% and 11.7% for the TG and PG groups, respectively (Cohen's D 0.656) during postoperative year 1 and 15.0% and 10.8% for TG and PG (Cohen's D 0.543), respectively, during postoperative year 3, indicating that the PG group achieved a better trend with a moderate effect size. According to the PGSAS-37, the PG group experienced a better trend in the indigestion subscale (Cohen's D –1.085) and total symptom score (Cohen's D –0.59) during postoperative year 3 compared with the TG group. In contrast, the EORTC-QLQ-C30 identified no difference between the groups at any time point during the 3-year postoperative period. Conclusions: The CCOG1602 demonstrates that PG tended to be more favorable compared with TG with respect to postoperative weight loss and QOL, particularly regarding indigestion. Clinical trial information: UMIN000020070 .
Feasibility of functional evaluation in older adults with gastroesophageal cancer using fitness trackers.
Authors: Laderman Lauren , Meeker Caitlin R. , Handorf Elizabeth A. , Filchner Kelly A. , Tejani Mohamedtaki Abdulaziz , Williams Grant Richard , Winer Arthur , Arora Sukeshi Patel , Vijayvergia Namrata , Dotan Efrat 
Published: January 2024

298 Background: With advances in treatment and an aging population, gastroesophageal cancer (GEC) in older adults (OA) is increasing. Geriatric assessment (GA) is recommended as part of treatment decision in patients ≥ 65. Unfortunately, due to the complex nature and multiorgan effects of GEC, it is often difficult for oncologists to discern whether GA abnormalities are secondary to aging or the GEC itself. Because of their objectivity, fitness trackers are becoming increasingly popular in the functional evaluation of cancer patients. While fitness trackers have shown feasibility and validity in some cancers, data for their use in OA is currently limited. Objective: Evaluate the feasibility of functional status assessment via Fitbit activity tracker (FB) in comparison to traditional geriatric assessments in OA with GEC. Methods: Patients age ≥65 with any stage of GEC completed a GA and were given a FB to wear for 3 days in line with the battery life of the device. GA included a comprehensive evaluation of all geriatric domains with functional status assessed by performance status (PS), falls, Timed Up and Go (TUG), Activities of Daily Living (ADLs), and Instrumental Activities of Daily Living (IADLs). FB collected total steps per day (SPD), and patients’ mean SPD was calculated. We compared patient characteristics and outcomes using Fisher’s exact and Wilcoxon tests grouped by below and above median SPD. Results: 82 patients completed GA, of which 69 (84%) wore FB for ≥8 hours. Mean SPD for all patients was 2827 (38 – 11032), median SPD was 2264. Patients with ≤ median SPD were older (75 vs 72 p=0.034), female (32% vs 14% p=0.093), Black (24% vs 9% p=0.068), and living alone (29% vs 14% p=0.153). Patients SPD below and above the median had similar distributions of education level (≤12 yrs 35% vs 31% p=0.802) and Stage (>2 82% vs 80% p=0.99). Patients with SPD below the median were more likely to have ≥ 2 abnormalities on GA (68% vs. 40%, p=0.03), self-reported PS >2 (24% vs 0% p=0.013), and impaired IADL (33% vs 9% p=0.064). Patients with lower SPD had higher rates ≥Gr 3 toxicity (47% vs 20% p=0.022) and hospitalization (32% vs 6% p=0.006). The rate of abnormal TUG was similar in both groups (21% vs 17%, p=0.285). Conclusions: FB use for short objective evaluation functional status is feasible among OA with GEC and provides data which correlates with other GA abnormalities and treatment tolerance. Additional research is warranted to further incorporate this assessment tool into clinical care.
Moving towards a personalised understanding of the nutritional impact of self-expanding metallic stents (SEMS) in gastro-oesophageal cancer: A retrospective case note review of a tertiary referral oncology centre.
Authors: Cunningham Aimee , Alattal Taibah , Foulkes Lindsey , Lewis Alexandra R , Backen Alison Catherine , Williamson Fiona , McQueenie Esther , Owen-Holt Vikki , Williams Kate , Hubner Richard , Waddell Tom , Valpione Sara , Laasch Hans-Ulrich , Mansoor Wasat , Weaver Jamie 
Published: January 2024

301 Background: Dysphagia is a common life-impacting complication for patients with gastro-oesophageal (O-G) cancer. Options to alleviate dysphagia include insertion of SEMS or percutaneous endoscopic gastrostomy (PEG). SEMS improve quality of life by enabling a person to eat a varied diet, but are associated with complications including pain and need for reintervention. Although studies have shown SEMS improve dysphagia, consequent longitudinal impact on nutritional status has not been evaluated. There is a need to better characterise risks and benefits of SEMS to allow a personalised approach to both insertion and follow-up. Methods: We identified patients with a confirmed diagnosis of O-G cancer, who underwent SEMS insertion at The Christie NHS Foundation Trust in 2021 and 2022. Data was retrospectively collected about patient and stent characteristics, and patient outcomes to quantify benefits and risks of SEMS. Results: 112 patients had 127 SEMS inserted at The Christie. Patients’ International Dysphagia Diet Standardisation Initiative (IDDSI) score significantly improved after SEMS insertion (N=120); prior to SEMS 62% were only managing liquids and purees (IDDSI 3 and 4) and 24% were not able to eat enterally. Post SEMS, 76% tolerated textured foods (IDDSI 5 and above) and only 21.5% were limited to liquids/purees. We observed a significant reduction in the rate of weight loss (% body weight/10 days) following SEMS insertion (-0.010 ± 0.009 vs. -0.001 ± 0.010, P < 0.001). 12% of patients experienced grade 3 SEMS-related toxicity or stent failure within 30 days, and 20% developed significant pain within 24 hours of SEMS insertion. Conclusions: SEMS provide meaningful nutritional benefit in the majority of patients with O-G cancer, as weight loss is significantly slowed following insertion. However, we identified two groups of patients who did not benefit from SEMS; those who continued to lose weight and those who had stent failure. We did not find predictive factors for stent failure from multivariate analysis of baseline demographics or stent characteristics. Therefore, more detailed analysis of tumour factors, imaging findings and SEMS location from a larger cohort of patients may be required to identify patients who are unlikely to benefit from SEMS, and alternative interventions such as PEG feeding could be considered.
Efficacy and safety of nivolumab and CapeOX in patients with previously untreated FGFR2-positive, PD-L1-positive advanced gastric cancer: A single-arm, multicenter, phase 2 study NIVOFGFR2.
Authors: Tsimafeyeu Ilya , Musayeva Gunel , Samira Mahmudova , Otkhozoria Nana , Abbasov Bahadur , Kahharov Alisher 
Published: January 2024

303 Background: Nivolumab in combination with chemotherapy has been approved in the first-line treatment of PD-L1-positive metastatic gastric cancer (GC). Fibroblast growth factor receptor 2 (FGFR2) is overexpressed in 30% of patients with GC and is a potential new target for targeted therapy with monoclonal antibodies1 or allosteric extracellular inhibitors.2 The aim of the NIVOFGFR2 study was to evaluate the preliminary efficacy of nivolumab in metastatic GC co-expressing PD-L1 and FGFR2. Methods: In this single-arm, multi-center, phase 2 study, eligible patients had metastatic untreated HER2-negative gastric adenocarcinoma with centrally confirmed expression of PD-L1 (CPS≥5; DAKO 28-8) and FGFR2 (moderate (2+) and strong (3+) membranous staining in more than 1% of tumor cells; Abсam EPR24075-418). Patients received nivolumab 360 mg with CapeOX (capecitabine and oxaliplatin) every 3 weeks. The primary endpoint was 1-year progression-free survival (PFS). Secondary endpoints included median PFS and overall survival (OS), objective response rate (ORR) and Grade ≥3 adverse events rate. Results: Seventy-four HER2-negative patients were screened and23 (31%) patients were enrolled (median age 61 years, men 74%, Caucasian 91%, ECOG PS 1-2 78%, organs with ≥2 metastases 78%; CPS (5-9) 22%, (≥10) 78%). 1-year PFS rate was 30,4%. The median PFS was 6.2 months (95% CI 4.4-7.6). The ORR was 21.7% with 1 complete response. With a median follow-up of 11.8 months at data cutoff, the median OS was not reached. Grade ≥3 treatment-related adverse events were reported in 9 (39.1%) patients. Conclusions: An interim analysis demonstrates modest efficacy and an acceptable safety profile of nivolumab in combination with chemotherapy in patients with FGFR2-positive, PD-L1-positive metastatic GC. Further follow-up is ongoing. 1. Wainberg, Lancet Oncol. 2022. 2. Tsimafeyeu, Invest New Drugs. 2023. Clinical trial information: NCT05859477 .